Karsinoma kolon dan depresi

Jurnal 1
Support Care Cancer. 2012 February; 20(2): 319324.
Publise! online 2011 "anuary 1#. !oi: 10.100$%s00&20'010'10#2'#
P(C)*: P(C3244+03
The Beck Depression Inventory (BDI-II)
and a single screening question as
screening tools for depressive disorder in
Dutch advanced cancer patients
Franca ,ar-eno.en/
1
0ric .an 1i2s3i24/
2
5.onne 0n6els/
1
Cornelis 7an/
3
"u!it Prins/
4
Cris .an ,eel/
2
an! 7ris 8issers
1
9utor in:or-ation ; 9rticle notes ; Copyri6t an! <icense in:or-ation ;
=o to:
Abstract
Purpose
*epression is i6ly pre.alent in a!.ance! cancer patients/ but te !ia6nosis o:
!epressi.e !isor!er in patients 3it a!.ance! cancer is !i::icult. Screenin6 instru-ents
coul! :acilitate !ia6nosin6 !epressi.e !isor!er in patients 3it a!.ance! cancer. >e ai-
o: tis stu!y 3as to !eter-ine te .ali!ity o: te ?ec4 *epression )n.entory (?*)'))) an!
a sin6le screenin6 @uestion as screenin6 tools :or !epressi.e !isor!er in a!.ance! cancer
patients.
ethods
Patients 3it a!.ance! -etastatic !isease/ .isitin6 te outpatient palliati.e care
!epart-ent/ 3ere as4e! to :ill out a sel:'@uestionnaire containin6 te ?ec4 *epression
)n.entory (?*)'))) an! a sin6le screenin6 @uestion A9re you :eelin6 !epresse!BC >e
-oo! section o: te P1)(0'(* 3as use! as a 6ol! stan!ar!.
!esults
SiDty'one patients 3it a!.ance! -etastatic !isease 3ere eli6ible to be inclu!e! in te
stu!y. Co-plete !ata 3ere obtaine! :ro- 4+ patients. >e area un!er te cur.e o: te
recei.er operatin6 caracteristics analysis o: te ?*)')) 3as 0.#2. >e opti-al cut'o::
point o: te ?*)')) 3as 1+ 3it a sensiti.ity o: 90E an! a speci:icity o: +9E. >e sin6le
screenin6 @uestion so3e! a sensiti.ity o: &0E an! a speci:icity o: 94E.
"onclusions
>e ?*)')) see-s an a!e@uate screenin6 tool :or a !epressi.e !isor!er in a!.ance!
cancer patients. >e sensiti.ity o: a sin6le screenin6 @uestion is poor.
#ey$ords% *epression/ 9!.ance! cancer/ 8ali!ation/ Screenin6 tool/ ?*)'))
=o to:
Introduction
*epression see-s i6ly pre.alent in patients 3it a!.ance! cancer. )n !i::erent stu!ies/
a lar6e .ariation o: pre.alence o: !epression in a!.ance! cancer (4E to &#E) is reporte!
F1G. >is lar6e .ariation in pre.alence can be eDplaine! by te use o: !i::erent researc
sa-ples 3it !i::erent ris4 :actors li4e cancer type/ a6e/ seD/ istory o: !epression/
alcool abuses/ an! by te use o: !i::erent assess-ent tools F24G. )n so-e patients 3it
a!.ance! cancer/ a !epressi.e !isor!er as !e:ine! in te *S(')8 can be !ia6nose!/
3ereas oters eDperience sy-pto-s o: !epression an! lo3 -oo! but !o not -eet te
!ia6nostic criteria o: te *S(')8. ?ot situations are associate! 3it a lo3er @uality o:
li:e an! conse@uently cause a bur!en :or te patient an! is care6i.ers F&/ +G.
)n patients 3it a!.ance! cancer/ se.eral :actors can in:luence te !ia6nostic process o:
!epression. Firstly/ speci:ic pysical si6ns an! sy-pto-s presente! in a patient 3it
a!.ance! cancer/ suc as 3ei6t loss or :ati6ue/ can ori6inate :ro- a!.ance! cancer or
:ro- !epression F$G. Pysical sy-pto-s an! !epressi.e sy-pto-s -ay partly sare a
co--on pat3ay o: !istress F#G/ 3ic -a4es it !i::icult to !istin6uis bet3een cause
an! e::ect: pysical sy-pto-s -ay increase a !epresse! :eelin6 on te one an! an! on
te oter an! a !epresse! :eelin6 -ay result in -ore pysical co-plaints F9/ 10G.
Secon!ly/ it -ay be !i::icult to !istin6uis 6rie: :ro- !epression in patients 3it
a!.ance! cancer F11G. >ir!ly/ :or bot patient an! pysician e-otional issues are
!i::icult to a!!ress in tis pase o: li:e. Hnly a -inority (1$E) o: a!.ance! cancer
patients eDplicitly eDpress teir e-otional !istress to teir pysician an! pysicians
te-sel.es !o not o:ten a!!ress e-otional proble-s in con.ersations 3it a!.ance!
cancer patients/ possibly because tey !o not :eel 3ell traine! in co--unication 3it
palliati.e care patients F12/ 13/ 1$G.
>e reco6nition o: !epression is not opti-al :or oncolo6ists F14/ 1&G an! oter pysicians
as 3ell F1+G because o: te reasons -entione!. ): patients 3it a!.ance! cancer 3o are
su::erin6 :ro- a !epressi.e !isor!er are not i!enti:ie!/ tey 3ill not be able to bene:it
:ro- te par-acolo6ical an! psycolo6ical treat-ents tat are consi!ere! bene:icial
F1+/ 1#/ 19G.
Screenin6 instru-ents coul! :acilitate reco6niIin6 !epressi.e !isor!er in tis population
F20G. Syste-atic screenin6 :or sy-pto-s li4e !epression :its into te principles o:
a!.ance! care plannin6 tat is pro-ote! in patients 3it a!.ance! cancer or in nee! o:
palliati.e care F21G. >e i!eal screenin6 instru-ent co-bines a i6 sensiti.ity 3it a
i6 speci:icity. ,en usin6 a cut score in a screenin6 instru-ent/ te opti-al cut score
:or a speci:ic patient 6roup can be !eter-ine! 3it a recei.er operatin6 caracteristics
analysis. >e use:ulness o: a screenin6 tool !epen!s on te positi.e an! ne6ati.e
pre!icti.e .alue consi!erin6 te -ain ai- o: te screenin6. ,en screenin6 :or
!epression in patients in a palliati.e tra2ectory/ 6i.en te .ulnerability o: tese patients
an! te conse@uences o: !epression :or teir ealt status an! @uality o: li:e/ a i6
ne6ati.e pre!icti.e .alue see-s -ost i-portant. False positi.e cases can be rule! out in
:urter !ia6nostic assess-ent.
1ecently/ screenin6 :or !epression 3it one or t3o si-ple @uestions 3as su66este! to be
i6ly speci:ic F22G/ altou6 !i::erent stu!ies report !i::erent :in!in6s on psyco-etric
.alues o: sort screenin6 -eto!s F23G. 9 sort screenin6 -eto! is appealin6 because
te costs 3oul! be consi!erably lo3er tan oter -eto!s :or !ia6nosin6 !epressi.e
!isor!er; it is ti-e e::icient an! -any people can be screene! :or !epression in a @uic4
an! si-ple 3ay.
>e ?ec4 *epression in.entory (?*)'))) is one o: te -ost 3i!ely use! screenin6 tools
:or !epression an! it -ay pro.i!e a use:ul -eto! :or screenin6 :or !epression in
palliati.e care F242+G. >is in.entory is a sel:'report @uestionnaire tat 3as ori6inally
!e.elope! to rate te se.erity o: !epressi.e sy-pto-s F2$G. >e ?*)')) as so3n 6oo!
psyco-etric @ualities as a screenin6 tool :or !epression. Jo3e.er/ te ?*)')) contains
se.eral ite-s on so-atic sy-pto-s o: !epression (:or eDa-ple/ @uestions about loss o:
ener6y/ :ati6ue/ an! loss o: appetite)/ 3ic -ay lea! to an o.eresti-ation o: positi.e
cases in a patient 6roup 3it so-atic illness. >e ?*)')) as been .ali!ate! in -any
sa-ples inclu!in6 cancer patients F2#G.
>e ai- o: te present stu!y 3as to assess te .ali!ity o: te ?*)')) an! a sin6le
screenin6 @uestion as screenin6 tools :or !epression in *utc'spea4in6 patients 3it
a!.ance! cancer. >e ypotesis 3as tat bot te ?*)')) an! te sin6le screenin6
@uestion are a!e@uate screenin6 tools :or !epressi.e !isor!ers in *utc a!.ance! cancer
patients.
=o to:
ethods
&thical approval and infor'ed consent
>e stu!y recei.e! appro.al o: te -e!ical etical co--ittee o: te 1a!bou! Kni.ersity
Li2-e6en (e!ical Centre. 9:ter obtainin6 in:or-e! consent/ patients 3ere as4e! to :ill
out a sel:'report @uestionnaire. Patients 3o 3ere unable to rea! an! un!erstan! te
*utc lan6ua6e 3ere eDclu!e! :ro- participatin6 in tis stu!y.
(a'ple and design
Fro- *ece-ber 2003 until (arc 200$/ all consecuti.e patients 3it a!.ance!/ non'
curable sta6es o: -etastatic cancer re:erre! to a ne3 outpatient palliati.e care !epart-ent
at te 1a!bou! Kni.ersity Li2-e6en (e!ical Centre 3ere as4e! to participate in te
stu!y by teir treatin6 pysician. Patients consi!ere! by teir pysician to be too ill to
participate 3ere not as4e!.
)uestionnaires and data collection
Patients 3ere as4e! to pro.i!e !e-o6rapic in:or-ation. >e ?*)')) an! a sin6le
screenin6 @uestion A9re you :eelin6 !epresse!BC 3ere use! to screen :or !epression. >e
?*)')) is a 21'ite- sel:'report @uestionnaire 3it :our response options :or eac ite-.
)te-s o: te ?*)')) relate to !i::erent sy-pto-s o: !epression suc as sa!ness/
opelessness/ sel:'bla-e/ 6uilt/ :ati6ue/ an! loss o: appetite. Hn eac ite-/ patients are
as4e! to coose te state-ent tat best !escribes teir attitu!e to3ar!s te ite-. Scores o:
te ?*)')) can .ary :ro- 0 to +3 an! are o:ten classi:ie! as :ollo3s: 013 no !epression/
1419 -il! !epression/ 202# -o!erate !epression/ an! 29+3 se.ere !epression F29G.
Patients 3ere as4e! to :ill out te @uestionnaire !urin6 teir .isit at te outpatient
!epart-ent or at o-e. >e -oo! section o: te P1)(0'(* F30G 3as a!-inistere! as a
6ol! stan!ar! :or te clinical !ia6nosis o: a !epressi.e !isor!er by te pysician/ 3o
3as blin! to te results o: te @uestionnaire. >e P1)(0'(* is a structure! inter.ie3
base! on te *S(')8 classi:ication :or !epressi.e !isor!er an! as been .ali!ate! in
oncolo6y patients F31G. >e P1)(0'(* pro.i!es stan!ar!iIe! @uestions tat :ocus
!irectly on 4ey !ia6nostic sy-pto-s an! a !epressi.e !isor!er 3as !ia6nose! 3en
patients :ul:ille! te *S(')8 criteria. >e ti-e re@uire! to co-plete te P1)(0'(*
-oo! section is approDi-ately 10 -in.
(tatistical analysis
Statistical analysis 3as per:or-e! 3it SPSS 1+.0. (eans/ sensiti.ity/ speci:icity/ an!
positi.e an! ne6ati.e pre!icti.e .alue 3ere co-pute!. 9 recei.er operatin6
caracteristics (1HC) analysis 3as per:or-e! to !eter-ine te opti-al cut score :or te
?*)')) as a screen :or !epression in tis population.
=o to:
!esults
Fro- *ece-ber 2003 until (arc 200$/ +1 patients (29 -en/ 32 3o-en) 3ere eli6ible to
be inclu!e! in te stu!y. >e inclusion perio! o: tis stu!y as been relati.ely lon6
because te outpatient !epart-ent :or palliati.e care patients 3as a ne3 :acility in te
ospital an!/ conse@uently/ re:erral nu-bers 3ere lo3. Patients su::ere! :ro- a .ariety o:
a!.ance! cancers (23E colon carcino-a/ 1+E breast cancer/ #E ea! an! nec4 cancer/
#E lun6 cancer/ 4&E so-e oter -ali6nancy). H: te +1 eli6ible patients/ 20 patients
(33E) !ecease! 3itin + -onts. Se.en eli6ible patients re:use! to participate in te
stu!y.
9-on6 te &4 patients 3o enrolle! in te stu!y/ a!-inistration o: te P1)(0'(* 3as
not co-plete! in ei6t patients (Fi6. 1). >ere:ore/ co-plete !ata 3ere obtaine! o: 4+
patients (2+ 3o-en/ 20 -en/ -ean a6e +0 years/ -e!ian a6e &# years). >e -ean ?*)'))
score o: te 4+ patients 3o participate! in te stu!y 3as 14.$ (S* 9.9).
Fi6. 1
)nclusion o: patients
>en out o: 4+ patients (22E) 3ere !ia6nose! 3it a -a2or !epressi.e !isor!er usin6 te
P1)(0'(*. >e area un!er te cur.e (9KC) o: te 1HC analysis o: te ?*)')) 3as
0.#2 (Fi6. 2). Ksin6 te tra!itional cut score o: 14/ te ?*)')) !e-onstrate! 90E
sensiti.ity an! +4E speci:icity. >e positi.e an! ne6ati.e pre!icti.e .alues 3ere 4&E
an! 9$E/ respecti.ely. Jo3e.er/ usin6 a i6er cut score o: 1+ retaine! i6 sensiti.ity
(90E) 3ile increasin6 speci:icity to +9E. >e positi.e an! ne6ati.e pre!icti.e .alues
3ere &&E an! 9+E/ respecti.ely. >e sin6le screenin6 @uestion !e-onstrate! &0E
sensiti.ity an! 94E speci:icity. >e positi.e an! ne6ati.e pre!icti.e .alues o: te sin6le
screenin6 @uestion 3ere $1E an! #$E/ respecti.ely (>able 1).
Fi6. 2
1ecei.in6 operatin6 caracteristic bec4 !epression in.entory (?*)')))
>able 1
Psyco-etric properties o: sin6le screenin6 @uestion an! ?*)'))
=o to:
Discussion
>is stu!y so3s tat te ?*)')) is an a!e@uate screenin6 tool to !etect !epressi.e
!isor!er in patients 3it a!.ance! cancer. Ksin6 a cut'o:: point o: 1+/ it as 6oo!
sensiti.ity (90E) an! acceptable speci:icity (+9E). >e sin6le screenin6 @uestion
per:or-e! unsatis:actory/ !e-onstratin6 only &0E sensiti.ity an! 94E speci:icity. =i.en
te conse@uences o: not reco6niIin6 a !epression in tis .ulnerable patient 6roup an! te
possibility to rule out !epression in :urter !ia6nostic assess-ent in patients 3o screen
positi.e :or !epression/ a i6 sensiti.ity an! i6 ne6ati.e pre!icti.e .alue o: screenin6
tools are i-portant an! a lo3er speci:icity an! positi.e pre!icti.e .alue are accepte!.
>e results o: tis stu!y !i::er so-e3at :ro- pre.ious :in!in6s on psyco-etric
properties o: te ?ec4 *epression )n.entory in a cancer patient sa-ple. 7atI et al. :oun!
tat 3it a cut score o: 1+ te ?*) a! a sensiti.ity o: $3E an! speci:icity o: 100E in a
sa-ple o: +0 a-bulatory patients 3it a -ali6nancy o: te ea! an! nec4 re6ion an!
i!enti:ie! te opti-u- cut score at 13 3it a sensiti.ity o: 92E an! a speci:icity o: 90E
F32G. )n te present stu!y/ te participants ori6inate! :ro- a etero6eneous 6roup o:
patients 3it a!.ance! cancer/ 3ereas 7atI et al. use! a -ore o-o6eneous 6roup o:
a-bulatory ea! an! nec4 cancer patients. Furter-ore/ 7atI et al. use! a !i::erent
instru-ent/ te Sce!ule :or 9::ecti.e *isor!ers an! SciIoprenia/ as a 6ol! stan!ar!.
9 possible sortco-in6 o: te ?*)')) as a screenin6 tool in a!.ance! cancer patients is
tat te nu-ber o: i!enti:ie! cases coul! be o.eresti-ate! because o: te so-atic ite-s
o: te @uestionnaire. >e speci:icity o: te ?*)')) in a!.ance! cancer patients -i6t be
increase! by eDclu!in6 te so-atic ite-s (e.6./ 3ei6t loss/ loss o: appetite/ etc.). >e
?ec4 *epression )n.entory Sort For- (?*)'SF)/ consistin6 o: se.en ite-s tappin6
eDclusi.ely a::ecti.e sy-pto-s/ -i6t be -ore appropriate :or tis population. <o.e et
al. per:or-e! a stu!y in 22$ 3o-en 3it -etastatic breast !isease in 3ic te ?*)'SF
a! a speci:icity o: +3E an! a positi.e pre!icti.e .alue o: 0.&2 F33G. >is nee!s :urter
stu!y to !eter-ine te psyco-etric properties in a -ore etero6eneous patient 6roup.
>e sensiti.ity o: te sin6le screenin6 @uestion in tis stu!y appeare! &0E/ 3ic is
al-ost si-ilar to te reporte! sensiti.ity o: &&E in an earlier stu!y in $4 palliati.e care
patients F34G. Hter pre.ious stu!ies/ o3e.er/ report a -uc i6er sensiti.ity o: a
sin6le screenin6 @uestion in palliati.e care patients ($2100E) F23/ 3&G. >e lo3
sensiti.ity o: te sin6le screenin6 @uestion in tis stu!y -ay point to !i::iculties
re6ar!in6 te -eanin6 o: te @uestion. >e 3or! !epression 4no3s !i::erent translations
an! !i::erent interpretations in te *utc lan6ua6e. >e eDact 3or!s tat a.e been use!
-i6t a.e in:luence! te results F3+G.
>is stu!y as so-e li-itations. Firstly/ te relati.ely s-all sa-ple siIe 3as recruite!
:ro- te recently starte! outpatient !epart-ent :or palliati.e care. S-all sa-ple siIe is
not unusual in palliati.e care/ in 3ic recruit-ent is !i::icult an! !ropout rates are i6
!ue to !eterioration o: ealt status an! !eat. Secon!ly/ te selection o: participants in
tis stu!y 3as per:or-e! by te treatin6 pysician. >e nu-ber o: patients tat te
pysicians consi!ere! too ill to participate 3as not recor!e!. )n 6eneral/ tou6/ te
participation o: patients in researc is i6/ 3en teir ApersonalC treatin6 pysician
in.ites te- :or participation/ but it -i6t intro!uce selection bias i: te pysician lea.es
out i6ly !istresse! patients. =i.en te relati.ely i6 scores on te ?*)')) in tis
sa-ple/ se.ere bias see-s unli4ely. >ir!ly/ 3e use! te P1)(0'(* as a 6ol! stan!ar!.
>e P1)(0'(* an! oter psyciatric inter.ie3s are not .ali!ate! :or advanced cancer
patients speci:ically. Jo3e.er/ tey a.e been .ali!ate! in cancer patients F31G.
>is stu!y o::ers a contribution to te !ia6nosis an! screenin6 o: !epressi.e !isor!er in
a!.ance! cancer patients. >e ?ec4 *epression )n.entory o::ers a -eto! :or brie: an!
sensiti.e !etection o: !epressi.e !isor!er in tis speci:ic 6roup o: patients. ): use!
syste-atically in all a!.ance! cancer patients/ tis screenin6 tool -ay increase an!
i-pro.e pysicianMs e.aluations o: not only so-atic/ but also psycolo6ical co-plaints
o: teir patients.
>o our 4no3le!6e/ tis is te :irst .ali!ation stu!y o: te *utc ?ec4 *epression
)n.entory an! o: a sin6le screenin6 @uestion to screen :or !epression in a etero6eneous
6roup o: a!.ance! cancer patients. Secon!ly/ it 6i.es a pre.alence o: !epression in
a!.ance! cancer patients/ base! on a clinical !ia6nosis 3it te P1)(0'(*/ contrary to
pre.alence nu-bers ac@uire! by @uestionnaires. )n clinical practice/ te screenin6 tool
can ser.e to alert pysicians to te possibility o: !epressi.e !isor!er an! ence 6i.e
attention to te -ental ealt status o: palliati.e care patients/ i: necessary :ollo3e! by
:urter !ia6nostic assess-ent an! appropriate treat-ent.
=o to:
"onclusions
>e ?*)')) see-s to be an a!e@uate screenin6 tool :or !epressi.e !isor!ers in *utc
a!.ance! cancer patients 3en usin6 a cut score o: 1+. >e sin6le screenin6 @uestion is
less a!e@uate to !etect !epression in palliati.e care patients/ consi!erin6 te lo3
sensiti.ity.
*ia6nosin6 !epression in patients 3it a!.ance! cancer re-ains a callen6e. Ksin6 a
.ali! screenin6 tool can :acilitate te process o: !ia6nosin6 !epression in tis speci:ic
6roup o: patients.
=o to:
Ackno$ledg'ents
"onflict of interest >e autors !eclare no con:lict o: interest relatin6 to tis -anuscript.
>e autors a.e :ull control o: te pri-ary !ata an! te !ata can be re.ie3e! on re@uest.
*pen Access >is article is !istribute! un!er te ter-s o: te Creati.e Co--ons
9ttribution Lonco--ercial <icense 3ic per-its any nonco--ercial use/ !istribution/
an! repro!uction in any -e!iu-/ pro.i!e! te ori6inal autor(s) an! source are cre!ite!.
=o to:
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an! treat-ent. ?iol Psyciatry. 2003;&4:2#3294. !oi: 10.101+%S000+'3223(03)00413'O.
FPub(e!G FCross 1e:G
11. Periya4oil "/ Jallenbec4 8S. )!enti:yin6 an! -ana6in6 preparatory 6rie: an!
!epression at te en! o: li:e. 9- Fa- Pysician. 2002;+&:##3#90. FPub(e!G
12. 9n!erson ,=/ 9leDan!er SC/ 1o!ri6ueI 7</ "e::reys 9S/ Hlsen (7/ Polla4 7)/
>uls4y "9/ 9rnol! 1(. ,at concerns -e is. 0Dpression o: e-otion by a!.ance! cancer
patients !urin6 outpatient .isits. Support Care Cancer. 200#;1+:#03#11. !oi:
10.100$%s00&20'00$'03&0'#. FP(C :ree articleG FPub(e!G FCross 1e:G
13. Polla4 7)/ 9rnol! 1(/ "e::reys 9S/ 9leDan!er SC/ Hlsen (7/ 9bernety 9P/ Su66
SC/ 1o!ri6ueI 7</ >uls4y "9. Hncolo6ist co--unication about e-otion !urin6 .isits
3it patients 3it a!.ance! cancer. " Clin Hncol. 200$;2&:&$4#&$&2. !oi:
10.1200%"CH.200$.12.41#0. FPub(e!G FCross 1e:G
14. Le3ell S/ Sanson'Fiser 1,/ =ir6is 9/ ?ona.entura 9. Jo3 3ell !o -e!ical
oncolo6istsM perceptions re:lect teir patientsM reporte! pysical an! psycosocial
proble-sB *ata :ro- a sur.ey o: :i.e oncolo6ists. Cancer. 199#;#3:1+401+&1. !oi:
10.1002%(S)C))109$'0142(199#101&)#3:#P1+40::9)*'CLC121Q3.0.CH;2'R. FPub(e!G
FCross 1e:G
1&. Passi4 S*/ *u6an ,/ (c*onal! (8/ 1osen:el! ?/ >eobal! *0/ 0!6erton S.
Hncolo6istsM reco6nition o: !epression in teir patients 3it cancer. " Clin Hncol.
199#;1+:1&941+00. FPub(e!G
1+. <loy!',illia-s (. *i::iculties in !ia6nosin6 an! treatin6 !epression in te
ter-inally ill cancer patient. Post6ra! (e! ". 2000;$+:&&&&&#. !oi:
10.113+%p-2.$+.#99.&&&. FP(C :ree articleG FPub(e!G FCross 1e:G
1$. ?arclay S/ ,yatt P/ Sore S/ Finlay )/ =ran!e =/ >o!! C. Carin6 :or te !yin6: o3
3ell prepare! are 6eneral practitionersB 9 @uestionnaire stu!y in ,ales. Palliat (e!.
2003;1$:2$39. !oi: 10.1191%02+921+303p-++&oa. FPub(e!G FCross 1e:G
1#. 94eci >/ H4uya-a >/ Hnisi "/ (orita >/ Furu4a3a >9 (200#) Psycoterapy :or
!epression a-on6 incurable cancer patients. Cocrane *atabase Syst 1e. (2):C*00&&3$.
FPub(e!G
19. Jop4o *1/ 1obertson S(/ Car.alo "P. Su!!en 6ains in !epresse! cancer patients
treate! 3it bea.ioral acti.ation terapy. ?ea. >er. 2009;40:34+3&+. !oi:
10.101+%2.bet.200#.09.001. FPub(e!G FCross 1e:G
20. 7elly ?/ (cCle-ent S/ Cocino. J(. (easure-ent o: psycolo6ical !istress in
palliati.e care. Palliat (e!. 200+;20:$$9$#9. !oi: 10.11$$%02+921+30+0$234$.
FPub(e!G FCross 1e:G
21. (urray S9/ Sei4 9/ >o-as 7. 9!.ance care plannin6 in pri-ary care. ?(".
200+;333:#+##+9. !oi: 10.113+%b-2.39009.&+9#+1.#0. FP(C :ree articleG FPub(e!G
FCross 1e:G
22. 9rroll ?/ =oo!year'S-it F/ 7erse L/ Fis-an >/ =unn ". 0::ect o: te a!!ition o: a
AelpC @uestion to t3o screenin6 @uestions on speci:icity :or !ia6nosis o: !epression in
6eneral practice: !ia6nostic .ali!ity stu!y. ?(". 200&;331:##4. !oi:
10.113+%b-2.3#+0$.4+4&3$.$C. FP(C :ree articleG FPub(e!G FCross 1e:G
23. (itcell 9"/ 7aar S/ Co66an C/ Jer!-an ". 9cceptability o: co--on screenin6
-eto!s use! to !etect !istress an! relate! -oo! !isor!ersSpre:erences o: cancer
specialists an! non'specialists. Psycooncolo6y. 200#;1$:22+23+. !oi:
10.1002%pon.122#. FPub(e!G FCross 1e:G
24. 1icter P/ ,erner "/ Jeerlein 9/ 7raus 9/ Sauer J. Hn te .ali!ity o: te ?ec4
*epression )n.entory. 9 re.ie3. Psycopatolo6y. 199#;31:1+01+#. !oi:
10.11&9%0000++239. FPub(e!G FCross 1e:G
2&. (ysta4i!ou 7/ >sili4a 0/ Parpa 0/ S-yrniotis 8/ =alanos 9/ 8laos <. ?ec4
*epression )n.entory: eDplorin6 its psyco-etric properties in a palliati.e care
population o: a!.ance! cancer patients. 0ur " Cancer Care 0n6l. 200$;1+:2442&0. !oi:
10.1111%2.13+&'23&4.200+.00$2#.D. FPub(e!G FCross 1e:G
2+. 8o!e-aier 9/ <in!en ,/ Siu C. Screenin6 :or e-otional !istress in cancer patients: a
syste-atic re.ie3 o: assess-ent instru-ents. " Latl Cancer )nst. 2009;101:14+414##.
!oi: 10.1093%2nci%!2p33+. FP(C :ree articleG FPub(e!G FCross 1e:G
2$. ?ec4 9>/ ,ar! CJ/ (en!elson (/ (oc4 "/ 0rbau6 ". 9n in.entory :or -easurin6
!epression. 9rc =en Psyciatry. 19+1;4:&+1&$1. !oi:
10.1001%arcpsyc.19+1.01$10120031004. FPub(e!G FCross 1e:G
2#. Jop4o *1/ ?ell "</ 9r-ento (0/ 1obertson S(/ Junt (7/ ,ol: L"/ (ullane C.
>e peno-enolo6y an! screenin6 o: clinical !epression in cancer patients. " Psycosoc
Hncol. 200#;2+:31&1. !oi: 10.1300%"0$$.2+n01T03. FPub(e!G FCross 1e:G
29. ?ec4 9>/ Steer 19/ ?ro3n =7 (199+) (anual :or te ?ec4 *epression )n.entory')).
1e: >ype: 1eport.
30. Fra6uas 1/ "r/ Jenri@ues S=/ "r/ <ucia (S/ )osi:escu *8/ Sc3artI FJ/ (eneIes P1/
=attaI ,F/ (artins (9. >e !etection o: !epression in -e!ical settin6: a stu!y 3it
P1)(0'(*. " 9::ect *isor!. 200+;91:111$. !oi: 10.101+%2.2a!.200&.12.003. FPub(e!G
FCross 1e:G
31. <eopol! 79/ 9les >9/ ,alc S/ 9-!ur 1"/ (ott <9/ ,ie6an!'Pac4ar! </ HD-an
>0. Pre.alence o: -oo! !isor!ers an! utility o: te P1)(0'(* in patients un!er6oin6
ra!iation terapy. )nt " 1a!iat Hncol ?iol Pys. 199#;42:110&1112. !oi: 10.101+%S03+0'
301+(9#)0034+'0. FPub(e!G FCross 1e:G
32. 7atI (1/ 7ope4 L/ ,al!ron "/ *e.ins =(/ >o-linson =. Screenin6 :or !epression
in ea! an! nec4 cancer. Psycooncolo6y. 2004;13:2+92#0. !oi: 10.1002%pon.$34.
FPub(e!G FCross 1e:G
33. <o.e 9,/ =rabsc ?/ Clar4e *(/ ?loc S/ 7issane *,. Screenin6 :or !epression in
3o-en 3it -etastatic breast cancer: a co-parison o: te ?ec4 *epression )n.entory
Sort For- an! te Jospital 9nDiety an! *epression Scale. 9ust L N " Psyciatry.
2004;3#:&2+&31. !oi: 10.10#0%2.1440'1+14.2004.013#&.D. FPub(e!G FCross 1e:G
34. <loy!',illia-s (/ *ennis (/ >aylor F. 9 prospecti.e stu!y to co-pare tree
!epression screenin6 tools in patients 3o are ter-inally ill. =en Josp Psyciatry.
2004;2+:3#43#9. !oi: 10.101+%2.6enosppsyc.2004.04.002. FPub(e!G FCross 1e:G
3&. Cocino. J(/ ,ilson 7=/ 0nns (/ <an!er S. A9re you !epresse!BC Screenin6 :or
!epression in te ter-inally ill. 9- " Psyciatry. 199$;1&4:+$4+$+. FPub(e!G
3+. Lo6uera 9/ Centeno C/ Car.a2al 9/ >e2e!or (9/ Kr!iroI "/ (artineI (. Spanis
A:ine tunin6C o: lan6ua6e to !escribe !epression an! anDiety. " Palliat (e!. 2009;12:$0$
$12. !oi: 10.10#9%2p-.2009.0024. FPub(e!G FCross 1e:G
Jurnal 2
Cancer Causes Control. 9utor -anuscript; a.ailable in P(C 2011 February 1.
Publise! in :inal e!ite! :or- as:
Cancer Causes Control. 2010 February; 21(2): 191199.
Publise! online 2009 Lo.e-ber 3. !oi: 10.100$%s10&&2'009'9449'1
P(C)*: P(C2#$2112
L)J(S)*: L)J(S19#100
Depression and cancer risk% +, years of
follo$-up of the Balti'ore &pide'iologic
"atch'ent Area sa'ple
9l!en <. =ross/ "osep ". =allo/ an! ,illia- ,. 0aton
9utor in:or-ation ; Copyri6t an! <icense in:or-ation ;
>e publiserUs :inal e!ite! .ersion o: tis article is a.ailable at Cancer Causes Control
See oter articles in P(C tat cite te publise! article.
=o to:
Abstract
*b-ective
>e ob2ecti.e 3as to caracteriIe te relationsip bet3een !epression an! inci!ent
cancer. Fe3 stu!ies a.e e-ploye! population'base! prospecti.e !ata on subtypes o:
cancer to a!!ress te @uestion.
ethod
9 population'base! sa-ple o: 3/1$$ cancer':ree a!ults :ro- te ?alti-ore 0pi!e-iolo6ic
Catc-ent 9rea Stu!y 3o a.e been :ollo3e! :or 24 years. CoD proportional aIar!s
-o!els 3ere use! to esti-ate relati.e aIar!s :or bot o.erall an! subtype'speci:ic
cancers a-on6 tose 3it a istory o: !epression.
!esults
>e ris4 set containe! 334 inci!ent cancer cases an! 40/&30 person'years o: obser.ation.
*)S%*S('))) -a2or !epression 3as associate! 3it a i6er aIar! :or o.erall cancer
(J1: 1.9/ 9&E C): 1.2/ 3.0) an! a statistically si6ni:icant increase! aIar! :or breast
cancer (J1: 4.4/ 9&E C): 1.0#/ 1$.+) a-on6 3o-en. >ere 3as a positi.e association
bet3een istory o: !epression an! prostate cancer/ but con:i!ence boun!s inclu!e! te
null. Lo reliable associations 3ere :oun! bet3een colon/ lun6/ or s4in cancers an!
!epression. >e pattern o: results 3as si-ilar :or !ysporia/ but not :or pobia or any
oter -ental !isor!er stu!ie!.
"onclusions
1esults re.eal a speci:icity to te association bet3een !epression an! or-onally
-e!iate! cancers/ 3ic pro.i!es support to ypoteses about a co--on biolo6ical
pat3ay bet3een !epression an! cancer. Furter researc can buil! on obser.ational
stu!ies to eDa-ine te -ecanis-s trou6 3ic our e-otions a::ect our ealt.
#ey$ords% Cancer/ *epression/ 0pi!e-iolo6y/ Coort
=o to:
Introduction
>e eDtent to 3ic psycosocial :actors a::ect cancer !e.elop-ent is i-portant because
unco.erin6 ris4 :actors :or cancer -ay open ne3 a.enues :or pre.ention an!
inter.ention. 9 lin4 bet3een a istory o: !epression an! cancer inci!ence as been
postulate! :or -illennia/ since te ti-e o: te ancient =ree4s F1G. )n!ee!/ statistical
e.i!ence :or suc an association 3as reporte! as early as 1#93 F1G. >3o -eta'analyses o:
lar6e epi!e-iolo6ic coort stu!ies a.e been per:or-e! 3itin te past t3o !eca!es to
a!!ress tis @uestion F2/ 3G. ?ot conclu!e! tat !epression presents a s-all/ barely
statistically si6ni:icant increase in te ris4 :or cancer/ but tat tere is consi!erable
etero6eneity in associations across stu!ies. (o!ern lar6e'scale epi!e-iolo6ic stu!ies
con!ucte! o.er te course o: te last se.eral !eca!es/ in te absence o: conclusi.e
biolo6ical e.i!ence o: co--on or causal etiolo6ies/ a.e pro.i!e! te best .enues in
3ic to stu!y !epression as a ris4 :actor :or cancer. So-e stu!ies :in! support F4+G/
3ile oters report ne6ati.e :in!in6s F$1&G. Still oter stu!ies/ analyIin6 !ata :ro- te
sa-e coort 3it !i::erent a-ounts o: :ollo3'up/ a.e :oun! associations bet3een
!epression an! speci:ic cancer subtypes/ suc as breast cancer F13/ 1+G.
Se.eral teories an! eDplanations/ restin6 on pysiolo6ical/ psycolo6ical/ an! 6enetic
6roun!s/ a.e been entertaine! to eDplain 3y !epression -i6t be a ris4 :actor :or
cancer. Pysiolo6ically base! eDplanations re.ol.e aroun! ypoteses tat !epression
eiter co-pro-ises i--une syste- :unction or inibits *L9 repair -ecanis-s F1$G.
Stress an! !epression can inibit *L9 repair enIy-es tat are critical :or apoptosis an!/
tere:ore/ !e:ense a6ainst -ali6nant tu-or 6ro3t F1#/ 19G. 9!!itionally/ !ecrease!
natural 4iller (L7) cell :unction as consistently been associate! 3it cronic stressors/
an! tese cells are i-portant to i--une syste- :unction because tey :i6t o:: .iral
in:ections an! !estroy tu-or cells F20G. >eories in.ol.in6 innate psycolo6ical reasons
:or a lin4 bet3een !epression an! cancer 6enerally propose te eDistence o: suc latent
ris4 :actors :or cancer as poor e6o !e:ense -ecanis-s/ copin6 s4ills/ or a sa! !isposition
:ollo3in6 loss F21/ 22G. >ese teories are !i::icult to test e-pirically 3it prospecti.e
coort stu!ies. (ore recently/ 6enetic caracteristics a.e been propose! tat -i6t lea!
to bot !epression an! certain subtypes cancer. For eDa-ple/ !ysre6ulate! proto'
onco6enes o: te ras :a-ily/ 3ic are proteins tat !irect cell 6ro3t/ can inibit
!opa-ine an! serotonin syntesis/ tereby lea!in6 to !epression F232+G. Certain
cancers/ speci:ically o: te pancreas/ lun6/ colon/ an! s4in/ a.e been associate! 3it
!isruption o: tis onco6ene :a-ily F23G.
0Distin6 prospecti.e coort stu!ies a.e se.eral li-itations tat a.e been cite! as
potential sources o: null or con:lictin6 :in!in6s F13/ 23G. <i-itations inclu!e relati.ely
sort :ollo3'up ti-es/ 3it -ost stu!ies a.in6 bet3een 10 an! 1& years o: prospecti.e
:ollo3'up; inco-plete or unreliable ascertain-ent o: !epression status at baseline; an! a
lac4 o: proper statistical control o: potential con:oun!ers. >e ?alti-ore 0pi!e-iolo6ic
Catc-ent 9rea (0C9) Stu!y resol.es -any o: tese 3ea4nesses. >o !ate/ te coort as
been :ollo3e! :or 24 years. *epression status 3as ascertaine! in 19#1 an! a6ain in
:ollo3'up 3a.es 3it :iel!3or4 :ro- 1993 to 199+ (abbre.iate! belo3 to A1994C) an!
:ro- 2004 to 200& (abbre.iate! belo3 to A200&C) usin6 te *ia6nostic )nter.ie3
Sce!ule (*)S)/ a .ali!ate! lay assess-ent tool 4eye! to *S('))) criteria establise! by
te 9-erican Psyciatric 9ssociation F2$G. >e !epression'cancer lin4 3as a!!resse!
usin6 0C9 !ata pre.iously in =allo et al. F13G usin6 13 years o: :ollo3'up an! 203
inci!ent cases o: cancer. >e present stu!y inclu!es 24 years o: :ollo3'up !ata an! 334
cancer cases. )n tis stu!y/ 3e up!ate esti-ates usin6 -ore :ollo3'up ti-e an! ne3
inci!ent cancer cases. Secon!/ 3e eDpan! upon pre.ious analyses usin6 !i::erent
statistical -eto!s/ na-ely sur.i.al analysis. >ir!/ 3e co-pare cancer ris4s :or oter
-ental ealt proble-s to pro.i!e in:or-ation about te speci:icity o: te !epression'
cancer association.
=o to:
ethods
>e 0C9 pro6ra- 3as te :irst coor!inate! lar6e'scale/ -ulti'site/ co--unity'base!
epi!e-iolo6ic sur.ey o: psyciatric !isor!ers a-on6 a 6eneral population in te Knite!
States. Ksin6 probability sa-plin6/ persons a6e! 1# an! ol!er li.in6 in ouseol!s/
prisons/ nursin6 o-es/ an! -ental institutions in 6eo6rapically !e:ine! catc-ent areas
3ere inter.ie3e! usin6 te *)S in 19#1 at :i.e uni.ersity'base! sites. 9t tis baseline/
respon!ents 6a.e in:or-e! consent an! per-ission to be inter.ie3e! a6ain at later ti-es.
1espon!ents at all sites 3ere re'inter.ie3e! 12 -onts later/ an! 3/4#1 persons resi!in6
in ouseol!s at baseline at te ?alti-ore site 3ere :urter inter.ie3e! in 1993199+
(A1994C) an! a6ain in 2004200& (A200&C). 9tte-pts a.e been -a!e to trace an! re'
inter.ie3 all participants :ro- 19#1 at eac :ollo3'up 3a.e. >e sur.ey co-pletion rate
in 19#1 3as $#E an! .ital status is currently 4no3n :or 99E o: te ori6inal coort.
Furter !etails o: te 0C9 sa-plin6 an! stu!y !esi6n are a.ailable else3ere F2#/ 29G.
For tese analyses/ 3e eDclu!e! persons 3o at teir baseline inter.ie3 in 19#1 reporte!
any li:eti-e istory o: cancer/ tus creatin6 a Aris4 setC o: persons 3o !i! not a.e a
istory o: cancer.
easure'ent strategy
Depression status
*epression status 3as te pri-ary eDposure o: interest an! 3as ascertaine! in a
stan!ar!iIe! :asion usin6 te *)S in all 0C9 3a.e inter.ie3s. >e *)S is co-pose! o:
stan!ar!iIe! @uestions tat can be use! to buil! *S('))) !ia6noses o: -ental !isor!ers
base! on sy-pto-s/ co'occurrence o: sy-pto-s in ti-e/ an! oter rele.ant :actors.
)n:or-ation about istory o: li:eti-e -a2or !epression an! !ysporia 3as a.ailable at te
sy-pto- le.el/ an! a co-puteriIe! al6orit- 3as use! to construct *S('))) !ia6noses.
>e *)S as been :oun! to be an i-per:ect tou6 conser.ati.e -easure o: !epressi.e
!isor!er 3en co-pare! to a psyciatristMs eDa-ination (sensiti.ity: 0.9#; speci:icity:
0.40) F30G. <i:eti-e istory o: !ysporic episo!e 3as assesse! at baseline an! !urin6
eac :ollo3'up 3a.e usin6 te @uestion/ AJa.e you e.er a! 2 3ee4s or -ore 3en you
:elt sa!/ blue/ or !epresse!/ or 3en you lost interest in tin6s you nor-ally en2oye!BC
For te present analysis/ 3e @uanti:ie! !epression status by sortin6 respon!ents into tree
-utually eDclusi.e 6roups: persons 3o reporte! a li:eti-e istory o: -a2or !epression/ a
li:eti-e istory o: a !ysporic episo!e/ or neiter a istory o: -a2or !epression nor
!ysporic episo!e.
"ancer
Cancer status 3as te pri-ary outco-e o: interest. )t 3as ascertaine! trou6 sel:'reports
:ro- respon!ents inter.ie3e! at te 1994 an! 200& :ollo3'up inter.ie3s/ an! also :ro-
te Lational *eat )n!eD (L*)) trou6 200$. Cancer 3as consi!ere! present i: it 3as
eiter a pri-ary or contributin6 cause o: !eat on a !eat certi:icate. Cancer status 3as
:urter classi:ie! by type into breast/ colon/ lun6/ prostate/ an! s4in cancers. 5ear o:
cancer onset/ nee!e! :or te sur.i.al analyses !escribe! belo3/ 3as !eter-ine! !urin6
te 2004200& 3a.e inter.ie3s by as4in6 about te year o: cancer onset :or tose 3o
reporte! a.in6 cancer. Participants 3o reporte! a istory o: cancer !urin6 te 1994
inter.ie3 3a.e/ o3e.er/ 3ere not as4e! 3en tey 3ere :irst !ia6nose! 3it cancer.
Furter/ ti-e o: cancer !ia6nosis 3as not a.ailable :or cancers ascertaine! trou6 te
L*). Hnset !ates 3ere i-pute! :or tese cancers by usin6 pre!icti.e e@uations tat too4
into account seD/ s-o4in6 status/ an! etnicity a-on6 4no3n !ates o: cancer onset :ro-
te 200& inter.ie3 3a.e. 9 nu-ber o: sensiti.ity analyses/ !escribe! later/ teste! te
robustness o: :in!in6s by calculatin6 ti-e o: onset in !i::erent 3ays.
*ther covariates
9ll .ariables 3ere selecte! base! on a priori teory. ,e too4 into consi!eration a6e/ sel:'
reporte! race/ seD/ -arital status at eac 3a.e/ s-o4in6 status at eac 3a.e/
socioecono-ic status (S0S)/ an! istory o: alcool abuse%!epen!ence as possible
con:oun!ers in te relationsip bet3een !epression an! cancer. ,e also controlle! :or
parity 3en consi!erin6 aIar!s :or breast cancer. >o control :or s-o4in6 status/ 3e
cate6oriIe! respon!ents into ne.er s-o4ers/ :or-er s-o4ers/ current s-o4ers consu-in6
one pac4 or less o: ci6arettes per !ay/ an! current s-o4ers consu-in6 -ore tan one
pac4 per !ay. S0S in 19#1 3as represente! by a co-posite score a66re6atin6
occupational status/ annual ouseol! inco-e le.el/ an! i6est le.el o: e!ucation
co-plete! F13G. 1ace 3as !icoto-iIe! into ,ite an! non',ite :or analytic purposes.
Analysis plan
,e esti-ate! te relati.e aIar!/ 3ic approDi-ates a relati.e ris4/ o: inci!ent cancer
a-on6 tose 3it a istory o: !epression usin6 se-i'para-etric CoD proportional
aIar!s -o!els. >is -o!el type allo3s :or a nonpara-etric baseline aIar! rate an!
re@uires tat te ratio o: a aIar! rate to tat baseline aIar! be constant o.er ti-e; tis is
calle! te proportional aIar!s assu-ption. (o!els esti-ate te aIar! ratio/ or ris4/ o:
cancer onset as an eDponential :unction o: co.ariates/ an! allo3 :or inco-plete co.ariate
in:or-ation !ue to censorin6/ 3ic is co--on in epi!e-iolo6ical coort stu!ies 3it a
lon6 !uration li4e te 0C9 F31G. Hur -o!els 3ere also able to ta4e into account ti-e'
.aryin6 in!epen!ent .ariables. Proportional aIar!s -o!els 3ere cosen o.er lo6istic
re6ression because lo6istic re6ression is unable to account :or !i::erential a-ounts o:
:ollo3'up ti-e.
Person'years o: :ollo3'up 3ere calculate! in te :ollo3in6 :asion. >e ris4 set be6an in
19#1 3it te :irst baseline inter.ie3/ an! respon!ents stoppe! contributin6 person'ti-e
3en tey !ie! or 3ere !ia6nose! 3it cancer. For cancer cases in 3ic year o: onset
3as una.ailable/ 3e use! pre!icti.e e@uations to pre!ict years o: onset tat too4 into
account seD/ s-o4in6 status/ an! etnicity a-on6 4no3n !ates o: cancer onset :ro- te
200& 3a.e.
,e esti-ate! aIar! ratios :or cancer o.er ti-e separately :or -a2or !epression an!
!ysporia. First/ cru!e/ una!2uste! -o!els 3ere :it/ 3it cancer as te outco-e an!
!epression type as te only pre!ictor. Secon!/ -o!els 3ere :urter a!2uste! :or a6e/ sel:'
reporte! race/ seD/ -arital an! s-o4in6 status/ baseline S0S/ an! alcool
abuse%!epen!ence. 96e an! S0S 3ere centere! at teir -eans. (arital status/ s-o4in6
status/ alcoolis-/ an! li:eti-e istory o: !epression (to allo3 :or inclusion o: inci!ent
cases o.er 24 years o: :ollo3'up) 3ere allo3e! to .ary o.er ti-e. >e re:erence 6roup
:or all analyses 3as tose 3itout a istory o: -a2or !epression or !ysporia.
Proportional aIar!s -o!els 3ere :it in a si-ilar :asion :or eac subtype o: cancer.
Co.ariates tat 3ere statistically nonsi6ni:icant :or o.erall cancer 3ere !roppe! in tese
-o!els :or cancer subtypes because te nu-ber o: outco-es :or speci:ic cancers 3as
s-aller tan tat :or all cancers co-bine!. For tese cancer subtypes/ !epression 3as
also caracteriIe! in se.eral ne3 3ays. For eac cancer subtype/ !epression 3as
@uanti:ie! at te le.el o: sy-pto- counts/ !isre6ar!in6 cut points use! :or a clinical
!ia6nosis. Jistory o: -a2or !epression 3as separate! into cases o: sin6le an! recurrent
episo!es/ un!er te supposition tat i: stress'relate! !ysre6ulation o: i--une syste-
:unction or or-onal allostasis !oes lea! to so-e subtypes o: cancer/ ten ris4s :or
cancer soul! be i6er a-on6 tose 3it recurrent episo!es o: -a2or !epression. 9
sin6le'episo!e istory o: -a2or !epression is -ore in!icati.e o: eDo6enous li:e
circu-stances tan o: an en!urin6 trait.
>o pro.i!e a contrast 3it esti-ates associate! 3it !epression/ 3e calculate! aIar!s o:
cancer onset 6i.en *)S%*S('))) pobia at baseline usin6 CoD proportional aIar!s
-o!els. Pobia 3as selecte! because it is also a -oo!'relate! !isor!er/ an! tere 3ere
plenty o: *)S%*S('))) cases in te 0C9 !ata. ,e neDt eDecute! si-ilar -o!els :or any
-ental ealt proble- eDcept -a2or !epression/ 3ic inclu!e! *)S%*S('))) alcool
abuse or !epen!ence/ -ania/ !ru6 abuse or !epen!ence/ obsessi.e co-pulsi.e !isor!er/
pobia/ an! so-atiIation !isor!er.
9 series o: tree sensiti.ity analyses 3ere per:or-e! to e.aluate te robustness o: our
:in!in6s. First/ because so-e stu!ies a.e su66este! cancer ris4 a-on6 tose 3it
!epression is only i6er a-on6 s-o4ers F10G/ -o!els 3ere :it 3it interaction ter-s
bet3een s-o4in6 status an! !epression type. Secon!/ participants 3o at baseline rate!
teir ealt status as ApoorC on a scale o: A0Dcellent/C A8ery =oo!/C A=oo!/C AFair/C or
APoorC 3ere eDclu!e! so as to rule out potentially spurious associations !ri.en by
pre.alent cancer cases. >ir!/ :ollo3'up ti-e :or tose 3it cancer 3as calculate! in
tree a!!itional 3ays to test robustness o: results. Speci:ically/ 3e calculate! :ollo3'up
ti-e un!er te :ollo3in6 assu-ptions: cancer onset coinci!e! 3it year o: !eat or report
o: cancer :or tose 1994 3a.e respon!ents 3o reporte! cancer/ cancer onset 3as 10
years prior to !eat or 10 years prior to te 1994 report/ an! tat cancer onset 3as 1&
years prior to !eat or 10 years prior to te 1994 report. )n all cases/ -o!el :its an! te
.ali!ity o: te proportional aIar!s assu-ption 3ere assesse! usin6 6rapical !isplays o:
Scoen:el! resi!uals as 3ell as bot co.ariate'speci:ic an! 6lobal ci's@uare! tests o: te
proportional aIar!s assu-ption F32G.
