Lung Cancer I

Cerard A. SllvesLrl Mu, lCC

rofessor of Medlclne
Medlcal unlverslLy of SouLh Carollna

D|sc|osure
CranL fundlng/speakers bureau/SA8/Consulung:
C|ympus Amer|ca
A||ergro d|agnosncs
Integrated D|agnosncs
Cook Med|ca|
8I
8SC
Cb[ecnves
Lung Cancer l
undersLand Lhe followlng aspecLs of Lung cancer:
Lpldemlology
Classlcauon
ulagnosls
Screenlng
Sn
SLaglng
LIDLMICLCG
The US numbers are staggering:
222,320 will receive this diagnosis

137,300 will die of the disease

CA: A Cancer Journal for Clincians 2010;60(5):277-300

Lung Cancer
Worldwide numbers are worse
1- 2 million people die each year
Projected to be 10 million by 2030
Full consequences of the tobacco epidemic are
yet to come
350 million smokers in China
Chinese males smoke 11 cigs/day
uesnon 1
Cuesuon 1: ln Lerms of lncldence Lhe mosL common
cancer ln males and females ls:

A. Lung cancer ln boLh
8. 8reasL cancer ln females and lung cancer ln males
C. rosLaLe cancer ln males and lung cancer ln females
u. rosLaLe cancer ln males and breasL cancer ln
females

uesnon 1
Cuesuon 1: ln Lerms of lncldence Lhe mosL common
cancer ln males and females ls:

A. Lung cancer ln boLh
8. 8reasL cancer ln females and lung cancer ln males
C. rosLaLe cancer ln males and lung cancer ln females
D. rostate cancer |n ma|es and breast cancer |n
fema|es

Ma|e
Lno|ogy of Lung Cancer
1obacco causes 80 - 90
Clear dose response relauonshlp
asslve smoklng may cause up Lo 23 of lung cancer ln
non-smokers (2.3 - 3 of all)

lndlvldual (geneuc) suscepublllLy
10 - 13 of acuve smokers wlll develop lung cancer

Lno|ogy of Lung Cancer
CLher causes lnclude asbesLos, radon, polycycllc
hydrocarbons, cadmlum, chloromeLhyl eLher, chromlum,
nlckel, arsenlc may cause lung cancer
Age ls a rlsk facLor
Average age aL dx ls 70
CCu ls a rlsk facLor
More so Lhan [usL shared euology (4x more llkely Lhan smoklng alone)

Lung Cancer |n Never Smokers
Some lndlvlduals develop lung cancer wlLhouL a
slgnlcanL smoklng hlsLory
uened as < 100 clgareues ln llfeume
ln Lhe uS, 10-13 occur ln never smokers
3 - 10 of lung cancer ln men
13 of lung cancer ln women
More Lhan Lhe number who develop ovarlan cancer
or Podgklns dlsease
LCINS
Worldwlde, 13 of men and 33 of women wlLh
lung cancer are never smokers
AccounLs for x of all cases
lf consldered separaLely, LClnS would rank as Lhe 7
Lh

mosL common cause of cancer deaLh world wlde
C|ass|hcanon of Lung Cancer WnC
n|sto|og|c C|ass

Ma[or Lypes
Adenocarclnoma 32
3 of LoLal are pure 8AC
Squamous cell carclnoma 29
Small cell carclnoma 18
Large cell carclnoma 9
unclassled/undlerenuaLed 12
Squamous Ce||
93 are smokers
usually cenLrally locaLed
Lower raLe wlLh meLasLauc dlsease
Can CavlLaLe
AssoclaLed wlLh PC and hypercalcemla
Adenocarc|noma
MosL common hlsLologlc subLype.
lncreased lncldence ln never smokers
usually locaLed perlpherally
Plgher raLe of meLasLauc dlsease
Sma|| Ce||
AlmosL 100 are smokers
usually cenLrally locaLed
vasL ma[orlLy presenL wlLh meLasLauc dlsease
lf you have Lo choose paraneoplasuc syndromes
relaLed Lo lung cancer plck sma|| ce||.
Large Ce||
90 are smokers
usually perlpherally locaLed
80 presenL wlLh meLasLauc dlsease
Iormer|y known as 8ronchoa|veo|ar Ce||
SubLype of adenocarclnoma (3)
new classlcauon whlch does away wlLh Lhe word 8AC
Cen non-smokers, more female
May presenL as SollLary nodule, Lobar consolldauon, or
Muluple nodules
ulerenL presenLauons may be dlerenL dlseases wlLh dlerenL
prognoses