=o to:
!esults
9t baseline/ 3/4#1 participants 3ere inter.ie3e! at te ?alti-ore 0C9 site. H: tese/ 1&$
respon!ents 3ere eDclu!e! a:ter reportin6 a istory o: cancer. <i:eti-e !epression status
at baseline 3as not 4no3n :or anoter 14$ respon!ents. >is resulte! in a ris4 set o:
3/1$$ persons/ representin6 40/&30 person'years/ 3o a! co-plete in:or-ation on
!epression status an! no pre.alent cancer at baseline. H: tese/ 1/02# 3ere ali.e an! re'
inter.ie3e! in 200&/ !eat certi:icates 3ere a.ailable :ro- te L*) :or 1/112 persons/
an! -ortality in:or-ation 3as 6atere! :ro- te :iel! !urin6 eiter te 1994 or 200&
:ollo3'ups :or anoter 13$ participants. >e re-ainin6 900 3ere assu-e! to be ali.e in
200&/ but eiter 3ere lost to :ollo3'up or re:use! to be re'inter.ie3e! at te 200& 3a.e/
altou6 -ost o: te- 3ere inter.ie3e! at te 1994 3a.e. ?aseline participant
caracteristics are so3n in >able 1. (ost respon!ents at eac 3a.e 3ere :e-ale an!
3ite (>able 1). >e -ean a6e in 19#1 3as 4+ years.
>able 1
*e-o6rapic caracteristics a-on6 respon!ents in 19#1 an! at subse@uent 3a.es
trou6 200&: !ata :ro- te ?alti-ore 0pi!e-iolo6ic Catc-ent 9rea Stu!y
Associations bet$een depression and overall cancer
9-on6 334 cases o: cancer reporte!/ 1$ cases a! a istory o: *)S%*S('))) -a2or
!epression an! #& a! a istory o: !ysporia prior to 19#1. )n an una!2uste! CoD
proportional aIar!s -o!el/ -a2or !epression 3as not si6ni:icantly associate! 3it an
increase! aIar! :or o.erall cancer/ but it 3as a:ter a!2ustin6 :or co.ariates (>able 2).
*ysporic episo!e 3as also si6ni:icantly associate! 3it an increase! aIar! o: cancer
(>able 2). Hl!er a6e 3as si6ni:icantly associate! 3it an increase! ris4 :or o.erall cancer/
an! ne.er a.in6 -arrie! 3as protecti.e. Current an! ea.y s-o4in6 3as pro6ressi.ely
-ore stron6ly associate! 3it an increase! ris4 :or cancer/ altou6 te associate! aIar!
ratios only barely inclu!e! te null (>able 2).
>able 2
JaIar! ratios :or te associations o: *)S%*S('))) (*0 or !ysporic episo!e 3it cancer
at 24 year :ollo3'up
Associations bet$een depression and subtypes of cancer
>able 3 so3s relati.e aIar!s :ro- una!2uste! an! a!2uste! -o!els :or te ris4 o:
inci!ent cancer type an! istory o: !epression. ?ecause o: concerns about o.er':ittin6
-o!els !ue to lo3 counts a-on6 cancer subtypes/ co.ariates tat :aile! to reac
statistical si6ni:icance in -o!els 3it o.erall cancer (alcool abuse%!epen!ence/
etnicity/ an! S0S) 3ere !roppe!. *epression 3as @uanti:ie! in separate -o!els as
*)S%*S('))) -a2or !epression/ !ysporia/ *)S%*S('))) -a2or !epression 3it recurrent
episo!es/ *)S%*S('))) sin6le'episo!e -a2or !epression/ an! nu-ber o: !epressi.e
sy-pto- 6roups out o: nine. ,en 3e esti-ate! aIar!s :or any cancer 6i.en tese
subtypes o: !epression/ aIar!s 3ere not increase! :or any o: te latter tree subtypes
(results not so3n).
>able 3
JaIar! ratios an! 9&E C)s :or associations bet3een cancer subtypes an! !epression
Four o: te 119 3o-en 3it istory o: -a2or !epression a! an onset o: breast cancer/
si6ni:icantly -ore tan tat a-on6 te 3o-en 3itout a istory o: !epression (>able 3).
>ere 3as also e.i!ence o: a linear !oseresponse relationsip bet3een breast cancer ris4
an! nu-ber o: sy-pto- 6roups e.er present :or !epression (>able 3). Statistical
si6ni:icance at te stan!ar! le.el o: p V 0.0& 3as not reace! in eiter case/ o3e.er (p V
0.0# an! p V 0.0+/ respecti.ely). *ysporia !i! si6ni:icantly increase te aIar! :or
breast cancer a-on6 3o-en. >ere 3ere no statistically si6ni:icant associations bet3een
breast cancer an! any subtypes o: -a2or !epression/ altou6 te point esti-ates
in!icate! associations in a positi.e !irection.
9n increase! aIar! o: prostate cancer 3as not si6ni:icantly associate! 3it a istory o:
-a2or !epression or !ysporia a-on6 -en/ but tere 3as a si6ni:icant relationsip :or
sin6le'episo!e -a2or !epression (>able 3). *ysporia increase! te aIar! :or colon
cancer (>able 3). For prostate an! colon cancers/ o3e.er/ tere 3as only one case o:
cancer eac a-on6 tose 3it -a2or !epression/ an! analyses o: Scoen:el! resi!uals
su66este! poor -o!el :its !ue to .iolations o: proportional aIar!s assu-ptions. <un6
an! s4in cancers 3ere not statistically associate! 3it any @uanti:ication o: eDposure
status/ altou6 3i!e con:i!ence inter.als re:lect li-ite! po3er (>able 3). )t is 3ort
obser.in6 ere tat 3ile current s-o4in6 status 3as only -ar6inally associate! 3it
o.erall cancer (>able 2)/ it 3as .ery stron6ly associate! 3it aIar! :or lun6 cancer (J1
:or current s-o4in6: 34.3; 9&E C): 4.30/ 2$3.$4). Se.eral aIar! ratios coul! not be
calculate! !ue to insu::icient nu-bers o: cancer cases.
"o'parisons $ith other disorders
,e constructe! a :orest plot to 6rapically !isplay our results :or te aIar! o: cancers
an! !epression alon6si!e aIar! ratios bet3een cancer types an! any -ental ealt
proble- an! also *)S%*S('))) Pobia (Fi6. 1). Leiter *S('))) pobia nor any -ental
ealt proble- in te a66re6ate 3as si6ni:icantly associate! 3it o.erall cancer or any
subtype/ tou6 associations 3ere 6enerally in a positi.e !irection.
Fi6. 1
JaIar! ratios 3it 9&E C)s :or associations bet3een !epression type an! cancer type :or
!epression in te ?alti-ore 0C9/ :or any oter -ental ealt proble-/ an! :or pobia in
te ?alti-ore 0C9. 9ny -ental ealt ((J) proble- enco-passes *S('))) alcool ...
(ensitivity analyses
9n analysis o: interactions bet3een s-o4in6 status an! !epression type re.eale! tat
s-o4in6 !i! not si6ni:icantly -o!i:y te association bet3een -a2or !epression an!
o.erall cancer; tere 3ere insu::icient cases to esti-ate reliable interaction coe::icients
:or any o: te cancer subtypes. )n a secon! set o: analyses/ 3e eDclu!e! 14& respon!ents
3o at baseline rate! teir ealt status as poor/ 24 o: 3o- a! a li:eti-e istory o:
-a2or !epression. For o.erall cancer/ altou6 te -a6nitu!e o: te association re-aine!
relati.ely i6/ -a2or !epression 3as no lon6er statistically si6ni:icantly associate! 3it
an increase! cancer aIar! (J1: 1.&+/ 9&E C): 0.90/ 2.$0). 9ll oter associations
oter3ise re-aine! constant/ an! no oter in:erences can6e!. >ir!/ recalculatin6
:ollo3'up ti-e usin6 para-eters !escribe! earlier !i! not can6e any in:erences.
=o to:
Discussion
,e in.esti6ate! !epression as a ris4 :actor :or inci!ent cancer usin6 a co--unity'base!
population o: a!ults :ollo3e! bet3een 19#1 an! 200&. ,e :oun! a si6ni:icant
relationsip bet3een bot a li:eti-e istory o: *S('))) -a2or !epression as 3ell as o:
!ysporia an! ris4 o: o.erall cancer. (a2or !epression appeare! to increase te aIar! :or
cancer/ particularly in te case o: breast cancer a-on6 3o-en. Furter/ te aIar! :or
breast cancer increase! linearly 3it te nu-ber o: !epressi.e sy-pto- 6roups. ,ile
te absolute ris4 o: cancer is not i6 6i.en !epression/ te population attributable ris4 is
li4ely siIeable 6i.en te consi!erable pre.alence o: !epression in te 6eneral population/
li:eti-e pre.alence esti-ates o: 3ic ran6e :ro- 4.4E to 14.1E across KS'base!
stu!ies F33/ 34G.
Co-pare! 3it oter epi!e-iolo6ic stu!ies tat a.e stu!ie! associations bet3een
!epression an! eiter o.erall cancer or certain subtypes usin6 stan!ar!iIe! inter.ie3'
a!-inistere! !ia6nostic criteria/ te 0C9 as a-on6 te lar6est nu-ber o: cancer cases
an! one o: te lon6est :ollo3'up ti-es F3G. Stu!ies 3it lon6er :ollo3'up ti-es ten! to
report stron6er associations especially :or cancer subtypes 3it or-onally -e!iate!
patolo6ies suc as breast cancer F3/ 1+G/ peraps because -ost cancers a.e lon6 latent
perio!s F3G. Hter a!.anta6es inclu!e te 0C9Ms prospecti.e !esi6n an! statistical control
:or ti-e'.aryin6 con:oun!er in:or-ation. (ost stu!ies a.e a!2uste! at least :or a6e an!
seD/ an! ere 3e a.e a!2uste! :or tose caracteristics as 3ell as S0S/ etnicity/ -arital
status/ s-o4in6 status/ an! istory o: alcool abuse%!epen!ence.
9 co--on li-itation in -any epi!e-iolo6ic stu!ies in.ol.in6 !epression 6enerally
re.ol.es aroun! te -eto! o: !epression ascertain-ent; ere/ -a2or !epression 3as
!eter-ine! usin6 te *)S/ 3ic is a stan!ar!iIe!/ inter.ie3er'a!-inistere! assess-ent
tool. ,ile any -easure o: !epression ine.itably -ust rely on sel:'reports/ te *)S is a
.ali!ate! tool tat so3s 6oo! reliability an! -o!erate concor!ance 3it structure!
clinical eDa-inations F30G. Furter/ because !ysporia 3as -easure! usin6 2ust one ite-/
it is inerently less reliable tan a scale 3it se.eral ite-s. Knless !ysporia 3as
syste-atically en!orse! !i::erentially by cancer status/ o3e.er/ tis soul! attenuate
aIar! esti-ates to3ar! null .alues/ 3ic 6i.es so-e3at stron6er -eanin6 to our
si6ni:icant :in!in6s.
Se.eral li-itations soul! be a!!resse!. First/ loss to :ollo3'up -i6t be !i::erential by
eiter cancer status or !epression status/ 3ic coul! 6i.e rise to biase! esti-ates o:
associations an! stan!ar! errors. ParticipantsM cancer status 3as ascertaine! !urin6
:ollo3'up inter.ie3s an! :ro- te L*) :or all !ecease! persons as o: 200&. Jo3e.er/
&+0 respon!ents in 19#1 3ere neiter !ea! nor :ollo3e! up in 1994 or 200&. ,ile tese
-issin6 participants !i! not !i::er statistically by baseline !epression status/ seD/ -arital
status/ or etnicity/ te potential re-ains :or bias !ue to !i::erential :ollo3'up. 9noter
li-itation relates to -isspeci:ication o: te ris4 -o!el. >ere -i6t still be oter
i-portant con:oun!ers not accounte! :or/ suc as 6enetic pre!ispositions or innate/
un-easure! psycolo6ical traits F21/ 23G. 9 tir! li-itation relates to -easure-ent o: our
eDposure .ariable o: !epression. ,ile te speci:icity o: te *)S is relati.ely i6 :or
!etectin6 -a2or !epression (bet3een 9&E an! 9#E o: true ne6ati.es are :oun! to be
ne6ati.e)/ sensiti.ity esti-ates .ary :ro- approDi-ately 30E to 40E F30/ 3&G. ,e
belie.e -isclassi:ication o: te eDposure .ariable 3ill bias our esti-ates to3ar! te null
so tat esti-ates are conser.ati.e. >e :in!in6 o: a -ar6inally si6ni:icant linear
association bet3een nu-ber o: !epressi.e sy-pto- 6roups an! probability o: breast
cancer alle.iates tis concern to so-e !e6ree because it so3s a relationsip bet3een
cancer an! !epression tat is not !epen!ent on selection o: a particular tresol!/ as
i-plie! by !ia6nostic criteria. 9 :ourt potential li-itation is tat cancer status 3as sel:'
reporte! :or participants inter.ie3e! in te 1994 or 200& 3a.es but 3o 3ere not yet
!ea! 3en te L*) 3as consulte!. >is -easure-ent error soul! also attenuate our
esti-ates.
9 :inal li-itation is tat since te entire coort as not yet been :ollo3e! to !eat or until
a cancer onset/ it is concei.able tat so-e -e-bers o: te 0C9 coort are too youn6 to
a.e reace! an a6e typically associate! 3it te onset o: -ost cancers. >e youn6est
participant in 200& 3as 41 years ol!/ an! te -e!ian a6e o: onset :or lun6 cancer/ to use
an eDa-ple/ is $0 years F3+G. (e!ian a6es o: onset .ary across subtypes o: cancer/ an!
!epen! to a certain eDtent on ne3 tecnolo6ies an! screenin6 pro6ra-s F3$G.
>e :orest plot (Fi6. 1) pro.i!es e.i!ence :or te speci:icity o: te association bet3een
!epression or !epressi.e -oo! an! or-onally -e!iate! cancers because suc an
association !oes not eDist :or pobia or :or oter -ental ealt !isor!ers. ,ile it appears
tat te association o: !epression 3it colon cancer 3as stron6ly associate! 3it a
istory o: -a2or !epression/ te esti-ate 3as in:luence! by te one person 3o a! bot
colon cancer an! -a2or !epression. So-e in:erences about possible etiolo6ic teories :or
te relation bet3een !epression an! cancer can be !ra3n :ro- our :in!in6s. ,it respect
to 6enetic teories/ 3e :oun! no e-pirical e.i!ence to support te ypotesis tat ras
proto'onco6enes are responsible :or te association bet3een !epression an! cancer. >is
teory pre!icts tat subtypes o: cancer -ost associate! 3it tese onco6enes/ speci:ically
s4in an! lun6 cancers/ soul! be si6ni:icantly associate! 3it !epression -ore tan oter
types o: cancer/ an! prostate an! breast cancers soul! be least associate! F23G. >is 3as
not :oun!. Presence o: a co--on un!erlyin6 6enetic :actor is still plausible/ but :urter
6enetic association an! lin4a6e stu!ies are nee!e! to i!enti:y -ore can!i!ate 6enes. ,e
3ere unable to @uanti:y suc caracteristics as copin6 style or e6o !e:ense -ecanis-s
usin6 0C9 !ata because speci:ic -easures o: tese constructs 3ere not a.ailable/ an! so
3e cannot co--ent on psycolo6ically base! teories. ?ea.iors tat -ay in:luence ris4
o: cancer relate! to -e!ical screenin6 or li:estyle -ay operate trou6 psycolo6ical
:actors.
Jypoteses about a co--on biolo6ical pat3ay lea!in6 to !epression an! cancer/ or a
pysiolo6ical process by 3ic !epression causes cancer/ appear to be supporte! by our
stu!y as 3ell as :ro- recent re.ie3s o: oter stu!ies 3it lar6e epi!e-iolo6ical coorts
F3G. ,e :oun! tat a istory o: -a2or !epression 3as associate! 3it a i6er ris4 o:
breast cancer. Furter/ sin6le'episo!e cases o: -a2or !epression 3ere si6ni:icantly
associate! 3it a i6er ris4 o: prostate cancer/ tou6 te esti-ate a! 3i!e con:i!ence
boun!s. ?reast an! prostate cancers are bot or-onally -e!iate! types o: cancer. Hne
concei.able biolo6ical -ecanis- :or te association bet3een !epression an! cancer
in.ol.es te ypotala-icpituitarya!renal (JP9) aDis. Cortisol/ a stress or-one/ is
release! :ro- te a!renal 6lan!s a:ter !etection o: increase! le.els o: 9C>J in te
bloo!strea- secrete! :ro- te pituitary 6lan! an! acti.ate! by C1F release! :ro- te
ypotala-us. Cronic stress an! aberrant acti.ation o: te JP9 aDis !isre6ulates
cortisol le.els/ suc tat cronic stressors o.er ti-e !estroy re6ular cortisol response
patterns an! !isrupt oneMs ability to respon! to stresses F3#G. 9s irre6ular patterns o:
eDcite-ent beco-e te nor-/ as is te case :or !epression/ ris4 :or -ental
psycopatolo6y in turn increases .ia a :ee!bac4 loop. 9t te sa-e ti-e/ cortisol is also
in.ol.e! in te acti.ation o: si6nalin6 tat controls cell 6ro3t an! re6ulation o: te cell
cycle F3941G. )n particular/ :lattenin6 o: cortisol le.els trou6out te course o: a !ay
as been so3n to increase te ris4 :or breast cancer in particular F42/ 43G. >e role o: te
JP9 aDis -ay not tell te 3ole story because breast cancer ris4 3as not ele.ate! a-on6
-a2or !epression cases 3it a recurrent episo!e in te present stu!y/ as 3oul! be
pre!icte! by a cronically actin6 biolo6ical -ecanis-.
*epressionMs role in alterin6 biolo6ical processes !irectly -ay be s-all co-pare! 3it
oter ris4 :actors :or cancer/ suc as s-o4in6 an! a!.ancin6 a6e. Jo3e.er/ te
pre.alence o: !epression su66ests a consi!erably lar6e attributable ris4. *epression -ay
eiter a.e a lon6 !elaye! e::ect on cancer ris4/ or !epression -ay pri-arily act in
co-bination 3it 4no3n ris4 :actors li4e a!.ance! a6e to increase cancer ris4. Furter
stu!ies soul! buil! on obser.ational stu!ies to :urter eDa-ine te -ecanis-s trou6
3ic our e-otions an! psycolo6ical 3ell'bein6 a::ect our ealt.
=o to:
Ackno$ledg'ents
>is 3or4 3as supporte! by te Lational )nstitute o: (ental Jealt (6rants >32'
(J14&92/ 101'(J4$44$/ an! F31'(J$#443).
=o to:
"ontributor Infor'ation
9l!en <. =ross/ *epart-ent o: (ental Jealt/ "ons Jop4ins ?loo-ber6 Scool o:
Public Jealt/ $9# Ja-pton Jouse/ +24 L. ?roa!3ay/ ?alti-ore/ (* 2120&/ KS9.
"osep ". =allo/ *epart-ent o: (ental Jealt/ "ons Jop4ins ?loo-ber6 Scool o:
Public Jealt/ +24 L. ?roa!3ay/ ?alti-ore/ (* 2120&/ KS9. *epart-ent o: Fa-ily
(e!icine/ Kni.ersity o: Pennsyl.ania Scool o: (e!icine/ Pila!elpia/ P9/ KS9.
,illia- ,. 0aton/ *epart-ent o: (ental Jealt/ "ons Jop4ins ?loo-ber6 Scool o:
Public Jealt/ #&0 Ja-pton Jouse/ +24 L. ?roa!3ay/ ?alti-ore/ (* 2120&/ KS9.
=o to:
!eferences
1. Sno3 J<. Cancer an! te cancer process. Curcill: <on!on; 1#93.
2. (c=ee 1/ ,illia-s S/ 0l3oo! (. *epression an! te !e.elop-ent o: cancer: a -eta'
analysis. Soc Sci (e!. 1994;3#:1#$192. FPub(e!G
3. Herle-ans (0/ .an !en 944er (/ Scuur-an 9=/ 7ellen 0/ ?untinD F. 9 -eta'
analysis on !epression an! subse@uent cancer ris4. Clin Pract 0pi!e-iol (ent Jealt.
200$;3:29. FP(C :ree articleG FPub(e!G
4. Hl!eroy =/ *aelin </ H6rei! *. <o3':re@uency -utation o: Ja'ras an! 7i'ras
onco6enes in transitional cell carcino-a o: te bla!!er. 9nticancer 1es.
199#;1#(49):2+$&2+$#. FPub(e!G
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FPub(e!G
Jurnal 3
Psycol (e!. 9utor -anuscript; a.ailable in P(C 2011 (ay 1.
Publise! in :inal e!ite! :or- as:
Psycol (e!. 2010 Lo.e-ber; 40(11): 1$9$1#10.
Publise! online 2010 "anuary 20. !oi: 10.101$%S0033291$099922#&
P(C)*: P(C293&92$
L)J(S)*: L)J(S203992
Depression and cancer 'ortality% a 'eta-
analysis
(. Pin@uart
1/Y
an! P. 1. *uberstein
2
9utor in:or-ation ; Copyri6t an! <icense in:or-ation ;
>e publiserUs :inal e!ite! .ersion o: tis article is a.ailable at Psycol (e!
See oter articles in P(C tat cite te publise! article.
=o to:
Abstract
Background
>e 6oal o: te present stu!y 3as to analyIe associations bet3een !epression an!
-ortality o: cancer patients an! to test 3eter tese associations 3oul! .ary by stu!y
caracteristics.
ethod
(eta'analysis 3as use! :or inte6ratin6 te results o: 10& sa-ples !eri.e! :ro- $+
prospecti.e stu!ies.
!esults
*epression !ia6nosis an! i6er le.els o: !epressi.e sy-pto-s pre!icte! ele.ate!
-ortality. >is 3as true in stu!ies tat assesse! !epression be:ore cancer !ia6nosis as
3ell as in stu!ies tat assesse! !epression :ollo3in6 cancer !ia6nosis. 9ssociations
bet3een !epression an! -ortality persiste! a:ter controllin6 :or con:oun!in6 -e!ical
.ariables. >e !epression-ortality association 3as 3ea4er in stu!ies tat a! lon6er
inter.als bet3een assess-ents o: !epression an! -ortality/ in youn6er sa-ples an! in
stu!ies tat use! te ?ec4 *epression )n.entory as co-pare! 3it oter !epression
scales.
"onclusions
Screenin6 :or !epression soul! be routinely con!ucte! in te cancer treat-ent settin6.
1e:errals to -ental ealt specialists soul! be consi!ere!. 1esearc is nee!e! on
3eter te treat-ent o: !epression coul!/ beyon! enancin6 @uality o: li:e/ eDten!
sur.i.al o: !epresse! cancer patients.
#ey$ords% Cancer/ !epression/ -eta'analysis/ -ortality/ oncolo6y
=o to:
Introduction
>ere is scienti:ic an! public interest in 3eter psycolo6ical :actors coul! can6e te
course o: cancer an! oter li:e'treatenin6 !iseases (Coyne et al . 200$). Clinical
!epression is pre.alent a-on6 cancer patients 3it rates ran6in6 bet3een 13 an! 40E
(Sellic4 Z Croo4s/ 1999). (any patients eDperience subtresol! or subsyn!ro-al
sy-pto-s 3itout -eetin6 criteria :or a !epression !ia6nosis (e.6. =rassi et al . 199+).
*epression as been so3n to con:er ris4 :or all'cause -ortality (,ulsin et al . 1999)/ but
its i-plications :or cancer -ortality are unclear. Pre.ious narrati.e re.ie3s a.e been
inconsistent (Se4ele et al . 19#1; C3in4el et al . 199$; =iese'*a.is Z Spie6el/ 2003). 9
prior -eta'analysis on te prospecti.e association o: !epression 3it te !e.elop-ent o:
cancer :oun! tat !epression -ar6inally increase! te ris4 :or !e.elopin6 cancer ((c=ee
et al . 1994) but recent -eta'analyses su66est tat te association bet3een !epression an!
cancer -ortality is robust (Ci!a et al . 200#; Satin et al . 2009). Hne so3e! tat
!epression 3as associate! 3it i6er cancer -ortality/ bot in co--unity'base!
sa-ples Fei6t stu!ies/ ris4 ratio (11) 1.34G an! cancer patients (1& stu!ies/ 11 1.0#;
Ci!a et al . 200#). 9noter :oun! tat !epression pre!icte! i6er -ortality (2& stu!ies/
11 1.2&1.39; Satin et al . 2009). Jo3e.er/ -any a.ailable stu!ies on !epression an!
cancer -ortality 3ere eDclu!e! :ro- tese -eta'analyses an! -o!erator analyses coul!
not be con!ucte!. ?y eDpan!in6 te nu-ber o: inclu!e! stu!ies/ te present -eta'
analysis eDplore! potentially i-portant -o!erators. ,e a!!resse! t3o @uestions. First/ is
tere an association bet3een !epression an! -ortality o: cancer patients in tis broa!er
sa-ple o: stu!iesB Secon!/ are tese e::ects -ore li4ely to be obser.e! in particular
sub6roups o: patients or in stu!ies tat use! particular -eto!s or instru-entationB
Depression and cancer 'ortality
Spie6el Z =iese'*a.is (2003) i!enti:y tree reasons 3y !epression -ay enance
-ortality ris4 in cancer patients. First/ !epression -ay a.e a patopysiolo6ical e::ect
.ia neuroen!ocrine an! i--unolo6ical :unctions tat in:luence -ortality (e.6.
!ysre6ulation o: te ypotala-ic'pituitary'a!renal aDis/ especially !iurnal .ariation in
cortisol an! -elatonin). Secon!/ !epresse! patients -ay be less li4ely to a!ere to
pre.enti.e screenin6 proce!ures/ cancer treat-ents or reco--en!ations :or -aintainin6
ealt. For eDa-ple/ !epresse! patients -ay be less li4ely to en6a6e in re6ular eDercise
or oter :or-s o: pysical acti.ity/ -ay be -ore li4ely to s-o4e an! !rin4 alcool to
eDcess (,ulsin et al . 1999) an! -ay not a!ere to prescribe! -e!ication re6i-ens or
-iss terapy appoint-ents (*i(atteo et al . 2000). Jo3e.er/ not all a.ailable stu!ies
:oun! poorer treat-ent a!erence in !epresse! cancer patients (e.6. 9yres et al . 1994).
>ir!/ -any o: te sy-pto-s o: cancer an! te si!e'e::ects o: its treat-ent are si-ilar to
tose o: !epression/ inclu!in6 te .e6etati.e sy-pto-s o: sleep an! appetite !isturbance/
:ati6ue an! concentration !i::iculties. >us/ !epressi.e sy-pto-s -ay be a proDy :or
!isease se.erity. )n!ee!/ !epressi.e sy-pto-s appear to be -ore pre.alent in a!.ance!
cancer tan in earlier sta6es ((assie Z Pop4in/ 199#). ,ereas te :irst t3o eDplanations
in.o4e substanti.e -ecanis-s (patopysiolo6y/ treat-ent a!erence)/ te tir! re:ers
to a statistical an! -easure-ent issue/ sy-pto- o.erlap. )nterpreti.e proble-s pose! by
sy-pto- o.erlap can be rule! out by lon6itu!inal stu!ies initiate! prior to cancer
!ia6nosis an! tey can be -iti6ate! by controllin6 statistically :or con:oun!in6 -e!ical
.ariables suc as !isease sta6e.
?eyon! te eDplanations consi!ere! :or te associations bet3een !epression an!
-ortality (Spie6el Z =iese'*a.is/ 2003)/ oters are also plausible. *epresse! patients
-ay be less li4ely tan non'!epresse! patients to recruit/ retain an! bene:it :ro- social
support an! :ro- oter :or-s o: social capital. Si-ilarly/ tey -ay be less e::ecti.e at
elicitin6 or culti.atin6 ealin6 relationsips 3it ealtcare pro.i!ers (0pstein Z Street/
200$) an! na.i6atin6 co-pleD ealtcare !eli.ery syste-s. Furter-ore/ e::ects o:
!epression -ay be -e!iate! trou6 te use o: ine::ecti.e copin6 strate6ies/ suc as
passi.e copin6 or so3in6 elpless resi6nation. )n tis case/ !epression 3oul! increase
te le.el o: ine::ecti.e copin6/ 3ic a6ain 3oul! lea! to increase! -ortality (Faller Z
Sc-i!t/ 2004). Finally/ !epression -ay con:er ris4 :or non'cancer causes o: !eat/ suc
as suici!e (94eci et al . 2004).
9 narrati.e re.ie3 reporte! positi.e associations bet3een !epression an! cancer
pro6ression or -ortality in 1& o: 24 stu!ies (=iese'*a.is Z Spie6el/ 2003). For eDa-ple/
*ero6atis et al . (19$9) an! ,atson et al . (1999) reporte! associations bet3een !epression
an! ele.ate! -ortality o: cancer patients/ but Co!y et al . (1994) !i! not. >e apparently
null :in!in6s -ay si-ply re:lect a s-all as oppose! to nil association because e::ects are
-ore !i::icult to !etect in s-aller sa-ples. >us/ in line 3it Ci!a et al . (200#) an!
Satin et al . (2009)/ 3e eDpecte! tat tere 3oul! be an o.erall positi.e association
bet3een !epression an! cancer -ortality 3en te e::ects are poole! across a.ailable
stu!ies. ?ase! on te assu-ption tat !epressionUs e::ect on cancer -ortality is not a
-easure-ent arte:act base! on sy-pto- o.erlap 3it se.erity o: cancer/ 3e eDpecte!
tat te e::ect o: !epression on cancer -ortality 3oul! also be :oun! 3en controllin6 :or
in!icators o: se.erity o: te !isease/ suc as sta6e o: cancer.
oderating effects of study characteristics
(o!eratin6 e::ects occur 3en te siIe o: te association bet3een !epression an!
-ortality is in:luence! by a tir! .ariable. Se.eral stu!y caracteristics -ay ser.e as
-o!erators.
!ecruit'ent site
9s co--unity'base! stu!ies on -ortality usually start 3it people a.in6 no 4no3n
cancer !ia6nosis/ initially -easure! !epression -ay a::ect !isease onset/ !isease
pro6ression an! -ortality. )n contrast/ stu!ies tat :ollo3 a coort o: cancer patients
analyIe e::ects o: !epression on !isease pro6ression an! -ortality. *epression -ay a::ect
bot cancer inci!ence an! course. 0::ects -ay be lar6er in co--unity sa-ples because
!epression is -ore li4ely to a.e a::ecte! bot cancer inci!ence an! course. )n :act/
Ci!a et al . (200#) :oun! sli6tly stron6er associations o: !epression 3it -ortality in
co--unity'base! stu!ies tan in clinical sa-ples. >us/ 3e ypotesiIe! tat
!epressionUs co-bine! e::ect (on inci!ence an! course) -ay lea! to stron6er associations
o: !epression 3it cancer -ortality in co--unity stu!ies tan in cancer sa-ples.
(tatistical control for confounding variables
Patients 3it -ore a!.ance! !isease 3ill a.e i6er !epression scores. Failin6 to
control :or in!icators o: !isease se.erity coul! lea! to an in:late! esti-ate o: !epressionUs
e::ect i: !isease se.erity is a -ore i-portant !ri.er o: -ortality tan !epression. )n Satin
et al.Us -eta'analysis/ te results 3ere inconclusi.e as only one out o: teir tree analyses
:oun! a si6ni:icant association o: !epression an! -ortality a:ter controllin6 :or
con:oun!ers. Jo3e.er/ ,atson et al . (1999) :oun! tat te association o: !epression 3it
-ortality 3as stren6tene! a:ter statistically controllin6 :or pro6nostic so-atic :actors.
(tage of the disease
)t as been su66este! tat/ in a!.ance! sta6es o: cancer/ biolo6ical :unctions -ay beco-e
increasin6ly i-portant in re6ar! to patient -ortality (C3in4el et al . 199$) 3ile
psycosocial :actors -ay play a lar6er role in te outco-es o: less pro6resse! cancer.
>us/ i: !epression is consi!ere! to a.e psycosocial ori6ins an! conse@uences/ 3e
-i6t eDpect s-aller e::ects 3en patients a.e -ore a!.ance! !isease. Hn te oter
an!/ i: te -easure-ent o: !epression taps sy-pto-s o: te !isease/ 3ic coul! be
-a6ni:ie! in -ore a!.ance! !isease sta6es/ ten 3e -i6t eDpect lar6er e::ect o:
!epression 3en patients a.e -ore a!.ance! !isease.
"ancer site
)t as been su66este! tat psycolo6ical :actors -ay play less o: a role in lun6 cancers
an! oters 3it .irulent cell istopatolo6y because tese cancers rarely !e.iate :ro- an
eDpecte! course (<e.y Z 1oberts/ 1992). Hnitilo et al . (200+) :oun! no !i::erences in te
association o: !epression an! -ortality 3en co-parin6 :i.e cancer sites.
/ength of study interval
9s te se.erity o: !epressi.e sy-pto-s -ay can6e o.er ti-e/ !epression scores at te
:irst ti-e o: !ata collection -ay lose pre!icti.e po3er 3it increasin6 ti-e inter.al. )n
:act/ Spie6el an! =iese'*a.is (2003) reporte! tat prospecti.e stu!ies tat :oun! no
association bet3een !epression an! cancer pro6ression a!/ on a.era6e/ 10'year
inter.als/ 3ereas te oter stu!ies a!/ on a.era6e/ only &'year inter.als. Si-ilarly/
Satin et al . (2009) :oun! si6ni:icant associations o: !epression an! cancer -ortality in
stu!ies 3it ti-e inter.als P& years but te results o: stu!ies 3it lon6er inter.als 3ere
inconclusi.e. >us/ 3e ypotesiIe! tat stu!ies 3it sorter inter.als so3 stron6er
associations o: !epression an! cancer -ortality.
easure'ent of depression
,ereas so-e stu!ies assesse! !epression !ia6nosis/ oter :ocuse! on !epressi.e
sy-pto-s. Clinical !epression -ay a.e stron6er e::ects on -ortality because !epressi.e
sy-pto-s in te lo3er ran6e -ay be less li4ely to a::ect te su66este! -o!erators o: te
!epression-ortality relationsip/ suc as lo3 co-pliance (Spie6el Z =iese'*a.is/
2003). )n :act/ !epression as a clinical syn!ro-e/ in contrast 3it less se.ere !epressions/
-ay -ore o:ten in.ol.e te loss o: te 3ill to li.e/ 3ic -ay cause te re2ection o:
cancer treat-ents/ lo3 co-pliance an! ele.ate! ris4 :or suici!e (SculI et al . 199+;
,ulsin et al . 1999). Satin et al . (2009) :oun! tat !epression !ia6nosis so3e! sli6tly
lar6er associations 3it -ortality tan !epressi.e sy-pto-s/ but te !i::erence !i! not
reac statistical si6ni:icance in tat s-aller !atabase.
Age
>e !ile--a ere is si-ilar to tat :or o::erin6 a ypotesis about !isease sta6e. ):
!epression is consi!ere! psycosocial in ori6in an! sy-pto-atolo6y/ 3e -i6t eDpect
s-aller e::ects in sa-ples 3it a 6reater proportion o: ol!er patients because a6e'
associate! so-atic ris4 :actors :or !eat/ cancer plus co'-orbi! -e!ical bur!en/ 3oul!
play a lar6er role in ol!er patients !ue to teir 6reater -e!ical bur!en. 9lternati.ely/ i: te
-easure-ent o: !epression pri-arily taps neuro.e6etati.e an! oter so-atic sy-pto-s/
ten 3e -i6t eDpect lar6er e::ects 3en patients are ol!er because suc sy-pto-s -ay
be an in!icator o: a co'-orbi! !isease tat coul! cause !eat.
0ender
9s !epression is -ore pre.alent in 3o-en tan in -en/ 3e 3ere also intereste! in
3eter te siIe o: te association bet3een !epression an! -ortality -ay .ary by 6en!er.
1esults o: a.ailable stu!ies not speci:ic to cancer a.e been inconsistent re6ar!in6
3eter te association o: !epression an! -ortality 3oul! be stron6er in 3o-en (e.6.
7a3a-ura et al . 200$) or -en (e.6. 9nstey Z <usIcI/ 2002).
(u''ary
)n su-/ 3it re6ar! to -o!erators/ 3e co-pare! te e::ects on -ortality o: !epression as
a :unction o: 3en an! o3 !epression 3as assesse!/ !isease sta6e/ patient a6e/ 6en!er
an! 3eter con:oun!s 3ere controlle! statistically. ,e !i! not assi6n @uality scores to
in!i.i!ual stu!ies as tis practice is contro.ersial (e.6. "uni et al . 1999). 1ele.ant aspects
o: stu!y @uality are consi!ere! 3en co-putin6 e::ect siIes an! teir 3ei6ts (sa-ple
siIe) an! 3en analyIin6 -o!eratin6 e::ects (e.6. statistical control :or con:oun!in6
.ariables).
=o to:
ethod
,e i!enti:ie! a co-preensi.e sa-ple o: stu!ies searcin6 electronic !atabases
((e!line/ Cocrane *ata ?ase/ Psyclit/ PS5L*0O); searc ter-s: F(-ali6nant or cancer
or carcino-a) an! !epression an! (sur.i.al or -ortality or !eat or 7aplan(eier or
CoD)G an! cross're:erencin6. Criteria :or inclusion in te -eta'analysis 3ere:
1. >e participants 3ere cancer patients or 3ere enrolle! in a prospecti.e
co--unity'base! sa-ple :or 3ic cancer -ortality is reporte!.
2. *epressi.e !isor!ers 3ere !ia6nose! accor!in6 to stan!ar! !ia6nostic criteria in
te )C*'10/ *S(')))/ )))'1 or )8 or !epressi.e sy-pto-s 3ere assesse! 3it
sel:'ratin6 scales or inter.ie3er ratin6s.
3. )n:or-ation on -ortality is pro.i!e!.
4. Statistics coul! be co-pute! or esti-ate! :or associations bet3een !epression an!
-ortality Fe.6. 11s an! teir con:i!ence inter.als (C))/ sur.i.al cur.es/ p .alues
o: CoD re6ression or 7aplan(eier analysisG.
H: te ## e-pirical stu!ies initially i!enti:ie!/ $+ -et all inclusion criteria (NV1$+ #+3).
>e re-ain!er 3ere eDclu!e! because tey co-bine! !ata on cancer pro6ression an!
-ortality (:i.e stu!ies) or pro.i!e! insu::icient in:or-ation :or co-putin6 e::ect siIes
(se.en stu!ies). H: te $+ stu!ies/ 11 reporte! results :or -ore tan one sa-ple (e.6. :or
-en an! 3o-en or :or !i::erent cancer sites)/ yiel!in6 a total o: 10& sa-ples.
"oding of variables
,e entere! te year o: publication/ te nu-bers o: participants/ a6e/ 6en!er/ -eto! :or
assessin6 !epression (1Vclinical !ia6nosis/ 0Vratin6 scales)/ ratin6 scales use! F1VC0S'*
(1a!lo::/ 19$$); 2VJospital 9nDiety an! *epression Scale (J9*S; Ni6-on! Z Snait/
19#3; 3V?ec4 *epression )n.entory (?*); ?ec4 Z Steer/ 19$9); 4VotersG/ sa-ple
co-position (1Vcancer patients only/ 0Vco--unity sa-ple)/ cancer site (1Vbreast/
2Vleu4e-ia%ly-po-a/ 3Vlun6/ 4Vbrain/ &Voter sites/ +V-iDe! sites)/ cancer sta6e
F1Vearly ()/ )))/ 2V-iDe!%not reporte!/ 3Vlate ()))/ )8)G/ ti-in6 o: !epression assess-ent
(1Vprior to cancer !ia6nosis/ 2Va:ter !ia6nosis) an! stu!y inter.al (years). ,it re6ar! to
control :or con:oun!in6 .ariables/ 3e create! siD !u--y .ariables (1Vyes/ 0Vno)/
in!icatin6 3eter te stu!y controlle! :or cancer site/ sta6e/ :unctional status/ -e!ical
co-orbi!ities/ a6e an! socio'econo-ic status. 9ssociations bet3een !epression an!
-ortality 3ere co!e! as 11s. >e 11 is a su--ary o: te !i::erence bet3een t3o
7aplan(eier cur.es or CoD re6ression cur.es an! represents te o.erall increase in te
ris4 o: !eat o.er te perio! o: :ollo3'up. )t as been especially use:ul :or co-parin6
t3o sur.i.al cur.es because it allo3s :or censorin6 an! ti-e o: an e.ent.
For stu!ies reportin6 on !i::erent perio!s o: :ollo3'up/ 3e inclu!e! te results o: all
:ollo3'ups but a!2uste! teir 3ei6t so tat te su- o: te subresultsU 3ei6t 3oul! be
e@ual to te 3ei6t 3en only inclu!in6 one result (<ipsey Z ,ilson/ 2004).
(tatistical integration of research findings
Calculations :or te -eta'analysis 3ere per:or-e! usin6 ran!o-'e::ects -o!els an! te
non'iterati.e -eto! o: -o-ents (Je!6es Z 8e.ea/ 199#)/ 6i.en te eDpecte! .ariability
in e::ect siIes bet3een stu!ies beyon! sub2ect'le.el sa-plin6 error. Calculations 3ere
con!ucte! as :ollo3s.
1. 11s 3ere calculate!. ): te 11 3as not reporte!/ it 3as co-pute! :ro-
in:or-ation about te nu-bers o: !ecease! an! li.in6 patients 3it lo3 versus
i6 le.els o: !epressi.e sy-pto-s (or !epression !ia6nosis versus lac4 o: suc
!ia6nosis/ respecti.ely)/ te lo6ran4 statistics/ an! sur.i.al cur.es/ base! on
Par-ar et al . (199#). For eDa-ple/ i: only sur.i.al cur.es are a.ailable/ te
nu-bers o: !eats an! persons at ris4 :or !eat are co-pute! :or eac ti-e unit
:or te !epresse! an! non'!epresse! 6roups/ :ollo3e! by te co-putation o: te
lo6 11 :or eac ti-e unit an! te o.erall lo6 11 as te 3ei6te! su- o: te
in!i.i!ual esti-ates. Hutliers tat 3ere Q2 S.*. :ro- te -ean o: te e::ect siIes
3ere reco!e! to te .alue at 2 S.*. (<ipsey Z ,ilson/ 2004).
2. 0::ect siIes 3ere 3ei6te! by te in.erse o: te S.*. an! co-bine! to co-pute an
o.erall 3ei6te! -ean e::ect siIe. >e o-o6eneity o: e::ect siIes 3as teste! by
use o: te o-o6eneity statistics Q. >e si6ni:icance o: te -ean 3as teste! by
!i.i!in6 te 3ei6te! -ean e::ect siIe by te esti-ate! stan!ar! error o: te
-ean. >en C) tat inclu!e 9&E o: te e::ects 3ere co-pute! :or eac e::ect siIe.
3. 9n analo6 to te analysis o: .ariance 3as applie! :or testin6 3eter te e::ect
siIes 3oul! !i::er bet3een con!itions/ suc as early an! late sta6e o: cancer. 9
si6ni:icant Q score in!icates tat te siIe o: te e::ects !i::ers si6ni:icantly
bet3een stu!ies. *i::erences bet3een t3o con!itions 3ere interprete! as
si6ni:icant 3en te 9&E C) !i! not o.erlap.
4. Su--ary statistics o: te e::ect siIe an! te 9&E C) 3ere con.erte! bac4 to 11s
by ta4in6 te anti'lo6arit-s.
=o to:
!esults
H: te $+ prospecti.e stu!ies/ 2+ inclu!e! patients 3it -iDe! cancer sites an! !i! not
report results :or in!i.i!ual sites; 1& reporte! results :or leu4ae-ia an! ly-po-as/ 14
:or breast cancer/ 10 :or lun6 cancer/ :i.e :or brain cancer an! ei6t stu!ies :or oter
cancer sites (e.6. colon/ pancreas). >e -a2ority co-bine! patients 3it early an! late
sta6es o: te !isease (NV&9); siD :ocuse! on patients 3it early sta6e cancer ()%))) an! 11
on late sta6e !isease ()))%)8). (ost (nV+2) assesse! !epression a:ter cancer !ia6nosis; 14
eDa-ine! te in:luence o: !epression prior to cancer !ia6nosis. (ost o: te latter stu!ies
3ere co--unity'base! coort stu!ies tat assesse! ris4 :or !i::erent sources o: -ortality.
For te present analyses/ only !ata on cancer -ortality 3ere use!. )n a!!ition/ &9 stu!ies
use! ratin6s o: !epressi.e sy-pto-s an! 1$ stu!ies assesse! !epression !ia6noses base!
on structure! clinical inter.ie3s. >e -ost o:ten use! ratin6 scales 3ere te J9*S
(Ni6-on! Z Snait/ 19#3; 1& stu!ies)/ te C0S'* (11 stu!ies) an! te ?*) (?ec4 Z
Steer/ 19$9; se.en stu!ies). 9 total o: &# stu!ies reportin6 bi.ariate associations an! 3$
stu!ies reportin6 -ulti.ariate analyses 3ere a.ailable. >e latter controlle! :or (so-e)
con:oun!in6 .ariables/ suc as a6e (kV33)/ sta6e (kV29)/ :unctional status (kV9)/ socio'
econo-ic status (kV#)/ -e!ical co-or'bi!ities (kV+)/ an! cancer site (kV4). >e inclu!e!
stu!ies are i!enti:ie! in te 1e:erence section.
1espon!ents 3ere/ on a.era6e/ +4.& years ol! (S.*.V11.+). 9bout $2E o: te respon!ents
(S.*.V42) 3ere 3o-en an! 49E 3ere -arrie! (S.*.V13).
9s so3n in Fi6. 1/ e::ect siIes .arie! consi!erably bet3een stu!ies. Loneteless/ 91E
o: te bi.ariate associations bet3een !epression an! -ortality as 3ell as 90.&E o: te
-ulti.ariate analyses tat controlle! :or con:oun!in6 .ariables reporte! 11s Q1.0/ tus
in!icatin6 tat !epression 3as associate! 3it i6er -ortality. Separate e::ect siIes 3ere
co-pute! :or uncontrolle! an! controlle! stu!ies. )n line 3it our eDpectations/ bot
6roups o: stu!ies so3e! tat !epression 3as associate! 3it ele.ate! -ortality (>able
1). For eDa-ple/ te uncontrolle! 11 o: 1.19 in stu!ies tat !i! not control :or
con:oun!in6 .ariables in!icates tat te relati.e ris4 :or -ortality increases by 19E in
te !epresse! as co-pare! 3it te non'!epresse! 6roup. 9s in!icate! by te non'
o.erlap o: te 9&E C)/ te siIe o: te association bet3een !epression an! cancer
-ortality !i! not .ary si6ni:icantly bet3een stu!ies tat controlle! :or con:oun!in6
.ariables an! stu!ies tat !i! not. )n te neDt step 3e analyIe! 3eter te e::ect siIes
-ay .ary by -o!erator .ariables.
Fi6. 1
*istribution o: e::ect siIes o: te in!i.i!ual stu!ies. [/ Kncontrolle!; \/ controlle!.
>able 1
Association of depression $ith cancer 'ortality
>o !o so/ 3e co-bine! te controlle! an! uncontrolle! e::ect siIes. ,en bot 3ere
reporte! in te sa-e stu!y/ te controlle! e::ect siIes 3ere use! because tey are
presu-e! to be -ore .ali!. >is a.era6e! e::ect siIe also so3e! tat !epression
increase! te ris4 :or cancer -ortality (>able 1).
0::ect siIes !i! not !i::er si6ni:icantly bet3een prospecti.e stu!ies tat assesse!
!epression prior to cancer !ia6nosis an! tose tat !i! so :ollo3in6 cancer !ia6nosis. Lor
!i! e::ect siIes !i::er as a :unction o: !isease sta6e. >e -a6nitu!e o: te association
bet3een !epression an! sur.i.al 3as si-ilar across sa-ples 3it early sta6e/ late sta6e
an! -iDe! sta6es o: cancer.
,it re6ar! to cancer site/ !epression pre!icte! sorter sur.i.al in leu4e-ia%ly-po-a
patients/ in breast cancer patients/ in lun6 cancer patients/ brain cancer patients an! in
patients 3it oter o-o6eneous sites/ an! in -iDe! sa-ples. 9ll te C) o.erlappe!.
,it re6ar! to te len6t o: te inter.al bet3een te assess-ents o: !epression an!
sur.i.al/ 3e co-pare! stu!ies 3it ti-e inter.als up to 2 years/ inter.als o: 24 years/ 4
+ years an! lon6er inter.als. >e Q'statistics in!icates tat te siIe o: te association
bet3een !epression an! -ortality .aries by te len6t o: stu!y inter.al. Stron6est
associations 3ere :oun! in stu!ies 3it te sortest ti-e inter.al/ altou6 te 9&E C)
o.erlappe! 3it tose o: te oter 6roups.
*epression !ia6nosis as 3ell as te le.el o: !epression pre!icte! -ortality o: cancer
patients an! te siIe o: association !i! not .ary bet3een tese t3o -eto!s o:
assess-ent. ,e also cec4e! 3eter te siIe o: association bet3een !epression an!
-ortality 3oul! .ary by te use o: !i::erent ratin6 scales. Si6ni:icant associations
e-er6e! in stu!ies tat use! te C0S'* an! te J9*S. Jo3e.er/ no si6ni:icant
associations e-er6e! in stu!ies tat use! te ?*).
,it re6ar! to te a6e !istribution o: te sa-ples/ 3e :oun! stron6er associations o: a6e
an! cancer -ortality in te ol!est sub6roup tan in te youn6est sub6roup (>able 1). >e
siIe o: te association bet3een !epression an! -ortality !i! not .ary by te 6en!er
co-position o: te sa-ple.
=o to:
Discussion
>e present -eta'analysis so3e! tat !epression/ !e:ine! cate6orically or
!i-ensionally/ is associate! 3it ele.ate! ris4 :or -ortality in cancer patients an! tose
3o !e.elop cancer. 9ssociations 3ere stron6er in stu!ies 3it sorter ti-e inter.als an!
in ol!er sa-ples. 9-on6 te sel:'report instru-ents use! to assess !epression/ only te
?*) yiel!e! a non'si6ni:icant e::ect siIe.
,ereas so-e in!i.i!ual stu!ies a.e :oun! no e.i!ence :or te i!ea tat !epression is
associate! 3it ele.ate! -ortality in cancer patients (e.6. Co!y et al . 1994)/ te present
-eta'analysis pro.i!es clear e.i!ence :or suc a relationsip. >e present stu!y :urter
supports prior -eta'analyses (Ci!a et al . 200#; Satin et al . 2009) 3it a -uc lar6er
!ataset. )t as been su66este! tat associations bet3een !epression an! -ortality -ay/ at
least in part/ re:lect te e::ect o: illness se.erity (e.6. Spie6el Z =iese'*a.is/ 2003). )n
tis scenario/ te e::ect o: !epression is -ore apparent tan real/ a result o: sare!
-eto! .ariance an! o.erlappin6 sy-pto-atolo6y/ suc as :ati6ue an! appetite
!isturbance. <ittle e.i!ence :or tis -easure-ent con:oun! ar6u-ent 3as unco.ere! in
tis -eta'analysis. Stu!ies tat assesse! !epression years be:ore cancer !ia6nosis :oun!
si-ilar associations 3it -ortality tan stu!ies tat assesse! !epression :ollo3in6 cancer
!ia6nosis. Lor 3ere e::ects stron6er in -ore a!.ance! !isease sta6es. Stu!ies tat
controlle! statistically :or !isease'relate! con:oun!s a! si-ilar e::ect siIes tan tose
tat !i! not. Loneteless/ 3e reco6niIe tat tese statistical controls 3ere li-ite!. )n :act/
-ost controlle! stu!ies use! only 6lobal -easures o: se.erity o: illness (-ost o:ten
sta6e).
Se.eral autors a.e su66este! tat psycolo6ical .ariables -ay a.e a stron6er e::ect
on !isease pro6ression an! -ortality in early sta6es o: cancer (e.6. C3in4el et al . 199$).
9ltou6 3e obser.e! a so-e3at stron6er e::ect in stu!ies on early sta6es tan on
-iDe! an! later sta6es o: cancer/ tese !i::erences !i! not reac statistical si6ni:icance/
peraps !ue to te paucity o: sa-ples on early sta6e (kV+) an! late sta6e (kV14) cancer.
9t present/ te -ost parsi-onious conclusion is tat !epressionUs in:luence on -ortality
is in!epen!ent o: !isease sta6e. Si-ilarly/ co-parable associations 3ere :oun! :or
leu4e-ia%ly-po-a/ breast cancer/ brain cancer an! lun6 cancer. >e -ost parsi-onious
eDplanation is tat !epressionUs in:luence on -ortality is in!epen!ent o: site.
9ssociations bet3een !epression an! -ortality are stron6est in stu!ies 3it inter.als o:
]2 years bet3een assess-ent o: !epression an! assess-ent o: -ortality. ?ecause te
correlati.e stability o: !epression !eclines 3it increasin6 stu!y inter.als (e.6. <o.ibol!/
199#)/ T1'!epression scores lose pre!icti.e po3er o.er ti-e. )n a!!ition/ as sur.i.al ti-e
is eDten!e!/ oter inter.enin6 :actors are -ore li4ely to account :or -ortality/ tereby
obscurin6 any possible relationsips bet3een !epression an! -ortality o: cancer patients.
Contrary to our eDpectations/ 3e !i! not :in! stron6er associations 3it -ortality in
stu!ies on clinical !epression/ !e:ine! cate6orically/ tan in stu!ies tat use! continuous
-easures o: sel:'rate! !epressi.e sy-pto-s. Jo3e.er/ te e::ect o: clinical !ia6nosis
-ay a.e been un!eresti-ate! as so-e stu!ies use! cru!e !ia6nostic in!icators/ suc as
3eter te patients a! e.er been ospitaliIe! or a.e a! outpatient contact :or clinical
!epression (e.6. *alton et al . 200#). >us/ !epression -ay a.e been un!ia6nose! in
so-e cases/ 3ic 3oul!/ a6ain/ attenuate te siIe o: association 3it -ortality.
)nterestin6ly/ associations bet3een !epressi.e sy-pto-s an! -ortality 3ere not
si6ni:icant in stu!ies tat use! te ?*). Lote tat ei6t out o: te 21 ite-s o: te ?*)
assess so-atic sy-pto-s/ 3ereas only :our out o: te 20 C0S'* ite-s assess tese
sy-pto-s. 9s so-atic sy-pto-s -ay/ at least in part/ in!icate cancer'relate! sy-pto-s/
so-atic co'-orbi!ity/ or si!e'e::ects o: te treat-ent/ te ?*) is less 3ell suite! :or
stu!ies intereste! in isolatin6 te in:luence o: psycolo6ical (co6niti.e/ a::ecti.e) as
oppose! to neuro.e6etati.e processes on ealt outco-es in cancer/ e.en tou6
e.i!ence :or its .ali!ity in te cancer settin6 as been pro.i!e! ((ysta4i!ou et al . 200$).
,ereas SculI et al . (199+) a! obser.e! stron6er associations o: pessi-is- an!
-ortality in youn6er patients tan in ol!er patients/ te present -eta'analysis :oun! so-e
e.i!ence :or stron6er associations o: !epression an! -ortality in te ol!est cancer
patients. Hl!er cancer patients -ay be less li4ely to recei.e a!e@uate treat-ent :or
!epression (1ot Z (o!i/ 2003). >is -ay be true :or a ost o: reasons/ inclu!in6 6reater
sti6-a (Sirey et al . 2001)/ co-petin6 !e-an!s (7lin4-an/ 199$)/ lo3er -oti.ation to
see4 !epression treat-ent an! te concern tat :rail el!erly patients cannot tolerate
anti!epressant treat-ent !ue to si!e'e::ects or interactions 3it oter -e!ications (7in6
et al . 200&).
So-e li-itations o: te present stu!y a.e to be -entione!. First/ altou6 our -eta'
analysis inclu!e! $+ stu!ies/ subanalyses coul! only be -a!e :or :our cancer sites.
Secon!/ so-e potential -o!erators o: te siIe o: te association bet3een !epression an!
-ortality coul! not be teste! !ue to te lac4 o: su::icient !ata (e.6. cronicity o:
!epression/ receipt o: !epression treat-ent/ cancer istory/ ti-e inter.al bet3een cancer
!ia6nosis an! assess-ent o: !epression/ per:or-ance status). >ir!/ because -ost
a.ailable stu!ies !i! not !i::er bet3een cancer'relate! -ortality an! oter causes o:
-ortality in cancer patients/ 3e 3ere not able to test :or e::ects on speci:ic causes o:
!eat. Finally/ 3e !i! not inclu!e unpublise! stu!ies tat 3ere not cite! in te electronic
!atabases. 9ltou6 non'si6ni:icant results :ro- s-all stu!ies -ay be less li4ely to be
publise!/ teir lac4 o: si6ni:icance is o:ten base! on s-all sa-ple siIes rater tan on
belo3'a.era6e e::ect siIes. >us/ it is unli4ely tat our :in!in6s 3oul! a.e !i::ere! a!
3e inclu!e! unpublise! stu!ies.
Se.eral !irections :or :uture researc coul! be pursue!. First/ -ore stu!ies on
associations o: !epression 3it -ortality are 3elco-e! :or tose cancer sites tat coul!
not be inclu!e! in te analysis o: site'speci:ic associations.
Secon!/ -ore e::orts are nee!e! :or i!enti:yin6 -o!erators an! -e!iators o: te
relationsip bet3een !epression an! -ortality in cancer patients. Future stu!ies soul!
inclu!e -ore !i::erentiate! -easures o: con:oun!in6 -e!ical .ariables/ suc as
per:or-ance status/ co'-orbi!ity an! receipt o: curati.e versus palliati.e treat-ent. )n
a!!ition/ tey soul! report 3eter tere is a bi.ariate association o: !epression status
3it cancer -ortality an! 3eter tis association persists a:ter a -ore co-preensi.e
control :or te se.erity an! type o: cancer/ use o: !i::erent :or-s o: cancer terapies/
6eneral pysical status an! oter con:oun!in6 .ariables. Surprisin6ly :e3 stu!ies
assesse! pysical :unction an! treat-ent'relate! si!e'e::ects/ ealt'relate! bea.iours/
or personality .ariables (suc as neuroticis-) as potential con:oun!ers. Consensus
re6ar!in6 3ic control .ariables soul! be inclu!e! in te analysis 3oul! also increase
te co-parability o: results across stu!ies.
,it re6ar! to clinical practice/ 3e conclu!e tat te association o: !epression 3it
-ortality is o: clinical si6ni:icance. Practitioners soul!/ :irst/ be -ore a3are o:
!epressi.e sy-pto-s an! !epressi.e !isor!ers o: cancer patients. Care:ul consi!eration
soul! be 6i.en to routine screens :or !epression as part o: te -ulti!isciplinary
assess-ent o: cancer patients (<loy!',illia-s et al . 200$). 1eco6niIin6 te li-itations
o: routine !epression screenin6 pro6ra-s in pri-ary care (=ilbo!y et al . 200+)/ te
assess-ent o: !epression -ay be construe! as a central ele-ent in patient'centere!
cancer care (0pstein Z Street/ 200$). 1e:errals to -ental ealt specialists soul! be
consi!ere!. Secon!/ as e::ecti.e treat-ents o: !epression in cancer patients are a.ailable
(e.6. Jop4o et al . 200& ; Stoc4ler et al . 200$)/ early reco6nition an! a!e@uate treat-ent o:
!epression coul!/ beyon! enancin6 @uality o: li:e/ potentially i-pro.e -e!ical
outco-es/ suc as :unctional status. ^uestions a.e been raise! about 3eter
psycosocial inter.entions a.e li:e'prolon6in6 e::ects (see S-e!slun! Z 1in6!al/
2004; Coyne et al . 200$). >e present results in!icate tat i: suc e::ects !o in!ee! eDist
(Coyne et al . 200$)/ tey are li4ely to be :oun! a-on6 patients 3it ele.ate! le.els o:
!epression an!%or !epressi.e !isor!ers. Syste-atic researc on e::ects o: suc
inter.entions on sur.i.al o: !epresse! cancer patients is nee!e!.
=o to:
Ackno$ledg'ents
,or4 on tis -anuscript 3as supporte! by te :ollo3in6 6rants :ro- te Knite! States
Public Jealt Ser.ice: 724(J0$2$12 an! 1249=0310#9.
=o to:
Appendi1% *vervie$ of included studies
Authors (a'ple
si2e
(cancer)
"ancer site Assess'ent of
depression
Ti'e of
assessing
depression
/ength of
study
interval
(years)
94eci et al .
2009
122<un6 PH(S Post 2
9n!ry4o3s4i et
al . 1994
42<eu4e-ia PH(S Post 3
?eres:or! et al .
200+
#+(iDe! ?*) Post &
?er6@uist et al .
200$
940osopa6us J9*S Post 1
?lac4 Z
(ar4i!es/ 1999
24#9(iDe! C0S'* Pre 2
?roers et al .
199#
123<eu4e-ia SC<'90 Post $.2
?ro3n et al .
2003
20&(iDe! C0S'* Post 10
?ucceri/ 199# 9&<un6 S*S Post 2
Can6/ 2004 a 122<eu4e-ia ?*) Post 1
Can6/ 2004 b 114<eu4e-ia ?*) Post 2.&
Colon et al . 1991 100<eu4e-ia *ia6nosis Post 2
Coryell 19#1 $+(iDe! *ia6nosis Pre 40
*alton et al .
200#
+01<y-po-a/
leu4e-ia
*ia6nosis Pre &
*alton et al .
200#
24 391?reast *ia6nosis Pre &
*alton et al .
200#
20 490<un6 *ia6nosis Pre &
*alton et al .
200#
2#&4(out *ia6nosis Pre &
*alton et al .
200#
19#2Sto-ac/
esopa6us/
pancreas
*ia6nosis Pre &
*alton et al .
200#
9&90Colon/ rectu- *ia6nosis Pre &
*alton et al .
200#
2$$47i!ney/
bla!!er
*ia6nosis Pre &
*alton et al .
200#
2#$1Fe-ale 6enital *ia6nosis Pre &
*alton et al .
200#
1$24(ale 6enital *ia6nosis Pre &
Authors (a'ple
si2e
(cancer)
"ancer site Assess'ent of
depression
Ti'e of
assessing
depression
/ength of
study
interval
(years)
*alton et al .
200#
+$&&(elano-a *ia6nosis Pre &
*alton et al .
200#
&31+?rain/ CLS *ia6nosis Pre &
*ero6atis et al .
19$9
3&?reast SC<'90 Post 2
0!3ar!s et al .
19#&
2+>estes ?S) Post $
0lers/ 2002 130Jea!/ nec4 ?*) Post 2.$
Faller et al . 1999 103<un6 Nerssen Post $.&
Faller Z
Sc-i!t/ 2004
&9<un6 J9*S Post 4
Fors_n/ 1991 #$?reast Jo-e -a!e Pre #
Fric4 et al . 200& 99<y-po-a/
-yelo-a
PH(S Post 2.4
=antin2i et al .
2009
10&2?rain *ia6nosis Pre &
=iral!i et al .
199$
9&?reast C0S'* Pre +
=oo!3in et al .
2004
24 +9+?reast *ia6nosis Pre 3
=ripp et al . 200$ 1#4(iDe! J9*S Post .&
=roen.ol! et al .
200$
1&##?reast J9*S Post 12.9
=rul4e et al .
200#
13#<eu4e-ia/
ly-po-a
J9*S Post 1.&
Jerr-ann et al .
199#
9+(iDe! J9*S Post 1.#
Jislop et al .
19#$
133?reast Jo-e -a!e Post 4
J2erl et al . 2003 &191?reast *ia6nosis Pre/ post +.2
"a-ison et al .
19#$
49?reast S*S Post 2.&
Joo!in et al .
2004
30&<eu4e-ia/
ly-po-a
((P) Post 3.&
7aplan Z
1eynol!s/ 19##
+#01(iDe! 1oberts Pre 1$
7ar.onen'
=utierreI et al .
200#
49&Jea!/ nec4 =*S Post &.1
Authors (a'ple
si2e
(cancer)
"ancer site Assess'ent of
depression
Ti'e of
assessing
depression
/ength of
study
interval
(years)
7a3a-ura et al .
200$
#+(iDe! *ia6nosis Pre 1&
7issane et al .
200$
4#&?reast *ia6nosis Post 2
<a- et al . 200$ 1+2(iDe! Ja-ilton Post 0.&
<eto et al . 200+ 102?reast Salo4an6as Post 10
<eto et al . 200$ &9(elano-a *0PS Post $.&
<ei6 et al . 19#$ 101(iDe! ?*) Post 3
<ito:s4y et al .
2004
&9#?rain *ia6nosis Post 2
<loy!',illia-s
et al . 2009
#$(iDe! 0*S Post 1
<oberiIa et al .
2002
193<eu4e-ia Jo-e -a!e Post 1
(ainio et al .
200&
$$?rain ?*) Post &
(ainio et al .
200+
$&?rain ?*) Post 10
(urpy et al .
199+
&+<eu4e-ia/
ly-po-a
C)*) Post 2.&
La4aya et al .
200+
229<un6 PH(S/ SC)* Post &.$&
La4aya et al .
200#
11$#<un6 J9*S Post 2
Lau6ton et al .
2002
+$<un6 C0S'* Post 1
Hnitilo et al .
200+
#$+(iDe! C0S'* Post #
Hsborne et al .
2004
+1?reast J9*S Post $
`sby et al . 2001 1404(iDe! *ia6nosis Pre 10
Pal-er Z Fisc/
200&
22&(iDe! >^SS Post 2
PenninD et al .
199#
4#2&(iDe! C0S'* Pre +
Pers4y et al .
19#$
210$(iDe! ((P) Pre 22
Pilipps et al .
200#
$0#?reast J9*S Post #.2
Pirl et al. 2009 43<un6 J9*S Post 2.&
Authors (a'ple
si2e
(cancer)
"ancer site Assess'ent of
depression
Ti'e of
assessing
depression
/ength of
study
interval
(years)
Prieto et al . 200& 199<eu4e-ia/
ly-po-a
*ia6nosis Post &
1atcli::e et al .
199&
+3<y-po-a J9*S Post &
1icar!son et al .
1990
92<eu4ae-ia S*S Post 4.#
1icar!son et al .
1990
4$Colon ?*) Post 4.#
1in6!al et al .
199+
231(iDe! J9*S Post 2
Saito'La4aya et
al . 200+
#1+<un6 J9*S Post 2
SculI et al .
199+
23#(iDe! C0S'* Post 0.$
Seibani'1a! Z
8elano.ic/ 200+
2&#Pancreas *ia6nosis Post 0.$&
Se4ele et al .
19#1
2020(iDe! C0S'* Pre 1$
Steel et al . 200$ 103<i.er C0S'* Post 2
Stein et al . 19#9 90(iDe! Psyciatric
Hutpatient
(oo! Scale
Post 0.2&
Stoc4ler et al .
200$
1#9(iDe! C0S'*/ J9*S Post 4.33
Sto--el et al .
2002
#$1(iDe! C0S'* Post 1.+
>ian et al . 2009 113(iDe! *S) Post 1
>scusc4e et al .
2001
&2<eu4e-ia SC<'90 Post &
,atson et al .
1999
&$#?reast J9*S Post &
,atson et al .
200&
&$#?reast J9*S Post 11
,ooley Z
?ro3ner/ 199#
$40+(iDe! =*S Pre $
,ilson et al .
200$
3#1(iDe! *ia6nosis Post 0.&
Non!er-an et al .
19#9
&$93(iDe! C0S'*/ =,?'
*
Pre #.#
Non!er-an et al . 1#12(iDe! C0S'*/ =,?' Pre 13.#
Authors (a'ple
si2e
(cancer)
"ancer site Assess'ent of
depression
Ti'e of
assessing
depression
/ength of
study
interval
(years)
19#9 *
CLS/ Central ner.ous syste-; ?*)/ ?ec4 *epression )n.entory; ?S)/ ?rie: Sy-pto-
)n.entory; C)*)/ Co-posite *ia6nostic )nter.ie3; *0PS/ *epression Scale; *S)/
*epression Status )n.entory; 0*S/ 0!inbur6 *epression Scale; J9*S/ Jospital
9nDiety an! *epression Scale; ((P)/ (innesota (ultipasic Personality )n.entory;
PH(S/ Pro:ile o: (oo! States; SC)*/ Structure! Clinical )nter.ie3 *epression; SC<'
90/ Sy-pto- Cec4list 90; S*S/ Nun6as Sel: 1atin6 *epression Scale; >^SS/ >3o'
^uestion Screenin6 Sur.ey; pre/ be:ore cancer !ia6nosis; post/ a:ter cancer !ia6nosis.
=o to:
3ootnotes
*eclaration o: )nterest: Lone.
=o to:
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Y )n!icates te stu!ies inclu!e! in te -eta'analysis.
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Jurnal 4
Jealt ^ual <i:e Hutco-es. 2011; 9: #&.
Publise! online 2011 Septe-ber 30. !oi: 10.11#+%14$$'$&2&'9'#&
P(C)*: P(C3192++3
Does self-regulation and autono'ic
regulation have an influence on survival
in breast and colon carcino'a patients4
results of a prospective outco'e study
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9utor in:or-ation ; 9rticle notes ; Copyri6t an! <icense in:or-ation ;
>is article as been cite! by oter articles in P(C.
=o to:
Abstract
Background
Cancer 1elate! Fati6ue (C1F) an! circa!ian ryt- a.e a 6reat i-pact on te @uality o:
li:e (J1^<) o: patients 3it breast (?C) an! colon cancer (C1C). Hter patient relate!
outco-es in oncolo6y are -easure! by ne3 instru-ents :ocusin6 on a!apti.e
caracteristics suc as sense o: coerence or sel:'re6ulation/ 3ic coul! be -ore
appropriate as a pro6nostic tool tan classical J1^<. >e ai- o: tis stu!y 3as to assess
te association o: autono-ic re6ulation (a1) an! sel:'re6ulation (S1) 3it sur.i.al.
ethods
14+ cancer patients an! 120 ealty controls too4 part in an initial e.aluation in
2000%2001. 9t a -e!ian :ollo3 up o: &.9 years later/ +2 o: 9& ?C/ 1$ o: &1 C1C patients/
an! #& o: 11$ ealty controls too4 part in te :ollo3'up stu!y. 41 participants a! !ie!.
For te :ollo3'up e.aluation/ participants 3ere re@ueste! to co-plete te stan!ar!iIe! a1
an! S1 @uestionnaires.
!esults
Hn a.era6e/ cancer patients a! sur.i.e! :or 10.1 years 3it te !isease. Ksin6 a CoD
proportional aIar! re6ression 3it step3ise .ariables suc as a6e/ !ia6nosis 6roup/
Carlson co'-orbi!ity in!eD/ bo!y -ass in!eD (?())) a1 an! S1. S1 3ere i!enti:ie! as
in!epen!ent para-eters 3it potential pro6nostic rele.ance on sur.i.al ,ile a1 !i! not
si6ni:icantly in:luence sur.i.al/ S1 so3e! a positi.e an! in!epen!ent i-pact on
sur.i.al (H1 V 0.&#9; 9&E'C): 0.3&4 ' 0.9$9). >is positi.e e::ect persiste! si6ni:icantly
in te sensiti.ity analysis o: te sub6roup o: tu-our patients an! in te subscale U9cie.e
satis:action an! 3ell'bein6U an! by ten!ency in te K)CC sta6es neste! :or te !i::erent
!ia6noses 6roups.
"onclusions
Sel:'re6ulation -i6t be an in!epen!ent pro6nostic :actor :or te sur.i.al o: breast an!
colon carcino-a patients an! -erits :urter prospecti.e stu!ies.
#ey$ords% 9utono-ic re6ulation (a1)/ breast cancer/ colorectal cancer/ copin6/ sel:'
re6ulation (S1)
=o to:
Background
Cancer 1elate! Fati6ue (C1F) is one o: te -ost co--on sy-pto-s eDperience! by
cancer patients recei.in6 palliati.e care F1G an! patients treate! 3it ce-o' or
ra!ioterapy F2G; it is also relati.ely co--on in !isease':ree cancer patients. )n a ?ritis
stu!y &#E o: all oncolo6y outpatients reporte! tat :ati6ue a::ecte! te- Uso-e3at or
.ery -ucU an! !escribe! it as te -ost i-portant sy-pto- 3ic is o:ten not bein6
3ell'-ana6e! F3G.
C1F is o:ten associate! 3it sleep !isturbances. Fro- te 31E o: all cancer patients
su::erin6 :ro- inso-nia in a lar6e cross sectional stu!y/ $+E reporte! !isturbe! sleep
continuation F4G *isturbe! rest%acti.ity an! a::ecte! circa!ian ryt-s -ay a66ra.ate
C1F an! !epressi.e sy-pto-s in a!2u.ant treate! breast cancer patients F&G an!
!i-inises ealt'relate! @uality o: li:e (J1^<) in breast F&G an! colorectal cancer
patients F+G. )n -etastasiIe! colon carcino-a patients acti-etrically -easure! !isturbe!
rest%acti.ity ryt- is associate! 3it sorter sur.i.al F$G an! in breast cancer patients
(?C) !i-inise! circa!ian cortisol ryt- is associate! 3it i6er -ortality F#G. ?esi!e
pysiolo6ical -easures/ anoter epi!e-iolo6ical a.ailable approac is -easurin6
rest%acti.ity re6ulation 3it a .ali!ate! assess-ent applicable in clinical settin6s as a part
o: a @uestionnaire -easurin6 !i::erent :unctions (1. rest%acti.ity/ 2. ortostatic'
circulatory/ 3. !i6estion) o: autono-ic re6ulation (a1)/ 3ic to our 4no3le!6e is te
:irst scale -easurin6 autono-ic :unctionin6 3it su::icient .ali!ity F9G.
>ere is so-e e.i!ence tat @uestionnaires -easurin6 patientsU a!apti.e capacity to3ar!s
!isease an! ealt'orientate! li:e'style can6e/ suc as te Usense o: coerenceU (SHC)
F10G or Usel:'re6ulationU (S1) F11G/ coul! a.e stron6er association 3it pro6nosis in
oncolo6y or oter cronic con!itions tan J1^< scales F12'1&G. Hne o: tese tools is
base! on 9ntono.s4yUs core @uestion U,at -ay 4eep one ealtyBU For 9ntono.s4y/
SHC is base! on tree co-ponents 3ic are prere@uisites :or saluto6enesis/ i.e./
co-preensibility/ -eanin6:ulness/ an! -ana6eability F10G. Kp to no3/ in.entories 3ic
capture te SHC base! on 9ntono.s4yUs concept o: saluto6enesis are pre!o-inantly
.ali!ate! :or patients 3it psycoso-atic or -ental ealt con!itions/ psyciatric
patients. (oreo.er/ tey are o:ten use! in sociolo6ical stu!ies as a stable personality trait
-ar4er/ 3ile tey a.e not been !e.elope! as clinical -easures :or pysical an!
oncolo6ical con!itions F10/1+'1#G.
9noter scale base! on saluto6enesis 3it a clinical application is te psycoso-atic
Sel:'1e6ulation Scale (S1) !e.elope! by =rossart'(atice4. >is @uestionnaire !eals
3it te eability to acti.ely acie.e 3ell'bein6/ inner e@uilibriu-/ appropriate
sti-ulation/ a :eelin6 o: co-petence/ an! a sense o: bein6 able to control stress:ul
situationse F19G. =rossart'(atice4 Z 0ysenc4 caracteriIe! tis concept as a sort'an!
personality trait ter- 3ic eco.ers a con6lo-erate o: conceptse relate! to reaction to a
.ariety o: stressors an! copin6 -ecanis-s an! not only as Ulocus o: controlU F1&G. >e
S1 scale as been !e.elope! as an epi!e-iolo6ical/ pre.enti.e ealt care an! clinical
-easure in a lon6 an! sort .ersion/ an! as been .ali!ate!/ applie! an! e.aluate!
a6ainst pysical ris4 :actors prospecti.ely in breast an! colorectal cancer patients F11/14G.
S1 sort .ersion is capturin6 t3o :actors: 1) ability to Ucan6e bea.iour to reac a 6oalU
an! 2) a subscale calle! U9cie.e satis:action an! 3ell'bein6U F20G.
>e ai- o: our stu!y 3as to assess te in:luence on o.erall sur.i.al o:
1) te .ali!ate! autono-ic re6ulation scale (a1) (an! its subscale :or rest%acti.ity ryt-
(1%9.a1)) F9G an! o:
2) te sort .ersion o: te psycoso-atic Sel:'1e6ulation Scale (S1) (an! its subscales
UCan6e bea.iour to reac 6oalU an! U9cie.e satis:action an! 3ell'bein6U) F20G.
=o to:
ethods
Patients
>is -ulticenter obser.ational stu!y 3as con!ucte! at te *epart-ent o: )nternal
(e!icine/ Sur6ery an! =ynaecolo6y o: te Ja.elWe Co--unity Jospital/ ?erlin/ te
`scelbronn Hncolo6ical Practice an! te ,uppertal 0n!ocrinolo6y Practice :ro- 9pril
2000 ' Lo.e-ber 2001. >e participants o: te stu!y consiste! o: ealty .olunteers an!
in total se.en 6roups o: patients. >e latter 3ere recruite! consecuti.ely a-on6 inpatients
at te Ja.elWe Jospital an! :ro- outpatients in te t3o practises. )n tis paper 3e
report te results :ro- te breast cancer an! colorectal cancer 6roup an! te ealty
controls.
>e inclusion criterion 3as istolo6ically pro.en breast or colorectal cancer. >e control
6roup 3as recruite! :ro- te Ja.elWe Jospital sta:: an! teir relati.es. 0Dclusion
criteria 3ere oter se.ere or6anic !iseases/ -ani:est psycosis/ se.ere i--obilisation or
a 7arno:s4y in!eD (7P)) P &0E/ uncontrolle! pain/ recent operations (P 1 3ee4 prior to
stu!y recruit-ent) an! recent ce-o' or ra!ioterapy (P 3 3ee4s prior recruit-ent).
9-on6 131 ealty .olunteers/ 9& breast cancer (all :e-ale) patients an! &1 colorectal
cancer patients (30 :e-ale%&#.#E)/ all cancer patients an! 120 ealty controls (#0
:e-ale%++.$E) (C) 6a.e teir 3ritten consent an! too4 part in an initial e.aluation in
2000%2001 (table (table1). 1). 9ccor!in6 to our institutional stan!ar! in 2000/ 3e !i! not
as4 etical appro.al in anony-ous @uestionnaire base! obser.ational stu!ies.
>able 1
Socio!e-o6rapic !ata o: te stu!y 6roups inclu!in6 sta6e/ terapies/ participation rate
Fro- 9pril 200+ to Hctober 200$ 3e con!ucte! a re'assess-ent o: all participants o: te
2000'2001 stu!y. 9:ter cec4in6 our -e!ical patients !ocu-ents 3e cec4e! tan i:
participants 3ere still re6istere! 3it te local a!-inistration; i: tey 3ere no lon6er
re6istere! 3e in.esti6ate! 3eter tey a! !ie! (re6istere! !eat !ate) or -o.e!.
(Fi6ure (Fi6ure1/ 1/ table table1 1).
Fi6ure 1
3lo$ chart of participants recruiting +5556+557 and +5586+559.
easures
Participants 3ere 6i.en te a1'scale (table (table2)/ 2)/ te S1 scale (table (table3) 3) an!
te Jospital 9nDiety an! *epression Scale (J9*S) F21G in 2000%2001 an! 200+%200$/
an! a sel:'co-pletion .ersion o: te 7arno:s4y in!eD (7P)).
>able 2
)te-s on autono-ic re6ulation
>able 3
)te-s o: te sel:'re6ulation @uestionnaire 3it te t3o subscales 1) 9bility to Can6e
?ea.iour in Hr!er to 1eac =oals an! 2) 9cie.e Satis:action an! ,ell'?ein6
1) >e autono'ic regulation (a1) scale a!!resses te state o: re6ulation o: !i::erent
autono-ic :unctions. >e 1#'ite- scale -easures te tree :actor -o!el Hrtostatic'
Circulatory/ 1est%9cti.ity an! *i6esti.e re6ulation 3it a tree'point <i4ert scale an! as
a satis:yin6 internal consistency (Cronbac'f: rf V 0.+&'0.$&)/ an! satis:yin6 to 6oo!
test'retest reliability (rrt V 0.$0 ' #&)/ an! 6oo! .ali!ity F9G.
2) >e short questionnaire on self-regulation (S1) is a scale 3it 1+ ite-s to -easure
oneUs acti.ity to3ar!s ar-oniIin6 an! ealt orientation 3it a siD'point <i4ert scale
ran6in6 :ro- 1 (.ery 3ea4) to + (.ery stron6) (a!!ition o: te 1+ ite-s an! !i.ision by
1+: 1an6e 1'+. >e @uestionnaire consists o: t3o subscales 3it ei6t ite-s eac: 1)
UCan6e bea.iour to reac 6oalU an! 2) U9cie.e satis:action an! 3ell'bein6U. Ji6er
scorin6 in!icates better sel:'re6ulation. >e sel:'re6ulation @uestionnaire is i6ly
reliable an! .ali! 3it a 6oo! ' .ery 6oo! internal consistency (Cronbac'f: rf V 0.#0'
0.9&) an! satis:yin6 ' 6oo! test'retest reliability V 0.$3'0.#2) F11/20G.
3) >e #arnofsky perfor'ance inde1 (7P)) is a co--only use! :unctional -easure :or
oncolo6y patients F22G. 9ltou6 it 3as !esi6ne! :or clinical assess-ent by pysicians/
its cate6oriIation is easy to un!erstan! :or patients as 3ell an! 3as tus be use! :or a
patient'base! e.aluation.
4) >e =er-an .ersion o: te U:ospital An1iety and Depression (caleU (J9*S'*)
consists o: 14 ite-s ($ :or anDiety an! $ :or !epression) 3it a :our'point <i4ert scale (0'
21 :or bot). Ji6er scorin6 in!icates -ore sy-pto-s. >e J9*S is i6ly reliable an!
.ali! an! is an eDtensi.ely use! scale in internal -e!icine researc F21G.
&) >e "harlson co-'orbidity inde1 is an o:ten use! in!eD in internal -e!icine an!
oncolo6y :or co'-orbi!ity 3it a robust correlation 3it outco-e F23G.
(tatistical analysis
9nalysis 3as per:or-e! 3it SPSS 1+.0 an! S9S 9.1.3 so:t3are pac4a6es. 1ele.ant
:actors in:luencin6 sur.i.al 3ere i!enti:ie! by a .ariable selection proce!ure usin6 CoD
proportional aIar! re6ression. Para-eters inclu!e! in te selection process as
in!epen!ent :actors inclu!e! !ia6nostic 6roups/ a6e/ seD/ Carlson co'-orbi!ity in!eD/
nicotine abuse/ bo!y -ass in!eD (?())/ anDiety an! !epression scores o: te J9*S/
aller6y an! -arital status/ a1 an! S1S. Pri-ary .ariable selection 3as a step3ise
selection proce!ure/ a co-bination o: :or3ar! an! bac43ar! .ariable selection. >is
proce!ure co-pute! te score statistic :or eac e::ect not yet in te -o!el. >e para-eter
3it te lar6est o: tese score statistics/ 3en si6ni:icant at an error le.el o: 0.2&/ 3as
a!!e! to te -o!el. 9ny para-eter coul! a6ain be re-o.e! :ro- te selecte! .ariables
-o!el i: its p'.alue increase! o.er a tresol! o: 0.1& a:ter inclusion or re-o.al o: oter
para-eters. >e outco-e o: te step3ise selection 3as co-pare! 3it pure :or3ar! an!
bac43ar! selection tecni@ues. 9ll proce!ures resulte! in te sa-e para-eters re-ainin6
in te -o!el. >is consistency in para-eter selection 3as also te case in te sensiti.ity
analyses.
>e proportionality assu-ption o: te selecte! -o!el 3as cec4e! by a resa-ple
7ol-o6oro. supre-u- test 3it 1000 si-ulation iterations as su66este! by <in et al.
F24G. Jere/ a6e turne! out to si6ni:icantly !e.iate :ro- proportionality assu-ptions. 9:ter
6rapical inspection/ a6e 3as s@uare! :or inclusion. >ereby not only te non'
proportionality o: tis para-eter 3as resol.e! but te CoD -o!el resulte! in s-aller p'
.alues :or all oter para-eters eDcept :or ?().
?ecause o: !i::erences in pro6nosis bet3een bot cancer 6roups/ sta6e accor!in6 to
Knion )nternationale Contre le Cancer (K)CC)/ neste! in te !i::erent !ia6nostic 6roups/
3as inte6rate! in a sensiti.ity analysis (ealty sub2ects 3ere allocate! to K)CC sta6e 0).
Furter sensiti.ity analyses re6ar!e! only te sub'6roup o: tu-or patients/ 3it an!
3itout a!!itionally inclu!in6 tu-or an! ly-p no!e sta6in6/ presence o: -etastases/
6ra!in6/ an! te use o: ce-o'/ ra!io' or -istletoe terapy in te para-eter selection
process. 9n analysis ai-in6 to inclu!e bot K)CC sta6in6 an! tu-or patient sub'sa-ple
:aile! to result in a reliable -o!el esti-ate !ue to an insu::icient nu-ber o: e.ents.
)n or!er to illustrate te in:luence o: S1S :or all !ia6nosis 6roups/ in a 7aplan'(eier
sur.i.al plot 3e allocate! all patients at a S1S o: 3.#& (3ic is a clinical use:ul cut'o::
bet3een -o!erate an! 6oo! S1S) into a i6 S1S (Q 3.#&) or lo3 S1S (P 3.#&) class/
respecti.ely.
=o to:
!esults
9t stu!y inclusion breast cancer patients participatin6 in te stu!y a! a -ean !isease
!uration o: 4.$ years/ 13 (13.$E) o: te- a !isease !uration o: less tan 1 year/ only 3
(3.2E) an operation bet3een 2 an! 4 3ee4s be:ore. 9bout al: te participants 3ere
post-enopausal at !ia6nosis (&&.2E) an! $&.#E (4.2E in K)CC 3) !i! not a.e
-etastatic !isease sta6e. 9$.9E a! been operate! an! &$.9E o: all a! recei.e! stan!ar!
ra!io'ce-oterapy an! 3ere still recei.in6 or-onal treat-ent (table (table1). 1).
Colorectal cancer patients participatin6 in te stu!y a! a -ean !isease !uration o: 1.$
years/ 23 (4&.1E) o: te- a !isease !uration o: less tan 1 year/ 13 (2&.&E) in te last
-ont. Hnly +3E !i! not a.e -etastatic !isease (29E K)CC 3). 44E a! recei.e!
ce-oterapy an! 1&.$E ra!ioterapy (table (table1). 1). ?ot 6roups a! a i6 rate o:
conco-itant -istletoe terapy (#3.2E an! $1.$E) (table (table1 1).
,it a -e!ian :ollo3 up o: &.9 years/ +2 o: #1 breast cancer patients (?C)/ 1$ o: 2+
colorectal cancer patients (C1C)/ an! #& o: 11$ controls (C) (in total $3.2E) participate!
in te :ollo3'up stu!y (e@ui.alent to +1.+E o: te initial sa-ple). Fro- te initial coort/
41 o: 2++ participants (14 ?C/ 2& C1C/ 2 C) a! !ie! (1&.4E)/ 3it $$.1E o: patients o:
te entire initial coort (table (table1) 1) respon!in6 (table (table1). 1). (ean sur.i.al ti-e
o: te cancer 6roups 3as 10.1 years (S* V 3.9). (ean a6e o: te 3ole 6roup 3as +0.2
years (S* V 12.2); :or !etails o: te stu!y 6roups re:er to table table1 1.
>e 7arno:s4y per:or-ance in!eD (7P)) o: te cancer sur.i.ors 3as 9+.$E (all 92.&E)
in breast cancer an! ##.2E in colorectal cancer (all #3.3E) at baseline. 91 su- scale
correlates 3it S1 initially 3it r V 0.34.
>ere 3ere tree bi.ariate correlations 3itin tese .ariables abo.e 0.&/ 3it te i6est
.alue o: 0.+2 bet3een te anDiety an! te !epression scale o: te J9*S an! 7P) 3it
!ia6nosis an! K)CC sta6e ('0.&3''0.+1); tus/ -ulti'collinearity 3as o: no concern/ as
3as con:ir-e! by ri!6e analysis. Le.erteless/ 7P) 3as not inte6rate! in te step3ise
.ariable selection because o: its -o!erate to stron6 correlation 3it !ia6nosis an! K)CC
sta6e.
)n te :inal -o!el a:ter .ariables selection te !ia6nosis 6roups colorectal carcino-a (J1
V 23.&1&/ C) V &.1#3'10+.+#3/ p P 0.0001 an! breast cancer (J1 V &.244/ C) V 1.111'
24.$&$/ p V 0.03+4)/ te Carlson co'-orbi!ity in!eD (J1 V 1.3#9/ C) V 1.043'1.#4#/ p V
0.024&) an! i6 sel:'re6ulation so3 positi.e an! in!epen!ent i-pact on sur.i.al/ 3it
an J1 o: 0.&#9 (9&E'C): 0.3&4'0.9$9) (table (table4). 4). >is positi.e e::ect is
corroborate! by te analysis o: te t3o subscales :or U9cie.e satis:action an! 3ell'
bein6U (J1 V 0.&+0; 9&E'C): 0.3&0'0.#9&) an! by ten!ency :or UCan6e bea.iour to
reac 6oalU (J1 V 0.++3; 9&E'C): 0.413'1.0++). Hn te oter an! a1 su- scale an!
rest%acti.ity re6ulation subscale (1%9.a1) a.e no si6ni:icant in:luence on sur.i.al (a1:
J1 V 1.0+9/ C) V 0.992'1.1&2; 1%9.a1: J1 V 1.0+9/ 0.94#'1.20&).
>able 4
Final -o!el a:ter .ariable selection :or breast an! colorectal cancer an! control 6roup/
si6ni:icant results are printe! in bol!
,e con!ucte! a secon! step3ise .ariables selection li-ite! to te t3o cancer 6roups 3it
te abo.e use! can!i!ates an! inclu!e! ce-oterapy/ ra!ioterapy/ -istletoe terapy/
-etastases (yes%no)/ 6ra!in6 (1'3). )n te :inal -o!el entere! te :ollo3in6 can!i!ates:
!ia6nosis colorectal cancer (J1 V 22.10+/ C) V &.404'90.424)/ -etastasis (J1 V 2&.9&4/
C) V $.&&#'#9.12#)/ 6ra!in6 (J1 V 0.1$9/ C) V 0.0$2'0.44+)/ a6e (J1 V 1.+10/ C) V
1.03$'2.49#) an! sel:'re6ulation (J1 V 0.42+/ C) V 0.1#4'0.9#&) (table (table& &).
>able &
Final -o!el a:ter .ariable selection :or breast an! colorectal cancer/ si6ni:icant results are
printe! in bol!
>e sensiti.ity analysis/ 3it neste! K)CC sta6es :or bot cancer 6roups/ clearly resulte!
in a re!uction in te para-eters a6e an! Carlson co'-orbi!ity in!eD/ e.en i: tese
.ariables 3ere only -o!erately correlate! 3it K)CC sta6e (0.1$ an! 0.1+/ respecti.ely).
0sti-ates o: S1S/ on te oter an!/ 3ere nearly una::ecte! in tis -o!el (J1 V 0.&+&/
9&E'C): 0.30+'1.04&) but :aile! te &E tresol! (p V 0.0+#+) because o: !ecrease
sa-ple nu-ber an! consecuti.e increasin6 con:i!ence inter.al (table (table+). +). )n te
7aplan (eier sur.i.al plot/ colorectal cancer patients 3it lo3 S1 a! te i6est
-ortality/ :ollo3e! by te C1C'patients 3it i6 S1 an! breast cancer patients 3it lo3
S1 an! i6 S1 (Fi6ure (Fi6ure2 2).
>able +
Sensiti.ity analysis/ :inal -o!el a:ter .ariable selection an! K)CC sta6es instea! o:
!ia6nosis classes/ si6ni:icant results are plotte! in bol!
Fi6ure 2
The #aplan-eyer survival function $as separately plotted for high and lo$ self-
regulation for control; breast cancer and colorectal cancer patients group.
=o to:
Discussion
)n tis stu!y 3e :oun! tat/ in a!!ition to !ia6nostic 6roup/ K)CC sta6es an! te
Carlson co'-orbi!ity in!eD/ te sel: re6ulation (S1) scale (in particular its subscales
U9cie.e satis:action an! 3ell'bein6)U 3as a si6ni:icant in!epen!ent positi.e pre!ictor o:
sur.i.al o: breast an! colorectal cancer patients. >e autono-ic re6ulation (a1) scale a!
no si6ni:icant pro6nostic .alue.
Hur :in!in6s on sel:'re6ulation are consistent 3it results o: anoter researc 6roup tat
:oun! tat sel:'re6ulation is positi.ely associate! 3it patients sur.i.al 3it a ran6e o:
soli! tu-ours F11/19G. Sel:'1e6ulation (S1) is tou6t to represent te eability to acti.ely
acie.e 3ell'bein6/ inner e@uilibriu-/ appropriate sti-ulation an! :eelin6 o: co-petence
to control an! -ana6e stress:ul situationseF20G an! so3s repeate!ly lo3'-o!erate
correlations 3it a1 (0.30'0.3#) F2&/20G. Knpublise! !ata :ro- our stu!y 6roup so3 a
stron6 correlation bet3een S1 an! te tree SHC'subscales (co-preensibility/
-ana6eability an! -eanin6:ulness) :ro- r V 0.$0 to 0.$3 (p P 0.0&) 3ic su66est tat
SHC%resilience -i6t be connecte! 3it a 6oal'orientate! can6e o: li:estyle an!
orientation to3ar!s 3ellbein6. =en!er speci:ic copin6 strate6ies a.e been articulate!/
3it 3o-en usin6 a -ore e-otion'base! an! -en a -ore proble-'orientate! strate6y.
>is !istinction correspon!s to te t3o subscales o: sel:'re6ulation an! te stron6er
relationsip o: e3ell'bein6 orientatione to pro6nosis coul! be a :unction o: our
pre!o-inantly :e-ale sa-ple F2+G. FrentIel'?ey-e Z =rossart ypotesiIe! tat i6ly
sel:'re6ulate! persons are -ore capable copin6 3it sources o: uncertainty an!
instability. >e autors assu-e tat people 3it 3ell're6ulate! bea.iour a.e a psyco'
neuro'pysiolo6ical basis :or better co-petence an! !e:ence a6ainst ealt aIar!s F2$G.
>e actual -ecanis- :or te interaction o: sel:'re6ulation an! SHC 3it pysiolo6ical
processes re-ains unclear F2#G. ?ot cross'sectional an! prospecti.e !ata so3 a positi.e
association o: te SHC scale to cancer sur.i.al an! lo3er cancer inci!ence tat are
consistent 3it our results F13/29G i: tis !epen!s on a i6er resilience to3ar!s social
stress/ an! a i6er ability to a!apt re-ains unclear F30G. Jo3e.er/ tis -atc 3it !ata
:ro- te sel:'re6ulation scale tat autono-y elps :or better stress -ana6e-ent/ less
neurotics-/ better J1^< an! initiati.e po3er an! coul! be tere:ore elp:ul tool in
pre.enti.e -e!icine F14/20G.
Hur :in!in6s support te case :or !e.elopin6 inter.entions to i-pro.e sel:'re6ulation in
cancer patients. =rossart'(atice4 Z 0ysenc4 propose autono-y trainin6 :or te
i-pro.e-ent o: patientsU sel:'re6ulation F31G an! tis as been teste! in breast cancer
pre.ention F32G 3it initial positi.e :in!in6s F1&G. >ere is still a nee! :or lar6er
prospecti.e obser.ational stu!ies alon6si!e robust pra6-atic trials o: inter.entions base!
on te !e.elop-ent o: sel:'re6ulation. 9ltou6 it as been reporte! tat te application
o: -istletoe eDtracts -ay i-pro.e te sel:'re6ulation an! sur.i.al o: breast cancer an!
6ynaecolo6ical cancer patients F33/34G/ in tis stu!y 3e !i! not :in! a si6ni:icant
in:luence o: -istletoe eDtract application on sel:'re6ulation an! sur.i.al/ 3ic 3ere
in:luence! by operation/ ce-o' an! ra!ioterapy. >is e::ect coul! be !ue to te i6
operation rate an! -istletoe baseline application rate an! te s-all sa-ple siIe (co-pare
table table1 1).
Colorectal cancer patients a.e in co-parable sta6es 3it breast cancer patients an
in:erior sur.i.al 3ic is banal ne3s F3&G. )n our !ata C1C patients are -ore li4ely to be
in sta6e ))) or )8 3it a relati.e lo3 ce-oterapy treat-ent :re@uency probably because
o: te stron6 co-ple-entary terapy !esire o: tese patients in our centre :or inte6rati.e
-e!icine an! a i6 -istletoe treat-ent rate etc. >e breast cancer 6roup consiste! o:
-ore lon6 ter-'sur.i.ors. )n bot cancer 6roups K)CC sta6e an! 6ra!in6 3ere stron6
pro6nostic :actors alon6si!e sel:'re6ulation. )n cross'sectional stu!ies lo3 sel:'re6ulation
3as correlate! 3it i6er anDiety/ !epression an! lo3er J1^< F20G. )n a prospecti.e
stu!y/ -ulti.ariate analysis in!icate! tat sel:'re6ulation can be a co:actor to6eter 3it
autono-ic re6ulation :or anDiety an! an in!epen!ent :actor :or !epression. Jence/ in
conclusion/ :urter stu!ies are necessary to clari:y i: i6 sel:'re6ulation is an
in!epen!ent in:luencin6 :actor/ or is in:luence! !ue to te lac4 o: anDiety/ !epression/
!e-oralisation or ris4 :actors. >us/ in te sel:'re6ulation concept 3e still a.e to !eal
3it te sa-e crucial @uestion as :or SHC/ i.e./ 3eter it is cause or e::ect F3+G.
Stu!ies a.e -easure! te i-pact o: !isturbe! rest%acti.ity in -etastasiIe! colorectal
cancer on sur.i.al F$/3$G an! J1^< F+G. 9ccor!in6 to -eta'analysis/ pysical acti.ity
stabiliIes not only !aily acti.ity an! rest%acti.ity ryt- but is actually te treat-ent 3it
te i6est e.i!ence o: i-pro.in6 cancer'relate! :ati6ue F3#G. )n lar6e tertiary pre.ention
stu!ies it acie.es intensity !epen!ent a relati.e'ris4 re!uction :or colon an! breast
carcino-a until &0'&$E F39/40G. )n -etastasiIe! breast cancer/ a re!uce! circa!ian
cortisol ryt- is associate! 3it i6er -ortality F#G. >ese results principally re:lect
t3o aspects: :irstly te potential i-portance o: !isturbe! circa!ian ryt- on sur.i.al/
an! secon!ly tat !isturbe! an! :lattene! cortisol ryt- is a !istress -ar4er 3it an
in:luence on re!uce! J1^</ i6er :ati6ue le.el F#G an! i6er pre.alence o: un'
re:resin6 an! !isturbe! sleep in breast cancer F41G. 0.en i: tere are !i::erences in te
:re@uency o: inso-nia bet3een breast an! colorectal cancer F41/42G/ tere is a 6ro3in6
a-ount o: basic researc so3in6 tat a !isturbe! circa!ian ryt- coul! play an
i-portant role in -ali6nant 6ro3t control in tese an! oter cancers F43/44G. )n spite o:
unclear un!erlyin6 -ecanis-s/ tere is 6ro3in6 e.i!ence tat !isturbe! rest%acti.ity an!
circa!ian ryt- are interrelate! 3it C1F an! sleep !isturbances in bot cancer 6roups
F&/41/4&G. C1F i6ly correlates 3it 6lobal J1^< an! pysical :unctionin6 F4+G an! in
:ace o: contra!ictory results :ati6ue/ pysical an! e-otional :unctionin6 in breast cancer
an! 6lobal ealt an! particularly social :unctionin6 in colorectal cancer coul! be
pro6nostic in!ictors o: sur.i.al F4$/4#G. >o clari:y i: an! o3 stron6ly psyco-etrically
-easure! rest%acti.ity re6ulation is correlate! 3it acti6rapically -easure! rest%acti.ity/
3e are actually con!uctin6 t3o on6oin6 stu!ies. )n a prospecti.e stu!y 3e !eter-ine!
tat psyco-etrically -easure! autono-ic re6ulation is si6ni:icantly re!ucin6 cancer'
relate! :ati6ue an! co6niti.e :ati6ue F49G. Jo3e.er/ te rele.ance o: a !isturbe!
rest%acti.ity or circa!ian ryt- in -etastasiIe! cancer patients re@uires :urter researc
an! is still unclear in non'-etastasiIe! cancer patients an! :or te autono-ic an!
rest%acti.ity re6ulation -easurin6 @uestionnaire.
>ere are se.eral li-itations in our stu!y. >e stu!y 6roup is etero6eneously
constitute!/ te ti-e'span :or :irst !ia6nosis an! stu!y inclusion in particular as a i6
.ariability. 0.en i: 3e a.e initial e.i!ence supporte! by tis !ata tat sel:'re6ulation
-ay a.e an in:luence on sur.i.al o: cancer patients F19G/ 3e nee! -ore researc 3it
lar6er sa-ples inclu!in6 su::icient -ale participants/ tat allo3 :or e.ery cancer type a
sta6e a!2uste! analysis inclu!in6 !etaile! biolo6ical pro6nostic :actors an! terapies.
Furter-ore/ rest%acti.ity ryt- soul! be co'-easure! acti6rapically.
=o to:
"onclusions
,e a.e :oun! tat sel:'re6ulation -i6t be an in!epen!ent pro6nostic :actor :or te
sur.i.al o: breast an! colon carcino-a patients. Furter prospecti.e stu!ies 3it lar6er
populations/ -ore !etaile! penotypin6 o: patients an! lon6er :ollo3'up are re@uire! to
con:ir- tis :in!in6. Klti-ately 3e nee! to test -eto!s to i-pro.e sel:'re6ulation in
cancer patients as part o: oncolo6ical -ana6e-ent.
=o to:
/ist of abbreviations
a1: autono-ic re6ulation; ?C: breast cancer; C: control; C1C: colorectal cancer; C1F:
Cancer relate! :ati6ue; J1^<: Jealt'relate! @uality o: li:e; SHC: Sense o: coerence;
S1: sel:'re6ulation; K)CC: Knion )nternationale Contre le Cancer
=o to:
"o'peting interests
>e autors !eclare tat tey a.e no co-petin6 interests/ an! 3ere :ree to interpret te
!ata accor!in6 to a strict scienti:ic rationale.