Iormer|y known as 8ronchoa|veo|ar Ce||
SLaged and LreaLed as an adeno
lf pure 8AC, may conslder lesser resecuon
30 are responslve Lo LCl8 lnhlblLors

Slow growlng wlLh laLe meLasLases
oLenual for aerogenous and lymphauc spread
Lower llkellhood of a (+) L1
8ronchorrhea may be a problem
Can complaln of salLy Lasung spuLum
CopyrlghL 2011 !ournal of 1horaclc Cncology. ubllshed
by Llpplncou Wllllams & Wllklns.
24
Categor|es of New Adenocarc|noma C|ass|hcanon
Where Iormer 8AC Concept was Used

DIAGNCSIS
Patient Identication
History
PlsLory
MosL common sympLoms are:
Cough, uyspnea, ChesL aln, PemopLysls
Less common sympLoms:
Clubblng, Poarseness, uysphagla, Wheeze
Cnly 3 - 13 are asympLomauc
13 have exLra-pulmonary sympLoms
10 may presenL wlLh a paraneoplasuc syndrome
Ask quesuons relaLed Lo a cancer dx: new onseL
headaches, bone paln, eLc
uesnon 2
Whlch of Lhe followlng sLaLemenLs regardlng Lhe resulLs of
Lhe nauonal Lung Screenlng 1rlal for lung cancer ls noL
Lrue?

A. lL randomlzed >30,000 persons Lo elLher low dose
chesL C1 or chesL x-ray
8. 1here was a lung cancer speclc morLallLy reducuon of
20 ln Lhe C1 arm
C. 1here was no reducuon ln overall morLallLy
u. ApproxlmaLely 23 of Lhe C1 screens dlscovered an
abnormallLy

uesnon 2
Whlch of Lhe followlng sLaLemenLs regardlng Lhe
resulLs of Lhe nauonal Lung Screenlng 1rlal for lung
cancer ls noL Lrue?

A. lL randomlzed >30,000 persons Lo elLher low dose
chesL C1 or chesL x-ray
8. 1here was a lung cancer speclc morLallLy reducuon of
20 ln Lhe C1 arm
C. 1here was no reducnon |n overa|| morta||ty
u. ApproxlmaLely 23 of Lhe C1 screens dlscovered an
abnormallLy


Screen|ng
Nanona| Lung Screen|ng 1r|a|
33,434 paruclpanLs
Age 33-74
CurrenL or former smokers - 30 pack years
8andomlzed Lo Low uose C1 (LuC1) vs Cx8
Scanned for 3 years followed for 3.3 years
8educed Lung-Cancer MorLallLy wlLh Low-uose
CompuLed 1omographlc Screenlng. n Lngl ! Med.
uCl:10.1036/nL!Moa1102873
Screen|ng
Nanona| Lung Screen|ng 1r|a|
20 reducuon ln lung cancer morLallLy
6.7 reducuon ln overall morLallLy
26,309 LuC1 screens
7191 (27) 96.4 false posluves
MosL false posluves needed only radlographlc f/u
1 morLallLy wlLh surgery
no cosL emcacy sLudles
Mulu-socleLy guldellne recommends screenlng for
same populauon LesLed ln Lrlal
anent Idennhcanon - hys|ca| Lxam
(S|gns)
hyslcal exam
llndlngs usually parallel sympLoms
SvC Syndrome, apllledema
LymphadenopaLhy (parucularly supraclavlcular)
osluve only laLe ln Lhe course
lf rsL clue ls from physlcal, Loo laLe
anent Idennhcanon
30 have evldence of unresecLablllLy aL Lhe ume of
rsL dlagnosls
lurLher Lesung reveals anoLher 13
3 - 10 wlll be unresecLable aL surgery
Cnly 23 - 30 are surglcal candldaLes and Lhus
poLenually curable
anent Idennhcanon -
araneop|asnc Syndromes
Many paraneoplasuc syndromes
PC (clubblng)
Pypercalcemla
Cen due Lo producuon of 1P-llke hormone
More common wlLh nSCLC (Squamous)
SlAuP
MosL common syndrome ln SCLC
Cushlngs Syndrome
uoes noL preclude curauve Lx
So||tary u|monary Nodu|e
D|erenna| D|agnos|s: 8en|gn SN
non-speclc or healed granulomas (23)
lnfecuous granulomas (13)
8enlgn neoplasms (13)
PamarLoma
Llpoma, broma, counLless oLhers (rare)
CLhers: lung abscess, pseudoLumor, round
aLelecLasls, AvM, lnfarcL, mucold lmpacuon,
hemaLoma, rheumaLold nodule, Wegeners
D|erenna| D|agnos|s: Ma||gnancy
Adenocarclnoma (~30)
8ronchoalveolar cell carclnoma (~3)
Squamous cell carclnoma (~20)
SollLary meLasLasls (~10)
undlerenuaLed nSCLC (~10)
Small cell carclnoma (<2)
SN
re-LesL robablllLy: laclllLaLes selecuon and
lnLerpreLauon of subsequenL LesLs
valldaLed model from Mayo Cllnlc
Slx lndependenL predlcLors of mallgnanL Sn
auenL characLerlsucs: Age, smok|ng status,
h|story of extrathorac|c ma||gnancy
nodule characLerlsucs: dlameLer, splculauon,
upper lobe locauon