=o to:
Authors< contributions
(7/ 1N/ J?.</ (= initiate! te pro2ect/ an! contribute! to te pro2ect !esi6n an! !ata
collection/ (1 an! 9?o participate! in te initiation o: te pro2ect an! per:or-e!
statistical analyses/ (7/ (1/ 1N/ =F/ 9?/ 9?o/ SL,/ J(/ (= contribute! to
interpretation/ an! (7/ (1/ =F/ 9?/ 9?o contribute! to te 3ritin6 o: te paper. 9ll
autors rea! an! appro.e! te :inal -anuscript.
=o to:
Ackno$ledge'ents
,e tan4 Clau!ia ,itt :or -eto!olo6ical a!.ice/ Cristian Jec4-ann an! Licole
7unert :or recruit-ent o: participants an! *a6-ar ?rauer :or te :ollo3'up -onitorin6
an! !atabase !ocu-entation. (7/ 1N an! *? ac4no3le!6e :inancial support :ro- te
Ju-anus')nstitut e.8./ ?erlin/ =er-any/ (7 an! J( :ro- So:t3are 9='Sti:tun6
*ar-sta!t/ =er-any.
=o to:
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Jurnal 5
?(C Cancer. 2010; 10: &+9.
Publise! online 2010 Hctober 20. !oi: 10.11#+%14$1'240$'10'&+9
P(C)*: P(C29$+$&3
Pancreatic cancer and depression% 'yth
and truth
(artina (ayr
1
an! 1olan! ( Sc-i!
1
9utor in:or-ation ; 9rticle notes ; Copyri6t an! <icense in:or-ation ;
>is article as been cite! by oter articles in P(C.
=o to:
Abstract
Background
8arious stu!ies reporte! re-ar4able i6 inci!ence rates o: !epression in cancer patients
co-pare! 3it te 6eneral population. Pancreatic cancer is still one o: te -ali6nancies
3it te 3orst pro6nosis an! tere:ore it see-s @uite lo6ical tat it is one o: te
-ali6nancies 3it te i6est inci!ence rates o: -a2or !epression.
Jo3e.er/ 3at about te scienti:ic bac46roun! o: tis relationsipB )s !epression in
patients su::erin6 :ro- pancreatic cancer 2ust !ue to te con:rontation 3it a li:e
treatenin6 !isease an! its so-atic sy-pto-s or is !epression in tis particular 6roup o:
patients a :eature o: pancreatic cancer per seB
Discussion
Se.eral stu!ies pro.i!e e.i!ence o: !epression to prece!e te !ia6nosis o: pancreatic
cancer an! so-e stu!ies e.en bla-e it :or its !etri-ental in:luence on sur.i.al. >e
i--ense i-pact o: e-otional !istress on @uality o: li:e o: cancer patients enances te
nee! :or its early !ia6nosis an! a!e@uate treat-ent. 7no3le!6e about un!erlyin6
patopysiolo6ical -ecanis-s is re@uire! to pro.i!e te opti-al terapy.
(u''ary
9 re.ie3 o: te literature on tis issue soul! re.eal 3ic are te :acts an! 3at is -yt.
=o to:
Background
8arious stu!ies a.e !e-onstrate! te i--ense i-pact o: psycolo6ical !istress on li:e
@uality an! illness tra2ectory in pancreatic cancer patients. (oreo.er/ ?ultI et al. entitle!
e-otional !istress ete siDt .ital si6n in cancer caree F1/2G. 9ccor!in6ly tey re@ueste!
ealt care pro.i!ers to attac no less i-portance to te -onitorin6 o: e-otional !istress
tan to te -onitorin6 o: etra!itionale .ital si6ns suc as bloo! pressure or eart rate.
Patients -ay bene:it :ro- early reco6nition an! a!e@uate treat-ent o: e-otional bur!en
or e.en !epression as !ocu-ente! in se.eral stu!iesF3G. Jo3e.er it is still a -atter o:
!ebate 3eter in!i.i!ual psycolo6ical copin6 strate6ies a.e si6ni:icant i-pact on
o.erall sur.i.al in cancer patients F4G.
Pancreatic cancer in particular is one o: te tu-or entities 3it a stri4in6ly i6 inci!ence
o: !epression as 3ell as one o: tose 3it te 3orst pro6nosis. )s tis 2ust a coinci!ence
or a si6n o: a reciprocal interactionB ,at is te i-pact o: psyce on cancer -ortalityB
>o a!!ress tis issue 3e re.ie3e! publise! !ata on pancreatic cancer relate! !epression
:or e.i!ence o: a relationsip bet3een psycolo6ical !istress an! te course o: tis
!isease.
=o to:
Discussion
Pancreatic cancer and depression
9 co-preensi.e stu!y by JinI et al. as reporte! tat te pre.alence o: anDiety an!
!epression in cancer patients is nearly as t3ice as i6 as in te 6eneral population F&G.
>is obser.ation is consistent 3it !ata :ro- te lar6e nor!'tron!ela6 ealt stu!y by
Stor!al et al. F+G. Se.eral prece!in6 stu!ies reporte! si-ilar results but a :e3 !i! not
so3 ele.ate! !epression scores relate! to cancer F$'10G. 1e6ar!in6 te !i.ersity o:
stu!ies on tis topic any inconsistency in :in!in6s can be -ainly attribute! to lo3 sa-ple
siIe/ te lac4 o: !i::erentiation by 6en!er/ a6e an! ti-e since !ia6nosis/ treat-ent an!
oter -eto!olo6ical :la3s as 3ell F&/10'12G. >ose stu!ies e.aluatin6 !i::erent tu-or
entities separately a.e re-ar4ably i6 !epression rates associate! 3it speci:ic tu-or
types in co--on. )n particular patients 3it pancreatic/ lun6/ oroparyn6eal an! breast
cancer are seriously a::ecte! by e-otional bur!en an! -a2or !epression F10/11/13/14G. )n
tis respect pancreatic cancer is te tu-or entity 3it te i6est inci!ence rate o:
!epression a-on6 all oter tu-ors o: te !i6esti.e syste- F1&'1$G.
>is stri4in6ly close relationsip bet3een pancreatic cancer an! -a2or !epression as
been 4no3n :or -ore tan $0 years F1#G. >e initial !escription !ates bac4 to 5as4in in
1931 F19G. Jis report on te association bet3een pancreatic cancer an! te tria! o:
anDiety/ !epression an! esense o: i-pen!in6 !oo-e 3as te ori6in o: se.eral ensuin6
stu!ies F1#'20G. )n 19+$ Fras et al. re.ie3e! te a.ailable eori6inal contributions/ 3ic
-entione! -ental sy-pto-s as a part o: sy-pto-atolo6y o: carcino-a o: te pancrease.
)n tis stu!y !epression 3as !ia6nose! in $+E o: te patients 3it pancreatic cancer an!
only in 20E o: te patients 3it colon cancer. >is in.esti6ation 3as -a!e prior to
sur6ery an! -ore tan &0E o: te patients 3it pancreatic cancer reporte! psycolo6ical
sy-pto-s/ up to 43 -onts be:ore so-atic co-plaints F1&G. >is arouse! a !ebate about
e-ental sy-pto-s as an ai! :or early !ia6nosis o: pancreatic cancere F21G. "acobsson et
al. :oun! initial !epression in 14E o: patients 3o 3ere a:ter3ar!s !ia6nose! 3it
cancer o: te pancreas but only in 4E o: patients 3it subse@uent !ia6nosis o: 6astric
cancer F22G. 9 si-ilar stu!y by "o::e et al. 19#+ reporte! se.ere !epression in o.er al:
te patients 3o 3ere :inally !ia6nose! 3it pancreatic cancer but none in te patients
3it 6astric cancer F23G. So-e case reports inscribe psycolo6ical sy-pto-s li4e panic
or anDiety as a arbin6er o: te subse@uent tu-or !ia6nosis F24/2&G. KneDpecte! i6
inci!ence rates 3ere con:ir-e! by a stu!y in 1993 so3in6 sy-pto-s o: !epression in
$1E o: te eDa-ine! pancreatic cancer patients an! eanDiety'relate! sy-pto-se in 4#E
o: te patients F2+G. )n te a:ore-entione! co-preensi.e re.ie3 by (assie et al. te
pre.alence o: !epression in pancreatic cancer 3as bet3een 33 an! &0E F10G.
For -ost o: te stu!ies a.e in.esti6ate! patients recently !ia6nose! 3it cancer/ te
possibility o: recall bias as be to be consi!ere!. Jollan! et al. e-ploye! sel:'assess-ent
@uestionnaires to assess !epression/ anDiety/ :ati6ue an! -oo! s3in6s in patients 3it
a!.ance! cancer F1+G. Finally patients 3it pancreatic cancer a! i6er sel:'ratin6s o:
!epression tan patients 3it oter a!.ance! ab!o-inal tu-ors. )n contrast a prospecti.e
stu!y by <abori et al. 3ic e-ploye! sel:'report -easures as te 0!-onton Sy-pto-
9ssess-ent Scale (0S9S) also note! relati.ely lo3 le.els o: !epression in patients 3it
a!.ance! pancreatic carcino-a/ but te s-all sa-ple siIe o: tis stu!y an! te lar6e
stan!ar! !e.iations put te !e:inite i-pact o: te result up :or !iscussion F2$/2#G. >ese
-eto!olo6ical li-itations co-plicate te :inal appraisal o: te a.ailable stu!ies. 9noter
callen6e is te !i::erentiation bet3een -a2or !epression an! te e@uite nor-ale
psycolo6ical !istress o: patients copin6 3it cancer !ia6nosis. So tere is in!ee! a
!e-an! :or an appropriate instru-ent to i!enti:y cancer relate!/ cancer speci:ic
!epression.
Diagnosis of depression-screening tools
>e reliability o: any !ata on te inci!ence o: !epression in cancer patients is i6ly
!epen!e! on te appropriate coice o: te assess-ent tool. >e respecti.e tool as to be
suitable not only :or !i::erentiation bet3een !epression an! e@uite nor-ale psycolo6ical
!istress o: patients copin6 3it cancer !ia6nosis but also :or a.oi!in6 -isattribution o:
sy-pto-s o: te tu-or !isease to !epression F20G. Kn:ortunately stu!ies on te
pre!icti.e .alue o: te !i::erent screenin6 tools are sparse F29/30G. >e basic structures o:
te establise! !epression assess-ent tools are -ainly !ia6nostic inter.ie3s/ patient sel:'
report :or-s or obser.er ratin6s F31G. )n 6eneral/ te classi:ication o: !epression as a
.ariety o: a::ecti.e !isor!ers co-plies 3it te *ia6nostic an! Statistical (anual o:
(ental *isor!ers *S(')8 e!ite! 1994 by 9-erican Psyciatric 9ssociation
(correspon!in6 to )C*'10). >e current .ersion *S(')8'>1 3as publise! "uly 2000/ a
re.ise! .ersion/ te *S('8 is bein6 !e.elope! at present.
>e anDiety !isor!ers inter.ie3 sce!ule :or *S(')8/ a structure! clinical inter.ie3/
-ay be e-ploye! to assess a ran6e o: !isor!ers 6oin6 trou6 !i::erent ite-s F29/32G.
>e *S(')8'classi:ication 3as o:ten @uestione! to be a!e@uate :or application in cancer
patients. >e a!.anta6e o: structure! clinical inter.ie3s is un!oubte!/ but tey a.e to be
con!ucte! by s4ille! sta:: an! tere:ore re@uire enor-ous a-ounts o: resources F31G.
Patient sel:'report screenin6 in.entories are brie: enou6 an! tere:ore -ore use:ul in
routine application in cancer patients F30G. Furter-ore/ sel:'report :or-s are suppose! to
be -ore sensiti.e to i!enti:y si6ni:icant :unctional i-pair-ent !urin6 :ollo3 up F29G.
>ere:ore/ it is o:ten reco--en!e! to use sel:'report :or-s as a :irst step to i!enti:y
!epression :ollo3e! by a structure! inter.ie3 in te e-er6in6 cases F31G. Kp to te
present ti-e a .ariety o: assess-ent instru-ents a.e been !e.elope! an! te !i::erent
:or-s 3ere e-ploye! in -ultiple stu!ies. >e -ost co--on ones applie! in cancer
patients are re:erre! to belo3.
>e :a'ilton !ating (cale for Depression (:AD) as been a stan!ar! instru-ent
:or peer assess-ent o: !epressionUs se.erity since 19$0 F33G. <in et al. -ost recently use!
te J9(*'24 as te ratin6 scale :or !epression to screen patients 3it 6astrointestinal
tu-ors F1$G. J9(*'24 contains 24 ite-s 3ic are recalle! 3itin te -o!i:ie! J9(*
.ersion o: 19#& F34G. ?ut J9(* as 3ell as "P!( (Co-preensi.e Psycopatolo6ical
1atin6 Scale) or AD!( ((ont6o-ery'9sber6 *epression 1atin6 Scale) are in :act no
a!e@uate !ia6nostic instru-ents :or !epression but -easures o: illness se.erity an! it is
still !ebatable 3eter tese ratin6 scales are suitable :or pri-ary i!enti:ication o: -a2or
!epression F11/3&'3$G. )n cancer patients !ia6nosis o: !epression re@uires special e::ort
because so-atic sy-pto-s o: !epression li4e :ati6ue/ anoreDia an! 3ei6t loss are @uite
co--on in -ali6nancies. >ere:ore te :ocus as to be on e.aluation o: psycolo6ical
an! co6niti.e sy-pto-s li4e opelessness/ loss o: a-bition/ ane!onia or suici!al
i!eation F1#/3#/39G. >o -eet tese !e-an!s assess-ent instru-ents li4e te Distress
Ther'o'eter; te Brief (y'pto' Inventory (B(I)/ te (y'pto' "hecklist =5-!
(("/-=5) or te Proble' "o''on "hecklist a.e been !esi6ne! F9/14/2#/40G. >e
currently -ost establise! sel:'assess-ent instru-ents are te Becks Depression
Inventory (BDI) an! te :ospital An1iety and Depression (cale (:AD()
questionnaire. >e ?*) as been !e.elope! :or clinical i-ple-entation o: psyciatric
patients to rate se.erity o: !epression sy-pto-s an! -ay be co-bine! 3it te ?ec4
Jopelessness Scale (?JS) to assess co6niti.e aspects o: !epression F41G. ?ut it
co-prises so-e so-atic ite-s 3ic -ay cause :alse positi.e results by te in:luence o:
un!erlyin6 !isease an! conco-itant terapy F31G. >e Jospital an! 9nDiety *epression
Scale (J9*S) as been !esi6ne! to a.oi! in particular an i--o!erate in:luence o:
so-atic sy-pto-s in screenin6 :or !epression F11G. )ts .ali!ity an! reliability in cancer
patients as been !e-onstrate! in se.eral stu!ies F31G.
Pathophysiological aspects of cancer related depression
>ere are t3o pi.otal @uestions to a!!ress. First/ is !epression a speci:ic :eature o: cancer
or coul! it be trace! to te !iseaseUs se.ere conco-itant sy-pto-s an! its :atal
pro6nosisB ' Secon!/ is !epression itsel: a pro-oter o: tu-or !e.elop-ent or are
patopysiolo6ical can6es !ue to cancer responsible :or te i6 inci!ence o:
!epressionB
Hne possible approac to te e.i!ent bi!irectional relationsip bet3een !epression an!
pancreatic cancer is to re6ar! te eDtent o: psycolo6ical !istress patients eDperience
bein6 :ace! 3it suc :atal !ia6nosis. For pancreatic cancer patients te i-pact o:
-e!ical/ psycolo6ical an! social :actors is 6enerally -ore se.ere tan :or patients 3it
oter intestinal cancers F1#G. 9noter approac to te ori6in o: cancer'relate! !epression
co-prises te researc o: possible patopysiolo6ical -ecanis-s.
So-e autors ascribe cancer relate! !epression to paraneoplastic li-bic encepalitis
F42/43G ' but to con:ir- tis !ia6nosis a ran6e o: neuropatolo6ical tests are necessary.
Sy-pto-s o: paraneoplastic li-bic encepalitis o:ten prece!e cancer !ia6nosis as
!epression prece!es pancreatic cancer F20G. 9l-ost &0E o: pancreatic cancer patients
so3 !epressi.e sy-pto-s in a!.ance o: teir tu-or !ia6nosis F1#/20/2+G. )n a stu!y
3it stri4in6ly i6 inci!ence o: !epression in pancreatic cancer <in et al. reporte! no
statistically si6ni:icant !i::erence in patients 4no3in6 !ia6nosis or not F1$G. 9-on6 tese
patients !e.elop-ent o: !epression 3as in!epen!ent o: te a3areness o: ei-pen!in6
!oo-e. 9ccor!in6ly it is still un!er !iscussion 3eter pancreatic cancer in!uces
!epression or 3eter !epression enances te ris4 o: tu-or !e.elop-ent F20/44G.
)n tis !ebate a !ysre6ulate! i--une response is suppose! to be te causal lin4 bet3een
!epression an! cancer. 9ni-al -o!els in!icate tat proin:la--atory cyto4ines can elicit
e!epression'li4ee sy-pto-s F12/4&G. )n pancreatic cancer patients in!ee! increase! le.els
o: se.eral cyto4ines suc as )<'+/ )<'1# an! >LF'alpa can be :oun!. >ese :actors -ay
a.e i-pact on te ypotala-ic'pituitary'a!renal (JP9) aDis an! te C1F
(corticotropin'releasin6 :actor). So-e autors assu-e tis pat3ay to be te cause :or
patolo6ic results in te !eDa-etason suppression test/ in analo6y to a paraneoplastic
sy-pto-. 0le.ate! )<'+ plas-a le.els in particular see- to be associate! 3it -a2or
!epression in pancreatic cancer patients an! tu-or cells can in:luence pro!uction o:
serotonin receptor antibo!ies acti.e in central ner.ous syste- F23/4+'49G.
Antidepressant therapy - an essential part of supportive care
*epression is one o: te crucial :actors i-pairin6 li:e @uality o: cancer patients.
9ccor!in6ly early an! a!e@uate anti!epressant treat-ent is an essential co-ponent o: all'
e-bracin6 supporti.e care. (ana6e-ent o: !epression re@uires su::icient pain control
an! psycolo6ical support as 3ell as use o: anti!epressants F&0G. 9ny possible or6anic
causes o: !epression li4e -etabolic !isor!er/ in:ections/ !ru6 si!e e::ects (i.e.
ce-oterapeutic substances) or brain ra!iation soul! be consi!ere! be:ore
a!-inistration o: par-acolo6ic terapy F1#/39G.
Clinical trials a.e so3n te e::icacy o: .arious anti!epressants to be co-parable
F1#/39/&0G. >e coice o: te appropriate anti!epressant substance soul! be !eter-ine!
by te -ain tar6et sy-pto-s re:errin6 to te patientUs current -e!ical proble-s an! te
si!e e::ect pro:ile F&0G. 9-on6 te .ariety o: anti!epressants an! antipsycotic !ru6s a
selection o: te -ost establise! ones is liste! belo3.
>ricyclic anti!epressants are te -ost co--only a!-inistere! !ru6s F11/1#/&1G. >ey
-ay e.en be e::ecti.e as conco-itant terapy :or patients 3it neuropatic pain/
inso-nia an! speci:ic coliner6ic sy-pto-s. >ere is an uneDplaine! s-aller terapeutic
ran6e o: tricyclic a6ents in cancer patients 3ic is to be consi!ere! F1#G. *ue to
increase! serotonin le.els in pancreatic cancer selecti.e serotonin re'upta4e inibitors
(SS1)s) -ay be e::ecti.e as a 4in! o: etar6ete! terapye F20G. (irtaIapine/ a speci:ic
serotoner6ic anti!epressant/ !e-onstrate! i6er sustaine! re-ission rate tan
a-itriptylin an! -ore rapi! onset in se.eral stu!ies. >ere:ore -irtaIapine is applicable
e.en in el!erly patients an! reco--en!e! :or tose 3it a sort li:e eDpectancy. ?esi!es
it is assu-e! to a.e e::ects on pain/ nausea/ e-esis an! appetite loss F&2'&4G.
9-isulpri!e as an atypical antipsycotic enances !opa-iner6ic trans-ission in te
:rontal corteD an! li-bic areas. Conco-itant treat-ent !urin6 ce-oterapy acie.e!
si6ni:icant re!uction o: !epressi.e sy-pto-s 3it -ini-al si!e e::ects F&&G. Patients
3it pre.alent sy-pto-s o: anDiety recei.e better treat-ent response 3it
benIo!iaIepines F1#/3#/4#G. ?ut benIo!iaIepines -ay increase psyco-otoric slo3in6
an! :ati6ue 3ic is a .ery 6eneral co-plaint o: cancer patients. Jence !i::erent !ru6s
a.e been teste! to !ecrease 3ea4ness. 9-on6 .arious psycosti-ulants
-etylpeni!ate is te -ost establise!/ but :irstly te results o: te !i::erent trials are
inconsistent an! secon!ly tolerance -ay !e.elop F1#/20/39G. Finally so-e autors re:er
to current 6ui!elines 3ic su66est psycosti-ulants eto be reasonable to consi!er :or
se.ere :ati6uee F&+G.
?eyon! par-acolo6ic treat-ent o: !epression supporti.e psycoterapy inclu!in6
teacin6 copin6 strate6ies plays an i-portant role in an!lin6 cancer relate! !epression.
0.en i: it is re6ar!e! as an essential treat-ent approac restricte! li:e eDpectancy as to
be ta4en in account 3en constitutin6 te type o: psycoterapy or supporti.e counselin6
F11/1#/39G.
Depression and cancer 'ortality
>e relationsip bet3een a::ecti.e !isor!ers an! -ortality as been in te scienti:ic :ocus
:or -ore tan +0 years. 7err et al. reporte! 19+9 an eincrease! -ortality rate :ro-
pysical !isease in patients 3it a::ecti.e !isor!ers/ particularly :ro- carcino-ae F&$G.
>ey also notice! re-ar4ably i6 rates o: pancreatic cancer an! lun6 carcino-a a-on6
tese patients. >e :ollo3in6 !eca!es nu-erous in.esti6ations on !epression in cancer
patients a.e been con!ucte!. Ji6 pre.alence rates o: !epression particularly in patients
su::erin6 :ro- tu-or entities 3it 3orse pro6nosis li4e pancreatic cancer le! to te
crucial @uestion :or te i-pact o: !epression on -ortality. >e istory o: !epression in
cancer patients as been lin4e! to 3orse o.erall sur.i.al rates !ue to i-paire! i--une
response an! i6er rates o: suici!e in so-e but not all stu!ies F11/3#/&#G. )n a
retrospecti.e analysis o: sur.i.al !ata o: 2&# patients by Seibani'1a! et al. pancreatic
cancer associate! !epression !i! not a::ect sur.i.al F&9G.
8ice .ersa te e::ect o: anti!epressant terapies on -ortality 3as in.esti6ate!. First
!escriptions o: te in:luence o: psycoterapeutic inter.entions on te sur.i.al o: tu-or
patients 3ere publise! o.er 30 years a6o. So-e stu!ies reporte! tat 6roup terapies le!
to prolon6e! sur.i.al rates in te participatin6 patients F+0G. >ey 3ere sarply criticiIe!
:or -eto!ical :la3s an! bias li4e te poor sur.i.al !ata o: te control 6roup but te
@uestion :or te lin4a6e bet3een psycolo6ical :actors an! te course o: cancer
re-aine!.
Se.eral re.ie3s an! -eta'analyses eDa-ine! te suppose! lin4a6e critically. )n 2002
Petticre3 et al. re.ie3e! a selection o: prospecti.e obser.ational stu!ies to 2u!6e te
i-pact o: psycolo6ical copin6 styles on te sur.i.al :ro- or te recurrence o: cancer.
Consistent e.i!ence :or te o:ten cite! bilateral relationsip coul! ar!ly be asserte!. >e
autors state! te positi.e results to be econ:ine! to s-all an! -eto!olo6ically :la3e!
stu!iese. )n a6ree-ent 3it oter autors tey assu-e! in:luential publication bias F+1G.
Le.erteless -ore an! -ore trials on tis topic a.e been con!ucte! in recent years.
9l-ost all report on te i6 inci!ence o: !epressi.e sy-pto-s an! conse@uently/ te
si6ni:icant i-pact on sur.i.al. )n 200$ Steel et. al per:or-e! a note3orty prospecti.e
stu!y to establis a -e!itational -o!el o: !epression/ i--unity an! sur.i.al in patients
3it epatobiliary carcino-a F&#G. 9s soon as te paper 3as publise! a
counterstate-ent put it up :or !iscussion !ue to a .ariety o: con:oun!in6 :actors
inclu!in6 te s-all sa-ple siIe F+2G. Currently a -eta'analysis on !epression an! cancer
-ortality by Pin@uart et al. reassesse! te reliability o: results !epen!in6 on .aryin6
stu!y caracteristics. Finally ete associations bet3een !epression an! -ortality persiste!
a:ter controllin6 :or con:oun!in6 -e!ical .ariablese/ but te autors e-pasiIe te
!e-an! :or :urter researc also F4/+1G.
=o to:
(u''ary
>e peno-enon o: cancer relate! !epression as been obser.e! an! in.esti6ate! in
e.ery possible 3ay o.er te last !eca!es. (ost o: te stu!ies !e-onstrate stri4in6ly i6
inci!ence rates o: !epression in cancer patients particularly a-on6 tose 3it :atal
pro6nosis li4e pancreatic cancer. (oreo.er/ a recently publise! trial co-plains about a
lac4 o: attention to psycolo6ical !istress in pancreatic cancer patients F2#G ' altou6 te
i--ense i-pact o: !epression on @uality o: li:e as been establise! an! -ean3ile
assess-ent o: li:e @uality is i6ly stan!ar!iIe!. Co-parin6 pancreatic cancer patients
3it an! 3itout !epression a si6ni:icant !eterioration o: li:e @uality as been
!e-onstrate!. )n clinical stu!ies patients 3it pancreatic cancer so3e! -ost si6ni:icant
i-pair-ent in scores o: pysical/ e-otional an! co6niti.e :unctionin6 3it a special
i-pact on social :unctionin6. >e score o: sy-pto- scales in particular :ati6ue an! pain
3as si6ni:icantly i6er in te pancreatic cancer 6roup co-parin6 it to oter intra'
ab!o-inal -ali6nancies F1$G. >e association bet3een pain an! !epression is 3ell
!ocu-ente! F3#/41G. )t is still un!er !iscussion 3eter te presence o: !epression
increases te ris4 o: cronic pain per se or su::erin6 :ro- cronic pain e.ol.es -a2or
!epression itsel: F11G/ but cronic pain is un!oubte!ly a crucial :actor in 2u!6in6 @uality
o: li:e F&0G.
Concernin6 te lin4a6e bet3een !epression an! te course o: cancer an! sur.i.al a lot o:
stu!ies 3ere con!ucte!. Se.eral o: te- !escribe! a stron6 relationsip bet3een
!epression an! -ortality an! so-e coul! not !etect a lin4a6e at all. ,it re6ar! to
co-preensi.e -eta'analyses tere is a ten!ency :or a correlation bet3een i6er le.els
o: !epressi.e sy-pto-s an! ele.ate! -ortality/ but 2u!6-ent o: a.ailable stu!y results is
con:ine! to s-all sa-ple siIes an! .arious con:oun!in6 :actors F4/+1G. )n.esti6ations
concernin6 te patopysiolo6ical bac46roun! inspire! te ope :or a better
un!erstan!in6 o: te correlation bet3een so-atic an! psyciatric illness an! te possible
i-pact on -ortality. *isor!ers in en!ocrinolo6ical an! i--unolo6ical pat3ays a.e
been suppose! to be responsible :or te in:luence o: ne6ati.e psycolo6ical aspects on
sur.i.al but tese bioce-ical can6es a.e e.en been assu-e! to elicit !epressi.e
reactions te-sel.es F+3/+4G. )t is a :easible aspect tat te correlation bet3een e-otional
!isor!ers an! illness tra2ectory is con:oun!e! by te o:ten poor clinical state o: te
patients. >e poor clinical state itsel: is associate! 3it a poor pro6nosis an! its so-atic
sy-pto-s are i6ly correlate! 3it !epressi.e reactions F+&/++G. So te e-ploye!
assess-ent tools :or !epression soul! -ini-iIe te in:luence o: clinical sy-pto-s.
)n su--ary tere is no :inal eDplanation :or te lin4a6e bet3een pancreatic cancer/
!epression an! sur.i.al an! tere is no reliable e.i!ence tat psycolo6ical copin6 styles
-ay !e:initely in:luence sur.i.al or recurrence o: cancer F+1G. >ere:ore cancer patients
soul! not be bla-e! o: 3orsenin6 teir situation 3en not participatin6 in 6roup
inter.entions or psycoterapeutic treat-ent F+2G. ?ut re.ie3 o: te !ata publise! so :ar
con:ir-s te ut-ost i-portance o: payin6 attention to !epressi.e reactions in cancer
patients an! care :or early a!e@uate treat-ent because te i-pact on @uality o: li:e is
assure! an! :or patients su::erin6 :ro- a -ali6nancy 3it suc a poor pro6nosis li4e
pancreatic cancer i-pro.in6 @uality o: li:e as to be te -a2or terapeutic 6oal. 9ctually
!ealin6 3it tis topic te :rontiers bet3een reality an! -yt are -er6in6 an! :urter
in.esti6ation is re@uire! to !eter-ine te eDtraor!inary correlation o: psycolo6ical an!
patopysiolo6ical :in!in6s in pancreatic cancer.
=o to:
"o'peting interests
>e autors !eclare tat tey a.e no co-petin6 interests.
=o to:
Authors< contributions
9ll autors a.e contribute! in 3ritin6 te re.ie3. 9ll te autors rea! an! appro.e! te
:inal -anuscript.
=o to:
Pre-publication history
>e pre'publication istory :or tis paper can be accesse! ere:
ttp:%%333.bio-e!central.co-%14$1'240$%10%&+9%prepub
=o to:
Ackno$ledge'ents
>e autors tan4 Peter Jerscbac :or re.isin6 te -anuscript.
=o to:
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Jurnal 6
Psycooncolo6y. 9utor -anuscript; a.ailable in P(C 2012 "une 1&.
Publise! in :inal e!ite! :or- as:
Psycooncolo6y. 2009 "anuary; 1#(1): &0+1.
!oi: 10.1002%pon.13$1
P(C)*: P(C33$&#3+
L)J(S)*: L)J(S3$&&$+
Do !ates of ental Disorders and
&1istential Distress a'ong Advanced
(tage "ancer Patients Increase as Death
Approaches4
,en!y =. <ictental/ P.*./
1
(atte3 Lilsson/ ?.S./
2
?aoui Nan6/ (.S./
2
0liIabet
*. >rice/ (.*./ P.*./
3
*a.i! ,. 7issane/ (.*./
1
,illia- ?reitbart/ (.*./
1
an! Jolly =.
Pri6erson/ P.*.
2
9utor in:or-ation ; Copyri6t an! <icense in:or-ation ;
>e publiserUs :inal e!ite! .ersion o: tis article is a.ailable at Psycooncolo6y
See oter articles in P(C tat cite te publise! article.
=o to:
Abstract
*b-ective
>o !eter-ine i: te pre.alence o: -ental !isor!ers an! relate! :actors increase as
a!.ance! cancer patients 6et closer to !eat.
ethod
?aseline/ cross'sectional !ata :ro- 2#9 patients 3o 3ere assesse! prior to teir !eat as
part o: a -ulti'site/ lon6itu!inal/ prospecti.e coort stu!y o: a!.ance! cancer patients.
(a2or *epressi.e *isor!er/ =eneraliIe! 9nDiety *isor!er/ Panic *isor!er/ an!
Posttrau-atic Stress *isor!er 3ere assesse! usin6 te Structure! Clinical )nter.ie3 :or
te DSM-IV 9Dis ) *isor!ers (SC)*')). Hter :actors eDa-ine! inclu!e! eDistential 3ell'
bein6/ patient 6rie: about teir illness/ pysical sy-pto- bur!en/ ter-inal illness
ac4no3le!6-ent/ peace:ulness/ an! te 3is to li.e or !ie.
!esults
Closeness to !eat 3as not associate! 3it i6er rates o: -ental !isor!ers. Patients
closer to !eat eDibite! increase! eDistential !istress an! pysical sy-pto- bur!en/
3ere -ore li4ely to ac4no3le!6e bein6 ter-inally ill/ an! 3ere -ore li4ely to report an
increase! 3is to !ie.
"onclusion
1esults !o not pro.i!e support :or te co--on clinical assu-ption tat te pre.alence o:
!epressi.e an! anDiety !isor!ers increases as !eat nears. Jo3e.er/ patientsU le.el o:
pysical !istress/ ac4no3le!6-ent o: ter-inal illness/ an! 3is to !ie/ possibly re:lectin6
acceptance o: !yin6/ increase! as !eat approace!. <on6itu!inal stu!ies are nee!e! to
con:ir- in!i.i!ual can6es in rates o: -ental !isor!er as patients approac !eat.
#ey$ords% a!.ance! cancer/ oncolo6y/ -ental !isor!ers/ eDistential !istress/ proDi-ity
to !eat/ ter-inal illness a3areness
=o to:
Introduction
9s !eat approaces/ it is co--on :or patients 3it ter-inal illness to eDperience an
eDacerbation in te nu-ber an! se.erity o: teir pysical an! psycosocial stressors.
>ese stressors can inclu!e 6ro3in6 :railty 3it !ebilitatin6 pysical sy-pto-s/ loss o:
in!epen!ence/ !ecrease! social connecte!ness/ increase! eDistential !istress/
!e-oraliIation F1G/ !eat anDiety/ conser.ation'3it!ra3al F2/ 3G/ an! preparatory'6rie:
F4G. >e pro6ression o: illness an! associate! stressors -ay re-in! patients o: teir
ter-inal ealt status/ increase teir eDistential !istress/ an! ei6ten teir ris4 :or
!e.elopin6 psyciatric !isor!ers. =i.en tis/ -any clinicians 3or4in6 in palliati.e care
settin6s a.e speculate! tat rates o: -ental !isor!ers increase as !eat approaces;
o3e.er/ 3e 3ere unable to locate a !irect e-pirical eDa-ination o: tis ypotesis.
0arlier/ -eto!olo6ically'li-ite! stu!ies o: cancer patients su66este! an association
bet3een !epression an! poorer :unctionin6 F912G. Jo3e.er/ tese in.esti6ations !i! not
:ocus on patients at te en! o: li:e. (ore recently/ 94eci an! collea6ues stu!ie!
psyciatric -orbi!ity a-on6 "apanese ter-inally ill cancer patients an! !e-onstrate! an
association bet3een a.in6 a!.ance! cancer an! te presence o: an a!2ust-ent or
!epressi.e !isor!er F131&G. 94eci et al. also eDa-ine! te clinical course o: psyciatric
!isor!ers a-on6 a!.ance! cancer patients usin6 only t3o assess-ent points F13/ 1&G. )n
one lon6itu!inal stu!y report/ tey o::ere! !escriptions o: te clinical course obser.e!
a-on6 patients (e.6./ approDi-ately $1E o: patients 3o -et criteria :or -a2or
!epressi.e !isor!er at baseline no lon6er -et criteria at :ollo3'up)/ but !i! not test
3eter rates o: !epression or oter -ental !isor!ers at baseline 3ere si6ni:icantly
!i::erent :ro- tose at :ollo3'up F14G. ,eter te "apanese eDperience is 6eneraliIable
to an 9-erican population is unclear.
)n contrast to :in!in6s su66estin6 a relationsip bet3een !isease pro6ression an!
increase! -ental ealt proble-s/ 7issane et al. F1+G :oun! tat si-ilar pre.alence rates
o: DSM-IV -ental !isor!er !ia6noses 3en co-parin6 early sta6e to a!.ance! breast
cancer patients. >is co-parison 3as -a!e/ o3e.er/ usin6 baseline assess-ents :ro-
t3o separate psycosocial inter.ention clinical trials tar6etin6 coorts o: early sta6e an!
a!.ance! breast cancer patients/ respecti.ely F1+G. ,e a.e not i!enti:ie! prior researc
tat as speci:ically eDa-ine! 3eter or not pre.alence rates o: !epressi.e or anDiety
!isor!ers increase as !eat approaces in a sin6le patient sa-ple.
Hur un!erstan!in6 o: o3 rates o: psyciatric con!itions can6e o.er ti-e 3itin te
conteDt o: cancer is co-plicate! in part by te inconsistent :in!in6s o: pre.ious
epi!e-iolo6ical stu!ies F&#G. ,ile researcers o:ten attribute te .ariation in point
pre.alence esti-ates to te use o: !i::erent assess-ent -eto!s F&/ $G/ te -iDe! results
-ay also be !ue to te :act tat stu!ies a.e co-pare! patients 3o 3ere at !i::erent
ti-e points in te course o: teir illness tra2ectory. (any psyciatric epi!e-iolo6y
in.esti6ations o: patients !ia6nose! 3it a ter-inal illness a.e 6roupe! participants into
broa! cate6ories/ inclu!in6 palliative care, terminally ill, advanced cancer, an! end-of-
life, 3ic !o not a!e@uately capture te potential !i.ersity o: suc sa-ples. Patients
.ary !ra-atically alon6 !i-ensions o: pysical :unctionin6 an! @uality o: li:e as teir
!isease pro6resses/ an! tus 3itin'sa-ple etero6eneity -ay eDplain 3y prior stu!ies
eDa-inin6 pre.alence esti-ates o: psycosocial :actors a.e reporte! !iscrepant results.
=rabsc et al. F1$G e-pasiIe! te i-portance o: un!erstan!in6 te epi!e-iolo6y o:
psyciatric -orbi!ity a-on6 a!.ance! cancer patients to -ini-iIe te :re@uency o:
clinicians ne6lectin6 cases tat 3arrant attention. 0Distential !istress at te en! o: li:e is
o:ten consi!ere! nor-ati.e/ 3ic -ay result in clinicians o.erloo4in6 or un!ertreatin6
psycolo6ical sy-pto-s F1#G. Furter-ore/ clinical !epression -ay be o.erloo4e!
because o: te !i::iculty !i::erentiatin6 it :ro- eDistential !istress F+/ 1#G. )n :act/ prior
stu!ies a.e su66este! tat clinicians un!eresti-ate te le.el o: !epression a-on6 -ore
se.erely !epresse! cancer patients F19/ 20G. >is -ay be particularly proble-atic 3en
pro.i!ers are 3or4in6 3it a!.ance! cancer patients/ as poor !etection o:
psycopatolo6y an! lo3 re:errals rates a.e been :oun! F1#/ 21G. ): proDi-ity to !eat is
in!ee! a ris4 :actor :or -ental illness/ ten tis -i6t in!icate tat pro.i!ers soul!
enance e::orts to !etect sy-pto-s o: psycopatolo6y suc as !epression as !isease
a!.ances so tat te appropriate inter.entions or re:errals -ay be -a!e. ):/ on te oter
an!/ pre.alence rates o: -ental !isor!ers are not associate! 3it closeness to !eat/ ten
tis 3oul! su66est tat practitioners -ay be able to !ia6nose an! treat -ental !isor!ers
as tey !o in any oter conteDt. Hbser.e! psycopatolo6y 3oul! not be consi!ere!
nor-ati.e.
)n te current stu!y/ 3e 3ere intereste! in eDa-inin6 rates o: psyciatric !isor!ers at
.arious sta6es o: !isease pro6ression (-easure! by proDi-ity to !eat at te ti-e o:
e.aluation) in or!er to test te ypotesis tat te pre.alence o: tese !isor!ers increases
as patients approac !eat. =i.en te una.ailability o: !ata 3it repeate! -ental ealt
assess-ents in en!'o:'li:e researc/ 3e use! 3at is ar6uably te best a.ailable !ata :or
te purpose: baseline assess-ents o: a patient coort recruite! :or te Copin6 3it
Cancer (C3C) stu!y. >e C3C is a -ulti'site/ prospecti.e/ lon6itu!inal in.esti6ation o:
an etnically an! 6eo6rapically !i.erse sa-ple o: a!.ance! cancer patients an! teir
care6i.ers !esi6ne! to ans3er @uestions about !ia6nosable !epressi.e an! anDiety
!isor!ers a-on6 a!.ance! sta6e cancer patients an! teir care6i.ers. 9 pre.ious
publication on !ata :ro- te C3C !e-onstrate! tat approDi-ately 12E o: patients -et
criteria :or at least one -a2or psyciatric con!ition at baseline F22G.
)n te present cross'sectional stu!y/ 3e eDa-ine! te rates o: -ental !isor!ers a-on6
patients to !eter-ine 3eter te pre.alence esti-ates .arie! in 6roups tat 3ere
cate6oriIe! by te-poral closeness to !eat/ ran6in6 :ro- 0 to 6reater tan + -onts.
1esults :ro- analyses 3ere a!2uste! :or pysical sy-pto- bur!en/ a potentially
i-portant con:oun! F23/ 24G/ in or!er to isolate te -ental !isturbance :ro- tat
attributable to un!erlyin6 !isease. ,e also in.esti6ate! oter psycolo6ical :actors tat
-i6t be eDpecte! to can6e in intensity as !eat approaces an! tat a.e pre.iously
been associate! 3it psyciatric -orbi!ity a-on6 patients/ suc as eDistential !istress
an! patientsU co6niti.e an! e-otional acceptance o: teir ter-inal ealt status F2&G. Prior
stu!ies a.e su66este! tat patientsU a3areness o: teir ter-inal pro6nosis (i.e./ co6niti.e
acceptance) ten!s to increase as tey approac !eat F2+/ 2$G. Pri6erson F2#G :oun! tat
ter-inally ill patients 3o ac4no3le!6e !eat (i.e./ ter-inal illness ac4no3le!6-ent
F>)9G) are -ore li4ely to recei.e palliati.e care 3itout :urter a66ressi.e inter.entions.
Patients eDibitin6 >)9 are also -ore li4ely to en6a6e in a!.ance care plannin6 F2&G as
also been associate! 3it increase! a!.ance care plannin6 F2&G. ,ile co6niti.e
acceptance in te absence o: e-otional acceptance -ay be associate! 3it 6reater
!istress/ 3en bot >)9 an! a sense o: peace:ulness are present/ care6i.ers a.e reporte!
i-pro.e! @uality o: !eat in patientsU last 3ee4 o: li:e F2&G. 0Da-ination o: tese
a!!itional in:luential :actors represents a no.el contribution to tis literature.
=o to:
&T:*D
(tudy 0roup and Design
>e participants in tis cross'sectional in.esti6ation 3ere 2#9 a!.ance! cancer patients
3o 3ere recruite! as part o: te C3C stu!y/ a -ulti'institutional lon6itu!inal e.aluation
(Lational )nstitutes o: Jealt FL)JG 6rants (J+3#92/ C910+3$0) o: te pre.alence o:
-ental illness an! patterns o: -ental ealt ser.ice utiliIation in a!.ance! cancer
patients an! teir pri-ary in:or-al (nonpai!) care6i.ers. >is report :ocuses on baseline
!ata :ro- patients :or 3o- !ate o: !eat !ata 3as a.ailable; patients 3o 3ere still
ali.e at te ti-e o: tese analyses 3ere not inclu!e!.
Participants 3ere recruite! bet3een 9u6ust 1/ 2002 an! (ay 2&/ 200$ :ro- te 5ale
Cancer Center (C>)/ te 8eterans 9::airs Connecticut Jealtcare Syste- Co-preensi.e
Cancer Clinics (C>)/ (e-orial Sloan'7etterin6 Cancer Center (L5)/ an! te Par4lan!
Jospital Palliati.e Care Ser.ice (>O). )nclusion criteria :or te stu!y 3ere: 1) !ia6nosis
o: a!.ance! cancer (presence o: !istant -etastasis an! :ailure o: :irst'line
ce-oterapy); 2) !ia6nosis at a participatin6 site; 3) a6e 20 years or ol!er; 4) i!enti:ie!
unpai!/ in:or-al care6i.er; an! &) a!e@uate sta-ina to co-plete te inter.ie3. Patients
3ere eDclu!e! 3en tey -et criteria :or !e-entia or !eliriu- usin6 te neurobea.ioral
co6niti.e status eDa-ination F29G or coul! not spea4 0n6lis or Spanis.
)nter.ie3ers :ro- eac site participate! in an initial 2'!ay trainin6 session :ollo3e! by
annual re.ie3 trainin6 sessions con!ucte! by researc sta:: at 5ale Kni.ersity. >ey 3ere
re@uire! to acie.e a i6 stan!ar! o: accuracy an! reliability base! on concor!ance 3it
te 5ale Pro2ect *irectorUs ratin6 o: te Structure! Clinical )nter.ie3 :or te DSM-IV F30G
!ia6noses (tar6et 4appa Q 0.#&). Patient inter.ie3s too4 4& -inutes to co-plete on
a.era6e. Patients 3o !ecline! participation 3ere as4e! to co-plete a brie: @uestionnaire
re6ar!in6 teir reasons :or re:usal/ a-ount o: e-otional an! pysical !istress/ an!
!e-o6rapics. 9ll stu!y protocol an! contact !ocu-ents 3ere re.ie3e! an! appro.e! by
te u-an sub2ects co--ittee at 5ale Kni.ersity an! at eac o: te participatin6
institutions.
H: te 92$ patients 3o 3ere approace! :or participation an! con:ir-e! to be eli6ible
:or te C3C/ 2#$ (31E) !ecline! participation. >e -ost co--on reasons :or
nonparticipation inclu!e! Anot intereste!C (n V 120)/ Acare6i.er re:usesC (n V 3$)/ an!
Atoo upsetC (n V 2#). Lonparticipants 3ere -ore li4ely to be 3ite (ci's@uare V 9.9+; p
V 0.04) an! to report 6reater !istress on a &'point <i4ert scale 3ose eDtre-es ran6e!
:ro- 1 (A-ini-al%noneDistentC) to & (A!istrau6tC; -ean score o: 3.# .s. 2.#; p P 0.0001).
>ere 3ere no si6ni:icant !i::erences bet3een nonparticipants an! participants in 6en!er/
a6e/ or e!ucation. C3C participants 3o 3ere not inclu!e! in te current stu!y 3ere
tose 3o 3ere still ali.e at te ti-e o: our analyses (n V 3&1). ,en co-pare! to
participants in te current stu!y/ tese sur.i.ors 3ere -ore e!ucate! (-ean 13.4 .s. 12.4
years; p V 0.002); an! 3ere -ore li4ely to a.e ealt insurance (ci's@uare V +$.$4; p P
0.0001); to be 3ite (ci's@uare V 23.91; p P 0.0001); Catolic/ Protestant/ or "e3is
(ci's@uare V 3&.+&; p P 0.0001); an! to be -arrie! (ci's@uare V 14.31; p P 0.000#).
Sur.i.ors 3ere not si6ni:icantly !i::erent :ro- participants in te present stu!y 3it
respect to 6en!er/ a6e/ or te presence o: any SC)*') !ia6nosis assesse! or psycotropic
-e!ication use! at baseline.
easures
Patients pro.i!e! !e-o6rapic in:or-ation/ inclu!in6 6en!er/ a6e/ etnicity/ e!ucation
le.el/ reli6ion/ -arital status/ an! ealt insurance status. >e Nubro! Per:or-ance Scale
F31G an! te 7arno:s4y Per:or-ance Status Scale F3234G 3ere use! to assess
per:or-ance status/ an! te Carlson Co-orbi!ity )n!eD F3&G 3as use! to assess se.erity
o: illness base! on -ultiple or6an :ailure. Pysical sy-pto- bur!en 3as assesse! usin6 a
co-posite o: tree ite-s :ro- te (c=ill ^uality o: <i:e ^uestionnaire F3+G/ a reliable
@uality o: li:e -easure .ali!ate! :or use 3it palliati.e care populations. Patients 3ere
as4e!: 1) to in!icate 3eter any o: 12 liste! pysical sy-pto-s 3ere present o.er te
past t3o !ays/ 2) to rate te eDtent to 3ic any pysical sy-pto-s tat tey a!
eDperience! o.er te past t3o !ays botere! te- usin6 an 11'point <i4ert scale ran6in6
:ro- 0 V A*i! not boter -e at allC to 10 V A?otere! -e tre-en!ously/C an! 3) to rate
o3 tey a.e :elt o.er te past t3o !ays on an 11'point <i4ert scale ran6in6 :ro- 0 V
APysically terribleC to 10 V APysically 3ell.C
PatientsU closeness to !eat 3as calculate! usin6 te recor!e! !ate o: !eat. First/ 3e :irst
co-pute! te nu-ber o: !ays bet3een te baseline inter.ie3 an! te recor!e! !ate o:
!eat. LeDt/ 3e con.erte! closeness to !eat into an or!inal .ariable tat 3as -easure!
in -onts rater tan !ays because o: te co--on clinical practice o: pysicians an!
pre:erence o: patients to !iscuss li:e eDpectancy usin6 rou6er esti-ates. 9:ter eDa-inin6
te !istribution o: tis .ariable/ 3e :oun! tat te -a2ority o: patients 3ere assesse!
3itin siD -onts o: teir !eat. ,e ten create! se.en Acloseness to !eatC te-poral
inter.als/ 3ic 3ere !e:ine! (in te nu-ber o: !ays :ro- !eat) as :ollo3s: 0 to 30 !ays
(n V 4+)/ 31 to +0 !ays (n V 3$)/ +1 to 90 !ays (n V 39)/ 91 to 120 !ays (n V 2+)/ 121 to
1&0 !ays (n V 1$)/ 1&1 to 1#0 !ays (n V 21)/ an! 1#1 to 13$$ !ays (n V 103) :ro- !eat.
>e C3C in.esti6ation con!ucte! co-preensi.e e.aluations o: pysical ealt an!
psycosocial :unctionin6/ inclu!in6 structure! clinical inter.ie3s usin6 te Structure!
Clinical )nter.ie3 :or te DSM-IV 9Dis ) *isor!ers (SC)*')) F30G to assess -ental
!isor!ers. >ese inclu!e! -a2or !epressi.e !isor!er ((**)/ 6eneraliIe! anDiety !isor!er
(=9*)/ panic !isor!er (P*)/ an! posttrau-atic stress !isor!er (P>S*). 1eliability an!
.ali!ity :or te SC)*') as been establise! F30/ 3$/ 3#G. Patients only co-plete! te :ull
SC)*') -o!ules assessin6 !isor!ers :or 3ic tey screene! positi.e.
>e rater'a!-inistere! .ersion o: te )n.entory o: Co-plicate! =rie:'1e.ise! ()C='1)
F39G 3as use! to !ia6nose Co-plicate! =rie:/ no3 calle! Prolon6e! =rie: *isor!er
(P=*) F40G/ te !ia6nostic criteria o: 3ic 3ere !eter-ine! an! applie! later in te
course o: te C3C. >e P=* criteria 3ere -o!i:ie! so tat patients 3ere as4e! to
e.aluate sy-pto-s relate! to te loss o: teir ealty sel: !ue to cancer (rater tan !ue
to interpersonal loss) an! !i! not inclu!e te !uration criterion.
(ental !isor!er !ia6noses 3ere analyIe! as !icoto-ous outco-es (i.e./ -et criteria
.ersus !i! not -eet criteria :or a !ia6nosis). (** 3as also e.aluate! usin6 te 0n!icott
sy-pto- substitution -eto! because sy-pto- en!orse-ent a-on6 a!.ance! cancer
patients coul! be a conse@uence o: pysical !isease an!%or treat-ent F41G. >e 0n!icott
-eto! in.ol.es -o!i:yin6 sy-pto- criteria suc tat 3ei6t loss is substitute! 3it
!epresse! appearance/ inso-nia 3it social 3it!ra3al or !ecrease! tal4ati.eness/ loss
o: ener6y 3it broo!in6/ sel:'pity/ or pessi-is-/ an! poor concentration 3it lac4 o:
reacti.ity%cannot be ceere! up F41G.
Sel:'report !ata about psycotropic -e!ication use (i.e./ anti!epressants/ anDiolytics/
an!%or antipsycotics) 3ere eDtracte! :ro- a @uestionnaire assessin6 -ental ealt
ser.ice utiliIation F22/ 42G a-on6 patients an! care6i.ers an! 3as co!e! as a
!icoto-ous .ariable.
PatientsU sel:'reporte! ter-inal illness ac4no3le!6-ent (>)9) 3as assesse! 3it te
@uestion/ AJo3 3oul! you !escribe your current ealt statusBC 1esponse options 3ere
as :ollo3s: 1 V A1elati.ely ealtyC; 2 V ASeriously but not ter-inally illC; an! 3 V
ASeriously an! ter-inally ill.C >)9 3as co!e! as a !icoto-ous .ariable; it 3as
consi!ere! present a-on6 tose patients 3o en!orse! response option 3 (ASeriously an!
ter-inally illC) an! absent a-on6 tose 3o selecte! 1 or 2 F2#G.
Patients reporte! to 3at eDtent tey :elt A!eep inner peace or ar-onyC on a siD'point
<i4ert scale/ 3ere 1 V A(any ti-es a !ay/C an! + V ALe.er or al-ost ne.er.C >is ite-
3as eDtracte! :ro- te L)9%FetIer (ulti!i-ensional (easure o:
1eli6iousness%Spirituality :or Kse in Jealt 1esearc F43G/ 3ic 3as inclu!e! as an
assess-ent o: 6eneral spiritual eDperiences. >e -e!ian response :or te stu!y sa-ple
3as 3 (A-ost !aysC). 1esponses o: 3 (A-ost !aysC) or 6reater 3ere co!e! as 1
(Apeace:ulC); oter3ise responses 3ere co!e! as 2. 9 one'ite- -easure o: peace:ulness
as been !e-onstrate! to a.e a stron6 association 3it a .ariety o: spirituality
constructs/ inclu!in6 :ait/ purpose/ an! e-otional an! spiritual 3ell'bein6 F44G. Peace:ul
a3areness 3as consi!ere! present a-on6 patients co!e! as bot peace:ul an! a3are (i.e./
:or 3o- >)9 3as present) an! absent a-on6 patients 3o 3ere peace:ul but una3are/
a3are but not at peace/ or neiter at peace nor a3are. 0Distential 3ell'bein6 3as assesse!
-ore 6enerally usin6 te eDistential subscale o: te (c=ill ^uality o: <i:e ^uestionnaire
F3+G.
Patients also co-plete! te 13'ite- 5ale 0.aluation o: Suici!ality (50S) scale/ 3ic
as been !e-onstrate! as a .ali! an! reliable -easure o: suici!ality F4&G. For te current
stu!y/ 3e eDa-ine! responses to te :irst t3o ite-s/ 3ic as4e! patients to e.aluate te
stren6t o: teir 3is to li.e an! te stren6t o: teir 3is to !ie in li6t o: teir current
circu-stances. >ese t3o sin6le ite-s 3ere rate! on a 4'point scale ran6in6 :ro- 1 V
AStron6C to 4 V AJa.e none.C ,e co!e! responses o: a Astron6C an! A-o!erateC 3is to
li.e%!ie as present an! A3ea4C an! Ano 3is to li.e%!ieC as absent.
Data Analysis
Participant caracteristics 3ere !eter-ine! usin6 !escripti.e statistics. <o6istic
re6ression -o!els 3ere constructe! to !eter-ine 3eter te :ollo3in6 :actors 3ere
si6ni:icantly associate! 3it closeness to !eat base! on te te-poral bins !escribe! in
te (eto!s section: 1) eac o: te :our psyciatric !ia6noses/ 2) at least one o: te :our
psyciatric !ia6noses/ 3) use o: psycotropic -e!ications/ 4) >)9/ &) peace:ulness/ +)
peace:ul a3areness/ $) patient 6rie:/ #) 3is to li.e/ an! 9) 3is to !ie. <inear re6ression
3as con!ucte! to pre!ict -ean pysical sy-pto- bur!en an! eDistential 3ell'bein6.
Colinearity 3as assesse! by cross'tabulations an! plots o: te analyIe! co.ariates.
Pysical sy-pto- bur!en 3as selecte! as a co.ariate in te a!2uste! re6ression analyses
!ue to its si6ni:icant association 3it closeness to !eat. *ata 3ere analyIe! 3it te
S9S Syste- :or ,in!o3s .. #.2 (S9S )nstitute/ )nc./ Cary/ LC) 3it t3o'taile! statistical
tests.
=o to:
!&(>/T(
Participant "haracteristics
>e -a2ority o: patients 3ere 3ite (+3E)/ -ale (&+E)/ o: relati.ely 6oo! ealt status
($+E 3it Nubro! Score ] 2/ 3ic correspon!s to patients bein6 a-bulatory at least
&0E o: teir 3a4in6 ours)/ insure! (#0E)/ an! 3ere on a.era6e at least i6 scool
e!ucate!. >e -e!ian a6e o: te stu!y participants 3as +0 years ol!. See >able 1 :or a
su--ary o: patient caracteristics. 9 .ariety o: pri-ary cancer sites 3ere represente!
a-on6 participants/ inclu!in6 lun6 (20E)/ colon (1&E)/ breast (9E)/ an! pancreatic (#E)
cancers.
>able 1
Patient Caracteristics at >i-e o: 9ssess-ent
ental Disorders
H.erall/ 10.#E (n V 30) o: te 2$# !ecease! patients 3it a.ailable SC)*') !ata in tis
sa-ple -et criteria :or at least one o: te :our psyciatric !ia6noses ((**/ =9*/ P*/
an! P>S*) assesse!. >e pre.alence rates o: psyciatric -orbi!ity in te current sa-ple
3ere co-parable to tose pre.iously reporte! on !ata :ro- te C3C F22G. Pre.alence
rates o: SC)*') !ia6noses by cancer type are !etaile! in >able 2. Patients 3it lun6/
colon/ pancreatic/ an! breast cancers eDibite! te i6est rates o: -ental !isor!ers
o.erall. >ere 3ere no si6ni:icant !i::erences in te type o: cancer a-on6 patients 3o
3ere !ia6nose! 3it at least one SC)*') !ia6nosis.
>able 2
Pre.alence 1ates o: (ental *isor!ers by Cancer Site
Patients 3o currently -et criteria :or at least one o: te SC)*') !ia6noses assesse! 3ere
si6ni:icantly youn6er tan tose patients 3itout psyciatric -orbi!ity/ but tere 3ere no
oter si6ni:icant !i::erences in !e-o6rapic or -e!ical caracteristics bet3een tese
6roups (all pUs Q 0.10; see >able 1).
Percenta6es o: patients 3o -et criteria :or at least one -ental !isor!er are 6rapically
illustrate! in Fi6ure 1. 1ates o: -ental illness a-on6 patients !i! not si6ni:icantly
increase or !ecrease as ti-e to !eat approace!. >at is/ closeness to !eat !i! not
pre!ict te presence o: (**/ =9*/ P*/ P>S*/ or te presence o: at least one o: tese
!isor!ers (all pUs Q 0.10; see >able 3). >ere si-ilarly 3as not a si6ni:icant association
bet3een psycotropic -e!ication use an! patientsU proDi-ity to !eat (p Q 0.10).
Fi6ure 1
Percentages of Patients $ith at /east *ne Depressive or An1iety Disorder
>able 3
9ssociations bet3een Closeness to *eat an! (ental *isor!ers a-on6 Patients
9ltou6 te tests o: association bet3een -ental !isor!ers an! closeness to !eat 3ere
nonsi6ni:icant/ 3e con!ucte! post-hoc analyses in or!er to :urter caracteriIe tose
patients close to !eat 3o !i! -eet criteria :or a SC)*') !ia6nosis. H: te 30 patients
3o -et criteria :or at least one SC)*') !ia6nosis/ o.er one'tir! (3+.$E) 3ere 3itin
t3o -onts or less o: !yin6. >ere:ore/ 3e !i.i!e! patients into t3o 6roups: Acloser to
!eatC (assesse! t3o -onts or less :ro- teir !eat; n V $9) an! Aless close to !eatC
(assesse! -ore tan t3o -onts :ro- teir !eat; n V 199). H: te $9 patients in te
closer to !eat 6roup/ 11 (13.9E o: closer to !eat 6roup; 4.0E o: total sa-ple) -et
criteria :or a SC)*') !ia6nosis. H: te 199 patients 3o 3ere :urter :ro- !eat/ 19
(9.+E o: less close to !eat 6roup; &.#E o: total sa-ple) -et criteria :or a SC)*')
!ia6nosis/ but tese 6roups !i! not si6ni:icantly !i::er.
Patients closer to !eat 3o carrie! a SC)*') !ia6nosis 3ere caracteriIe! by con!uctin6
separate lo6istic re6ressions pre!ictin6 te presence o: at least one -ental !isor!er
!ia6nosis in or!er to !eter-ine i: tere 3as a si6ni:icant interaction bet3een eac patient
caracteristic or outco-e .ariable o: interest an! te !icoto-ous closeness to !eat
.ariable. ,e :oun! tat patients 3o -et criteria :or at least one SC)*') !ia6nosis an!
3o 3ere close to !eat 3ere si6ni:icantly youn6er/ a! lo3er scores on te Carlson
Co-orbi!ity )n!eD/ 3ere less li4ely to use psycotropic -e!ication/ an! 3ere less li4ely
to ac4no3le!6e teir ter-inal ealt status or to be peace:ully a3are o: teir !ia6nosis
tan patients 3o !i! not -eet criteria :or a -ental !isor!er !ia6nosis an! 3ere close to
!eat (pgs P 0.0&). Si6ni:icant -ain e::ects o: close to !eat status 3ere obser.e! :or
eac o: tese .ariables/ as 3ell (all pUs P 0.02). Statistically si6ni:icant results are
su--ariIe! in >able 4.
>able 4
Pre!iction o: te Presence o: a (ental *isor!er *ia6nosis by Patient 8ariables an! Close
to *eat Status
Physical (y'pto' Burden
Closeness to !eat 3as si6ni:icantly associate! 3it patientsU pysical sy-pto- bur!en/
as reporte! in >able &. Patients 3o 3ere approacin6 !eat reporte! tat tey 3ere not
:eelin6 3ell an! a! -ore pysical sy-pto-s tat botere! te- to a 6reater eDtent/ h V
c0.31/ p P 0.0001.
>able &
9ssociations bet3een Closeness to *eat an! Hter (e!ical an! Psycosocial Factors
a-on6 Patients
Ter'inal Illness Ackno$ledg'ent; Peacefulness; and &1istential Distress
ProDi-ity to !eat also si6ni:icantly pre!icte! >)9 a-on6 patients/ 3o 3ere 1.3 ti-es
-ore li4ely to ac4no3le!6e teir ter-inal ealt status 3en tey 3ere closer to te en!
o: li:e (a!2uste! H1 V 1.2&/ 9&E C): 1.12 1.40). 1esults are presente! in >able &. >)9
3as :oun! a-on6 +&E (n V 30 % 4+) o: patients assesse! 3itin one -ont o: !yin6/ +0E
(n V 22 % 3$) assesse! 3itin t3o -onts/ 2#E (n V 11 % 39) assesse! 3itin tree
-onts/ &#E (n V 1& % 2+) assesse! 3itin :our -onts/ &3E (n V 9 % 1$) assesse! 3itin
:i.e -onts/ an! 43E (n V 9 % 21) assesse! 3itin siD -onts. 1ates o: >)9 3ere i6est
in te last t3o -onts o: li:e. >3enty't3o percent (n V 22 % 101) o: patients assesse!
-ore tan siD -onts a3ay :ro- teir !eat ac4no3le!6e! teir ter-inal ealt status.
Si-ilar to its association 3it >)9/ closeness to !eat pre!icte! peace:ul a3areness.
Patients 3ere 1.2 ti-es -ore li4ely to be peace:ully a3are as !eat approace! (a!2uste!
H1 V 1.21/ 9&E C): 1.0+ 1.3$). Pysical sy-pto- bur!en 3as associate! 3it bot
>)9 (r V 0.22/ p P 0.0001) an! peace:ul a3areness (r V 0.19/ p V 0.002)/ an! te
relationsip bet3een closeness to !eat an! tese outco-es re-aine! statistically
si6ni:icant e.en 3en controllin6 :or patientsU reporte! pysical bur!en. Jo3e.er/ as
peace:ulness alone 3as not si6ni:icantly relate! to closeness to !eat (p Q 0.10)/ te
statistical si6ni:icance o: te test o: te -o!est association bet3een closeness to !eat
an! peace:ul a3areness -ay a.e been !ri.en by te obser.e! increases in >)9.
,e :oun! a!!itionally support :or te ypotesis tat i6er rates o: peace:ul a3areness
3ere !ue to increases in >)9 rater tan a 6ro3in6 sense o: peace:ulness as !eat
approace! in our eDa-ination o: eDistential 3ell'bein6. *ecreases in eDistential 3ell'
bein6/ su66estin6 eDistential !istress/ 3ere associate! 3it proDi-ity to !eat in an
una!2uste! analysis/ h V 0.12/ p V 0.044. Jo3e.er/ application o: ?aron an! 7ennyUs F4+G
criteria :or e.aluatin6 te presence o: -e!iation !e-onstrate! tat pysical sy-pto-
bur!en -e!iate! te relationsip bet3een eDistential 3ell'bein6 an! closeness to !eat in
tis patient sa-ple. Pysical sy-pto- bur!en 3as positi.ely associate! 3it closeness to
!eat (see abo.e/ p P 0.0001) an! 3as ne6ati.ely associate! 3it eDistential 3ell'bein6
(h V c0.3&/ p P 0.0001). ,en pysical sy-pto- bur!en 3as controlle! :or in te
re6ression -o!el pre!ictin6 eDistential 3ell'bein6 :ro- closeness to !eat/ pysical
sy-pto- bur!en re-aine! a stron6 pre!ictor o: eDistential 3ell'bein6 (h V c0.31/ p P
0.0001)/ 3ereas closeness to !eat !i! not (h V 0.01/ p V 0.92#). 0Distential !istress 3as
6reater a-on6 patients 3o :elt pysically 3orse/ an! 3as tere:ore i6er as patients
approace! !eat because tey 3ere eDperiencin6 an increase in pysical sy-pto-
bur!en.
?ish to /ive; ?ish to Die; and Patient 0rief
Patients 3ere -ore li4ely to report a 3is to !ie as !eat approace! e.en a:ter a!2ustin6
:or pysical sy-pto- bur!en (a!2uste! H1 V 1.33/ 9&E C): 1.0& 1.&&). )n a!!ition/
closeness to !eat 3as associate! 3it a !ecrease! li4elioo! o: te 3is to li.e a-on6
patients (una!2uste! H1 V 1.3+/ 9&E C): 1.09 1.+#)/ tou6 tis :in!in6 3as only
-ar6inally si6ni:icant 3en controllin6 :or pysical sy-pto- bur!en (a!2uste! H1 V
1.23/ 9&E C): 0.9# 1.&4). >e association bet3een closeness to !eat an! patient 6rie:
o.er losses relate! to teir illness 3as nonsi6ni:icant (p Q 0.10).
=o to:
DI(">((I*@
>is cross'sectional stu!y eDa-ine! rates o: -ental !isor!ers alon6 !i::erent ti-e points
at te en! o: li:e to !eter-ine i: tey increase! a-on6 a!.ance! cancer patients as !eat
approace!. 1esearc a!!ressin6 te i-pact o: proDi-ity to !eat on te pre.alence rates
o: psyciatric illness is li-ite!. =i.en te li4elioo! o: stress:ul circu-stances suc as
-ultiple losses/ uncertain :uture/ an! pysical !isco-:ort increasin6 as !isease a!.ances/
3e ypotesiIe! tat .ulnerable patients 3oul! be at increase! ris4 o: !e.elopin6 9Dis )
psyciatric -orbi!ity as !eat approace!. Contrary to our ypoteses/ te pre.alence
esti-ates o: (**/ =9*/ P>S*/ or P* 3ere not associate! 3it closeness to !eat in te
current sa-ple. >ese :in!in6s be6in to a!!ress outstan!in6 @uestions about te course o:
!epressi.e an! anDiety !isor!ers at te en! o: li:e/ callen6in6 te lon6'stan!in6
assu-ption tat -ental ealt proble-s are 6enerally eDacerbate!.
Hur results are si-ilar to tose o: 7issane an! collea6ues F1+G/ 3o :oun! tat
psyciatric !isor!ers 3ere si-ilarly pre.alent a-on6 early sta6e an! a!.ance! breast
cancer patients. >o eDplain tis :in!in6/ te autors su66este! tat patients 3it
-etastatic !isease -ay not eDperience ei6tene! rates o: psyciatric -orbi!ity !espite
te potential increase in perception o: eDistential treat because tey -ay a!apt to initial
eDistential !istress/ to relate! :eelin6s o: uncertainty/ an! to te -ana6e-ent o:
sy-pto-s an! si!e e::ects tat are co--on a-on6 -ore ne3ly !ia6nose! patients F1+G.
Jo3e.er/ in te current sa-ple/ 3e obser.e! tat patients closer to !eat reporte!
increase! eDistential !istress 3itout a parallel increase in rates o: psyciatric !isor!ers.
>e association bet3een 6reater eDistential !istress an! proDi-ity to !eat appeare! to be
!ri.en by te ei6tene! pysical sy-pto- bur!en reporte! by -ore i--inently !yin6
patients. >is -ay ar6ue a6ainst te i!ea propose! by 7issane et al. F1+G tat -ore
a!.ance! patients a!apt to eDistential !istress .ia better -ana6e-ent o: teir pysical
sy-pto-s an! si!e e::ects; rater/ pysical sy-pto-s -ay play a -ore !irect role in
incitin6 eDistential concerns.
9noter eDplanation :or our :in!in6s is tat in!i.i!uals eDperiencin6 -ore so-atic
sy-pto-s 3ere tose 3o 3ere assesse! later in teir !isease course an!/ tere:ore -ore
li4ely to percei.e te-sel.es to be closer to !eat/ 3ere -ore li4ely to be eDistentially
!istresse!. Pysical :railty an! !isco-:ort are re-in!ers o: oneUs pysical eDistence tat
-ay result in increase! !epen!ence on oters an! a potential loss o: !i6nity an!/ in turn/
coul! !isturb eDistential 3ell'bein6. 9ltou6 pysical pain as been conceptually
!istin6uise! :ro- Aspiritual painC F4$G/ te role tat tese :actors an! teir interaction
play in te onset or eDacerbation o: 9Dis ) !isor!ers is not clear. 9 recent in.esti6ation
:oun! tat pysical sy-pto- bur!en 3as not associate! 3it anDiety an! -oo!
sy-pto-s a-on6 a!.ance! cancer patients F4#G. )n contrast/ oter stu!ies a.e
!e-onstrate! a relationsip bet3een psyciatric illness (particularly !epression) an!
pysical sy-pto-s F23/ 24G. ,ilson et al. F49G :oun! tat palliati.e care patients
!ia6nose! by se-i'structure! inter.ie3 3it an anDiety or !epressi.e !isor!er reporte! a
6reater nu-ber o: -o!erate or se.ere pysical sy-pto-s/ as 3ell as eDistential concerns/
tan patients 3itout a !isor!er. >e !iscrepancies bet3een tese :in!in6s -ay be
eDplaine! in part by !i::erences in assess-ent tecni@ues an! pre!icti.e abilities o:
scales.
)n a!!ition to obser.in6 a relationsip bet3een increase! eDistential !istress an!
closeness to !eat/ 3e :oun! tat rates o: >)9 an! peace:ul a3areness 3ere pre!icte! by
closeness to !eat as ypotesiIe!. Consistent 3it prior eDa-inations/ 3e :oun! tat
patientsU a3areness o: teir ter-inal ealt status increase! at te en! o: li:e F2+/ 2$G.
Jei6tene! a3areness -i6t a.e been !ue to patients :acin6 a 6reater nu-ber o:
pysical sy-pto-s an! :eelin6 :railer as !eat approace!. Jo3e.er/ our :in!in6 tat
closeness to !eat pre!icte! >)9 e.en 3en controllin6 :or pysical sy-pto- bur!en
su66ests tat :actors oter tan pysical !istress contribute! to patientsU ac4no3le!6-ent
tat !eat 3as i--inent. >ese :actors -ay not be relate! to -ental !istress (e.6./ social
cues)/ because psyciatric -orbi!ity in te current sa-ple !i! not appear to increase
-onotonically (a6ain/ e.en 3en a!2ustin6 :or pysical sy-pto- bur!en).
Hter reports :ro- te C3C a.e !e-onstrate! tat >)9 3as associate! 3it ele.ate!
!istress F&0G an! 3it increase! rates o: -ental !isor!ers a-on6 tose patients 3o 3ere
a3are/ but not at peace (altou6 tis result !i! not reac statistical si6ni:icance) F2&G.
Jo3e.er/ >)9 alone 3as also lin4e! 3it positi.e outco-es/ suc as te !e.elop-ent o:
a!.ance care plannin6 an! a!.ance !irecti.es F&0G. )n a!!ition/ 3en >)9 3as couple!
3it a sense o: peace:ulness/ !ecrease! psycolo6ical !istress an! 6reater @uality o:
!eat as been obser.e! a-on6 patients/ in a!!ition to i-pro.e! berea.e-ent outco-es
a-on6 teir care6i.ers F2&G. >e s-all nu-ber o: Aa3are/ but not peace:ulC patients
3itin eac te-poral bin proibite! us :ro- eDa-inin6 can6es in rates o: -ental
!isor!ers 3itin tis sub6roup.
Hur analyses also !e-onstrate! tat patients closer to !yin6 in 6eneral 3ere -ore li4ely
to report a 3is to !ie an! 3ere less li4ely to en!orse a 3is to li.e. >is :in!in6 is
particularly i-portant 6i.en tat patients are still at ris4 o: co--ittin6 suici!e !urin6
a!.ance! sta6es o: illness !espite increase! pysical !ebilitation F&1G. Jo3e.er/ te
increase in rates o: te 3is to !ie an! te relate!/ tou6 !istinct/ !ecrease in te
pre.alence o: te 3is to li.e obser.e! coul! also a.e re:lecte! a natural pro6ression o:
!eat acceptance. >e increases in >)9 an! peace:ul a3areness as !eat approace! tat
3e obser.e! support tis ypotesis/ as !o prior stu!ies o: patients at te en! o: li:e.
Jinton F2+G obser.e! tat acceptance increase! in te last ei6t 3ee4s o: li:e an! tat
a3areness o: !yin6 3as not associate! 3it sub2ecti.e !epression ratin6s. )n :act/
Cocino. an! collea6ues F2$G :oun! tat patients 3o !i! not ac4no3le!6e teir
pro6nosis in te :inal 3ee4s o: li:e 3ere tree ti-es -ore li4ely to -eet criteria :or
clinical !epression. (any patients eDperience 6ro3in6 acceptance once tey a.e
ac4no3le!6e! tat tey are !yin6; te co-plete absence o: >)9 3en !eat is i--inent/
o3e.er/ -ay be associate! 3it psycopatolo6y.
,ile a co--on clinical course o: -ental !isor!ers a-on6 !yin6 patients !i! not e-er6e
in tis stu!y/ 3e atte-pte! to better caracteriIe te subset o: in!i.i!uals 3o -et
criteria :or a !epressi.e an!%or anDiety !isor!er 3itin t3o -onts o: !yin6. Hn a.era6e/
tese patients 3ere youn6er an! tere:ore as eDpecte!/ a! lo3er scores on te Carlson
Co-orbi!ity )n!eD. Potentially 3arrantin6 -ore clinical concern 3ere te :in!in6s tat
-e-bersip in tis 6roup 3as associate! 3it !ecrease! use o: psycotropic -e!ication
(1E o: te total sa-ple) an! !ecrease! >)9 an! peace:ul a3areness (1E an! 0.$E o: te
total sa-ple/ respecti.ely). *espite -eetin6 criteria :or an 9Dis ) !isor!er/ tese patients
3ere not bein6 treate! psycopar-acolo6ically as :re@uently as patients :arter a3ay
:ro- !eat nor as :re@uently as patients 3o !i! not -eet criteria :or an 9Dis ) !isor!er.
>ere are se.eral possible eDplanations :or tis/ 3ic are co-plicate! by te :act tat it
is not clear 3en te onset o: 9Dis ) !isor!ers occurre! in tese patients. >ese :in!in6s
-i6t re:lect a lac4 o: a!erence to prescribe! psycotropic -e!ications. )t -ay also be
tat tese patients/ 3o 3ere 6enerally youn6er an! possibly less :rail/ !i! not 6arner te
sa-e attention :ro- clinicians as ol!er patients 3o appeare! -ore o.ertly ill. >is/ in
con2unction 3it te presentation o: teir psyciatric sy-pto-s (e.6./ 3it!ra3al !ue to
!epression or :re@uent re@uests :or reassurance or clinical attention !ue to anDiety)/ -ay
a.e resulte! in pro.i!ers o.erloo4in6 or un!er'treatin6 teir psycopatolo6y.
(tudy (trengths and /i'itations
Stren6ts o: tis stu!y inclu!e! te use o: stan!ar!iIe! clinical inter.ie3s :or te
assess-ent o: -ental !isor!ers in an etnically an! 6eo6rapically !i.erse sa-ple. 7elly
et al. F+G ar6ue! tat assess-ent o: psyciatric !ia6noses a-on6 ter-inally ill patients
3it structure! clinical inter.ie3s is particularly a!.anta6eous because it allo3s :or
a!aptations to be -a!e by te e.aluatin6 clinician as nee!e!. 9n a!!itional stren6t 3as
te 3i!e ran6e o: proDi-ity to !eat represente! in our sa-ple. >e .ariability in
closeness to !eat a.ailable pro.i!e! preli-inary e.i!ence tat su66ests tat/ in 6eneral/
rates o: !epression an! anDiety !isor!ers !o not increase at te en! o: li:e. Still/ tese
:in!in6s !o not un!er-ine te i-portance o: clinicians con!uctin6 :re@uent an!
co-preensi.e -ental ealt assess-ents. )n :act/ a subset o: in!i.i!uals -ay be at
ei6tene! ris4 :or !e.elopin6 eDistential !istress tat is !istinct :ro- psycopatolo6y
as it is conceptualiIe! in our stan!ar!iIe! !ia6nostic -anuals.
>is stu!y 3as also stren6tene! by its application o: screenin6 :or co6niti.e
!ys:unction. 0.aluation o: a luci! patient sa-ple li4ely increase! te .ali!ity o: te
!ia6noses -a!e by clinicians. 9t te ti-e o: tis report/ #.4E (n V 94) o: te 111&
patients screene! :or te C3C 3ere eDclu!e! because o: co6niti.e !ys:unction/ an!
1$.9E (n V 200) 3ere eDclu!e! because tey 3ere too :rail to participate. 0Dclusion o:
tese in!i.i!uals li4ely capture! patients 3o 3ere !elirious or !e-ente!. Jo3e.er/ an
un:ortunate conse@uence o: te eDclusion !eter-ination 3as its atten!ant li-itations on
:urter stu!y o: te eDclu!e! in!i.i!uals/ inclu!in6 a :or-al e.aluation o: te source or
type o: co6niti.e !ys:unction. =i.en tis/ 3e cannot pro.i!e in:or-ation about patients
3it !eliriu- or !e-entia/ a co6niti.ely i-paire! population 3o co-prise! a
substantial proportion o: tose cancer patients !ia6nose! 3it a -ental !isor!er at te
en! o: li:e in pre.ious epi!e-iolo6ical stu!ies F12/ 14G.
)n a!!ition/ episo!es o: !eliriu- can be brie:/ an! tus te inci!ence o: !ia6nosable
!epression an! anDiety !isor!ers tat 3e :oun! -ay a.e been lo3er tan teir true
pre.alence i: in!i.i!uals 3o 3oul! a.e -et criteria :or !epression 3en not !elirious
3ere eDclu!e! because o: co6niti.e i-pair-ent at te ti-e tey 3ere screene!. =i.en te
pre.alence o: !eliriu- increases as !eat approaces F&2/ &3G/ patients closer to !eat
(i.e./ sic4er patients) -ay a.e been eDclu!e!. *espite tis concern/ eDa-ination o: te
!istribution o: patients 3o 3ere assesse! 3itin te siD -onts be:ore !yin6 re.eale!
tat te 6reatest nu-ber o: patients 3ere inter.ie3e! !urin6 teir last -ont ali.e. Future
stu!ies soul! inclu!e assess-ent o: oter -ental !isor!ers/ inclu!in6 !eliriu-/
!e-entia/ an! a!2ust-ent !isor!ers.
0pi!e-iolo6ical !ata on psyciatric -orbi!ity is li-ite!/ lar6ely because o: te
-eto!olo6ical callen6es inerent in en!'o:'li:e researc/ 3ic tar6ets patients copin6
3it co-pleD sy-pto-s/ sce!ulin6 li-itations/ si:tin6 priorities/ an! teir i--inent
!eat F&4/ &&G. ?ecause accruin6 a sa-ple lar6e enou6 to !etect si6ni:icant tren!s is
!i::icult/ 3e use! cross'sectional !ata rater tan a lon6itu!inal !esi6n. Jo3e.er/ te
cross'sectional !esi6n o: te stu!y is one o: its pri-ary li-itations. ,ile it 3oul! li4ely
re@uire substantial stu!y resources an! :leDibility to con!uct repeate! assess-ents o: tis
.ulnerable population/ @uestions about te course o: -ental illness at te en! o: li:e
3oul! best be a!!resse! by lon6itu!inal in.esti6ations. Future stu!ies -i6t con!uct
repeate! lon6itu!inal assess-ents o: -ental ealt an! !eat acceptance/ but te
!i::iculties o: recruit-ent an! losin6 patients o.er ti-e 3ill continue to present a
callen6e to en! o: li:e researcers.
Hter li-itations inclu!e tose note! in pre.ious reports :ro- te C3C stu!y Fsee 22/
2&G/ suc as te potential presence o: a selection bias :or -ore -ental an! pysically
ealty participants 6i.en tat tose patients 3o re:use! to participate 3ere -ore
!istresse! tan tose 3o !i! participate. )n a!!ition/ 3e use! SC)*') screenin6
@uestions tat -ay a.e been insu::iciently sensiti.e/ possibly resultin6 in an
un!eresti-ation o: true -ental !isor!er pre.alence/ an! 3e assesse! peace:ulness 3it
only a sin6le ite- Fsee 22/ 2&G.
"linical I'plications and 3uture Directions
>is stu!y !i! not :in! support :or te co--on speculation tat rates o: !epressi.e an!
anDiety !isor!ers increase as patients approac !eat. >e callen6e clinicians o:ten :ace
!istin6uisin6 nor-ati.e !istress :ro- psycopatolo6y is only eDacerbate! at en! o:
li:e/ a ti-e !urin6 3ic patients are eDpecte! to eDperience! so-e !istress an! in
a!!ition/ su::er nu-erous o.erlappin6 pysical sy-pto-s F&+G. 9s a strate6y :or -eetin6
tis callen6e/ ?loc4 F1#G as reco--en!e! tat clinicians -aintain a lo3 tresol! :or
treatin6 !epression. =i.en te si6ni:icant treat-ent i-plications/ o3e.er/ it is
i-perati.e to !istin6uis eDpecte! sa!ness an! anDiety :ro- clinical sy-pto-s an! to
continue researc to i!enti:y ris4 :actors suc as proDi-ity to !eat !espite te nu-erous
callen6es o: con!uctin6 en! o: li:e researc F&4G.
Future in.esti6ations soul! atte-pt to replicate :in!in6s :ro- tis cross'sectional stu!y
usin6 a prospecti.e/ lon6itu!inal !esi6n. Hter :actors to eDplore in :uture in.esti6ations
inclu!e te course o: -ental !isor!ers a-on6 !i::erent patient sub6roups/ suc as .arious
a6e coorts/ cancer types/ an! ti-es since !ia6nosis. >e post'!eat i-pact o: te ti-in6
o: onset o: patient -ental !isor!ers close to !eat on sur.i.in6 si6ni:icant oters -i6t
also be eDa-ine!. 1esearcers soul! also i!enti:y an! !i::erentiate :actors associate!
3it eDistential !istress an! !eat acceptance so tat inter.entions tat elp resol.e te
:or-er an! :oster te latter -i6t be :urter !e.elope!. >rou6 a clearer un!erstan!in6
o: psycolo6ical peno-ena a-on6 patients 3it a!.ance! cancer/ it -ay be possible to
i-pro.e te application o: appropriate clinical approaces to opti-iIe te @uality o: li:e
o: tis .ulnerable population at te en! o: li:e.
=o to:
Ackno$ledg'ents
>is researc 3as supporte! in part by te :ollo3in6 6rants to *r. Pri6erson: (J+3#92
:ro- te Lational )nstitute o: (ental Jealt an! C9 10+3$0 :ro- te Lational Cancer
)nstitute; te Center :or Psyco'Hncolo6y an! Palliati.e Care 1esearc/ *ana'Farber
Cancer )nstitute. Support :or *r. <ictental 3as pro.i!e! in part by a Lational Cancer
)nstitute trainin6 6rant (>32 C90094+1'23).
=o to:
!eferences
1. 7issane *,/ Clar4e *(/ Street 9F. *e-oraliIation syn!ro-e''a rele.ant psyciatric
!ia6nosis :or palliati.e care. " Palliat Care. 2001;1$:1221. FPub(e!G
2. )ronsi!e ,. Conser.ation'3it!ra3al an! action'en6a6e-ent: on a teory o: sur.i.or
bea.ior. Psycoso-atic -e!icine. 19#0;42:1+31$&. FPub(e!G
3. 0n6el =</ Sc-ale 9J. Conser.ation'3it!ra3al: a pri-ary re6ulatory process :or
or6anis-ic o-eostasis. Ciba Foun!ation sy-posiu-. 19$2;#:&$$&. FPub(e!G
4. Periya4oil 8S/ 7rae-er JC/ Lo!a 9/ (oos 1/ Jallenbec4 "/ ,ebster (/ 5esa.a6e "9.
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ospitaliIe! a!.ance! cancer patients.FPalliat (e!. 200$G
9 prospecti.e stu!y to !eter-ine te association bet3een pysical sy-pto-s an!
!epression in patients 3it a!.ance! cancer.FPalliat (e!. 2004G
Pysical sy-pto- pro:iles o: !epresse! an! non!epresse! patients 3it cancer.
FPalliat (e!. 2004G
*epression an! anDiety !isor!ers in palliati.e cancer care.F" Pain Sy-pto-
(ana6e. 200$G
>e pro6ress o: a3areness an! acceptance o: !yin6 assesse! in cancer patients
an! teir carin6 relati.es.FPalliat (e!. 1999G
Pro6nostic a3areness an! te ter-inally ill.FPsycoso-atics. 2000G
Peace:ul a3areness in patients 3it a!.ance! cancer.F" Palliat (e!. 200+G
>e pro6ress o: a3areness an! acceptance o: !yin6 assesse! in cancer patients
an! teir carin6 relati.es.FPalliat (e!. 1999G
Pro6nostic a3areness an! te ter-inally ill.FPsycoso-atics. 2000G
>e pre.alence o: psyciatric !isor!er an! te 3is to asten !eat a-on6
ter-inally ill cancer patients.FPalliat Support Care. 2004G
>e pre.alence o: psyciatric !isor!ers a-on6 cancer patients.F"9(9. 19#3G
(a2or !epression/ a!2ust-ent !isor!ers/ an! post'trau-atic stress !isor!er in
ter-inally ill cancer patients: associate! an! pre!icti.e :actors.F" Clin Hncol.
2004G
>e :re@uency an! clinical course o: co6niti.e i-pair-ent in patients 3it
ter-inal cancer.FCancer. 199$G
1e.ie3 (eto!olo6ical an! structural callen6es in palliati.e care researc: o3
a.e 3e :are! in te last !eca!esBFPalliat (e!. 200+G
Callen6es in palliati.e care researc; recruit-ent/ attrition an! co-pliance:
eDperience :ro- a ran!o-iIe! controlle! trial.FPalliat (e!. 1999G
Psyciatric !isor!ers an! -ental ealt ser.ice use in patients 3it a!.ance!
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1e.ie3 Psyciatric !i-ensions o: palliati.e care.FLeurol Clin. 2001G
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1e.ie3 (eto!olo6ical an! structural callen6es in palliati.e care researc: o3
a.e 3e :are! in te last !eca!esBFPalliat (e!. 200+G
5ou are ere: LC?) Q <iterature Q Pub(e! Central (P(C)
,rite to te Jelp *es4
Jurnal 7
?(C Psyciatry. 2012; 12: $0.
Publise! online 2012 "uly 2. !oi: 10.11#+%14$1'244O'12'$0
P(C)*: P(C343401+
Prevalence of 'ental disorders;
psychosocial distress and need for
psychosocial support in cancer patients A
study protocol of an epide'iological
'ulti-center study
9n2a (enert/
1
K3e 7oc/
1
Jol6er SculI/
1
7arl ,e6scei!er/
2
"oaci- ,eis/
3

Jer-ann Faller/
4
(oni4a 7eller/
&
0l-ar ?rdler/
+
an! (artin Jdrter
1
9utor in:or-ation ; 9rticle notes ; Copyri6t an! <icense in:or-ation ;
>is article as been cite! by oter articles in P(C.
=o to:
Abstract
Background
0-pirical stu!ies in.esti6atin6 te pre.alence o: -ental !isor!ers an! psycolo6ical
!istress in cancer patients a.e 6aine! increasin6 i-portance !urin6 recent years/
particularly 3it te ob2ecti.e to !e.elop an! i-ple-ent psycosocial inter.entions
3itin te cancer care syste-. Pri-ary purpose o: tis epi!e-iolo6ical cross'sectional
-ulti'center stu!y is to !etect te 4'3ee4'/ 12'-ont'/ an! li:eti-e pre.alence rates o:
co-orbi! -ental !isor!ers an! to :urter assess psycolo6ical !istress an! psycosocial
support nee!s in cancer patients across all -a2or tu-or entities 3itin te in' an!
outpatient oncolo6ical ealt care an! reabilitation settin6s in =er-any.
ethods6Design
)n tis -ulticenter/ epi!e-iolo6ical cross'sectional stu!y/ cancer patients across all -a2or
tu-or entities 3ill be enrolle! :ro- acute care ospitals/ outpatient cancer care :acilities/
an! reabilitation centers in :i.e -a2or stu!y centers in =er-any: Freibur6/ Ja-bur6/
Jei!elber6/ <eipIi6 an! ,brIbur6. 9 proportional strati:ie! ran!o- sa-ple base! on te
nation3i!e inci!ence o: all cancer !ia6noses in =er-any is use!. Patients are
consecuti.ely recruite! in all centers. Hn te basis o: a !epression screener (PJ^'9) &0E
o: te participants tat score belo3 te cuto:: point o: 9 an! all patients scorin6 abo.e are
assesse! usin6 te Co-posite )nternational *ia6nostic )nter.ie3 :or Hncolo6y (C)*)'H).
)n a!!ition/ all patients co-plete .ali!ate! @uestionnaires -easurin6 e-otional !istress/
in:or-ation an! psycosocial support nee!s as 3ell as @uality o: li:e.
Discussion
0pi!e-iolo6ical !ata on te pre.alence o: -ental !isor!ers an! !istress pro.i!e !etaile!
an! .ali! in:or-ation :or te esti-ation o: te !e-an!s :or te type an! eDtent o:
psycosocial support inter.entions. >e !ata 3ill pro.i!e in:or-ation about speci:ic
!e-o6rapic/ :unctional/ cancer' an! treat-ent'relate! ris4 :actors :or -ental
co-orbi!ity an! psycosocial !istress/ speci:ic supporti.e care nee!s an! use o:
psycosocial support o::ers.
=o to:
Background
Cancer is one o: te lea!in6 causes o: -orbi!ity an! -ortality 3orl!3i!e F1/2G. 9n
esti-ate! 3.2 -illion ne3 cancer cases 3ere !ia6nose! in 0urope in 200# F1G. >e -ost
:re@uent :or-s o: cancer 3ere colorectal cancers (13.+E o: all cancer cases)/ breast
cancer (13.1E)/ lun6 cancer (12.2E) an! prostate cancer (11.9E). )n =er-any/ recent
epi!e-iolo6ical esti-ates in!icate a pro2ecte! annual inci!ence rate :or 2010 o: about
4&0/000 cancer cases F3G. Cancer inci!ence statistics so3 an enance! &'year sur.i.al
rate up to +2E :or 3o-en an! &$E :or -en/ inclu!in6 all cancer sta6es. >e a.era6e a6e
o: onset o: cancer is +9 years :or bot 6en!ers. For te population o: #2 -illion people in
=er-any/ tese !e.elop-ents lea! to a pre.alence o: 1.4 -illion cancer patients 3itin
te ran6e o: :i.e years post !ia6nosis an! 2.1 -illion cancer patients in 3o- te
!ia6nosis is bac4 up to 10 years F3G.
=i.en bot te i6 cancer inci!ence an! continuous a!.ances in cancer !etection/
-ulti-o!al treat-ents an! tar6ete! terapies/ te proportion o: cancer sur.i.ors
continues to 6ro3 in in!ustrialiIe! countries. Cancer sur.i.orsip co.ers a .ariety o:
-e!ical con!itions an! perio!s tat are !i.i!e! into acute sur.i.al/ -i!!le an! lon6'ter-
sur.i.al inclu!in6 !isease':ree sur.i.al as 3ell as cancer recurrence an! cronic !isease
F4G. >us/ sort/ -i!!le an! lon6'ter- sur.i.orsip as si6ni:icant i-plications :or bot
clinical an! psycosocial researc as 3ell as :or ealt care ser.ices researc F&'$G.
Co-preensi.e patient'centere! care in oncolo6y as been e-pasiIe! in international
6ui!elines an! stan!ar!s F#G/ i-plyin6 cancer pre.ention an! early !etection as 3ell as
i6 @uality e.i!ence'base! -e!ical treat-ent/ reabilitation an! palliati.e care.
)-pro.in6 te @uality o: care re@uires reco6nition an! a!!ressin6 patientsM !istress/
-ental !isor!ers an! supporti.e care nee!s !urin6 treat-ent an! a:ter care. >us/
psycosocial an! psyco'oncolo6ical support ser.ices consi!erably contribute to
i-pro.in6 te @uality o: li:e o: patients as a central outco-e criterion o: oncolo6ical care
F9G.
0-otional !istress is co--on a:ter a cancer !ia6nosis F10G/ an! is o:ten a result o: a
.ariety o: proble-s tat can a::ect e.ery aspect o: li:e accor!in6 to !i::erent sta6es o: te
!isease. >ypical issues relate to pysical sy-pto-s an! proble-s suc as pain/ :unctional
i-pair-ents an! states o: cronic :ati6ue/ :a-ily bur!en suc as te uncertainty about
in!i.i!ual roles an! responsibilities/ eDistential concerns suc as isolation or -eanin6 in
oneUs li:e as 3ell as social/ :inancial an! occupational proble-s F11G.
(any cancer patients su::er :ro- a i6 sy-pto- bur!en/ 3ic can re-ain :or -onts
an! years a:ter te initial cancer terapy or can occur a6ain in te :ace o: lon6'ter-
terapy or co-plications in te !isease tra2ectory. Ji6 sy-pto- bur!en is associate!
3it a si6ni:icant increase in :eelin6s o: elplessness an! opelessness an! -ay
a!.ersely i-pact a patientMs @uality o: li:e F12'14G. >e spectru- o: e-otional reactions
an! psycosocial conse@uences ran6es alon6 a continuu- inclu!in6 anDiety/ :ear/ sa!ness
an! !epression/ elplessness an! opelessness as 3ell as a!2ust-ent !isor!ers/ anDiety
!isor!ers/ posttrau-atic stress !isor!er/ !epression/ :a-ily con:licts or eDistential crises
F11/1&'1$G.
0-pirical stu!ies in.esti6atin6 te pre.alence o: -ental !isor!ers an! te :re@uency o:
psycosocial bur!en in cancer patients a.e 6aine! increasin6 i-portance !urin6 recent
years F1#G. >is researc is o: particular si6ni:icance :or te !e.elop-ent an!
i-ple-entation o: psycosocial support o::ers 3itin te ealt care syste-. 1ecent
-eta'analytical e.i!ence in!icates tat te o.erall pre.alence o: -ental !isor!ers a-on6
cancer patients ran6es :ro- 9.#E to 3#.2E in .arious cancer settin6s F19/20G. )n an
international re.ie3 con!ucte! by (itcell et al. F19G inclu!in6 94 inter.ie3'base!
stu!ies/ te pre.alence o: !epression by *S( or )C* criteria in oncolo6ical an!
e-atolo6ical settin6s ($0 stu!ies) 3as 1+.3E (9&E C) 13.419.&); te pre.alence o:
!ysty-ia 3as 2.$E (9&E C) 1.$4.0); te pre.alence o: a!2ust-ent !isor!er 3as 19.4E
(9&E C) 114.&24.#); an! te pre.alence o: anDiety !isor!ers 3as 10.3E (9&E C) &.1
1$.0). Jo3e.er/ co-bination !ia6noses 3ere pre.alent a-on6 up to 3#.2E (9&E C)
2#.44#.+) o: patients. >e pre.alence o: !epression by *S( or )C* criteria in
palliati.e'care settin6s (24 stu!ies) 3as 1+.&E (9&E C) 13.120.3); te pre.alence o:
a!2ust-ent !isor!er 3as 1&.4E (9&E C) 10.121.+); te pre.alence o: anDiety !isor!ers
3as 9.#E (9&E C) +.#13.2); an! co-bination !ia6noses 3ere pre.alent a-on6 up
29.0E (9&E C) 10.1&2.9) o: patients. 9ccor!in6ly/ Sin6er et al. F20G obser.e!
pre.alence rates up to 32E (9&E C) 2$3$) a-on6 cancer patients in acute ospitals.
Jo3e.er/ :e3 trials a.e eDa-ine! te pre.alence o: -ental !isor!ers in cancer patients
ta4in6 into account te 3i!e spectru- o: -ental !isor!ers inclu!in6 substance abuse or
so-ato:or- !isor!ers/ !i::erent ealt care settin6s as 3ell as !i::erent tu-or entities an!
!isease sta6es :or bot 6en!ers. Fe3er stu!ies a.e eDa-ine! te 4'3ee4'/ 12'-ont'/
an! li:eti-e pre.alence rates o: co-orbi! -ental !isor!ers in cancer patients F21G an! te
association bet3een co-orbi! -ental !isor!ers an! psycolo6ical !istress.
>e presence o: a -ental !isor!er or psycolo6ical sy-pto- bur!en is not necessarily
associate! 3it sub2ecti.e nee!s o: patients :or pro:essional psycosocial support an! te
utiliIation o: rele.ant o::ers F22G. 9ltou6 a .ariety o: psycolo6ical inter.entions a.e
been so3n to be e::ecti.e in te re!uction o: psycosocial sy-pto- !istress an! te
i-pro.e-ent o: @uality o: li:e F23'2&G/ o3e.er/ i-pro.in6 !istress screenin6 an! te
access o: cancer patients to a!e@uate psycosocial care re-ains a critical concern F2+G.
>us epi!e-iolo6ical !ata about -ental co-orbi!ity/ psycolo6ical sy-pto- bur!en an!
supporti.e care nee!s are essential :or te e.i!ence base! i-ple-entation o:
psycosocial support o::ers 3itin oncolo6ical ealt care.
*b-ectives
9ltou6 tere as been eDtensi.e researc loo4in6 at e-otional !istress a-on6 .arious
cancer entities/ tere is li-ite! e.i!ence re6ar!in6 pre.alence rates o: co-orbi! -ental
!isor!ers in cancer patients across !i::erent tu-or entities an! care settin6s :ro- an
epi!e-iolo6ical point o: .ie3. (ain researc ai- o: tis epi!e-iolo6ical cross'sectional
-ulti'center stu!y is to !etect te 4'3ee4'/ 12'-ont'/ an! li:eti-e pre.alence rates o:
co-orbi! -ental !isor!ers accor!in6 to te )C*'10%*S(')8 (or6anic/ inclu!in6
sy-pto-atic/ -ental !isor!ers/ -ental an! bea.ioral !isor!ers !ue to psycoacti.e
substance use/ -oo! !isor!ers/ neurotic/ stress'relate! an! so-ato:or- !isor!ers/ an!
bea.ioral syn!ro-es associate! 3it pysiolo6ical !isturbances an! pysical :actors);
an! to :urter assess psycolo6ical !istress an! psycosocial supporti.e care nee!s in
cancer patients across all -a2or tu-or entities 3itin te in' an! outpatient oncolo6ical
ealt care an! reabilitation settin6s in =er-any.
Secon!ary ai-s are to eDa-ine te i-pact o: !e-o6rapic/ :unctional/ cancer' an!
treat-ent'relate! ris4 :actors on te occurrence o: -ental co-orbi!ity/ psycosocial
!istress/ speci:ic supporti.e care nee!s an! use o: psycosocial support o::ers.
9ssociations bet3een -ental co-orbi!ity/ psycosocial !istress/ supporti.e care nee!s/
@uality o: li:e an! -e!ial !ecision'-a4in6 3ill be also eDa-ine!.
=o to:
ethods6Design
(tudy design
)n tis -ulticenter/ epi!e-iolo6ical cross'sectional stu!y/ cancer patients 3ill be enrolle!
:ro- acute care ospitals/ outpatient cancer care :acilities/ cancer reabilitation centers
an! clinics in :i.e -a2or stu!y centers in =er-any (Freibur6/ Ja-bur6/ Jei!elber6/
<eipIi6 an! ,brIbur6). >e centers are selecte! to represent .arious typical re6ions in
=er-any. Factors consi!ere! are te 6eo6rapic location inclu!in6 ne3 an! ol! :e!eral
states/ cities an! to3ns/ an! !i::erent cancer care :acilities. )n eac stu!y center an!
surroun!in6 areas/ te uni.ersity -e!ical center/ anoter ospital o::erin6 -aDi-u-
-e!ical care/ tree to :our outpatient care :acilities pro.i!in6 basic -e!ical care an!
tose ser.in6 as re6ional cancer centres as 3ell as a -ini-u- o: t3o reabilitation
clinics are inclu!e! :or !ata collection. Patients are consecuti.ely recruite! in all centers.
Fi6ure Fi6ure1 1 6i.es an o.er.ie3 o.er te researc !esi6n.
Fi6ure 1
H.er.ie3 o.er te researc !esi6n.
(tudy participants
Patient inclusion criteria contain te e.i!ence o: a -ali6nant tu-or an! a6e bet3een 1#
trou6 $& years !ue to te .ali!ity o: te Co-posite )nternational *ia6nostic )nter.ie3
(('C)*)) F2$G 3ic 3as a!apte! :or cancer patients (C)*)'H). >e oncolo6y'speci:ic
a!aption o: te C)*)'H enances te !ia6nostic spectru- o: te ('C)*) by a!!in6 te
!ia6nostic 6roup o: stress'relate! -ental !isor!ers/ particularly !ue to cancer !isease. 9
pro-inent -o!i:ication strate6y tat :ostere! te !e.elop-ent o: te C)*)'H is te
a!!in6'on o: cancer'relate! @uestions in te inter.ie3 sections :or !epressi.e !isor!ers/
anDiety !isor!ers an! P>S* assessin6 !i::erent types o: stressors an! speci:yin6 ti-e
association o: -ental sy-pto-s an! stressors. Patients across all tu-or entities an!
!isease sta6es are inclu!e! strati:ie! by nation3i!e inci!ence o: cancer !ia6noses (see
sa-ple strati:ication). Patient eDclusion criteria contain te presence o: se.ere pysical/
co6niti.e an!%or .erbal i-pair-ents tat 3oul! inter:ere 3it a patientMs ability to 6i.e
in:or-e! consent :or researc.
!ecruit'ent and data collection
>e stu!y recei.e! researc etics co--ittee appro.al in all in.ol.e! :e!eral states (>e
stu!y 3as appro.e! by te :ollo3in6 (e!ical 9ssociations: Ja-bur6: 1e:. Lr. 2$+#/
Scles3i6'Jolstein: 1e:.'Lr. +1%09; Freibur6: 1e:.'Lr. 244%0$/ Jei!elber6: 1e:.'Lr. S'
22#%200$; &01&&039; ,brIbur6: 1e:. Lr. 10$%0$; <eipIi6: 1e:. Lr. 200200$).
9ll patients 3o :ul:ill te stu!y inclusion criteria are contacte! by stu!y sta:: an!
consecuti.ely recruite! at te oncolo6ical ealt care settin6s an! institutions in all
centers. 9ll patients pro.i!e 3ritten in:or-e! consent prior to participation. Principles o:
6oo! researc practice are strictly a!ere! to in tis pro2ect inclu!in6 !ata an! patientMs
pri.acy protection.
Intervie$er training and quality standards
>e stu!y center Ja-bur6 is responsible :or te coor!ination o: te !ata collection also
ensurin6 te accuracy o: te assess-ent an! te !ata input. Stu!y inter.ie3ers 3ere
traine! eDtensi.ely in a 1'2'!ay 3or4sop on te use o: te co-puter'base! C)*)'H.
9:ter trainin6/ eac inter.ie3er con!ucte! se.eral test inter.ie3s o: 3ic one inter.ie3
3as .i!eotape! an! e.aluate! by one stu!y center responsible :or te @uality assurance
(Freibur6). 0.aluation criteria inclu!e! correct i-ple-entation o: te inter.ie3
@uestions/ correctness o: te patient in:or-ation as 3ell as interactional :actors. 0ac
inter.ie3er recei.e! a !etaile! :ee!bac4 on te i-ple-entation o: te inter.ie3s. )n
a!!ition/ all con!ucte! patient inter.ie3s 3ere e.aluate! by te stu!y center Freibur6.
)ncorrect inter.ie3s 3ere eDclu!e! :ro- te recor!.
!ando'i2ation
9ll patients tat score at te cuto:: point o: 9 or abo.e at te PJ^'9 (total score) F2#G are
inter.ie3e! (C)*)'H)/ an! &0E o: te participants tat score belo3 tis cuto:: point are
ran!o-iIe! to C)*)'H inter.ie3s. ?loc4 ran!o-iIation is use! in eac center by eac
inter.ie3er to allocate participants to C)*)'H inter.ie3s. ?loc4 siIe is !e:ine! by 20.
1an!o-iIation is -ana6e! by usin6 a co-puter'base! ran!o-iIation pro6ra-. 9t te
-o-ent o: ran!o-iIation/ te stu!y inter.ie3er enters te patient co!e an! PJ^ score
into te pro6ra- inter:ace to obtain te assi6n-ent.
(tudy 'easures
>able >able1 1 6i.es an o.er.ie3 o.er te stu!y -easures.
>able 1
H.er.ie3 o.er stu!y -easures
De'ographics; 'edical history and functional perfor'ance
Socio!e-o6rapic in:or-ation is collecte! trou6 use o: a stan!ar!iIe! sel:'report
@uestionnaire (a6e/ 6en!er/ -arital status an! partnersip/ cil!ren/ scool e!ucation/
.ocational trainin6/ -ontly ouseol! inco-e/ e-ploy-ent status an! occupational
situation).
(e!ical in:or-ation re6ar!in6 tu-or entity/ !ate o: an! ti-e since :irst an! recurrent
!ia6nosis/ K)CC !isease sta6e/ in:or-ation about re-ission/ cancer recurrence an!
pro6ress/ -etastasis/ curati.e or palliati.e treat-ent intention/ past an! current cancer
treat-ents recei.e! as 3ell as co-orbi! !isor!ers is 6atere! trou6 -e!ical recor!s.
>e 7arno:s4y per:or-ance status scale F29G is a 3i!ely use! per:or-ance -easure :or
ratin6 te ability o: a so-atically ill person to per:or- usual acti.ities/ e.aluatin6 a
patientUs pro6ress a:ter a terapeutic proce!ure/ an! !eter-inin6 a patientUs suitability :or
terapy. >e lo3er te 7arno:s4y score/ te 3orse te sur.i.al :or -ost serious illnesses
suc as cancer. 9 person is e.aluate! on a score ran6in6 :ro- 0 to 100/ 3ere 0 is A!ea!C
an! 100 is Anor-al/ no co-plaints/ an! no si6ns o: !iseaseC.
>e 0CH= Scale F30/31G is use! in a!!ition to assess o3 a patientUs !isease is
pro6ressin6/ an! to assess o3 te !isease a::ects te !aily li.in6 abilities o: te patient.
9 person is e.aluate! on a score ran6in6 :ro- 0 to &/ 3ere 0 is A:ully acti.e/ able to
carry on all pre'!isease per:or-ance 3itout restrictionC an! & is A!ea!C.
"o'posite international diagnostic intervie$ for oncology ("IDI-*)
>e ('C)*) 3as !e.elope! by te ,orl! Jealt Hr6aniIation (,JH) in collaboration
3it te KS 9lcool/ *ru6 9buse/ an! (ental Jealt 9!-inistration (9*9(J9) an!
translate! into =er-an lan6ua6e on beal: o: ,JH F2$G. 9s a 4ey ob2ecti.e o: tis stu!y/
te Co-posite )nternational *ia6nostic )nter.ie3 :or Hncolo6y (C)*)'H) 3as a!apte!
:or oncolo6y patients base! on te Co-posite )nternational *ia6nostic )nter.ie3 (('
C)*)) in te *)9'O .ersion. >e C)*)'H is a stan!ar!iIe! co-puter'base! inter.ie3
3ic enables te !ia6nosis o: -ental !isor!ers accor!in6 to te )C*'10 an! *S(')8 in
a reliable/ .ali! an! e::icient -anner. >e :ollo3in6 -ental !isor!ers are inclu!e!:
or6anic/ inclu!in6 sy-pto-atic/ -ental !isor!ers (F00'F09)/ -ental an! bea.ioral
!isor!ers !ue to psycoacti.e substance use (F10'F19)/ -oo! (a::ecti.e) !isor!ers (F30'
F39)/ neurotic/ stress'relate! an! so-ato:or- !isor!ers (F40'F4#) an! bea.ioural
syn!ro-es associate! 3it pysiolo6ical !isturbances an! pysical :actors (F&0'F&9).
>o co-pare te speci:ic psyco-etric properties (e.6. sensiti.ity an! speci:icity) o:
screenin6 -easure :or anDiety an! !epression in cancer populations/ te J9*S as 3ell as
te PJ^'9 an! te =9*'$ are use!.
Patient health questionnaire (P:)-=)
*epression is -easure! trou6 use o: te PJ^'9 =er-an .ersion/ te !epression
-o!ule o: te Patient Jealt ^uestionnaire F2#/32G. >e PJ^'9 is base! on te *S(')8
!ia6nostic criteria :or -a2or !epressi.e !isor!er an! as eDcellent reliability/ as 3ell as
criterion/ construct/ :actorial/ an! proce!ural .ali!ity. >e 9 ite-s assess te :re@uency o:
!epressi.e sy-pto-s 3itin te past t3o 3ee4s. )te-s are score! on a :our'point <i4ert
scale rate! :ro- 0 (not at all) to 3 (nearly e.ery !ay) 3it a total score ran6in6 :ro- 0 to
2$. 9 cuto:: point o: Q9 is reco--en!e! :or te screenin6 o: any !epressi.e !isor!er
inclu!in6 a!2ust-ent !isor!er 3it !epresse! -oo! 3it a sensiti.ity o: #$E (9&E C)
$992) an! a speci:icity o: $+E (9&E C) $2#0) F33G. )n a!!ition to te su- score :or
-easurin6 !epression se.erity/ te PJ^'9 o::ers a cate6orical al6orit- base! on
-o!i:ie! criteria o: X-a2or !epressi.e !isor!erM/ accor!in6 to *S(')8. 9 score up to 4
in!icates te absence o: !epression/ scores o: &9 represent -il!/ scores o: 1014
represent -o!erate an! scores o: 1& an! i6er represent se.ere !epression F33G.
0eneral an1iety disorder-scale (0AD-9)
>e =9*'$ =er-an .ersion F34/3&G is use! to i!enti:y probable cases o: 6eneraliIe!
anDiety !isor!er an! to assess sy-pto- se.erity. >e =9*'$ is base! on te -ost
pro-inent !ia6nostic :eatures o: te *S(')8 !ia6nostic criteria :or 6eneraliIe! anDiety
!isor!er an! as eDcellent reliability/ as 3ell as criterion/ construct/ :actorial/ an!
proce!ural .ali!ity. >e $ ite-s assess te :re@uency o: core sy-pto-s o: 6eneraliIe!
anDiety !isor!er 3itin te past t3o 3ee4s. )te-s are score! on a :our'point <i4ert scale
rate! :ro- 0 (not at all) to 3 (nearly e.ery !ay) 3it a total score ran6in6 :ro- 0 to 21. 9
score up to 4 in!icates te absence o: 6eneraliIe! anDiety !isor!er/ scores o: &9
represent -il!/ scores o: 1014 represent -o!erate an! scores o: 1& an! i6er represent
se.ere anDiety sy-pto- le.els F3&G.
:ospital an1iety and depression scale A 0er'an version (:AD()
>e J9*S is a .ali!ate! screenin6 instru-ent :or anDiety an! !epression in so-atically
ill patients F3+G an! eDclu!es sy-pto-s tat -ay arise :ro- so-atic aspects o: illness
(e.6. inso-nia/ 3ei6t loss an! :ati6ue). >e -easure consists o: 14 ite-s on a 4'point
<i4ert scale (ran6e 03) co-prisin6 an anDiety an! !epression subscale. For bot
subscales a total score is calculate! (ran6in6 :ro- 021). 9 score o: 0$ is cate6oriIe! as
nor-al/ a score o: # to 10 is consi!ere! to in!icate a possible anDiety or !epressi.e
!isor!er/ an! a score o: 11 or abo.e is consi!ere! to in!icate a probable anDiety or
!epressi.e !isor!er.
@""@ distress ther'o'eter
>e *istress >er-o-eter is a .ali! an! reliable -easure :or screenin6 psycolo6ical
!istress in patients 3it cancer. )nitially !e.elope! by te Lational Co-preensi.e
Cancer Let3or4 (LCCL) F3$G te =er-an .ersion 3as a!apte! by (enert et al. F3#G.
>e -easure contains a sin6le'ite- .isual analo6ue scale ran6in6 :ro- 0 (Ano !istressC)
an! 10 (AeDtre-e !istressC) to @uanti:y 6lobal le.el o: !istress an! a stan!ar!iIe!
sy-pto- cec4list. >e cec4list consists o: 3+ potential causes o: !istress (ans3ere!
XyesM or XnoM) tat are 6roupe! into :i.e cate6ories (practical proble-s/ :a-ily proble-s/
e-otional proble-s/ spiritual concerns an! pysical proble-s). 9 score o: & or i6er at
te .isual analo6ue scale is reco--en!e! as a cuto:: score :or a clinically si6ni:icant
le.el o: !istress.
Brief pain inventory (BPI)
Pain is assesse! on te basis o: te ?rie: Pain )n.entory (?P)) F39G. >e ?P) is a -easure
!e.elope! to assess pain istory/ pain intensity/ an! pain inter:erence 3it a .ariety o:
acti.ities. >e ?P) is 3ell .ali!ate! a-on6 cancer an! cronic !isease pain patients. )n
tis stu!y/ only pain intensity 3ill be analyIe!. Pain intensity !urin6 te last 3ee4 is
e.aluate! on a scale ran6in6 :ro- 0 (Xno painM) to 10 (X3orst pain i-a6inableM).
&uropean organi2ation for research and treat'ent of cancer quality of life
questionnaire (&*!T" )/) A "B5)
>e 0H1>C ^uality o: <i:e Core ^uestionnaire 0H1>C'^<^'C30 F40G is use! to
-easure cancer'relate! ^H<. >e -easure incorporates :i.e :unctional scales (pysical/
role/ co6niti.e/ e-otional/ social)/ tree sy-pto- scales (pain/ :ati6ue/ nausea%.o-itin6)/
a 6lobal ealt an! @uality'o:'li:e scale/ an! se.eral sin6le ite-s :or te assess-ent o:
a!!itional sy-pto-s co--only reporte! by cancer patients (e.6. appetite loss/ sleep
!isturbance) as 3ell as te percei.e! :inancial i-pact o: te !isease an! treat-ent. >e
0H1>C ^<^ C30 consists o: 30 ite-s tat are score! on 4'point <i4ert scales/ ran6in6
:ro- 1 (Anot at allC) to 4 (A.ery -ucC). >3o ite-s in te 6lobal ealt an! @uality'o:'li:e
sub'scale are score! on a $'point linear analo6ue scale. 9ll :unctional scales an!
in!i.i!ual ite- scores are trans:or-e! to a 0100 scale. Ji6er scores in te :i.e
:unctional scales an! 6lobal ealt status scale represent better :unctionin6/ 3ereas
i6er scores in sy-pto- scales re:lect a 6reater eDtent o: sy-pto- !istress.
Illness-specific social support scale short version-C (I(((-C)
>e )llness'speci:ic Social Support Scale ()SSS) 3as ori6inally !e.elope! by 1e.enson
an! Scia::ino F41G/ an! as been a!apte! to te =er-an lan6ua6e by 1a-- an!
Jasenbrin6 F42G. >e ne3ly !e.elope! #'ite- .ali!ate! =er-an .ersion F43G o: te )SSS
-easures positi.e support (4 ite-s) an! !etri-ental interaction (4 ite-s). >e t3o scales
Xpositi.e supportM an! X!etri-ental interactionM so3 internal consistencies 3it
CronbacMs alpa V .## an! .+#. )te-s are score! on a &'point <i4ert scale ran6in6 :ro- 0
(Xne.erX) to 4 (Xal3aysX).
The shared decision 'aking questionnaire ((D-)-=)
>e 9'ite- Sare! *ecision (a4in6 ^uestionnaire (S*('^'9) F44G is a brie:
@uestionnaire !e.elope! to assess te eDtent o: patientsM participation in sare! !ecision
-a4in6 in te -e!ical encounter. >e present re.ise! .ersion o: te -easure consists o:
nine ite-s !e.elope! on te basis o: te nine process ele-ents caracteriIin6 sare!
!ecision -a4in6/ ran6in6 :ro- te !isclosure tat a !ecision nee!s to be -a!e to a sare!
!ecision an! arran6e-ents o: :ollo3 up. )n te stu!y .ersion/ ite-s are score! on a &'
point <i4ert scale/ ran6in6 :ro- 0 (Astron6ly !isa6reeC) to 4 (Astron6ly a6reeC).
>ere:ore/ te S*('^'9 score can ran6e :ro- 0 to 3+; it is trans:or-e! to a 0100 scale
3it i6er .alues in!icatin6 a i6er eDtent o: patientsM participation in sare! !ecision
-a4in6.
"ontrol preference scale ("P()
>e Control pre:erence scale (CPS) F4&G enco-passes 3eter !ecision'-a4in6 is
controlle! by te !octor/ te patient/ or bot. )t contains :i.e state-ents on te eDtent o:
patientsM pre:erre! participation in !ecision'-a4in6/ ran6in6 :ro- an autono-ous
treat-ent !ecision to co-plete pysician responsibility :or te !ecision. ,itin te
@uestionnaire/ a ran4 or!er o: :i.e state-ents on te pre:erre! le.el o: participation nee!s
to be in!icate!. Patients can be cate6oriIe! into tree 6roups o: acti.e in.ol.e-ent (9
an! ?)/ passi.e role (* an! 0) an! collaborati.e role (C).
Infor'ation and supportive care needs and use of psychosocial support
^uestions 3ere !e.elope! :or tis stu!y capturin6 in:or-ation nee!s/ sources o:
in:or-ation an! satis:action 3it te in:or-ation obtaine! as 3ell as nee!s :or
psycosocial support. Kse o: psycosocial support is assesse! trou6 @uestions co.erin6
te type o: support o::ers use!/ satis:action 3it te support/ basic attitu!es to3ar!
psycoterapeutic support/ -e!ical re:errals an! reco--en!ations as 3ell as reasons :or
non'use o: psycosocial support.
(tatistical 'ethods
Po$er calculation
>e re@uire! sa-ple siIe 3as calculate! base! on te literature'base! 4'3ee4 pre.alence
rates o: -ental !isor!ers in !i::erent strata o: cancer patients !eter-ine! :ro- an
eDpecte! pre.alence o: 30E. 9 sa-ple siIe o: 2/400 inter.ie3s is re@uire! to re!uce te
stan!ar! error o: te 6lobal pre.alence esti-ate to 1E. >o reac 2/400 inter.ie3s/ 3400
patients nee!e! to be screene! by use o: te PJ^'9. Follo3in6 te sa-ple siIe
calculation it 3as !eter-ine! tat eac o: te :i.e centers a! to enroll approDi-ately
$20 patients: 40E eac in te inpatient acute an! outpatient care an! 20E in
reabilitation clinics.
(a'ple stratification
,e use a proportional strati:ie! ran!o- sa-ple base! on te nation3i!e inci!ence o: all
cancer !ia6noses in =er-any F4+G. )n tis :or- o: strati:ie! ran!o- selection/ eac
stratu- is represente! in te sa-ple in te sa-e proportion as in te population. >us/
tis :or- o: strati:ication allo3s esti-ates o: -ental co-orbi!ity :or all -a2or tu-or
entities an! in!i.i!ual care settin6s. >able >able2 2 so3s te cancer inci!ence rates in
=er-any/ 3ic are te basis :or te proportional strati:ie! ran!o- sa-ple.
>able 2
Annual cancer incidence statistics for 0er'any (+55BA+55,)F4+G
(tatistical analyses
Potential selection processes 3ill be analyIe! by co-parisons o: respon!ers an! non'
respon!ers on te basis o: !e-o6rapic an! clinical !ata.
0sti-ates o: te pre.alence o: -ental co-orbi!ity in te tar6et populations are
establise! on te basis o: obser.e! pre.alence rates. >3o 4in!s o: esti-ates 3ill be
reporte!:
1) 1a3 (una!2uste!) proportions as obser.e! in te total sa-ple or in strata/ to allo3
co-parisons 3it oter !ata sources/
2) 0sti-ates resultin6 :ro- :ittin6 a pre!icti.e ierarcal -o!el to te !ata tat ta4es into
account te !esi6n settin6s as :iDe! e::ects an! cluster structures as ran!o- e::ects/ to
allo3 reliable pro2ections o: co-orbi!ity :re@uencies to !e:ine! ealt care catc-ent
areas or to total =er-any.
For pro2ections/ te esti-ate! pre.alence rates 3ill be eDtrapolate! to te tar6et
population by usin6 eDternal or stu!y'speci:ic 3ei6t :actors. >e o.ersa-plin6 o:
patients :or te inter.ie3s 3it i6 !epression scores on te PJ^'9 3ill be ta4en into
account by a correspon!in6 3ei6tin6 o: te in!i.i!ual pre.alence rates as it as been
carrie! out in si-ilar epi!e-iolo6ical stu!ies F21/4$G.
=o to:
Discussion
Pri-ary purpose o: tis epi!e-iolo6ical -ulti'center stu!y 3as to !etect te 4'3ee4s'/
12'-onts'/ an! li:eti-e'pre.alence rates o: co-orbi! -ental !isor!ers accor!in6 to te
)C*%*S( in cancer patients. ,e ai- to enroll a representati.e sa-ple o: patients in
ter-s o: tu-or entities an! cancer care :acilities. Hn te basis o: epi!e-iolo6ical !ata on
te pre.alence o: -ental !isor!ers an! !istress/ te nee!s an! !e-an!s :or te type an!
eDtent o: psycosocial support o::ers can be esti-ate!.
>is stu!y 3as -eto!olo6ically stron6 relati.e to -any stu!ies pre.iously con!ucte!.
Hur stu!y use! a cancer'inci!ence'base! recruit-ent strate6y :or bot 6en!ers an! a
-ulti'-eto!olo6ical approac inclu!in6 a co-puter'base! structure! clinical inter.ie3
:or te assess-ent o: -ental !isor!ers inclu!in6 a!2ust-ent !isor!er as 3ell as .ali!ate!
@uestionnaires :or te assess-ent o: sub2ecti.e e-otional !istress an! supporti.e care
nee!s. Hur tar6ete! sa-ple siIe is lar6er tan tose o: earlier stu!ies in cancer patients
3ic allo3 a .ariety o: sub6roup analyses strati:ie! by i-portant ris4 :actors suc as
cancer pro6ress an! li-ite! pysical :unctionin6.
,e use a statistical -o!el tat ta4es !i::erent sources o: .ariability into re6ar! in or!er to
allo3 reliable pro2ections :or cancer co-orbi!ities tat a.e to be :ace! in =er-any o.er
te neDt years.
)n su--ary/ our stu!y 3ill pro.i!e a lar6e !ata set o::erin6 !etaile! an! .ali!
in:or-ation about te speci:ic -ental co-orbi!ities/ proble-s an! e-otional !istress
a-on6 cancer sur.i.ors 3it .arious tu-or entities an! !isease states. >e !ata :urter
3ill pro.i!e in:or-ation about speci:ic !e-o6rapic/ :unctional/ cancer' an! treat-ent'
relate! ris4 :actors :or -ental co-orbi!ity an! psycosocial !istress/ speci:ic supporti.e
care nee!s an! use o: psycosocial support o::ers.
>us/ epi!e-iolo6ical !ata pro.i!e an i-portant basis :or te i-ple-entation o: bot
in:or-ation an! psycosocial support o::ers in !i::erent ealt care settin6s. >e
i!enti:ication o: pre!ictors :or psycosocial support nee!s in cancer patients allo3 an
early an! speci:ic assi6n-ent an! re:erral o: tose patients to a!e@uate psycosocial
support o::ers. (e!ical ealt care 3ill be i-pro.e! by te pre.ention o: croni:ication
o: -ental !isor!ers an! te enance-ent o: co-pliance/ treat-ent satis:action/ @uality o:
li:e an! co--unication bet3een te cancer patient an! te ealt care tea-.
=o to:
"o'peting interests
>e autors !eclare tat tey a.e no co-petin6 interests.
=o to:
AuthorsD contribution
9ll autors collecti.ely !ra:te! te stu!y protocol an! appro.e! te :inal -anuscript. 9(
is its 6uarantor.
=o to:
Pre-publication history
>e pre'publication istory :or tis paper can be accesse! ere:
ttp:%%333.bio-e!central.co-%14$1'244O%12%$0%prepub
=o to:
Ackno$ledge'ents
>is stu!y is :un!e! by a 6rant :ro- te =er-an Cancer 9i! (=rant Lo: 10$4+&) 3itin
te psycosocial oncolo6y :un!in6 priority pro6ra-.
=o to:
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140. !oi: 10.101+%S01+&'032$(02)0023$'9. FPub(e!G FCross 1e:G
34. SpitIer 1</ 7roen4e 7/ ,illia-s "?/ <o3e ?. 9 brie: -easure :or assessin6
6eneraliIe! anDiety !isor!er: te =9*'$. 9rc )ntern (e!. 200+;1++:1092109$.
!oi: 10.1001%arcinte.1++.10.1092. FPub(e!G FCross 1e:G
3&. <W3e ?/ *ec4er H/ (uller S/ ?raler 0/ Scellber6 */ JerIo6 ,/ JerIber6 P.
8ali!ation an! stan!ar!iIation o: te =eneraliIe! 9nDiety *isor!er Screener
(=9*'$) in te 6eneral population. (e! Care. 200#;4+:2++2$4. !oi:
10.109$%(<1.0b013e31#1+0!093. FPub(e!G FCross 1e:G
3+. Jerr-ann C/ ?uss K/ Snait 1. Jospital 9nDiety an! *epression Scale '
*eutsce 8ersion (J9*S'*). (anual. Jans Juber/ ?ern; 199&.
3$. 1ot 9"/ 7ornblit 9?/ ?atel'Copel </ Peabo!y 0/ Scer J)/ Jollan! "C. 1api!
screenin6 :or psycolo6ic !istress in -en 3it prostate carcino-a: a pilot stu!y.
Cancer. 199#;#2:1904190#. !oi: 10.1002%(S)C))109$'
0142(199#0&1&)#2:10P1904::9)*'CLC113Q3.0.CH;2'O. FPub(e!G FCross 1e:G
3#. (enert 9/ (bller */ <e-ann C/ 7oc K. *ie !eutsce 8ersion !es LCCL
*istress'>er-o-eters ' 0-pirisce Prb:un6 eines Screenin6')nstru-ents Iur
0r:assun6 psycosoIialer ?elastun6 bei 7rebspatienten. Neitscri:t :br
Psyciatrie/ Psycolo6ie un! Psycoterapie. 200+;&4:213223. !oi:
10.1024%1++1'4$4$.&4.3.213. FCross 1e:G
39. Cleelan! CS/ 1yan 7(. Pain assess-ent: 6lobal use o: te ?rie: Pain )n.entory.
9nn 9ca! (e! Sin6apore. 1994;23:12913#. FPub(e!G
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!oi: 10.1093%2nci%#&.&.3+&. FPub(e!G FCross 1e:G
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!ouble'e!6e! s3or!: te relation o: positi.e an! proble-atic support to
!epression a-on6 reu-atoi! artritis patients. Soc Sci (e!. 1991;33:#0$#13.
!oi: 10.101+%02$$'9&3+(91)903#&'P. FPub(e!G FCross 1e:G
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Sup'port Scale un! ire teststatistisce jberprb:un6 bei- 0insatI an Patienten
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Psycolo6ie. 2003;12:293#.
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10.101+%0#9&'43&+(92)90110'9. FPub(e!G FCross 1e:G
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7iesc4e "/ 7ray3in4el 7/ (eyer (/ Stabeno3 1/ Ste6-aier C/ ?ertI "/
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Jurnal 8
Psychooncology. Author manuscript; available in PMC 2009 September 14.
Publishe in !nal eite "orm as#
Psychooncology. 2009 March; 1$ %&' # 2()*2)+.
oi# 10.1002,pon.1&94
PMC-.# PMC2)4&1+)
/-0MS-.# /-0MS122)42
:opelessness as a predictor of depressive
sy'pto's for breast cancer patients
coping $ith recurrence
1rittany M. 1rothers
1
an 1arbara 2. Anersen
234
Author in"ormation 5 Copyright an 2icense in"ormation 5
6he publisher7s !nal eite version o" this article is available at
Psychooncology
See other articles in PMC that cite the publishe article.
8o to#
Abstract
*b-ective
>e Jopelessness >eory o: *epression pro.i!es te :ra-e3or4 to test :eelin6s o:
opelessness an! social support as pre!ictors o: !epressi.e sy-pto-s in 3o-en recently
!ia6nose! 3it a recurrence o: breast cancer.
ethods
Patients (N V +$) 3ere assesse! 3itin 3ee4s o: recei.in6 teir recurrence !ia6nosis
(initial) an! a6ain 4 -onts later (:ollo3'up).
!esults
Controllin6 :or teir current pysical an! !epressi.e sy-pto-s/ opelessness at !ia6nosis
3as a si6ni:icant pre!ictor o: te -aintenance o: !epressi.e sy-pto-s a-on6 patients. 9
corollary o: te teory 3as also con:ir-e!: social support (i.e. te presence%absence o: a
ro-antic partner) interacte! 3it opelessness.
"onclusions
,o-en 3o reporte! :eelin6s o: opelessness an! 3o 3ere alone (i.e. 3itout a
partner) 3ere especially .ulnerable to later !epressi.e sy-pto-s. >e !ata pro.i!e
support :or te Jopelessness >eory an! su66est :actors con:errin6 ris4 :or !epressi.e
sy-pto-s :or tose copin6 3it a 3orsene! cancer pro6nosis.
Keywords: hopelessness3 hope3 epression3 social support3 breast cancer
recurrence3 oncology
>e !ia6nosis o: cancer is a si6ni:icant stressor/ lea!in6 to psycolo6ical stress F1G an!
poor @uality o: li:e :or -any patients F24G. Kp3ar!s o: &0E o: patients -ay -eet
criteria :or -oo!/ anDiety/ an!%or a!2ust-ent !isor!ers F&/+G/ 3it !epression bein6
co--on F$G. *epressi.e sy-pto-s are esti-ate! to be si6ni:icant :or 2229E in patients
3it early sta6e !isease F#G an! 1#40E :or patients 3it a!.ance! !isease F9G. Lotably/
rates o: !epression in cancer patients are consistently i6er tan rates :oun! a-on6
patients 3it oter -e!ical con!itions F10G. For so-e/ !epression is :atal. 9-on6 tose
!ia6nose! 3it breast cancer/ tere is a s-all but statistically si6ni:icant increase! ris4 o:
suici!e :or as lon6 as 30 years :ollo3in6 !ia6nosis F11G.
Hne circu-stance tat -ay en6en!er not only !epression but also opelessness is
recurrence. )n correlational stu!ies/ :eelin6s o: opelessness in recurrence patients are
associate! 3it psyciatric -orbi!ity an! oter e-otional !i::iculties F121+G/ poorer
@uality o: li:e F1$G/ an! less social support F1&G. )n te stu!y o: suici!e note! abo.e F11G/
te sub6roup 3it te i6est ris4 are patients 3it !istant -etastases (2.11)/ co-pare! to
tose 3it local (1.3#) or re6ional (1.&&) !isease.
>e Jopelessness >eory o: *epression by 9bra-son an! collea6ues F1#G is an
i-portant teoretical contribution to te un!erstan!in6 o: clinical !epression. >ey
propose tat so-e in!i.i!uals a.e a X!epresso6enic in:erential styleM tat in:luences
oneMs attributions 3en :ace! 3it a ne6ati.e li:e e.ent. 1ater tan percei.in6 an e.ent
in isolation/ in!i.i!uals -a4e speci:ic ne6ati.e attributions about te cause o: te e.ent/
its conse@uences/ or e.en onesel:. 9ccor!in6 to te teory/ only one attribution is nee!e!
to !e.elop opelessness/ te belie: tat te outco-e o: an e.ent 3ill be ne6ati.e an! tat
notin6 can be !one to can6e it. )n turn/ :eelin6s o: opelessness are tou6t to lea! to
sy-pto-s o: opelessness !epression.
Cancer recurrence -ay elicit opelessness/ as it is presently an incurable !ia6nosis. )t
brin6s -ore treat-ent F19G/ :ati6ue/ !eclinin6 ealt F3/20G/ an! te potential :or lo3ere!
@uality o: li:e F21G. Patients :ear an! 3orry about 3at 3ill appen as te !isease
pro6resses. 1ecurrence -ay be percei.e! to be substantially uni@ue to te patient (e.6. X)
a.e recurre!/ but ) 4no3 oters 3o a.e not.M)/ con6ruent 3it si-ilar situations (e.6.
X) 4ne3 tis 3oul! appen because -y ce-oterapy !i! not 6o 3ell.M)/ or consistent
3it prior e.ents (e.6. X) a.e al3ays a! poor ealt.M). Pre.ious researc su66ests tat
tose in!i.i!uals 3o attribute te cause o: teir cancer !ia6nosis to te-sel.es (trou6
:eelin6s o: sel:'bla-e F22/23G an! personal responsibility F24G) an! tose 3o attribute
-ultiple reasons F2&G report -ore !epressi.e sy-pto-s. )n a!!ition/ it as been :oun!
tat belie:s about te reasons 3y pysical sy-pto-s occur !urin6 ce-oterapy
treat-ent are relate! to !epresse! -oo! F2+G. 9 patientMs perspecti.e can @uic4ly si:t
:ro- tat o: a sur.i.or to one li4ely to !ie :ro- te !isease.
9bra-son et al F1#G su66est tat oter :actors/ alon6 3it opelessness/ -ay be
in:luential in !epression. >ese inclu!e !e.elop-ental :actors/ 6enetic :actors/ an!/
i-portantly/ interpersonal :actors/ suc as social support. "onson an! collea6ues F2$G
:oun! tat increases in opelessness -e!iate! te relationsip bet3een initial social
support an! increases in !epressi.e sy-pto-s + -onts later in -en 3o 3ere u-an
i--uno!e:iciency .irus (J)8) positi.e. Hter researc/ not testin6 te Jopelessness
>eory yet eDa-inin6 te sa-e .ariables/ as so3n social support to be in.ersely
correlate! 3it opelessness an! !epressi.e sy-pto-s in ealty in!i.i!uals (e.6.
F2#/29G) as 3ell as tose 3it ealt con!itions inclu!in6 J)8%9)*S F30G/ spinal cor!
in2uries F31G/ or cancer F32G. >o su--ariIe/ cancer patientsM perceptions o: social support
are associate! 3it better a!2ust-ent an! :e3er e-otional !i::iculties as is te case :or
oter patient 6roups. )t is unclear i: tis 3oul! be te case :or oter -easures o: social
support/ suc as nu-ber o: supporti.e relationsips. Finally/ it is not 4no3n i: social
support interacts 3it opelessness to increase .ulnerability to !epression as su66este!
F1#G.
>e stu!yMs ai- is to un!erstan! cancer patientsM stru66le 3it !epressi.e sy-pto-s as
tey cope 3it recurrence. Consistent 3it te teory/ 3e ypotesiIe tat opelessness
-easure! in te 3ee4s a:ter !ia6nosis 3ill pre!ict patientsM !epressi.e sy-pto-s -onts
later. 9ssess-ents are con!ucte! sortly a:ter !ia6nosis o: recurrence an! a6ain 4 -onts
later. ,e are uncertain i: interpersonal :actorsSsocial supportS3ill play eiter a !irect
role or a -o!eratin6 one/ as te teory is not speci:ic/ nor !oes it !i::erentiate bet3een
types o: social support tat -ay or -ay not be rele.ant. >ere:ore/ 3e inclu!e bot
structural (e.6. presence o: a si6ni:icant oter (SH)/ nu-bers o: :a-ily -e-bers an!
:rien!s) an! :unctional (e.6. patientsM perceptions o: support :ro- oters) aspects.
9nalyses also inclu!e rele.ant control .ariables/ 3it te -ost i-portant bein6 te
patientsM current sy-pto-s%si6ns/ illnesses/ an! any toDicities :ro- cancer treat-ents as
tey co.ary 3it !istress F33/34G. Poor ealt alone -i6t lea! to perceptions tat te
illness is uncontrollable an!/ tereby/ en6en!er opelessness. Socio!e-o6rapic an!
!isease .ariables are also consi!ere! alon6 3it initial le.els o: !epressi.e sy-pto-s in
tis repeate! -easures test o: opelessness as a pre!ictor o: !epressi.e sy-pto-s.
8o to#
ethod
Procedures and patients
Patients in -e!ical an! sur6ical oncolo6y clinics o: a uni.ersity'a::iliate!/ Lational
Cancer )nstitute'!esi6nate! Co-preensi.e Cancer Center 3ere sou6t. Le3/
consecuti.e cases 3it breast cancer recurrence (i.e. pre.iously !ia6nose! 3it Sta6e )/
))/ or ))) breast cancer) 3ere i!enti:ie!. 1ecurrence re:ers to te clinical !etection o:
-etastatic breast !isease in te sa-e area/ a!2acent to/ or !istant :ro- te ori6inal site.
Patients eDclu!e! 3ere tose !ia6nose! 3it a prior or current secon! pri-ary tu-or
(e.6. contralateral breast/ en!o-etrial)/ prior or current re:usal o: any cancer treat-ent/
-ental retar!ation/ se.ere or untreate! psyciatric !ia6noses (e.6. sciIoprenia/ bipolar
or bor!erline personality !isor!er)/ or neurolo6ical !isor!ers (inclu!in6 !e-entia).
Hne un!re! an! siD patients 3ere eli6ible an!/ o: tese/ #+ (#1E) 3ere accrue!. 9ll
3ere pro.i!e!/ in person/ 3it oral an! 3ritten in:or-e! consent in 4eepin6 3it
institutional 6ui!elines an! in accor!ance 3it an assurance appro.e! by an! :ile! 3it
te KS *epart-ent o: Jealt an! Ju-an Ser.ices. For te non'participants (n V 20;
19E)/ co--on re:usal reasons (o: 10 reasons sur.eye!) 3ere Xnot intereste!M (40E) an!
X!o not a.e ti-eM (20E). 9nalyses o: .ariance an! ci's@uare analyses/ as appropriate/
:oun! no si6ni:icant !i::erences (pMsQ0.1&) bet3een participants (n V #+) an! non'
participants (n V 20) in a6e/ racial 6roup -e-bersip/ absence%presence o: an SH/
-enopausal status/ or !isease sta6e at initial !ia6nosis.
Follo3in6 in:or-e! consent/ t3o assess-ents 3ere con!ucte! in te clinic an! laste!
approDi-ately 1.& . Patients co-plete! te initial assess-ent on an a.era6e o: $& !ays
(S* V 44; -e!ian V +0) post'!ia6nosis/ an! a :ollo3'up on an a.era6e o: 132 !ays (S* V
32; -e!ian V 12+)/ approDi-ately 4 -onts/ later. ,it te assistance o: a :e-ale
researc assistant/ 3o-en co-plete! a structure! inter.ie3 an! @uestionnaires. 9 :e-ale
researc nurse con!ucte! a ealt assess-ent 3it te patient (see Pysical Functionin6
belo3)/ abstracte! !ata :ro- te -e!ical cart/ an! consulte! 3it te patientMs
oncolo6ist as nee!e!. Participants 3ere co-pensate! k&0.00 per assess-ent.
H: te #+ participants/ 19 (22E) !i! not co-plete te :ollo3'up :or reasons o: rapi!
!isease pro6ression an! !eat (n V &)/ stu!y !ropout (n V +)/ or patient illness (n V #).
>ere 3ere no si6ni:icant !i::erences (pMsQ0.1$) bet3een patients co-pletin6 te 4'
-ont :ollo3'up assess-ent (N V +$) an! tose not (n V 19) on socio!e-o6rapic or
!isease caracteristics/ pysical :unctionin6/ or initial scores o: opelessness/ social
support/ or !epressi.e sy-pto-s. >able 1 pro.i!es !escripti.e !ata :or te sa-ple (N V
+$).
6able 1
Socioemographic an isease characteristics o" the sample %N 9 ()' an
cancer treatments on:going at initial an "ollo;:up assessments
easures
Predictor variables
Hopelessness
>e ?ec4 Jopelessness Scale (?JS) F3&G contains 20 true:alse ite-s. ?ec4 an! Steer
F3+G score te -easure as :ollo3s: 03/ nor-al; 4#/ -il! opelessness; 914/ -o!erate
opelessness; an! 1& an! abo.e/ se.ere opelessness. Pre.ious nor-ati.e !ata su66est a
ran6e o: scores :ro- 1.$0 to 4.4&/ 3it a -ean o: 3.0+ :or non'illness populations (S* V
3.11 F3$G). )nternal consistency 3as 0.#9.
Social support
>3o structural -easures are use!. (1) Presence o: SH%ro-antic partner is !eter-ine!. (2)
>e Social Let3or4 )n!eD (SL)) calculates total support as a :unction o: te nu-ber o:
an in!i.i!ualMs social ties an! co--unity in.ol.e-ent F3#G. >e -ain ele-ents o: te
SL) are nu-ber an! :re@uency o: contact 3it close :rien!s an! relati.es/ curc 6roup
-e-bersip/ an! oter 6roup -e-bersip (e.6. social or ser.ice'oriente!). (arital status
is inclu!e! but 3as eDclu!e! :ro- te calculation o: te score. SL) scores ran6e! :ro- 1
to 12.
>3o :unctional -easures are use!. >e Percei.e! Social Support :ro- Fa-ily (PSS'Fa)
an! Frien!s (PSS'Fr) Scales F39G -easure te !e6ree to 3ic one percei.es tat oneMs
:a-ily or :rien!s :ul:ill oneMs nee! :or support/ respecti.ely. ?ot contain 20 ite-s an!
scores ran6e :ro- 0 to 20 :or eac. For te analyses/ te scales 3ere co-bine! :or a total
score. )nternal consistency 3as 0.92 an! 0.#$/ respecti.ely.
*utco'e variable
>e Center :or 0pi!e-iolo6ical Stu!ies *epression Scale (C0S'* F40G) contains 20
!epression sy-pto- ite-s/ eac score! 3it a 4'point <i4ert scale 3it scores ran6in6
:ro- 0 to +0. 9 cuto:: score o: 1+ is use! as an in!icator o: clinically si6ni:icant
!epression F41/42G. For te re6ression analyses/ one ite-/ X) :eel ope:ul about te
:utureM/ 3as re-o.e! !ue to its si-ilarity 3it ?JS/ resultin6 in te scorin6 o: 19 ite-s
:or te re6ression analyses. )nternal consistency 3as 0.92.
"ontrol variables
Physical functioning
>3o -easures 3ere co-plete! by a researc nurse. (1) >e types an! se.erity o:
sy-pto-s/ si6ns/ an! toDicities :ro- cancer treat-ents 3ere assesse! (Sy-S%>oD F43G).
>3enty't3o bo!y syste-s (e.6. e-atolo6ic/ 6astrointestinal/ i--unolo6ic) eac
sa-ple! :our to se.en co--on si6ns%sy-pto-s an! treat-ent toDicities (e.6. alopecia).
)te-s are rate! on in!i.i!ualiIe!/ &'point scales/ su--e!/ an! a.era6e! :or a total score.
>otal scores ran6e :ro- 0 to 4 3it i6er scores in!icatin6 sy-pto-s%si6ns o: 6reater
se.erity an! li:e treat. (2) >e 7arno:s4y Per:or-ance Scale (7PS F44G) rates patient
:unctional status usin6 an 11'point <i4ert scale ran6in6 :ro- 100 (nor-al/ no co-plaints/
no e.i!ence o: !isease) to 0 (!ea!). Ji6er scores in!icate better :unctional status (e.6.
#0 V nor-al acti.ity 3it e::ort/ so-e si6ns%sy-pto-s o: !isease). )nter'rater reliability
ran6es :ro- 0.$0 to 0.9$ F4&/4+G an! te 7PS is pre!icti.e o: cancer en!points F4$G.
Analytic strategy
*escripti.e statistics are pro.i!e! (see >able 1). Correlational analyses eDa-ine! te
relationsip bet3een pre!ictor an! control .ariables (i.e. socio!e-o6rapic/ !isease/ an!
pysical :unctionin6) an! :ollo3'up C0S'* scores. Jierarcical -ultiple re6ression
-o!els 3ere use!. Follo3in6 entry o: control .ariables an! baseline C0S'*/ analyses
teste! te relationsip bet3een initial le.els o: opelessness (?JS)/ social support
(structural or :unctional)/ an! teir interaction/ an! !epressi.e sy-pto-s (C0S'*) at
:ollo3'up. 9s it 3as unclear i: structural an! :unctional social support -easures 3oul!
per:or- si-ilarly/ separate re6ression analyses 3ere use!. 9ll .ariables 3ere
stan!ar!iIe! by rescalin6 eac -ean to 0.0 3it a stan!ar! !e.iation o: 1.0 be:ore entry
into te re6ression analyses. >is stan!ar!iIation creates te sa-e -etric :or eac
.ariable an! :acilitates testin6 te uni@ue contribution o: any one in!epen!ent .ariable.
9s reco--en!e! by Preacer F4#G/ te interaction ter- -ultiplies te stan!ar!iIe!
opelessness .ariable 3it te stan!ar!iIe! social support .ariable.
8o to#
!esults
Preli'inary analyses
9t te initial assess-ent/ 2#E (19 o: te +$) o: te patients score! at or abo.e te clinical
cuto:: :or te ?JS. Speci:ically/ 1&/ 10/ an! 3E o: te sa-ple a! -il!/ -o!erate/ or
se.ere le.els o: opelessness sy-pto-s. 9lso/ 3+E (24 o: te +$) o: te 3o-en score!
abo.e te C0S'* cuto:: at te initial assess-ent an! 30E (20 o: te +$) at te :ollo3'up.
>e +E re!uction in te nu-ber o: cases 3as not si6ni:icant ( / pQ40.0&).
H.erall/ tere 3as a 2'point re!uction in te C0S'* 6roup -eans :ro- 14 (S* V 10) at
initial assess-ent to 12 (S* V 10; !1/++ V 4.4&/ pP0.0&; CoenMs d V 0.20). Correlations
3ere eDa-ine! (see >able 2). H: te control .ariables/ only -easures o: pysical
:unctionin6 (Sy-S%>oD an! 7PS) 3ere si6ni:icantly associate! 3it !epressi.e
sy-pto-s at :ollo3'up (r V 0.2& an! c0.31/ respecti.ely/ pMsP 0.0&; see >able 2) an!/
tus/ are inclu!e! in te pri-ary analyses.
6able 2
Correlation coe<cients among physical "unctioning3 preictors3 an
epressive symptoms outcome
Pri'ary analyses
>ree re6ression analyses 3ere con!ucte! (see >able 3) an! all -o!els 3ere si6ni:icant.
Pysical :unctionin6 an! baseline !epressi.e sy-pto-s accounte! :or 4$E o: te total
.ariance an! opelessness a!!e! an a!!itional/ si6ni:icant $E o: te .ariance in te
pre!iction o: :ollo3'up !epressi.e sy-pto-s. >e re-ainin6 steps o: te re6ression
analyses teste! te contribution o: interpersonal :actors an! teir interaction 3it
opelessness.
6able &
0ierarchical multiple regression analyses testing hopelessness3 three social
variables3 an their interaction terms as preictors o" epressive symptoms
at "ollo;:up among breast cancer patients ;ith recurrence %N 9 ()'
For te analysis 3it presence o: an SH/ te -o!el 3as si6ni:icant (!+/+0 V 1$.12/ pP
0.001; see >able 3/ (o!el 1)/ accountin6 :or +3E o: te total .ariance (total a!2uste! 1
2

V 0.&9). SH 3as a si6ni:icant pre!ictor (" V c0.2+/ pP0.01) an!/ :urter/ patientMs le.el o:
opelessness interacte! 3it partner status (" V c0.19/ pP0.0&). Fi6ure 1 pro.i!es a
representation o: te interaction. For te purposes o: illustration/ opelessness scores are
!icoto-iIe!/ usin6 te reco--en!e! cuto:: score o: 4 an! i6er F3+G. >e outco-e
.ariable/ !epressi.e sy-pto-s (C0S'* scores) at :ollo3'up/ is pro.i!e! :or :our 6roups
!e:ine! by le.el o: opelessness at te initial assess-ent (i6 .s lo3) an! SH status
(present .s absent). >e interaction in!icates tat te 3o-en at 6reatest ris4 :or later
!epressi.e sy-pto-s 3ere tose 3o reporte! 6reater :eelin6s o: opelessness at
!ia6nosis and 3o 3ere alone (3itout an SH) as tey :ace! cancer recurrence. )n te
-o!el 3it SL) as te social support in!icator (see >able 3/ (o!el 2)/ SL) 3as not a
si6ni:icant pre!ictor o: !epressi.e sy-pto-s (p V 0.$+). >e interaction ter- 3as also
not si6ni:icant (p V 0.##).
=igure 1
.epressive symptom %C>S:.' scores at "ollo;:up3 illustrating interaction o"
signi!cant other an hopelessness status
1e6ar!in6 patientsM perceptions o: support/ neiter te PSS'Fa nor te PSS'Fr scales
3ere correlate! 3it !epressi.e sy-pto-s at :ollo3'up. For te re6ression analysis/ te
PSS'Fa an! PSS'Fr scales 3ere co-bine! (see >able 3/ (o!el 3). PSS 3as not a
si6ni:icant pre!ictor o: !epressi.e sy-pto-s (p V 0.#9) nor !i! it interact 3it
opelessness (p V 0.++).
3ollo$-up analyses
9s te le.els o: !epressi.e sy-pto-s an! opelessness :or te sa-ple 3ere notable/ it
3oul! not be uneDpecte! tat so-e patients -i6t see4 psycolo6ical treat-ent at
!ia6nosis. 9nalyses 3ere con!ucte! to test te robustness o: te :in!in6s an! !eter-ine
te e::ect/ i: any/ o: recei.in6 terapy on te !epressi.e sy-pto- :in!in6s. 9t te ti-e o:
te initial assess-ent/ :our patients in!icate! tat tey 3ere recei.in6 in!i.i!ual terapy.
9ll :our patients eDcee!e! te cuto:: :or opelessness. )nterestin6ly/ t3o o: te :our
eDcee!e! te C0S'* cuto:: at bot assess-ents/ but te re-ainin6 t3o !i! not at eiter
assess-ent. >e tree re6ression analyses reporte! abo.e (opelessness an! its
interaction 3it SH/ SL)/ an! PSS) 3ere repeate! 3it psycolo6ical terapy status (0 V
not in psycolo6ical treat-ent/ 1 V in treat-ent) as a control .ariable an! te results 3ere
uncan6e!.
8o to#
Discussion
)n te current stu!y/ :eelin6s o: opelessness in 3o-en recently !ia6nose! 3it a
recurrence o: breast cancer pre!icte! -ore !epressi.e sy-pto-atolo6y 4 -onts later.
>is result is si6ni:icant as analyses controlle! :or pysical :unctionin6/ a 4no3n
correlate o: !epressi.e sy-pto-s F49G. )n a!!ition/ partner status interacte! 3it
opelessness to pre!ict subse@uent !epressi.e sy-pto-s. Speci:ically/ tose 3o-en
3itout a partner an! :eelin6 opeless 3ere at 6reatest ris4 :or !epressi.e sy-pto-s at
:ollo3'up.
>e central tesis o: te Jopelessness >eory o: *epression F1#G 3as supporte!. >at is/
results so3e! tat :eelin6s o: opelessness contribute to can6es in !epressi.e
sy-pto-s. ,e eDten! pre.ious researc by pro.i!in6 prospecti.e/ rater tan concurrent/
assess-ents. )n tis case/ control :or te patientsM pysical sy-pto-s an! :unctional
status is necessary/ an! !oin6 so pro.i!e! a ri6orous test. )-portantly/ pysical status 3as
assesse! in!epen!ently by researc nurses/ 3o 3ere una3are o: te patientsM !epression
an! opelessness ratin6s. Pysical status 3as correlate! 3it !epressi.e sy-pto-s an!
contribute! si6ni:icantly (12E o: te .ariance) to te pre!iction o: !epressi.e sy-pto-s.
>e !ata support te .ie3 tat opelessness is a !istinct construct an! not -erely a
sy-pto- o: !epression. *espite te po3er:ul contribution o: baseline !epression (34E o:
te .ariance) an!/ :urter/ te a!!ition o: pysical :unctionin6/ te $E a!!itional
.ariance contribute! by opelessness is note3orty. 9bra-son an! collea6ues F1#G ar6ue
tat opelessness can be a proDi-al/ su::icient cause o: !epression/ tri66ere! by a
co-bination o: ne6ati.e li:e e.ents an! a !epresso6enic in:erential style. Clar4e an!
7issane F&0G also ar6ue :or a conceptual !i::erence bet3een opelessness an! !epression.
>ey see opelessness as a 4ey co-ponent in :eelin6s o: X!e-oraliIationM/ 3ic also
inclu!es te persistent inability to cope an! -eanin6lessness. ,ile !e-oraliIation an!
!epression co'occur in te -e!ically ill F&1G/ tey see !e-oraliIation (a4a opelessness)
as caracteriIe! by sub2ecti.e inco-petence/ 3ereas !epression is caracteriIe! by
ane!onia.
>e !ata also support te Jopelessness >eoryMs corollary tat interpersonal :actors/ in
tis case presence o: an SH/ play a role in te relationsip bet3een opelessness an!
!epression. Prior stu!ies a.e !e-onstrate! poor social support concurrent 3it
!epression an! opelessness (e.6. F1&/32G)/ but tere a.e been :e3 pre!icti.e tests.
9bra-son an! collea6ues F1#G in!icate! tat te absence o: support -ay be in:luential in
te causal cain bet3een opelessness an! !epression but !i! not speci:y te eDact
-ecanis-. Ksin6 te teory as a :oun!ation/ "onson an! collea6ues F2$G eDa-ine!
opelessness/ !epression/ an! social support in J)8'positi.e -en an! :oun! tat te
relationsip bet3een social support an! !epression 3as -e!iate! by increases in
opelessness.
>e repeate! -easures !esi6n enable! stu!y o: a possible -o!eratin6 e::ect o: social
support. ,ile bot partner status an! social net3or4 siIe (SL)) 3ere correlate! 3it
!epressi.e sy-pto-s at :ollo3'up/ only partner status eDplaine! a si6ni:icant .ariance
(see Fi6ure 1). >e i-pact o: partner status :ollo3 a-ple e.i!ence illustratin6 te
i-portance o: te presence o: a partner 3en copin6 3it a serious illness. For eDa-ple/
-arrie! in!i.i!uals a.e lo3er -ortality rates tan all oters (e.6. F&2&&G). Con.ersely/
un-arrie! -e!ical patients a.e i6er rates o: ospital a!-issions/ -ore se.ere
illnesses/ lon6er len6ts o: stay/ an! i6er ris4 o: !eat :ollo3in6 sur6ery tan teir
-arrie! counterparts F&+G.
For te Jopelessness >eory/ te pre!icti.e po3er o: partner support is a no.el :in!in6/
but it -ay a.e particular rele.ance to clinical cancer literatures. Consistent 3it te
!iscussion abo.e/ unpartnere! cancer patients a.e been obser.e! to a.e si6ni:icantly
sorter sur.i.al ti-es tan partnere! in!i.i!uals/ e.en 3en analyses a!2uste! :or sta6e
o: !isease an! treat-ent recei.e! (e.6. F&$G). 9 recent -eta'analysis by Ci!a an!
collea6ues F&#G so3s an increase! ris4 o:/ as 3ell as pro6ression o:/ cancer :or tose
3it !istress/ 3it !epressi.e sy-pto-s bein6 -ost in:luential. ,it speci:ic re6ar! to
opelessness/ Sc-ale an! )4er F&9G 3ere te :irst to su66est te rele.ance o:
opelessness an! te !e.elop-ent o: cancer. (ore recently/ a prospecti.e stu!y by
,atson an! collea6ues F+0G 3it early sta6e breast cancer patients (N V &$#) as so3n
tat not only tose 3it i6 !epression scores but 3it i6 opelessness scores at
!ia6nosis a! an increase! ris4 o: relapse or !eat 3itin & years. Hur !ata i-plicate
opelessness as a psycolo6ical :actor -a!e 3orse 3en a person copes 3it cancer
alone. >is syner6y -ay ser.e as an eDplanatory -ecanis- lin4in6 !epression an!
partner status literatures to !isease pro6ression an!%or lo3ere! sur.i.al.
,e consi!er 3y te oter in!icators o: social support !i! not pre!ict !epressi.e
sy-pto-s. ,e :irst note tat te baseline assess-ent o: bot te SL) an! te PSS
-easures 3as a XsnapsotM (unli4e te assess-ent o: a .ariable suc as partner status) tat
-ay a.e i-pose! li-itations on teir pre!icti.e .alue. For te SL)/ scorin6 is base! in
part on participation in 6roup acti.ities/ 3ic -ay a.e alrea!y !i-inise! 3it te
i-pact o: !ia6nosis an! treat-ents. For te PSS scales/ tey 3ere not correlate! 3it
:ollo3'up !epressi.e sy-pto-s an!/ not surprisin6ly/ not si6ni:icant in te re6ression
analysis. Jo3e.er/ tis is not necessarily an e.i!ence :or a lac4 o: relationsip bet3een
percei.e! social support an! !epressi.e sy-pto-s/ as tere is consi!erable e-pirical
support :or suc a relationsip. )n our case/ te -ean scores o: te PSS 3ere 1$ o: a
possible 20/ in!icatin6 perceptions o: eDcellent support. Consistent 3it tis/ -any
3o-en ac4no3le!6e! an outpourin6 o: support :ro- :rien!s an! :a-ily. >us/ te
restriction o: ran6e (Xceilin6 e::ectM) o: te PSS -ay be responsible :or te null :in!in6s.
)n te case o: breast cancer recurrence/ 3e can speculate 3y partner status -ay be
bene:icial abo.e an! beyon! percei.e! support :ro- :a-ily an! :rien!s. H3in6 to te
ealt i-pact o: recurrence an! cancer treat-ent/ 3o-en o:ten report !i::iculty in
acco-plisin6 tas4s (e.6. ouse cleanin6/ coo4in6/ !oin6 laun!ry). Kn:ortunately/
patients are o:ten esitant to as4 :or tas4 support :ro- :rien!s an! :a-ily/ as tey !o not
3is to be bur!enso-e. ,en a partner is a.ailable/ s%e -ay be te rea!y source o: tas4
support tat can be relie! upon/ 3ic in turn -ay alle.iate so-e o: te associate!
!istress/ in a!!ition to tat alle.iate! by te partnerMs e-otional support.
>e 6oo! ne3s :ro- tese !ata is tat not e.eryone 3o recurs is or beco-es !epresse!
an!%or elpless. )n!ee!/ te -a2ority o: patients in our sa-ple 3ere not !epresse!.
9pproDi-ately one'tir! a! clinically si6ni:icant !epressi.e sy-pto-s/ an esti-ate
consistent 3it rates o: !epression :oun! in patients 3it a!.ance! cancer F9G. ):
re:lecti.e o: -oo! !isor!ers/ tis is a rate five times tat :oun! in te 6eneral population
(approDi-ately +E as su66este! by Sellic4 an! Croo4s F+1G). >e rates o: opelessness
:oun! ere are co-parable to tose :ro- oter stu!ies o: patients 3it recurrence (e.6.
F1$/+2G). Consi!erin6 bot -easures/ at te initial assess-ent/ patients 3o 3ere bot
!epresse! an! opeless accounte! :or 1+E o: te sa-ple. H: te re-ain!er/ so-e 3ere
!epresse! but not opeless (19E)/ an! a :e3 (12E) reporte! opelessness in te absence
o: !epressi.e sy-pto-s.
>ese :in!in6s soul! be consi!ere! in te conteDt o: teir -eto!olo6ical li-itations
an! possible li-itations in 6eneraliIability. 9n in!i.i!ualMs !epresso6enic in:erential style
is tou6t to be a contributor to !epression an! is an i-portant co-ponent o: te
Jopelessness >eory 3as not inclu!e!. Hter researc in!icates tat cancer is a type o:
e.ent tat coul! elicit attributions su::icient :or te !e.elop-ent o: opelessness F23G. ):
inclu!e!/ a test o: opelessness as a -e!iator bet3een te presence o: te in:erential style
an! te !e.elop-ent o: !epressi.e sy-pto-s 3oul! be acie.e!. >e partner status
:in!in6s are no.el an! nee! replication/ an! :uture researc 3it couples -i6t inclu!e
relationsip satis:action/ as it too as been relate! to !epressi.e sy-pto-s F+3G. Hur
:in!in6s co-e :ro- a pre!o-inantly Caucasian sa-ple 3it abo.e'a.era6e e!ucation
an! inco-e le.els. 1esearc su66ests tat lo3er socioecono-ic status (S0S) is associate!
3it poorer a!2ust-ent to illness F+4G an! :inancial stressors are pre!icti.e o: later stress
:or sur.i.ors F2G. ?y analo6y/ 3o-en o: lo3er S0S/ an! tere:ore :e3er resources/ -ay
eDperience e.en -ore opelessness an! i6er le.els o: !epressi.e sy-pto-s tan our
sa-ple.
>e Jopelessness >eory ar6ues tat !isco.ery o: te etiolo6y o: te patientMs
opelessness is an i-portant ele-ent in pro.i!in6 treat-ent. ): :eelin6s o: opelessness
are a proDi-al/ su::icient cause o: !epression/ ten tose inter.entions alle.iatin6 an!%or
pre.entin6 :eelin6s o: opelessness soul! pre.ent or alle.iate !epressi.e sy-pto-s.
)nter.entions tat tar6et ope a.e been teste! 3itin a co6niti.e bea.ioral :ra-e3or4
an! :oun! to be e::ecti.e :or cancer patients F+&G. >e Jope )nter.ention Pro6ra- o:
Jert F++G 3as !esi6ne! to instill ope in in!i.i!uals 3it recurrence. >is is !one
trou6 establisin6 connecte!ness 3it oters/ i!enti:yin6 treats to ope/ encoura6in6
utiliIation o: social support an! co--unity resources/ re:lectin6 on te -eanin6 o: li:e/
an! nurturin6 internal resources suc as opti-is-. Suc an inter.ention -ay be
i-portant :or patients/ as tese !ata so3 tat opelessness be6ets te -aintenance o:
!epressi.e sy-pto-s. Certainly :or tose :acin6 cancer alone/ te bur!en is 6reat.
)n conclusion/ :eelin6s o: opelessness in recurrent cancer patients appear to be co--on
an! con:er ris4 :or !epressi.e sy-pto-s. >is is beyon! te ris4 :or !epression incurre!
:ro- pysical status/ 3ic can beco-e increasin6ly i-paire! in tis population. >e
scenario is 3orsene! :or tose :eelin6 opeless and 3itout an SH. Fro- a teoretical
perspecti.e/ te Jopelessness >eory o: *epression pro.i!es a :ra-e3or4 :or
un!erstan!in6 -oo! !isor!er peno-ena :or an un!erstu!ie! cancer 6roup. ,e 3ill
continue to :ollo3 tese patients an! test :urter te teoryMs rele.ance :or cancer patients
3it co-orbi! !epression.
8o to#
Ackno$ledg'ents
,e tan4 te participants in te Stress an! )--unity ?reast Cancer Pro2ect an! te
pro:essional an! researc sta::. >e researc support 3as pro.i!e! by 9-erican Cancer
Society (P?1'#9/ 1S=P?'03'24#'01'P?P)/ <on6aber6er Co-pany'9-erican Cancer
Society =rant :or ?reast Cancer 1esearc (P?1'#99)/ KS 9r-y (e!ical 1esearc
9c@uisition 9cti.ity =rants (*9(*1$'94'"'41+&/ *9(*1$'9+'1'+294/ *9(*1$'9$'
1'$0+2)/ Lational )nstitutes o: (ental Jealt (1 101 (J&14#$)/ te Lational Cancer
)nstitute (70& C909#133/ 101 C992$04)/ te =eneral Clinical 1esearc Center ((01'
110034)/ an! >e Hio State Kni.ersity Co-preensi.e Cancer Center (P30 C91+0&#).
8o to#
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Cancer. 19$$;(1#$49*$+(. CPubMeD
4$. Preacher @B. A primer on interaction eQects in multiple linear regression.
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Jurnal 9
Cancer. 9utor -anuscript; a.ailable in P(C 200+ *ece-ber 1&.
Publise! in :inal e!ite! :or- as:
Cancer. 200& *ece-ber 1&; 104(12): 2#$22##1.
!oi: 10.1002%cncr.21&32
P(C)*: P(C14&92#3
L)J(S)*: L)J(S#30&
Psychiatric Disorders and ental :ealth
(ervice >se in Patients $ith Advanced
"ancer
9 1eport :ro- te Copin6 3it Cancer Stu!y
Lina S. 7a!an'<ottic4/ (.*./ (.S.P.J./
1
<auren C. 8an!er3er4er/ P.*./
2/3
Susan *.
?loc4/ (.*./
2/4
?aoui Nan6/ (.S./
2/3
an! Jolly =. Pri6erson/ P.*.
2/3
9utor in:or-ation ; Copyri6t an! <icense in:or-ation ;
>e publiserUs :inal e!ite! .ersion o: tis article is a.ailable at Cancer
See oter articles in P(C tat cite te publise! article.
=o to:
Abstract
BA"#0!*>@D. Psycolo6ical -orbi!ity as been propose! as a source o: !istress in
cancer patients. >is stu!y ai-e! to: 1) !eter-ine te pre.alence o: !ia6nosable
psyciatric illnesses/ an! 2) !escribe te -ental ealt ser.ices recei.e! an! pre!ictors o:
ser.ice utiliIation in patients 3it a!.ance! cancer.
&T:*D(. >is 3as a cross'sectional/ -ulti'institutional stu!y o: 2&1 eli6ible patients
3it a!.ance! cancer. 0li6ibility inclu!e!: !istant -etastases/ pri-ary terapy :ailure/
nonpai! care6i.er/ a6e l20 years/ sta-ina :or te inter.ie3/ 0n6lis or Spanis'spea4in6/
an! a!e@uate co6niti.e ability. >raine! inter.ie3ers a!-inistere! te Structure! Clinical
)nter.ie3 :or te *ia6nostic Statistical (anual )8 (*S(')8) -o!ules :or (a2or
*epressi.e *isor!er/ =eneraliIe! 9nDiety *isor!er/ Panic *isor!er/ Post'>rau-atic
Stress *isor!er/ an! a !etaile! @uestionnaire re6ar!in6 -ental ealt ser.ice utiliIation.
!&(>/T(. H.erall/ 12E -et criteria :or a -a2or psyciatric con!ition an! 2#E a!
accesse! a -ental ealt inter.ention :or a psyciatric illness since te cancer !ia6nosis.
Se.enteen percent a! !iscussions 3it a -ental ealt pro:essional; 90E 3ere 3illin6 to
recei.e treat-ent :or e-otional proble-s. (ental ealt ser.ices 3ere not accesse! by
&&E o: patients 3it -a2or psyciatric !isor!ers. Cancer patients 3o a! !iscusse!
psycolo6ical concerns 3it -ental ealt sta:: (o!!s ratio FH1G V 19.2; 9&E con:i!ence
inter.al F9&E C)G/ #.90'41.&0) an! non'Jispanic 3ite patients (H1 V 2.$; 9&E C)/ 1.01'
$.43) 3ere -ore li4ely to recei.e -ental ealt ser.ices in a!2uste! analysis.
"*@"/>(I*@(. 9!.ance! cancer patients eDperience -a2or psyciatric !isor!ers at a
pre.alence si-ilar to te 6eneral population/ but a::ecte! in!i.i!uals a.e a lo3 rate o:
utiliIin6 -ental ealt ser.ices. Hncolo6y pro.i!ers can enance utiliIation o: -ental
ealt ser.ices/ an! potentially i-pro.e clinical outco-es/ by !iscussin6 -ental ealt
concerns 3it teir patients.
#ey$ords% cancer/ psyciatric -orbi!ity/ !epression/ pre.alence/ co--unication/
-ental ealt ser.ices/ palliati.e care
H.er &00/000 in!i.i!uals in te K.S. !ie :ro- cancer eac year.
1
1elie: o: su::erin6/
3ile an essential co-ponent o: cancer care trou6out all pases o: te !isease
tra2ectory/ acie.es central i-portance as te patient approaces te en! o: li:e. )n
a!!ition to pysical su::erin6/ psyciatric syn!ro-es are increasin6ly reco6niIe! as
-a2or co-ponents o: !istress at te en! o: li:e. Se.eral :actors contribute to
psycolo6ical !istress in tis population/
2
inclu!in6 te 6rie: about current an!
anticipate! losses/ :ear o: !eat/ concerns about lo.e! ones/ te e::ect o: certain
ce-oterapeutic !ru6s on -oo!/
3'+
an! te biolo6y o: te -ali6nancy.
$
Kntreate!
psycolo6ical !istress in ter-inal cancer patients is associate! 3it a-pli:ie! pain/
#

increase! !esire :or astene! !eat/
9
increase! !isability/
10
i-paire! ability to participate
in en!'o:'li:e plannin6/
2
an! !i-inise! psycosocial :unctionin6 o: care6i.ers.
11
>e pre.alence o: sin6le or -ultiple psyciatric !isor!ers in a!.ance! cancer patients is
still poorly un!erstoo!. 0sti-ates :or !epression ran6e :ro- 3'3#E.
9/12'1#
0arly stu!ies
usin6 ri6orous -eto!s reporte! lo3er rates o: psyciatric !isor!ers in early'sta6e cancer
co-pare! to subse@uent stu!ies tat 3ere con!ucte! usin6 less sopisticate! -eto!s or
s-aller sa-ple siIes.
19/20
>e present stu!y sou6t to use state'o:'te'art inter.ie3
-eto!olo6y to assess pre.alence rates in patients 3it a!.ance! cancer. =eneraliIe!
anDiety !isor!er (=9*) as only been eDa-ine! pre.iously :ro- sy-pto- scales/
9/21
not
usin6 a stan!ar!iIe! !ia6nostic inter.ie3 applyin6 *S(')8 criteria. >e true pre.alence
o: =9* an! its co'occur'rence 3it -a2or !epressi.e !isor!er ((**) an! oter
psyciatric !isor!ers is not currently 4no3n. )n or!er to @uanti:y an! co-pare te rates o:
psyciatric !isturbance in te a!.ance! cancer population/ te pre.alence o: tese an!
oter -a2or psyciatric !isor!ers/ inclu!in6 posttrau-atic stress !isor!er an! panic
!isor!er/ -ust be !eter-ine! usin6 ri6orous !ia6nostic -eto!olo6y.
9ltou6 psyciatric !isor!ers in ter-inal cancer patients are i6ly treatable/
22
te
a.ailable stu!ies su66est tat ealtcare pro.i!ers !o not a!e@uately a!!ress -ental
illness in tis population.
23
For! et al.
24
au!iotape! patientS!octor outpatient clinic
encounters :or 11$ patients 3o recei.e! Aba! ne3sC about a cancer !ia6nosis at a
tertiary care center. 9ltou6 patients spent 14E o: teir total utterances 6i.in6
in:or-ation about teir psycosocial concerns/ clinicians only !e.ote! 3E o: teir
.erbaliIations to a!!ressin6 te-. )n a lar6e stu!y o: 1109 cancer patients/ oncolo6ists
3ere concor!ant 3it patient'co-plete! scales o: !epression in only 13E o: patients
reportin6 te se.ere ran6e o: sy-pto-s.
#
)n te sa-e stu!y sa-ple/ nurses ten!e! to
un!erreco6niIe se.ere !epressi.e sy-pto-s at si-ilar rates.
2&
1esearc as not yet
eDa-ine! te eDtent to 3ic cancer patients -eetin6 !ia6nostic criteria :or a -a2or
psyciatric !isor!er !iscuss an!%or recei.e elp :or teir -ental ealt issues.
Furter researc is nee!e! be:ore inter.ention strate6ies can be !esi6ne! to i-pro.e
reco6nition an! treat-ent o: psyciatric illnesses in patients 3it a!.ance! cancer. )n te
current stu!y/ a baseline inter.ie3 3as a!-inistere! to patients 3it a!.ance! cancer to
!eter-ine 1) te pre.alence o: -a2or psyciatric !isor!ers -eetin6 *S(')8 criteria; 2)
te :re@uency o: co--unication o: -ental ealt issues 3it oncolo6y clinic sta::/
re:errals :or -ental ealt care/ an! receipt o: -ental ealt inter.entions; an! 3) te
:actors tat pre!ict receipt o: -ental ealt ser.ices.
=o to:
AT&!IA/( A@D &T:*D(
Patients
Patients 3ere recruite! :ro- 9u6ust 1/ 2002 to 9u6ust 1/ 2004 as part o: an on6oin6
-ulti'institutional lon6itu!inal e.aluation (Lational )nstitutes o: Jealt FL)JG 6rants
(J+3#92/ C910+3$0) o: te pre.alence o: -ental illness an! patterns o: -ental ealt
ser.ice utiliIation in a!.ance! cancer patients an! teir pri-ary in:or-al (nonpai!)
care6i.ers in te Copin6 3it Cancer Stu!y. >is report :ocuses on te -ental ealt o:
te patients :ro- te baseline e.aluation; te care6i.er eDperience is reporte!
else3ere.
2+
)nclusion criteria :or te stu!y 3ere: 1) !ia6nosis o: a!.ance! cancer
(presence o: !istant -etastasis an! :ailure o: :irst'line ce-oterapy); 2) !ia6nosis at a
participatin6 site; 3) a6e l 20 years; 4) i!enti:ie! unpai!/ in:or-al care6i.er; an! &)
a!e@uate sta-ina to co-plete te inter.ie3. 0Dclu!e! 3ere patientScare6i.er !ya!s in
3ic eiter te patient or te care6i.er -et criteria :or !e-entia or !eliriu- (by neuro'
bea.ioral co6niti.e status eDa-ination
2$
) or coul! not spea4 0n6lis or Spanis. >e
participatin6 centers 3ere te 5ale Cancer Center (C>)/ te 8eterans 9::airs Connecticut
Jealtcare Syste- Co-preensi.e Cancer Clinics (C>)/ (e-orial Sloan'7etterin6
Cancer Center (L5)/ an! te Par4lan! Jospital Palliati.e Care Ser.ice (>O).
(e-bers o: te oncolo6y clinic sta:: at participatin6 centers i!enti:ie! potentially eli6ible
patients base! on te criteria !escribe! abo.e. 9ll potentially eli6ible patients 3ere ten
approace! by traine! researc sta:: an! o::ere! participation in te stu!y. )ntereste!
patients an! care6i.ers 3ere contacte! by telepone or a ospital roo- .isit 3itin te
3ee4 to obtain in:or-e! consent. 9:ter receipt o: te patientsU in:or-e! consent/
eli6ibility 3as con:ir-e! trou6 re.ie3 o: -e!ical recor!s an! consultation 3it clinic
sta::.
Separate patient an! care6i.er inter.ie3s 3ere ten sce!ule! to occur in te ospital
roo-/ clinic/ or o-e. Patients an! care6i.ers eac recei.e! k2& :or co-pletin6 te
inter.ie3. )nter.ie3ers :ro- eac site 3ere traine! by researc sta:: at 5ale Kni.ersity/
3ere tey 3ere re@uire! to acie.e a i6 stan!ar! o: accuracy an! reliability base! on
concor!ance 3it te 5ale Pro2ect *irectorUs ratin6 o: te Structure! Clinical )nter.ie3
:or te *S(')8 (SC)*) !ia6noses (tar6et 4appa Q 0.#&). )nter.ie3ers at eac site 3ere
re@uire! to participate in an initial 2'!ay trainin6 session :ollo3e! by annual re.ie3
trainin6 sessions. >e inter.ie3 !uration 3as an a.era6e o: 4& -inutes :or patients.
Patients 3o !ecline! participation 3ere as4e! to co-plete a brie: @uestionnaire
re6ar!in6 teir reasons :or re:usal/ a-ount o: e-otional an! pysical !istress/ an!
!e-o6rapics.
H: te 39$ patients 3o 3ere approace! :or participation an! con:ir-e! to be eli6ible/
14+ (3$E) !ecline! participation. >e -ost co--on reasons :or nonparticipation
inclu!e! Anot intereste!C (n V ++)/ Acare6i.er re:usesC (n V 22)/ an! Atoo upsetC (n V 19).
Co-pare! 3it participants/ nonparticipants 3ere -ore li4ely to be 3ite (ci's@uare V
4.0; # V 0.0&)/ youn6er (-ean a6e o: &#.2 yrs .s. +1.+ yrs/ # V 0.03)/ an! report -ore
!istress on a &'point <i4ert scale 3ose eDtre-es ran6e! :ro- 1 (A-ini-al%noneDistentC)
to & (A!istrau6tC) (-ean score o: 3.0 .s. 2.2; # P 0.0001). >ey !i! not !i::er
si6ni:icantly :ro- participants by 6en!er or e!ucation.
9ll stu!y protocol an! contact !ocu-ents 3ere re.ie3e! an! appro.e! by te u-an
sub2ects co--ittee at 5ale Kni.ersity an! at eac o: te participatin6 institutions.
&valuation
ental health
>e SC)* 9Dis ) (o!ules
2#
3ere use! to ascertain (a2or *epressi.e *isor!er ((**)/
=eneraliIe! 9nDiety *isor!er (=9*)/ Post'>rau-atic Stress *isor!er (P>S*)/ an! Panic
*isor!er (P*). 1eliability an! .ali!ity as been establise! :or tis instru-ent
29
(4appa V
0.92 :or =9* an! 0.&# :or P*). Patients only co-plete! te :ull SC)* -o!ules :or
!isor!ers :or 3ic tey screene! positi.e (i.e./ only tose 3o en!orse! one o: te t3o
!epression screenin6 ite-s o: sa!ness :or -ost o: te !ay/ nearly e.ery !ay/ :or at least 2
3ee4s/ or :eelin6 a lot less intereste! in tin6s or unable to en2oy te tin6s tey use! to
en2oy/ 3ent on to co-plete te :ull -o!ule :or (**; tose 3o !i! not screen positi.e
to eiter o: tese ite-s procee!e! to te neDt set o: @uestions). (ental ealt outco-es
3ere analyIe! as !icoto-ous outco-es (i.e./ -et criteria .ersus !i! not -eet criteria :or
a !ia6nosis). ?ecause tere as been !ebate re6ar!in6 te -ost .ali! -eto! to !ia6nose
(** in a!.ance! cancer patients 3ose co-plaints -ay be !i::icult to interpret/
30/31
te
!ia6nosis o: (** 3as also !eter-ine! by te 0n!icott sy-pto- substitution -eto! :or
co-parison. 0n!icott as reco--en!e! tat *S( criteria be -o!i:ie! suc tat 3ei6t
loss be substitute! 3it !epresse! appearance/ inso-nia 3it social 3it!ra3al or
!ecrease! tal4ati.eness/ loss o: ener6y 3it broo!in6/ sel:'pity/ or pessi-is-/ poor
concentration 3it lac4 o: reacti.ity%cannot be ceere! up.
30
(inor !epression/ 3ic is
!escribe! a-on6 *S(')8 ACriteria an! 9Des Pro.i!e! :or Furter Stu!y/C 3as !e:ine!
as -eetin6 t3o to :our i-pair-ent criteria (rater tan te :i.e or -ore :or (**)/ one o:
3ic 3as !epresse! -oo! or lac4 o: interest%pleasure in acti.ities. )n calculatin6 te
pre.alence o: -inor !epression/ 3e eDclu!e! all cases in 3ic te sub2ect en!orse!
prior istory o: (** to be consistent 3it *S(')8 (inor *epression eDclusion rules.
ental health service utili2ation
Patients un!er3ent a structure! inter.ie3 tat as4e! about co--unication about -ental
ealt concerns an! -ental ealt care utiliIation. Patients 3ere !irectly as4e! i: tey
!iscusse! teir -ental ealt 3it a A-ental ealt pro:essionalC be:ore an! a:ter te
cancer !ia6nosis. >ey 3ere also as4e! 3eter re:errals :or -ental ealt ser.ices 3ere
-a!e/ 3eter re:erre! -ental ealt ser.ices 3ere recei.e!/ source o: -ental ealt
ser.ices/ an! types o: terapies recei.e! (i.e./ psycoterapy/ anDiolytics/ or
anti!epressants) a:ter te cancer !ia6nosis.
*ther 'easures
>e Nubro! Per:or-ance Scale 3as co-plete!
32
as a su--ary -easure o: current ealt
status base! on :our cate6ories: acti.ity/ pain/ :oo! inta4e/ an! nausea. Nubro! scores l2
are consi!ere! poor per:or-ance.
33
1ace%etnicity 3as analyIe! as a potential
!eter-inant o: -ental ealt utiliIation because seriously ill cancer patients o: !i::erent
race%etnic 6roups a.e been :oun! to .ary in o.erall ealtcare utiliIation.
34/3&

1ace%etnicity 3as !eter-ine! by patient sel:'report in response to te open'en!e!
@uestion: A,at race or etnicity !o you consi!er yoursel: to beBC Patients 3o
i!enti:ie! te-sel.es as Jispanic 3ere analyIe! as suc/ re6ar!less o: 3eter tey
reporte! 3ite or blac4 status. Jispanic patients 3ere classi:ie! as 3ite i: tey en!orse!
tis as teir racial%etnic 6roup; Jispanic patients not in!icatin6 tey 3ere 3ite 3ere
classi:ie! as Xnon3ite.M
Data analysis
*escripti.e statistics 3ere use! to caracteriIe te !e-o6rapics o: te stu!y sa-ple.
>e pre.alence o: te -a2or psyciatric !isor!ers 3as calculate!. Fre@uencies o:
responses to te -ental ealt care utiliIation inter.ie3 3ere calculate!/ o.erall an!
strati:ie! by te presence o: a -a2or psyciatric !isor!er. Ci's@uare or Fiser eDact test
statistics 3ere use! to !eter-ine i: responses to te -ental ealt care utiliIation
inter.ie3 .arie! by te presence o: a -a2or psyciatric !isor!er. >e association bet3een
patient attributes an! receipt o: -ental ealt care ser.ices 3as !eter-ine! usin6
bi.ariate lo6istic re6ression analyses. 9 -ultiple lo6istic re6ression -o!el 3as
constructe! to inclu!e all te co.ariates tat 3ere si6ni:icantly associate! 3it receipt o:
-ental ealt care in una!2uste! analysis. Colinearity 3as assesse! by cross'tabulations
an! plots o: te analyIe! co.ariates be:ore procee!in6 to -ultiple lo6istic re6ression; no
appreciable colinearity 3as !etecte!. *ata 3ere analyIe! 3it te S9S Syste- :or
,in!o3s .. #.2 (S9S )nstitute/ )nc./ Cary/ LC) 3it 2'taile! statistical tests.
=o to:
!&(>/T(
Patient "haracteristics
>e caracteristics o: te 2&1 patients 3o enrolle! an! co-plete! te e.aluation are
!isplaye! in >able 1. )n 6eneral/ te sa-ple ten!e! to be 3ite ($1E)/ el!erly (-e!ian
a6e/ +0 yrs)/ at least i6 scool'e!ucate!/ o: relati.ely 6oo! ealt status ($0E 3it
Nubro! Score P2)/ an! insure! (#0E).
>9?<0 1
Caracteristics o: te Stu!y Population o: 9!.ance! Patients 3it Cancer
Prevalence of Psychiatric "onditions
H.erall/ 11.+E (n V 29; 9&E con:i!ence inter.al F9&E C)G/ $.9 '1+.1E) o: te 2&1
participants -et *S(')8 criteria :or at least one o: te -a2or psyciatric con!itions o:
(**/ =9*/ P*/ an! P>S*/ as !isplaye! in >able 2. >e -ost :re@uently i!enti:ie!
con!ition 3as (** (+.#E; 9&E C)/ 3.#'10.2E). >e pre.alence o: -a2or !epression by
te 0n!icott substitution -eto! 3as +.0E/ si-ilar to tat by *S(')8 criteria. 9n
a!!itional $.2E (n V 1#; 9&E C)/ 4'10.4E) o: patients -et criteria :or -inor !epression/
totalin6 14E o: te sa-ple 3it -inor or -a2or !epression. >e pre.alence o: -a2or
psyciatric !isor!ers 3as not i6er in patients enrolle! :ro- te Par4lan! Jospital
Palliati.e Care Ser.ice/ a-on6 tose 3it a Nubro! score o: 2/ or 3itin any
race%etnicity 6roups (!ata not so3n).
>9?<0 2
Pre.alence o: Psyciatric Con!itions (eetin6 *ia6nostic an! Statistical (anual o:
(ental *isor!ers (*S(')8) Criteria
>irty':i.e percent (n V 10) o: te 29 patients 3it a psyciatric !ia6nosis a! t3o or
-ore psyciatric !ia6noses. 9-on6 te 1$ patients 3o -et !ia6nostic criteria :or (**/
23.&E (n V 4) also a! =9*/ 1$.+E (n V 3) a! P*/ an! 29.4E (n V &) a! P>S*.
9 subanalysis strati:ie! patients accor!in6 to 3eter tey a! a istory o: li:eti-e (**
:ro- te SC)* (!ata not !isplaye!). ,e :oun! tat a-on6 te 29 patients 3it a current
psyciatric !isor!er/ 12 (41E) a! a istory o: (** by te li:eti-e SC)* an! 1$ (&9E)
a! no istory o: (**. >ese results in!icate tat a i6er percenta6e o: cases o: (**
a:ter te patientUs cancer !ia6nosis 3ere ne3 onset cases tan a perpetuation or
recurrence o: a preeDistin6 con!ition. Patients 3it a positi.e istory o: li:eti-e (**
a! a 29.3E (12 o: 41 patients) pre.alence o: a current -a2or psyciatric !isor!er .ersus
#.4E (1$ o: 202 patients) in patients 3itout li:eti-e (** (# V 0.001). >us/
preeDistin6 psycopatolo6y ei6tene! ris4 :or postcancer !ia6nosis psyciatric illness.
ental :ealth (ervice >tili2ation
Discussion $ith healthcare tea'
>3enty':our percent (+0 o: 2&1 patients) o: te sa-ple reporte! retrospecti.ely tat/ prior
to te cancer !ia6nosis/ tey a! !iscusse! -ental ealt concerns 3it a -ental ealt
pro:essional (>able 3).
>9?<0 3
(ental Jealt Ser.ice KtiliIation a-on6 Stu!y Sa-ple/ Strati:ie! by te Presence o:
(a2or Psyciatric Con!ition
a
Se.enteen percent o: patients (n V 43) reporte! a.in6 a! !iscussions about -ental
ealt since teir cancer !ia6nosis; 24E o: tose 3it a current -a2or psyciatric
!isor!er an! 1+E o: tose 3itout a current psyciatric !isor!er reporte! suc a
!iscussion. *iscussin6 -ental ealt concerns be:ore te cancer !ia6nosis 3as
si6ni:icantly associate! 3it !iscussin6 -ental ealt issues a:ter !ia6nosis (ci's@uare
1$.$; # P 0.0001)/ as so3n in >able 4. Le.erteless/ a-on6 te +0 cases 3o a!
!iscussions 3it a -ental ealt pro:essional be:ore te patientsU cancer !ia6nosis/ only
3&E (n V 21) a! suc !iscussions a:ter te !ia6nosis.
>9?<0 4
*iscussion 3it (ental Jealt Pro:essional be:ore an! a:ter Cancer *ia6nosis
9-on6 patients 3it a positi.e istory o: li:eti-e (** by te SC)*/ 44E (13 o: 41
patients) a! !iscusse! -ental ealt issues 3it a -ental ealt pro:essional be:ore te
cancer !ia6nosis co-pare! 3it 24E (10 o: 41 patients) a:ter te !ia6nosis. )n contrast/
19E o: patients (39 o: 202 patients) 3it no istory o: li:eti-e (** a! -ental ealt
!iscussions be:ore teir cancer !ia6nosis an! 14E (31 o: 202 patients) a! suc
!iscussions a:ter !ia6nosis.
!eferral and receipt of 'ental health services
)n te entire sa-ple/ 90E o: participants state! tat tey 3oul! see4 elp i: tey 3ere
a3are tat tey a! an Ae-otional proble-.C H: te #+ patients 3o !iscusse! -ental
ealt issues 3it a ealt pro:essional a:ter te cancer !ia6nosis/ &4 (+2.#E) 3ere
o::ere! treat-ent or 6i.en a re:erral :or -ental ealt ser.ices; o: tose &4 in!i.i!uals/
4# (##.9E) recei.e! te treat-ent o::ere! (!ata not so3n).
H.erall/ trou6 re:erral an! nonre:erral -ecanis-s/ -ental ealt ser.ices 3ere
accesse! by 2#E (n V $0) o: patients since te !ia6nosis o: cancer (>able 4). >is
proportion 3as 4&E in patients 3o -et criteria :or a psyciatric !isor!er/ in!icatin6 tat
-ore tan al: o: tose 3o -et criteria :or psyciatric illness !i! not access -ental
ealt ser.ices. 9-on6 te $0 in!i.i!uals 3o a! accesse! -ental ealt ser.ices/ only
1#.+E (n V 13) -et criteria :or one o: te psyciatric !isor!ers e.aluate!. >e :ollo3in6
are te proportions o: in!i.i!uals in te entire sa-ple recei.in6 -ental ealt ser.ices:
anti!epressants (22E)/ psycoterapy (13E)/ an! anDiolytics (#E).
Predictors of receipt of 'ental health services
>able & !isplays :actors analyIe! as potential !eter-inants o: receipt o: -ental ealt
inter.entions. )n una!2uste! analysis/ te :ollo3in6 :actors 3ere eac associate! 3it
recei.in6 -ental ealt treat-ent a:ter te !ia6nosis o: a!.ance! cancer: 1) !iscussion o:
-ental ealt concerns be:ore te cancer !ia6nosis (o!! ratio FH1G V +.$1; 9&E C)/ 3.+3'
12.41); 2) !iscussion o: -ental ealt concerns a:ter te cancer !ia6nosis (H1 V 22.9#;
9&E C)/ 11.1$'4$.29); 3) currently -eetin6 criteria :or a -a2or psyciatric illness (H1 V
2.3&; 9&E C)/ 1.0$'&.19); an! 4) 3ite race%etnicity (H1 V 3.$1; 9&E C)/ 1.$3'$.9&).
9lso eDa-ine!/ but not :oun! to be si6ni:icant/ 3ere insurance status/ 6en!er/ a6e/
e!ucation/ an! Nubro! score. )n a!2uste! analysis/ !iscussion o: -ental ealt concerns
3it a ealtcare pro:essional a:ter te cancer !ia6nosis 3as te stron6est pre!ictor o:
recei.in6 -ental ealt ser.ices (H1 V 19.21; 9&E C)/ #.90'41.&0). ,ite patients
re-aine! si6ni:icantly -ore li4ely tan non3ite patients to recei.e ser.ices (H1 V 2.$4;
9&E C)/ 1.01'$.43). Currently -eetin6 criteria :or a -a2or psyciatric !isor!er !i! not
si6ni:icantly pre!ict use o: ser.ices in a!2uste! analysis.
>9?<0 &
*eter-inants o: 1eceipt o: (ental Jealt >reat-ent a-on6 9!.ance! Cancer Patients
a
=o to:
DI(">((I*@
>is stu!y pro.i!es a co-preensi.e application o: *S(')8 criteria to te !eter-ination
o: te pre.alence o: psyciatric !isor!ers in a!.ance! cancer patients. )t is also a-on6
te :irst to eDa-ine an! relate tese !ia6noses to te utiliIation o: -ental ealt ser.ices
at te en!'o:'li:e. Knli4e prior stu!ies tat a.e use! sy-pto- cec4lists tat :ocus
pri-arily on sy-pto-s o: 6eneraliIe! !istress or !epression/
3+'39
traine! inter.ie3ers
use! current *S( )8 psyciatric !ia6nostic criteria to !eter-ine te pre.alence o: te
:ull ran6e o: -ental !isor!ers in a relati.ely lar6e/ etnically an! 6eo6rapically !i.erse
sa-ple o: en!'sta6e cancer patients. >e results in!icate! tat 12E o: a!.ance! cancer
patients -et establise! criteria :or at least one -a2or psyciatric !isor!er/ 3ic is a rate
tat is co-parable to tat o: te 6eneral population/
40
an! consistent 3it ol!er stu!ies in
cancer patients tat relie! on ri6orous inter.ie3 criteria.
9/12/1&/41
Jo3e.er/ our stu!y
i!enti:ie! te un!er'utiliIation o: -ental ealt ser.ices a-on6 a!.ance! cancer patients.
Fi:ty':i.e percent o: patients 3o a! a -a2or psyciatric !isor!er a! not recei.e!
-ental ealt ser.ices.
Hur results in!icate! tat -e-bers o: te oncolo6y tea- :re@uently :aile! to a!!ress
-ental ealt concerns o: patients 3it a!.ance! cancer. Hnly 1$E o: our sa-ple o:
a!.ance! cancer patients a! !iscussions o: -ental ealt issues 3it a -ental ealt
care pro:essional a:ter te cancer !ia6nosis. >is proportion is essentially te sa-e as te
rate reporte! prior to te cancer !ia6nosis o.erall; te proportion is !ecrease! by al:
(:ro- 44E to 24E) in patients 3it a positi.e istory o: li:eti-e (** by te SC)*. >is
su66ests tat -any o: te patients -ost .ulnerable to psyciatric illness (i.e./ tose 3o
a! !iscusse! -ental ealt concerns 3it a clinician prior to teir cancer !ia6nosis an!
tose 3it a positi.e istory o: li:eti-e (**) !o not !iscuss tese concerns a:ter tey
learn tat tey a.e cancer. >is also su66ests tat te po3er:ul e::ect o: postcancer
!ia6nosis -ental ealt !iscussions on accessin6 -ental ealt ser.ices is not a :unction
o: tappin6 into a preeDistin6 pattern o: elp'see4in6 bea.ior.
)n ter-s o: inter.ention/ only al: te in!i.i!uals 3o -et te criteria :or a -a2or
psyciatric !isor!er a! accesse! -ental ealt ser.ices. >e -ost robust pre!ictors o:
receipt o: -ental ealt ser.ices by a!.ance! cancer patients 3ere 1) !iscussin6 -ental
ealt issues 3it a ealtcare pro:essional/ an! 2) 3ite race%etnicity; not 3eter one
currently -eets criteria :or a psyciatric !ia6nosis. >ese results i6li6t te critical role
o: ealtcare pro.i!ers/ especially oncolo6ists 3o !irect o.erall care/ in assessin6 te
-ental ealt o: teir patients 3it li:e'treatenin6 cancer.
>e Lational )nstitutes o: Jealt State'o:'te Science Con:erence State-ent re6ar!in6
sy-pto- -ana6e-ent in cancer obser.e! tat tere is consi!erable etero6eneity in
publise! pre.alence rates o: !epression in tis population because o: Alac4 o: uni:or-ity
in -easure-ent an! -eto!olo6y.C
42
Hur esti-ates o: te (** pre.alence rates (+.#E)
usin6 *S(')8 criteria is co-parable to te point pre.alence o: !epression in ealty
3o-en (4.&'9.3E) an! -en (2.3'3.2E)/ su66estin6 tat tere is no eDcess !epression
associate! 3it a!.ance! cancer.
3
Contrary to te pre.ailin6 opinion/ our results are
si-ilar to reports 3ic relie! on strin6ent inter.ie3'base! !ia6nostic criteria :ro-
pre.ious .ersions o: te *S(.
43
*ero6atis et al.
12
conclu!e! tat &E o: 21& cancer
patients a! (** base! on *S('))) stan!ar!s. 9 2004 stu!y by 94eci et al.
1&
assesse!
129 patients 3it unresectable nons-all cell lun6 carcino-a 3it *S(')))1 criteria an!
also :oun! a &E pre.alence o: (**.
Hur stu!y i6li6ts te co-orbi!ity o: oter -a2or psyciatric con!itions in te
a!.ance! cancer population/ 3ic as been pre.iously i!enti:ie! in stu!ies o: te
6eneral cancer population.
43/44
>e pre.alence o: =9* an! P* in te cancer population
to6eter represent a bur!en tat is si-ilar to (**. )n our sa-ple/ a-on6 in!i.i!uals
3it (**/ 24E concurrently -et criteria :or =9*/ 1#E concurrently -et criteria :or
P*/ an! 30E also concurrently -eet criteria :or P>S*. >ese results are particularly
stri4in6 because 6reater !isability/ -ore se.ere sy-pto-s/ an! 6reater re:ractoriness to
terapy a.e been obser.e! in in!i.i!uals 3it -ultiple psyciatric con!itions/ co-pare!
to tose 3it a sin6le !isor!er.
3/4&
>ere is reason to belie.e tat our reporte! rates o: psyciatric !isor!ers -ay be a lo3
esti-ate o: te true pre.alence o: clinically si6ni:icant psyciatric !istress. Hur
co-parison o: participants an! nonparticipants in!icates tat 3e encountere! te typical
!i::iculty in recruitin6 te -ost !istresse! patients. 9noter potential eDplanation :or te
lo3 rates o: psyciatric !isor!ers is tat only patients 3o screene! positi.e ten
co-plete! te :ull SC)* -o!ule :or tat particular !isor!er an! peraps te screenin6
@uestions in te SC)* 3ere not su::iciently sensiti.e :or tis population. Hne :in!in6
su66esti.e o: tis is tat te traine! psyciatric inter.ie3ers i!enti:ie! 10 patients 3o
:aile! to -eet *S(')8 criteria :or current (** as clinically !epresse! base! on teir
personal i-pressions (rate! in!epen!ently :ro- te SC)*). )n a!!ition/ te poor
correspon!ence bet3een -eetin6 criteria :or psyciatric !isor!ers an! -ental ealt
ser.ice use (e.6./ -eetin6 criteria :or a psyciatric !isor!er !i! not pre!ict use o: -ental
ealt ser.ices/ -any persons 3it a psyciatric !isor!er !i! not access -ental ealt
ser.ices an! .ice .ersa) su66ests tat treat-ent e::ecti.ely re!uce! psyciatric -orbi!ity
an!%or potential proble-s relate! to !ia6nostic accuracy in te i!enti:ication o: -ental
illness in a!.ance! cancer patients. >is :in!in6 also raises te @uestion o: 3eter
patients -ay elect to utiliIe -ental ealt ser.ices :or !istress tat !oes not constitute a
psyciatric !isor!er (e.6./ :ear about te :uture/ anDiety about !eat/ concerns about
:a-ily -e-bers). Hur -easure-ent instru-ents are to our 4no3le!6e te best currently
a.ailable/ but -ay not be sensiti.e enou6 to te o.erlap o: pysical an! psycolo6ical
!istress tat are co--only seen a-on6 cancer patients. Hur :in!in6s i6li6t te nee!
to un!erstan! better te potential !e:iciencies in !ia6nostic precision in te i!enti:ication
o: psyciatric !isor!ers a-on6 a!.ance! sta6e cancer patients/ as 3ell as 3at
psycolo6ical issues :or 3ic patients belie.e tey nee! elp in te conteDt o: a!.ance!
cancer.
>o our 4no3le!6e/ :e3er tan al: o: te in!i.i!uals -eetin6 strin6ent criteria :or a
-a2or psyciatric con!ition a! been o::ere! a -ental ealt inter.ention. 9ll cancer
patients !eser.e opti-al terapy :or psyciatric !isor!ers/ particularly to enance @uality
o: li:e at te en! o: li:e. Pre.ious stu!ies su66est tat patients 3it breast cancer an! lun6
cancer 3o eDperience -ore !epression -ay a.e 3orse sur.i.al outco-es.
4+/4$

>erapeutic stu!ies in cancer patients a.e !e-onstrate! tat tis population is
responsi.e to bot psycotropic -e!ications an! psycoterapy.
42
Par-acoterapy as
been ter-e! te X-ainstayU o: !epression treat-ent in a!.ance! cancer patients an! is
3ell establise!.
4#/49
1an!o-iIe! controlle! trials o: anti!epressants 3ic 3ere o:
a!e@uate !ose an! !uration so3 bene:it in as -any as +&'$0E o: patients.
49/&0
Pirl
&1

su--ariIe! te results o: tree publise! -eta'analyses !esi6ne! to !eter-ine te
e::icacy o: publise! psycosocial inter.entions o: !epression in cancer patients. Je
conclu!e! tat psycoterapy inter.entions result in -o!erate i-pro.e-ent in sy-pto-s
in te .ast -a2ority o: stu!ies. )n a!!ition to eDperiencin6 i-pro.e! @uality o: li:e/
cancer patients 3o recei.e a!e@uate treat-ent o: teir -ental ealt are -ore co-pliant
3it ce-oterapy.
&2
Lu-erous barriers to treatin6 psycosocial !istress in a!.ance! cancer patients a.e
been !escribe!. >e 9-erican Colle6e o: PysiciansS9-erican Society o: )nternal
(e!icine Consensus Panel reco6niIe! tat Apatients an! clinicians :re@uently belie.e tat
psycolo6ical !istress is a nor-al :eature o: te !yin6 process.C
2
>e Lational )nstitutes
o: Jealt (L)J) State'o:'te'Science Panel i6li6te! te inability o: oncolo6y
pro.i!ers to reco6niIe !epression as bein6 a Aparticularly i-portantC i-pe!i-ent.
42
>e
panel also speculates tat patients -ay consi!er psyciatric !ia6noses an!%or -ental
ealt ser.ice use to be sti6-atiIin6. Hur stu!y :in!in6s con:ir- tat oncolo6y
ealtcare pro.i!ers !o not a!e@uately priori'tiIe -ental ealt issues/ 6i.en te lo3
proportion o: patients 3o !iscusse! psycosocial issues 3it oncolo6y clinicians as 3ell
as te i6 proportion o: patients 3it !ia6nose! psyciatric illness 3o !i! not access
-ental ealt ser.ices (4#E). Jo3e.er/ 93E o: te a!.ance! cancer patients 3o -et
criteria :or a psyciatric !isor!er state! tat tey 3oul! pursue -ental ealt ser.ices i:
tey 3ere a3are tat tey a! an e-otional proble-/ an! #9E o: tose re:erre! actually
3ent/ su66estin6 tat current coorts o: patients appear to be recepti.e to treat-ent :or
-ental ealt proble-s.
9noter i-portant barrier to receipt o: -ental ealt ser.ices i!enti:ie! by our stu!y/
pre.iously unreporte! in cancer patients/ is race%etnicity. =i.en tat no si6ni:icant
racial%etnic !i::erences in te pre.alence o: psyciatric !isor!ers e-er6e!/ !i::erent
-ental ealt nee!s cannot account :or racial%etnic !i::erences in -ental ealt ser.ice
use. 9s note! earlier/ nonparticipants 3ere -ore li4ely to be !istresse! an! o: 3ite
race%etnicity tan participants. Jo3e.er/ :urter analyses 3ere per:or-e! an! tere is
no si6ni:icant association note! bet3een race%etnicity an! !istress le.el a-on6
participants/ nonparticipants/ or te entire eli6ible sa-ple. Past stu!ies eiter !i! not
report race or consiste! o: sa-ples o: -ore tan #&E 3ite patients.
&2
Hur results :oun!
3ite patients to be al-ost tree ti-es -ore li4ely to recei.e a psyciatric inter.ention
tan non3ites/ a:ter a!2ustin6 :or oter :actors. 9ltou6 te eDplanation :or tis
!iscrepancy by race%etnicity is not clear/ tere is reason to belie.e tat access to -ental
ealt care (race%etnicity 3as closely associate! 3it insurance status)/ cultural attitu!es
about see4in6 assistance :or -ental ealt proble-s/ an! in6raine! belie:s about te nee!
to stru66le 3en con:ronte! 3it a!.ersity -ay be operatin6.
&3
)n a!!ition/ clinicians
-ay be less li4ely to eDplore tese issues 3it non'3ite patients/ or to attribute !istress
to oter psycosocial circu-stances (e.6./ po.erty) tan to psyciatric !isor!er. Hn6oin6
stu!ies are bein6 con!ucte! by our researc 6roup to eDplore te associations bet3een
racial%etnic status/ acculturation/ an! te 3illin6ness to see4 -ental ealt ser.ices (L)J
6rant C910+3$0). Suc stu!ies 3ill in:or- oter inter.ention strate6ies to -eet -ental
ealt nee!s o: non3ite cancer patients.
>ere are li-itations to te current stu!y. =i.en te +3E participation rates/ tere is te
potential :or selection bias. )n!i.i!uals 3o reporte! -ore !istress 3ere less li4ely to
participate. >ere:ore/ as !iscusse! -ore eDtensi.ely earlier/ te pre.alence rates reporte!
erein are li4ely an un!eresti-ate o: te bur!en o: psyciatric proble-s in tis
population. 9noter li-itation is tat 3e !i! not ascertain 3eter -ental ealt ser.ices
3ere accesse! be:ore te cancer !ia6nosis/ a :actor tat -ay be associate! 3it
postcancer use o: ser.ices.
9s cancer treat-ent beco-es -ore scienti:ically sopisticate!/ te :ocus is increasin6ly
on te treat-ents an! less on te patient. ): @uality o: li:e is an i-portant 6oal o:
treat-ent/ psycolo6ical sy-pto-s soul! be reco6niIe! as sources o: su::erin6 tat can
be as !ebilitatin6 as pysical co-plaints. *iscussion o: -ental ealt issues 3it a
ealtcare pro.i!er allo3s !istress to be !etecte!/ an! is te -ost i-portant pre!ictor o:
3eter ser.ices 3ill be recei.e!. (ore o: tese !iscussions nee! to occur in te
oncolo6y clinical care settin6. Furter stu!ies are nee!e! to better un!erstan! 3y
non3ite patients are less li4ely to access -ental ealt care ser.ices an! o3 to !etect
te ran6e o: clinically si6ni:icant psycolo6ical !isor!ers in cancer patients in a
-eanin6:ul 3ay.
=o to:
3ootnotes
Supporte! in part by te Lational )nstitute o: (ental Jealt 6rant C910+3$0; te
Lational Cancer )nstitute 6rants (J&+&29 an! (J+3#92; a Soros Hpen Society )nstitute
Pro2ect on *eat in 9-erica Faculty Scolarsip; a 19L*%Jart:or! )nter!isciplinary
=eriatric Jealt 1esearc Center 6rant; a FetIer 1eli6ion at te 0n!'o:'<i:e 6rant; an!
te Clau!e *. Pepper Hl!er 9-ericans )n!epen!ence Center 6rant P309=21342 :ro-
te Lational )nstitute on 96in6 (all to J.=. Pri6erson).
L.S. 7a!an'<ottic4 3as supporte! by te Lational Center :or 1esearc 1esources/ 6rant
712111$&94.
=o to:
!&3&!&@"&(
1. 1ies <9/ ,in6o P9/ (iller *S/ et al. >e annual report to te nation on te status o:
cancer/ 19$3'199$/ 3it a special section on colorectal cancer. Cancer. 2000;##:239#
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2. ?loc4 S*. 9ssessin6 an! -ana6in6 !epression in te ter-inally ill patient. 9CP'9S)(
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o: )nternal (e!icine. 9nn )ntern (e!. 2000;132:20921#. FPub(e!G
3. (assie (". " Latl Cancer )nst (ono6r. 2004. Pre.alence o: !epression in patients 3it
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4. ?esisi4 S7/ 7ocabey =/ Calis4an 5. (a2or !epression an! psoriasis acti.ation !ue to
inter:eron'alpa in a patient 3it cronic -yeloi! leu4e-ia; Ao.erloo4e! an!%or -is!ia6'
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1es Clin Hncol. 2004;130:32$333. FPub(e!G
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Psycoso-atics. 1993;34:20#221. FPub(e!G
#. Passi4 S*/ *u6an ,/ (c*onal! (8/ 1osen:el! ?/ >eobal! *0/ 0!6erton S.
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.ariables relate! to bone -arro3 transplantation sur.i.al in acute leu4e-ia.
Psycoso-atics. 1991;32:42042&. FPub(e!G
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Hncol. 1993;2:&0&1.
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patients be:ore an! a:ter participation in a cancer support 6roup. Patient 0!uc Couns.
2001;4&:19&19#. FPub(e!G
22. ?reitbart ,/ "acobsen P?. Psyciatric sy-pto- -ana6e-ent in ter-inal care. Clin
=eriatr (e!. 199+;12:32934$. FPub(e!G
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3it a!.ance! cancer: te accuracy o: clinician esti-ations an! te rele.ance o: spiritual
3ell'bein6Sa Joosier Hncolo6y =roup Stu!y. " Clin Hncol. 2003;21:2$&42$&9.
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2&. (c*onal! (8/ Passi4 S*/ *u6an ,/ 1osen:el! ?/ >eobal! *0/ 0!6erton S.
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1999;2+:&93&99. FPub(e!G
2+. 8an!er3er4er </ <a:: 1/ 7a!an'<ottic4 L/ (cColl S/ Pri6erson J. Psyciatric
!isor!ers an! -ental ealt ser.ice use a-on6 care6i.ers o: ter-inally )ll cancer
patients. " Clin Hncol. 200&;23:+#99+90$. FP(C :ree articleG FPub(e!G
2$. 7iernan 1"/ (ueller "/ <an6ston ",/ 8an *y4e C. >e Leurobea.ioral Co6niti.e
Status 0Da-ination: a brie: but @uantitati.e approac to co6niti.e assess-ent. 9nn )ntern
(e!. 19#$;10$:4#14#&. FPub(e!G
2#. First (/ SpitIer 1/ =ibbon (/ ,iliia-s ". Structure! Clinical )nter.ie3 :or *S(')8
9Dis ) *isor!ers'Patient 0!ition (SC)*')%P/ 8ersion 2.0) ?io-etrics 1esearc
*epart-ent/ Le3 5or4 State Psyciatric )nstitute; Le3 5or4: 199&.
29. ,illia-s "?/ =ibbon (/ First (?/ et al. >e Structure! Clinical )nter.ie3 :or *S('
)))'1 (SC)*). )). (ultisite test'retest reliability. 9rc =en Psyciatry. 1992;49:+30+3+.
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30. 0n!icott ". (easure-ent o: !epression in patients 3it cancer. Cancer.
19#4;&3:22432249. FPub(e!G
31. ?reitbart ,/ ?ruera 0/ Cocino. J/ <ync (. Leuropsyciatric syn!ro-es an!
psycolo6ical sy-pto-s in patients 3it a!.ance! cancer. " Pain Sy-pto- (ana6e.
199&;10:131141. FPub(e!G
32. Nubro! C/ Scnei!er-an (/ Frei 0/ ?rin!ley C/ =ol! =/ Sni!er ?. 9ppraisal o:
-eto!s :or te stu!y o: ce-oterapy o: cancer in -an: co-parati.e terapeutic trial o:
nitro6en -ustar! an! tri-etylene tiopospora-i!e. " Cron *is. 19+0;11:$33.
33. 0scalante CP/ ,eiser (9/ (anIullo 0/ et al. Hutco-es o: treat-ent pat3ays in
outpatient treat-ent o: lo3 ris4 :ebrile neutropenic cancer patients. Support Care Cancer.
2004;12:+&$++2. FPub(e!G
34. Crista4is L9/ 0scarce "". Sur.i.al o: (e!icare patients a:ter enroll-ent in ospice
pro6ra-s. L 0n6l " (e!. 199+;33&:1$21$#. FPub(e!G
3&. =essert C0/ Curry L(/ 1obinson 9. 0tnicity an! en!'o:'li:e care: te use o: :ee!in6
tubes. 0tn *is. 2001;11:9$10+. FPub(e!G
3+. Jop3oo! P/ Jo3ell 9/ (a6uire P. Psyciatric -orbi!ity in patients 3it a!.ance!
cancer o: te breast: pre.alence -easure! by t3o sel:'ratin6 @uestionnaires. ?r " Cancer.
1991;+4:3493&2. FP(C :ree articleG FPub(e!G
3$. Pin!er 7</ 1a-ireI 9"/ ?lac4 (0/ 1icar!s (9/ =re6ory ,(/ 1ubens 1*.
Psyciatric !isor!er in patients 3it a!.ance! breast cancer: pre.alence an! associate!
:actors. 0ur " Cancer. 1993;299:&24&2$. FPub(e!G
3#. Ja--erli! 0/ 9lner'0l-@.ist (/ ?2or!al 7/ et al. 9 prospecti.e -ulticentre stu!y
in S3e!en an! Lor3ay o: -ental !istress an! psyciatric -orbi!ity in ea! an! nec4
cancer patients. ?r " Cancer. 1999;#0:$++$$4. FP(C :ree articleG FPub(e!G
39. 7ra-er "9. Kse o: te Jospital 9nDiety an! *epression Scale (J9*S) in te
assess-ent o: !epression in patients 3it inoperable lun6 cancer. Palliat (e!.
1999;13:3&33&4. FPub(e!G
40. ,eiss-an ((/ ?lan! 1/ "oyce P1/ Le3-an S/ ,ells "0/ ,ittcen JK. SeD
!i::erences in rates o: !epression: cross'national perspecti.es. " 9::ect *isor!.
1993;29:$$#4. FPub(e!G
41. Cocino. J(/ ,ilson 7=/ 0nns (/ <an!er S. *epression/ opelessness/ an!
suici!al i!eation in te ter-inally ill. Psycoso-atics. 199#;39:3++3$0. FPub(e!G
42. Patric4 *</ Fer4etic S</ Fra-e PS/ et al. Lational )nstitutes o: Jealt State'o:'te'
Science Con:erence State-ent: sy-pto- -ana6e-ent in cancer: pain/ !epression/ an!
:ati6ue. " Latl Cancer )nst (ono6r; "uly 1&'1$/ 2002.pp. 91+.
43. Coyne "C/ Pal-er SC/ Sapiro P"/ >o-pson 1/ *e(icele 9. *istress/ psyciatric
-orbi!ity/ an! prescriptions :or psycotropic -e!ication in a breast cancer 3aitin6 roo-
sa-ple. =en Josp Psyciatry. 2004;2+:12112#. FPub(e!G
44. 1euter 7/ 1au6ust S/ ?en6el "/ Jarter (. *epressi.e sy-pto- patterns an! teir
conse@uences :or !ia6nosis o: a::ecti.e !isor!ers in cancer patients. Support Care Cancer.
2004;12:#+4#$0. FPub(e!G
4&. Hl:son (/ Fire-an ?/ ,eiss-an ((/ et al. (ental !isor!ers an! !isability a-on6
patients in a pri-ary care 6roup practice. 9- " Psyciatry. 199$;1&4:1$341$40.
FPub(e!G
4+. ,atson (/ Ja.ilan! "S/ =reer S/ *a.i!son "/ ?liss "(. )n:luence o: psycolo6ical
response on sur.i.al in breast cancer: a population'base! coort stu!y. <ancet.
1999;3&4:1331133+. FPub(e!G
4$. La4aara 5/ (ociIu4i 5/ (iya-oto 5/ et al. (ental state as a possible in!epen!ent
pro6nostic .ariable :or sur.i.al in patients 3it a!.ance! lun6 carcino-a. Cancer.
2002;94:300+301&. FPub(e!G
4#. "osi L/ ?reibart ,S. Psycopar-acolo6ic -ana6e-ent !urin6 cancer treat-ent.
Se-in Clin Leuropsyciatry. 2003;#:2412&2. FPub(e!G
49. Potas (/ ?reitbart ,. 9::ecti.e !isor!ers in a!.ance! cancer. Je-atol Hncol Clin
Lort 9-. 2002;1+:+$1$00. FPub(e!G
&0. =reenber6 *?. " Latl Cancer )nst (ono6r. 2004. ?arriers to te treat-ent o:
!epression in cancer patients; pp. 12$13&.
&1. Pirl ,F. " Latl Cancer )nst (ono6r. 2004. 0.i!ence report on te occurrence/
assess-ent/ an! treat-ent o: !epression in cancer patients; pp. 3239.
&2. >ras4 PC. " Latl Cancer )nst (ono6r. 2004. 9ssess-ent o: !epression in cancer
patients; pp. #092.
&3. Cra3ley </ Payne 1/ ?ol!en "/ Payne >/ ,asin6ton P/ ,illia-s S. Palliati.e an!
en!'o:'li:e care in te 9:rican 9-erican co--unity. "9(9. 2000;2#4:2&1#2&21.
FPub(e!G
Jurnal 10
Clin Pract 0pi!e-iol (ent Jealt. 200$; 3: 2.
Publise! online 200$ February #. oi# 10.11$(,1)4+:01)9:&:2
PMC-.# PMC1)9)1)&
Depression in cancer patients% a critical
revie$
Massimo PasEuini
132
an Massimo 1ioni
1
Author in"ormation 5 Article notes 5 Copyright an 2icense in"ormation 5
6his article has been cite by other articles in PMC.
8o to#
Abstract
Cancer patients eDperience se.eral stressors an! e-otional upea.als. Fear o: !eat/
interruption o: li:e plans/ can6es in bo!y i-a6e an! sel:'estee-/ can6es in social role
an! li:estyle are all i-portant issues to be :ace!. (oreo.er/ *epressi.e *isor!ers -ay
i-pact te course o: te !isease an! co-pliance. >e cost an! pre.alence/ te
i-pair-ent cause!/ an! te !ia6nostic an! terapeutic uncertainty surroun!in6
!epressi.e sy-pto-s a-on6 cancer patients -a4e tese con!itions a priority :or
researc. )n tis article 3e !iscuss recent !ata/ :ocusin6 on !etection o: *epressi.e
*isor!ers/ biolo6ical correlates/ treat-ents an! un-et nee!s o: !epresse! cancer patients.
8o to#
7. Background
Cancer accounts :or nearly 2&E o: !eats in te Knite! States/ eDcee!e! only by eart
!isease F1G. (a2or *epressi.e *isor!er accounts :or 4.4 percent o: te o.erall 6lobal
!isease bur!en/ a contribution si-ilar to isce-ic eart !isease or !iarroeal !isease F2G/
an! te *isability 9!2uste! <i:e 5ears (*9<5s) :or !epression in te near :uture 3ill be
6reater tan cancer or J)8 relate! !isease F3G. 9 stron6 bo!y o: e.i!ence !e-onstrates
te coeDistence o: !epression an! cancer/ reporte! pre.alence rates o: !epression :or
soli! tu-ours ran6in6 :ro- 20 to &0E. >ese results 6enerally inclu!e all te !epressi.e
!isor!ers not 2ust te (a2or *epressi.e *isor!er. =rassi an! 1osti :oun! tat out o: 201
recently !ia6nose! cancer patients/ 1&E -et te criteria :or a (a2or *epressi.e *isor!er
F4G. Sarpe esti-ate! at #E te pre.alence o: (a2or *epressi.e *isor!er in a lar6e
sa-ple o: cancer patients/ altou6 -ost o: te- a! an inacti.e !isease F&G. )n a sa-ple
o: ae-atolo6ical inpatients pre.alence o: (a2or *epression 3as 9E F+G/ te sa-e
reporte! by Coyne et al a-on6 breast cancer patients F$G. )n te screenin6 pro6ra-
con!ucte! by 0ll an! collea6ues a-on6 lo3'inco-e 3o-en 3it cancer te pre.alence
rate :or (a2or *epression 3as 24E F#G. >ere is reason to belie.e tat -any patients
a::ecte! by subclinical !epression 6o un!etecte!. >ese esti-ates are -a!e aroun! ti-e
o: cancer !ia6nosis. (ore researc is nee!e! to establis te pre.alence o: !epressi.e
!isor!ers in te years a:ter te !ia6nosis usin6 stan!ar!iIe! !ia6nostic criteria. >e
pre.alence o: (a2or *epressi.e *isor!er at ti-e o: te :irst breast cancer recurrence 3as
esti-ate! at 22E by H4a-ura F9G. )n a recent obser.ational coort stu!y/ con!ucte!
a-on6 222 3o-en 3it a !ia6nosis o: early breast cancer/ pre.alence o: !epression an!
anDiety 3as 33E at !ia6nosis/ 1&E a:ter one year/ an! 4&E a:ter !ia6nosis o: recurrence
F10G.
>e reporte! .ariability in pre.alence is attributable to se.eral :actors: -e!ical/ personal
an! :actors relate! to !i::erent stu!y -eto!s/ instru-ents an! proce!ures. Lot all cancer
patients are te sa-e: cancer site/ a6e/ !isease sta6e/ ti-e :ro- !ia6nosis/ cancer
treat-ent/ are a-on6 te -ost i-portant .ariables associate! 3it pre.alence o:
!epression a-on6 cancer patients an! tese soul! be ta4en into account. Psyciatric
-orbi!ity an! oter psycolo6ical aspects a-on6 breast cancer patients are .ery 3ell
stu!ie!/ 3ile :e3er reports re6ar! cancer o: oter sites. F+/11'13G. Personal .ariables
suc as cultural an! etnical caracteristics/ reli6ious attitu!es/ social econo-ic status/
personality traits/ copin6 styles/ social support/ !istance :ro- ospital are also .ery
i-portant. Lot all trials a.e ta4en into account te !i::erent sta6es o: te cancer process.
>e i-portance o: tese .ariables as been recently con:ir-e! by results obtaine! :ro-
an obser.ational stu!y/ con!ucte! on 2.+00 3o-en treate! :or early breast cancer/
so3in6 tat !epressi.e sy-pto-s 3ere not associate! 3it ob2ecti.e cancer'relate!
:actors F14G. )n te absence o: su::icient :or-al trial !ata in cancer patients/ clinical
!ecision soul! be in:luence! by eDperience in te 6eneral population/ an! naturalistic
stu!ies appearin6 in cancer literature F1&G.
H.er te last years -any e::orts a.e been -a!e in or!er to i-pro.e screenin6
proce!ures/ but at present no stan!ar!iIe! approac eDists :or te !ia6nosis o: !epression
a-on6 cancer patients. 9n a!!itional source o: .ariation is represente! by te bet3een
obser.er .ariability; but/ peraps/ in practice/ 3at really -atters an! -a4es te
!i::erence is te pro:essional bac46roun!/ 3it particular re:erence to 4no3le!6e in
psycopatolo6y an! clinical eDperience. )na!e@uate !ia6nosis o: (a2or *epression
a-on6 cancer patients causes re!uction in @uality o: li:e/ prolon6e! ospitaliIation an!
i6er rates o: non co-pliance 3it treat-ent plan F1+G. )n a!!ition social support as
been i!enti:ie! as an i-portant :actor alle.iatin6 !epression in cancer patients/
conse@uently/ :a-ily counsellin6 soul! be use:ully e-ploye! to e!ucate te :a-ily on
!epression tat acco-panies cancer F1$G.
8o to#
+. Assess'ent of depression a'ong cancer patients
)n te :iel! o: psyco'oncolo6y te 3i!ely use! instru-ents ?S) (?rie: Sy-pto-s
)n.entory) F1#G an! te J9*S (Jospital 9nDiety an! *epression Scale) F19G are
e-ploye! :or !etectin6 psycolo6ical !istress. Suc scales 3ere speci:ically !e.elope! to
i!enti:y sy-pto-s in non psyciatric -e!ical outpatients. >ese instru-ents contribute!
to te reco6nition o: psycolo6ical su::erin6 in !i::erent settin6s/ an! i-pro.e! psyco'
oncolo6y. Le.erteless too o:ten pre.alence o: psyciatric !isor!ers is reporte! only on
te basis o: stu!ies usin6 J9*S an! ?S). )n -any stu!ies te C0S'* (Centre :or
0pi!e-iolo6ical Stu!ies'*epression) F20G or te ?*) (?ec4 *epression )n.entory) F21G/
so3in6 acceptable sensiti.ities an! speci:icities in sa-ples o: cancer patients/ 3ere
e-ploye!.
Hn te oter an!/ patients 3it sy-pto-s o: !epression -ay not :ul:il te *S(')8
criteria :or *epressi.e *isor!ers F22G. >is is a crucial point. 9s an eDa-ple/ te reporte!
i6 rate o: 9!2ust-ent *isor!ers is !ue in part to te special status o: bein6 a cancer
patient/ an! in part to te ina!e@uacy o: *S(')8 criteria :or suc patients/ a sort o:
-a4esi:t solution.
(oreo.er te pre.alence o: !epression a-on6 cancer patients is o:ten un!eresti-ate!/
because -any sy-pto-s o: !epression/ suc as :ati6ue/ 3ei6t loss/ loss o: appetite or
sleep !isruption/ closely -irror te pysiolo6ic e::ects o: cancer; or te use o: certain
treat-ents an! oter sy-pto- -ana6e-ent -e!ication -ay preclu!e an appropriate
!ia6nosis. F1#G. 9s su66este! by so-e autors F23G it is necessary to a!opt an a!e@uate
approac :or !iscri-inatin6 te so-atic sy-pto-s o: cancer an! tose !ue to treat-ent
:ro- te criteria o: *S(')8 :or -a2or !epression. >ree -o!els 3ere propose!: te
inclusi.e ones/ 3ic su66est tat so-atic sy-pto-s are counte! re6ar!less o: te cause;
te substitute! ones/ 3ic su66est tat non so-atic sy-pto-s are substitute! :or
so-atic sy-pto-s; te eDclusi.e ones/ 3ic su66est tat so-atic sy-pto-s -ay be
!isre6ar!e! as !ia6nostic criteria F1$G. 9s an eDa-ple o: te eDclusi.e approac/ it as
been propose! to re-o.e :ati6ue :ro- te *S(')8 criteria. )n our opinion te -o!i:ie!
*S(')8 approac to !ia6nose (a2or *epression propose! at te (e-orial Sloan'
7etterin6 Cancer Centre/ tat eli-inates anoreDia an! :ati6ue :ro- te list o: te nine
criteria an! re@uires only :our o: te re-ainin6 se.en sy-pto-s :or !ia6nosis/ coul!
increase te speci:icity o: te !ia6nosis F+G. Le.erteless tere are still no !ata
con:ir-in6 te .ali!ity o: tese -o!els.
)t is to note tat/ as ?ailey su66este! F1$G/ culture -ay in:luence sy-pto- eDpression/ as
an eDa-ple in!i.i!uals o: te 9sian culture su::erin6 :ro- !epression ten! to present
so-atic sy-pto-s o: !epression ne6lectin6 te psycolo6ical sy-pto-s.
Le.erteless te issue o: 9!2ust-ent *isor!er re-ains unresol.e!. >is issue nee!s -ore
attention/ because tere are still -any clinicians tat erroneously consi!er 9!2ust-ent
*isor!er al3ays as a nor-al transition. >e real proble- is tat cancer relate! stressors
persist :or lon6 ti-e/ so tat !ia6nosis soul! be -o!i:ie! an!/ treat-ents are !eli.ere!
3it :urter !elay.
1ecently se.eral -ultipasic screenin6 stu!ies to !etect !epression a.e so3n an
increase in sensiti.ity an! speci:icity o: te !ia6nosis F&/24/2&G.
9noter issue in !etectin6 !epressi.e !isor!ers a-on6 cancer patients is te -eto!olo6y
o: te inter.ie3. ,ile a!-inisterin6 ratin6 scales in a 3aitin6 roo- or inter.ie3in6
patients o.er te telepone o::er practical a!.anta6es suc as si-plicity/ lo3 cost/ an!
applicability to lar6e sa-ples/ tere is no !oubt tat a co-preensi.e psyciatric
assess-ent is 3arrante! to !ia6nose a (a2or *epressi.e *isor!er/ an! tis is !i::icult
3itout seein6 te patient. (oreo.er/ patients nee! ti-e an! space. (ost i-portant !ata
are o:ten obtaine! in te last -inutes o: an our .isit in a !e!icate! roo-. 9n! tis as to
!o 3it relationsip/ not 3it -eto!olo6y.
8o to#
B. 3eatures of depression
>o better un!erstan! te co-pleD nature o: !epression in cancer patients/ it is use:ul to
consi!er se.eral aspects. 9 :un!a-ental issue is tat !epressi.e !isor!ers are syn!ro-es
not !iseases/ an! inclu!e a .ariety o: -oo! !isturbances an! clinical presentations.
Le6ati.e -oo! alon6 3it lo3 ener6y/ poor concentration/ loss o: interests/ -e-ory
!isturbances/ lo3 sel:'estee-/ 6uilt :eelin6s/ ypocon!riac preoccupation/ sleep an!
appetite !isturbances an! opelessness are te -ost co--on sy-pto-s o: (a2or
*epressi.e *isor!er. Features un!errepresente! in en!o6enous !epression/ suc as
psycic an! so-atic anDiety/ so-atic co-plaints are -ore co--on in atypical
!epression. Jo3e.er/ a 3i!e .ariety o: clinical pictures can actually be obser.e! in
!epresse! patients. 9s an eDa-ple/ current psyciatric classi:ication syste-s ten! to
un!eresti-ate te role playe! in !epresse! patients by sy-pto-s suc as an6er/
irritability/ an! ostility F2+/2$G.
9s an alternati.e -o!el in te assess-ent o: !epressi.e !isor!ers -any autors pro-ote!
a clini-etric approac rater tan te psyco-etric -o!el; tis because in clinical
practice/ psyciatrists -ay 3ei6 :actors suc as te pro6ression o: !isease/ te o.erall
se.erity o: te !isor!er/ te patientsU social support an! teir a!aptation an! resilience an!
reaction to stress:ul li:e circu-stances F2#/29G. Pysicians -ay :in! tis -o!el use:ul an!
practical in te assess-ent o: !epressi.e sy-pto-s a-on6 cancer patients. Copin6
strate6ies/ :eelin6s o: loss/ co6niti.e a!aptation an! transition are all :un!a-ental
psycolo6ical aspects tat a::ect !i::erent clinical -ani:estations o: e.ery sin6le cancer
patient F30G. >ese co-ponents .ary tre-en!ously 3eter you are assessin6 a :e-ale
3it breast cancer !ia6nose! an! treate! ten years a6o/ or i: you are !ealin6 3it a
:e-ale 3it colon cancer/ recently sto-iIe!.
9noter @uestion as to !o 3it :ati6ue/ te -ost :re@uently reporte! si!e e::ect o: cancer
treat-ent/ 3it a pre.alence ran6in6 :ro- 2&E to 99EF31G. Jo3e.er/ :ati6ue is also a
:eelin6 state not relate! to cancer treat-ents. 0.en tou6 :ati6ue -ay be associate! 3it
!epression in patients treate! 3it ce-oterapy/ too o:ten is ta4en :or !epression
F32/33G. (oreo.er/ in a ran!o-iIe! !ouble%blin! trial (orro3 !e-onstrates tat
paroDetine a::ects !epressi.e sy-pto-s but not :ati6ue F34G. )n :act/ :ati6ue !ue to
ce-oterapy !oes not inclu!e an e-otional co-ponent 3ile :ati6ue relate! to a
!epressi.e syn!ro-e !oes/ ob.iously an in!i.i!ual in ce-oterapy eDperiencin6 :ati6ue
can !e.elop :eelin6s o: !e-oraliIation. ?o3er :oun! tat in breast cancer patients not in
ce-oterapy/ :ati6ue 3as associate! 3it :latter cortisol slope/ 3at -ay re:lect a JP9
aDis alterations. F3&G. >o !e.elop cancer is a .ery trau-atic eDperience :or patients/
:acin6 te possibility o: !eat/ can6es in te bo!y i-a6e/ :ear o: in.asi.e treat-ents an!
pain/ can6es in teir role in te :a-ily/ in teir 3or4 en.iron-ent an! in te society at
lar6e/ all representin6 sources o: acute stress. Stress is !e:ine! by sti-uli (stressors)/
sub2ecti.e reports o: an eDperience/ a 6eneral non'speci:ic increase in arousal/ an! te
:ee!bac4 to te brain :ro- tis response.
Fortunately -any types o: cancer are beco-in6 cronic con!itions. ?ut un:ortunately
u-ans/ li4e oter ani-als/ are not prepare! to !eal 3it prolon6e! stressors. >ose
:a-iliar 3it tese patients 4no3 o3 teir or6aniIers are :ull o: :ollo3'up .isits an!
cec4'ups :or a lon6 ti-e. >al4in6 3it te- you can learn o3 tese in!i.i!uals .ie3
teir ti-e. )t is !i::icult to 6eneraliIe !epression in suc conteDt. )n tis prospecti.e 3e
coul! consi!er so-e -ani:estation o: psycolo6ical su::erin6 as a psyconeuroen!ocrinal
alteration. )n a!!ition/ te bea.ioural alterations tat !e.elop !urin6 illness are not 2ust
te result o: a !ecrease! ability to react to te eDternal 3orl! an! en6a6e in pysical
acti.ities. Pro'in:la--atory cyto4ines pro!uce! by periperal i--une cells coul!
:unction as a -oti.ational si6nal tat tells te brain to can6e te or6anis- priorities in
:ace o: te treat represente! by !an6er si6nals. >is reor6aniIation o: priorities results in
can6es at te sub2ecti.e/ bea.ioural an! pysiolo6ical le.els F3+G.
8o to#
,. Biological correlates
>ere a.e been se.eral stu!ies o: psyconeuroi--unolo6ical -ecanis-s an! cancer.
?iolo6ical alterations 3ere in.esti6ate! in relation to copin6 styles/ psycolo6ical status/
social support an! sur.i.al. (ost o: tese stu!ies 3ere con!ucte! a-on6 patients
a::ecte! by breast cancer/ 6i.en tat :or tis !isease sur.i.al at :i.e years is ##E F3$G.
)ncreasin6 e.i!ence as su66este! tat circa!ian patterns o: cortisol secretion are altere!
in cancer patients 3it a!.ance! !isease F3#'40G. 9berco-bie an! collea6ues so3e!
tat 3o-en 3it -etastatic breast cancer a! si6ni:icantly :latter !iurnal cortisol ryt-s
as co-pare! 3it ealty controls F41G. Septon :oun! tat :lattene! !iurnal cortisol
slopes 3ere associate! 3it !ecrease! sur.i.al ti-e a-on6 3o-en 3it -etastatic breast
cancer F42G/ 3ile HsborneUs stu!y :oun! no e.i!ence tat cortisol an! prolactin le.els
3ere associate! 3it i--une or psycosocial .ariables in breast cancer patients F43G/
si-ilar results 3ere obtaine! in a lar6est controlle! stu!y F44G.
9n i-portant :in!in6 is tat cortisol le.el in -etastatic breast cancer is relate! to te
@uality o: social support/ belon6in6/ appraisal/ an! tan6ible support F4&G.
Hnly one ran!o-iIe! controlle! stu!y so3e! tat le.els o: o-e6a'3 :atty aci! are
associate! 3it -inor (but not -a2or) !epression in lun6 cancer patients/ un:ortunately
psyciatric !ia6nosis 3as -a!e usin6 J9*S F4+G.
>ere are still inconsistent !ata re6ar!in6 te association bet3een -oo! !isor!ers/ L7
cells/ cyto4ines/ cancer !e.elop-ent an! sur.i.al F4$'&0G. )n 11+ breast cancer patients
eDposure to stress 3as associate! 3it lo3er L7 cell lysis an! !i-inise! responsi.eness
o: L7 to r)FL'm F&1G; 3ile a-on6 -en a::ecte! by prostate cancer opti-is- an! less
an6er suppression 3as associate! 3it 6reater natural 4iller cell cytotoDicity F&2G.
Consistently a structure! 6roup terapy in patients a::ecte! by -ali6nant -elano-a
re!uce! !istress an! so3e! increases in L7 cell cytotoDic acti.ity as co-pare! to
controls F&3G. (ussel-an :irst/ reporte! tat i6er tan nor-al plas-a )l'+ le.els 3ere
associate! 3it a !ia6nosis o: -a2or !epression in a s-all sa-ple o: cancer patients F&4G.
>is :in!in6 3as con:ir-e! in a lar6er sa-ple by "en et al./ tere:ore te autors
propose! te )<'+ increase! plas-a concentration as a bio-ar4er o: !epression a-on6
cancer patients F&&G.
CostanIo et al. :oun! tat a-on6 +1 patients 3it a!.ance! o.arian cancer social support
play a protecti.e role 3it respect to )<'+ ele.ations/ an! )<'+ -ay be an in!epen!ent
-ar4er o: ealt'relate! @uality o: li:e F&+G. 1aison an! (iller re.ie3e! te role o:
cyto4ines in cancer patients an! su66este! tat in:la--ation pro.i!es a pysiolo6ic
substrate tat pro-otes -oo! !isor!ers F&$G.
)n spite o: te increasin6 e.i!ence tat )<'+ an! oter pro'in:la--atory cyto4ines -ay
play a role in te patopysiolo6y o: -oo! !isor!ers an! cause bea.ioural an!
neuroen!ocrine conse@uences/ in cancer patients tese peno-ena are rater -ore
co-plicate!. )n :act/ !i::erent !ata re6ar!in6 te relation bet3een )<'+ an! cancer are
4no3n. Consistent results a.e been so3n tat )<'+ is a pleiotropic re6ulator o: prostate
cancer cell 6ro3t/ an! seru- )<'+ le.els as pro6nostic si6ni:icance in patients 3it
-etastatic prostate cancer F&#/&9G. (oreo.er )<%+ in!uce! basic :ibroblast 6ro3t :actor
!epen!ent an6io6enesis in basal cell carcino-a F+0G. )n a!!ition )<'+ -ay be in.ol.e! in
tu-or'ost interactions potentially :a.ourin6 u.eal -elano-a 6ro3t/ sur.i.al an!
proli:eration F+1G. 1ecently ?er6er reporte! tat te 6ene enco!in6 te )<+ is a
susceptibility :actor a::ectin6 racial an! etnic !i::erences in breast cancer sur.i.al. F+2G.
9ll tese !ata su66est tat te 6eneral assertion re6ar!in6 )<'+/ !epression an! cancer
nee!s 6reat caution. ?esi!es/ it is 3ell 4no3n tat proin:la--atory cyto4ines -ay cause
!epression or sic4ness bea.iour an! tat psyciatric inter.entions a::ect le.els o: pro'
in:la--atory cyto4ines. 9 ran!o-iIe! stu!y on te e::icacy o: Co6niti.e'?ea.ioral
>erapy in inso-nia secon!ary to breast cancer pro.i!es e.i!ence tat treatin6 inso-nia
can alter cyto4ine pro!uction F+3G. )n su--ary/ apaty/ social isolation/ sleep
!isturbance/ :ati6ue/ anoreDia/ 3ei6t loss/ co6niti.e !isturbance/ !ecrease! libi!o an!
psyco-otor retar!ation are sy-pto-s o: bot (a2or *epression an! cyto4ine'in!uce!
sic4ness syn!ro-e/ 3ereas 6uilt/ !epresse! -oo! an! suici!al i!eation are -ore
co--on in (a2or *epressi.e *isor!er.
Leuroi-a6in6 correlates are e-er6in6. (atsuo4a !e-onstrate! tat cancer sur.i.ors
3it intrusi.e recollections a! a si6ni:icantly s-aller total a-y6!ala .olu-e as
co-pare! 3it te total a-y6!ala .olu-e in cancer sur.i.ors 3itout intrusi.e
recollections F+4G. )n a case control stu!y/ 5osi4a3a reporte! an alteration in a-y6!ala
.olu-e associate! 3it !epresse! -oo! a:ter cancer !ia6nosis in &1 cancer sur.i.ors.
F+&G. *ata obtaine! usin6 P0> in !epresse! cancer patients so3e! cerebral :unctional
alterations si-ilar to tose :oun!e! a-on6 pri-ary !epresse! patients F++/+$G.
8o to#
E. Depression as a risk factor in the prognosis of cancer
*ata re6ar!in6 te in:luence o: psycolo6ical :actors on te pro6nosis o: cancer are
a.ailable. Psycolo6ical status see-s to pre!ict te len6t o: sur.i.al in se.eral types o:
cancer suc as -elano-a/ non's-all'cell lun6 cancer/ breast an! 4i!ney cancer. <on6er
:ollo3'up in!icate tat a i6 :i6tin6 spirit con:ers no sur.i.al a!.anta6e/ 3ile in
patients 3o 3ere !isease':ree at & years/ teir baseline elpless%opeless response still
eDerte! a si6ni:icant e::ect on !isease':ree sur.i.al beyon! & (an! up to 10) years. >e
e::ect is tere:ore -aintaine! :or up to 10 years o: :ollo3'up F+#G. >ese results 3ere
usually obtaine! by .ali!ate! instru-ents li4e te =eneral Jealt ^uestionnaires/ te
^uality o: <i:e )n!eD or te (ental 9!2ust-ent to Cancer.
Jo3e.er tere are :e3 !ata re6ar!in6 te uni@ue role o: -oo! in pre!ictin6 sur.i.al.
1esults :ro- #'year :ollo3'up stu!y a-on6 10.000 patients !e-onstrate! tat te
coeDistence o: cancer an! !epression is associate! 3it an increase! ris4 o: !eat F+9G.
Prieto/ in te lar6est oncolo6ic stu!y tat use! stan!ar!iIe! psyciatric criteria/ :oun!
tat a-on6 199 e-atolo6ic cancer patients a:ter ste-'cell transplantation/ (a2or
*epressi.e *isor!er pre!icte! i6er 1' an! 3'year case':atality'rate/ an! tere 3as a
tren! :or patients 3it -inor !epression to sur.i.e lon6er tan patients 3it no
!epression F+G. Faller reporte! tat in lun6 cancer patients e-otional !istress an!
!epressi.e copin6 style pre!ict sort sur.i.al F$0G. 1ecent stu!ies :oun! tat i6 scores
on a e-ini-iIin6 te illnesse scale pre!ict lon6er sur.i.al F$1/$2G. 9ltou6 e-ini-iIin6
te illnesse copin6 style -ay a.e clinical utility/ so :ar tis construct as not been
stu!ie! in relation to -oo! !isor!ers. >e i-pact o: !epression on -ortality as not been
!e:initi.ely so3n. Spie6el an! =iese'*a.is re.ie3e! te lin4 bet3een !epression an!
cancer pro6ression/ an! su66este! tat tere is not stron6 e.i!ence supportin6 a lin4 o:
!epression 3it cancer inci!ence/ tou6 so-e -eto!olo6ical proble-s -ay a.e
a::ecte! suc results F$3G. Jo3e.er untreate! !epressi.e !isor!ers -ay be lin4e! to :aster
pro6ression.
>e interpretation o: tese results is not uni.ocal: !epression -ay a.e a !irect
neuroi--une e::ect/ or !epresse! patients -ay so3 poorer a!erence to cancer
treat-ent/ or !epression relate! bea.iours a::ect se.eral aspects o: patients li:e suc as
ealt status/ @uality o: li:e/ parental role/ 3or4in6 role. 1esults as tose obtaine! by
Fa3Iy on -ali6nant -elano-a in a 10'year :ollo3'up stu!y/ su66est tat a brie:
structure! psycoe!ucational 6roup inter.ention can -o!erately a::ect sur.i.al. F$4G.
Le.erteless/ eDa-inin6 te e::ect on sur.i.al o: psycoterapy/ Pal-er an! Coyne
correctly notice! tat stu!ies in 3ic sur.i.al 3as not !esi6nate! as a pri-ary outco-e
cannot be 6i.en te sa-e 3ei6t as stu!ies !esi6ne! 3it sur.i.al as an a priori en! point
F$&G.
8o to#
8. Treat'ent
>e sin6le -ost i-portant :actor preclu!in6 treat-ent a-on6 !epresse! cancer patients is
te -isconception tat :or suc patients bein6 !epresse! is nor-al. (oreo.er -ost
oncolo6ists are un:a-iliar 3it !epressi.e !isor!ers. 0-er6in6 !ata con:ute te notion
tat !epression is ine.itable an! untreatable F$+G. >erapeutic niilis- is not 2usti:ie!
any-ore. >e e.i!ence'base! ealt care (screenin6 an! selecti.e treat-ent) currently
!eli.ere! to !epresse! cancer patients in selecte! oncolo6y centres soul! be 3i!esprea!.
9 ran6e o: options :or ser.ice !e.elop-ent soul! be outline!/ rater tan 2ust one
pre:erre! -eto! o: ser.ice !eli.ery. >e trainin6 nee!s o: sta:: -ust be :itte! into te
ser.ice -o!el/ as oppose! to teir trainin6 eDperience !ictatin6 te sape o: te ser.ice/
as it as appene! in te past F$$G. Kn:ortunately :e3 !ata :ro- clinical trials are
a.ailable on te e::ecti.eness o: treat-ent :or !epression a-on6 cancer patients F$#G.
8.7 Phar'acological treat'ent
Fisc pro.i!e! a brilliant re.ie3 o: te treat-ent o: *epressi.e *isor!ers a-on6 cancer
patients/ in 3ic e :ocuse! on te ina!e@uate @uality o: researc in tis :iel! F$9G. 9t
present tere are only 10 ran!o-iIe! trials co-parin6 anti!epressants to placebo. 9n
eDplanation/ su66este! by Fisc/ is te relati.e a.ersion o: patients an! :a-ily -e-bers
to te placebo controlle! stu!y !esi6n.
Hne coul! ar6ue tat te lac4 o: 1an!o-iIe! Controlle! >rials is te cause o: un!er
treat-ent o: suc !isor!ers. >ere are also !oubts about te pysicians ri6orous clinical
e.i!ence base! prescriptions. Furter-ore/ as so3n by 9sbury in lun6 cancer patients
tere is a 3ea4 correlation bet3een !etection o: !epressi.e !isor!ers an! treat-ent F1+G.
9noter i-portant issue is tat o: te etero6eneity o: te outco-es/ re:lectin6 te sa-e
proble-s o: assess-ent/ an! tere:ore !ata are !i::icult to co-pare. )t soul! also be
note! tat tere are se.eral open or uncontrolle! stu!ies su66estin6 potentially
i-pro.e-ents in !epresse! cancer patients. Probably/ tan4 to te clinical eDperience
3it ne3 anti!epressants e::ecti.eness/ in te near :uture 3e coul! a.e -ore 1C> !ata.
)n a!!ition anti!epressants a.e potential use:ulness :or te -ana6e-ent o: sy-pto-s
an! con!itions oter tan !epression/ suc as ot :lases an! pain F#0'#3G/ so tey are
o:ten prescribe! to cancer patients F#4/#&G.
Jo3e.er/ prescribin6 anti!epressants to cancer patients re@uires speci:ic 4no3le!6e/
eDperience an! caution. Hne -ust ta4e into account: te anticoliner6ic si!e e::ects o:
tricyclic anti!epressants/ te pro'e-etic e::ect o: SS1)s an! teir potential e::ects on te
par-aco4inetics o: oter !ru6s/ an! te speci:ic syn!ro-es occurrin6 in co-bination
3it ce-oterapy F#+G. (e!ication soul! be tailore! to eac cancer patient base! on
te !i::erent caracteristics o: te .arious !ru6s F#$'#9G. ,e !o not a6ree 3it te
reco--en!ations tat oncolo6ists soul! prescribe anti!epressant treat-ents/ as oter
autors su66este!. >ese !ecisions soul! be te responsibility o: te consultin6
psyciatrist/ because o: is%er speci:ic 4no3le!6e. Si-ply a!!in6 an anti!epressant to
oter -e!ications !i::ers notably :ro- a psyciatric prescription. Hne i-plication occurs
3it sleep !isturbances/ tat o:ten -irror a !epressi.e !isor!er/ 3ile patients recei.e
unsuitable -e!ication suc as benIo!iaIepines. (oreo.er/ te patientUs perception o:
bein6 part o: an acti.e treat-ent is by :ar !i::erent :ro- passi.ely 3aitin6 :or te
-e!ication e::ect.
8.+ Psychological treat'ent
0::icacy o: psycolo6ical inter.entions in cancer !epresse! patients as been
!e-onstrate!/ but e::ecti.eness stu!y are still lac4in6 F90G. 9 syste-atic re.ie3 o:
psycolo6ical inter.entions a-on6 cancer patients i!enti:ie! 129 trials tat in.ol.e!
psycosocial outco-es F91G; only 24 stu!ies so3e! an a!.anta6e :or te inter.ention in
ter-s o: te en!point o: !epression F$9G. Pre.ious re.ie3s 3ere -ore entusiastic about
te bene:its o: psycolo6ical inter.entions/ but teir approac 3as less conser.ati.e/
particularly re6ar!in6 te outco-e -easures :or !epression F92/93G. )t is !i::icult to
co-pare te e::ecti.eness o: psycoterapeutic inter.entions 3en te stu!ies inclu!e
se.eral !i::erent tecni@ues/ proce!ures are not clearly spelle!'out/ or outco-es are
!i::erent. Le3ell an! collea6ues propose! ten reco--en!ations to i-pro.e te reportin6
o: :uture ran!o-iIe! controlle! trials o: psycolo6ical terapies F91G. 9t present -ost
inter.entions are co6niti.e bea.ioural oriente!. So-e autors reco--en! a co6niti.e
approac to te treat-ent o: !epression a-on6 cancer patients/ oters reporte! tat 6roup
terapy is -ore e::ecti.e/ altou6 tese in!ications soul! ta4e into consi!eration te
clinical .ariables o: e.ery sin6le situation. )t is 4no3n tat in psycoterapy researc
tere are se.eral -eto!olo6ical !i::iculties/ an! tis is e.en -ore true a-on6 cancer
patients. 0le-ents o: :un!a-ental rele.ance o: te inter.entions are: brie: structure an! a
clear inter.ention tar6etin6. *espite tese scienti:ic issues/ te -ain proble- is tat too
o:ten pro.i!ers o: psycolo6ical terapies are not a!e@uately traine! in psyco'oncolo6y/
or tey a.e an ina!e@uate contact 3it te oncolo6y sta::. )t is i-portant to notice tat
!ata re6ar!in6 te e::ect o: psycolo6ical inter.entions on biolo6ical para-eters are
a.ailable in te :iel! o: psyco'oncolo6y -ore tan in oter :iel!s.
8o to#
9. >n'et needs of the cancer depressed patients
)n oncolo6y settin6s it is e-er6in6 te notion tat cancer patients soul! not tolerate teir
!epressi.e sy-pto-s an! te i-portance o: appropriately in:or-in6 te- about it.
Kn:ortunately -any issues are still unresol.e!. >e report :ro- te 0Dpert ,or4in6
=roup o: te 0uropean association :or Palliati.e Care as stresse! te -a2or unresol.e!
proble-s re6ar!in6 !epression an! cancer F90G. 9-on6 te se.eral reco--en!ations
pro.i!e!/ tere are te :ollo3in6 ones: te nee! :or specialiIe! -ental ealt
pro:essionals/ an! teir !i::erent roles !epen!in6 on local circu-stances; te nee! o: a
close relationsip bet3een te oncolo6y sta:: an! te consultation'liaison psyciatry; te
concept tat anti!epressants soul! be utiliIe! 3itout !elay once te !ia6nosis o: (a2or
*epression as been establise!. )t as also been su66este! tat sta:: trainin6 in !etectin6
*epressi.e *isor!ers -ay not be a su::icient con!ition :or a better -ana6e-ent o:
!epressi.e !isor!ers. ?esi!es/ Passi4 an! collea6ues !e-onstrate! tat rarely oncolo6ists
reco6niIe sy-pto-s o: !epression/ an! !epresse! patients re:erre! to a psyciatrist or a
psycolo6ist represent still a little percenta6e o: total F94G. )n a!!ition/ o:ten !i::erences
in cultural perceptions o: !isease are un!eresti-ate!. Psycolo6ical !i::erences by
bac46roun! can -a4e a -a2or !i::erence in te response o: in!i.i!uals to !isease F1$G.
9lso co-pliance .aries :or patients in te K.S./ Lort 0urope/ or oter countries/ suc as
)taly.
9s reporte! by 0ll F#G/ in er stu!y a-on6 te lo3'inco-e/ etnic -inority/ only 12E o:
all te 3o-en a::ecte! by (a2or *epression 3ere recei.in6 -e!ications/ 3ile a-on6
10E o: te -i!!le'to upper inco-e 3ite 3o-en 3o -et !ia6nostic criteria :or -a2or
!epression #0E 3ere recei.in6 anti!epressants F$G. Jo3e.er te (ulti:acete! Hncolo6y
*epression Pro6ra- )nter.ention/ or6aniIe! by *3i6t'"onson an! collea6ues/ so3e!
tat !epressi.e !isor!ers can be success:ully treate! in a public sector oncolo6y settin6
ser.in6 lo3'inco-e patients. >is -o!el so3s te i-portance o: collaboration bet3een
se.eral roles at !i::erent le.els: co--unity representati.es/ a!-inistrati.e an! clinical
co--ittees F$+G.
9noter un!errate! aspect is tat not all patients 3ant to a.e teir !epression reco6nise!
an! treate! F&/$9G. 8arious :actors can eDplain tis peno-enon/ culture/ patientUs
personality/ prior eDperience 3it cancer/ copin6 styles/ 6en!er !i::erences. Fisc
reporte! etat patients an! teir :a-ilies 4no3 tat a positi.e attitu!e or a e:i6tin6 spirite
is i-portant to eiter te ealt outco-e or te clinician 3illin6ness to treat te cancer
a66ressi.ely/ an! tis 4in! o: belie: can translate into a percei.e! ris4 in !isclosin6
!epressi.e sy-pto-se F$9G >is attitu!e coul! be relate! to te on'line in:or-ation/ -ore
an! -ore a.ailable 3itout an a!e@uate :ilter.
1ecently it as been su66este! tat spirituality an! spiritual copin6 are i-portant to
3o-en 3it 6ynaecolo6ical cancer an! tat sta:: -e-bers soul! consi!er tese issues
F9&G. 9noter i-portant un-et nee! is te lac4 o: lin4s bet3een psyciatric ser.ices an!
pain clinics; un:ortunately/ in -any 6eneral ospitals/ -ental ealt tea-s a.e scarce
resources an! s4ill :or -ana6in6 patients 3it cronic pain. )n a!!ition it is 3ell 4no3n
tat patients 3it !epressi.e !isor!ers a.e i6er costs o: 6eneral -e!ical'care ser.ices
co-pare! 3it teir non !epresse! peers. >reat-ent o: !epression -ay re!uce tese
costs/ in -any 3ays inclu!in6 re!uction o: sic4ness'absence.
)nstitutions -ay pro.i!e ne3 trainin6 pro6ra-s as psyciatric subspecialties. Hnly in
2003 te 9-erican ?oar! o: Psyciatry an! Leurolo6y/ trou6 te 9-erican ?oar! o:
(e!ical Specialties/ appro.e! Psycoso-atic (e!icine as a psyciatric subspecialty.
>is coul! be !ue to te :act tat in recent !eca!es -any !iseases/ inclu!in6 cancer/
beca-e cronic con!itions/ re@uirin6 -ore co-pleD ealt care !eli.ery.
8o to#
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