Swensen et a|. Arch Intern Med 1997,1S7:849
C1: S|ze Mauers
S|ze ma||gnant
2-3 mm 1
6-10 mm 24
11-20 mm 33
21-43 mm 80
Penschke eL al. LanceL 1999,334:9-103.
C1: Ldge Character|sncs
8order Lype L8
1. SmooLh 0.2
2. LobulaLed 0.3
3. SplculaLed 3.0
4. Corona radlaLa 14
Slegelman eL al. 8adlology 1986,160:307
Ckk: auerns of Ca|c|hcanon
Central Laminated Diffuse
Popcorn Stippled Eccentric
auerns A-u are benlgn, pauerns L and l are non-speclc
SN
re-LesL probablllLy of cancer
Low ls < 3
Serlal C1s
lnLermedlaLe ls 3 - 60
Conslder L1, 11nA, 8ronch
Plgh ls > 60
Lxclslonal blopsy wlLh frozen secuon
C1-Gu|ded INA
11 sLudles wlLh daLa abouL accuracy ln Sn:
Medlan sensluvlLy 90 (range 63 Lo 94)
Medlan speclclLy 100 (range 96 Lo 100)
SpeclclLy assumed Lo be 100 ln some sLudles
non-dlagnosuc resulLs 3x more common ln benlgn Lhan
mallgnanL nodules, buL non-dlagnosuc blopsy does noL
rule ouL mallgnancy
Medlan probablllLy of 1x 26.3 (range 13 Lo 43)
~3 requlred chesL Lube (range 4 Lo 18)
Wah|d| et a|. Chest 2007.
8|opsy: 11NA
ACC recs: ln pauenLs wlLh an lndeLermlnaLe Sn (10 mm) lL ls
approprlaLe Lo perform a 11nA or bronchoscopy ln Lhe followlng
clrcumsLances:
when cllnlcal pre-LesL probablllLy and ndlngs on lmaglng LesLs
are dlscordanL, for example, when Lhe pre-LesL probablllLy of
cancer ls hlgh and Lhe leslon ls noL hypermeLabollc by L1
when a benlgn dlagnosls requlrlng speclc medlcal LreaLmenL ls
suspecLed
when a fully lnformed pauenL deslres proof of a mallgnanL
dlagnosls prlor Lo surgery, especlally when Lhe rlsk of surglcal
compllcauons ls hlgh.
auenL non operauve and need ussue Lo rx
SN
kad|ograph|c Io||ow-up
Fleischner Society Recommendations
Radiology. 2005 Nov;237(2):395-400.
D|agnos|s of Lung Cancer
Sputum Cytology
Diagnostic in 20%
74% of central lesions
5% of peripheral lesions
Reasonable rst step for central lesions in
patients who need a diagnosis but are unlikely to
undergo treatment
Not commonly ordered for peripheral lesions
8ronchoscopy
CenLral leslons
30 sLudles, LoLal of 3,734 pauenLs
Cverall sensluvlLy 88
rocedure SensluvlLy
ulrecL endobronchlal 8x 74
Lndobronchlal brush 39
8ronchlal wash 48


ko|e of 8ronchoscopy

erlpheral leslons
30 sLudles, 4,136 pauenLs
Cverall sensluvlLy 30-60
lacLors aecung yleld:
Slze of Lhe leslon
>2cm sensluvlLy 62
<2cm only 33
8ronchus exLendlng Lo Lhe leslon (60)
use of uoroscopy, number of blopsles (>3)
D|agnos|s of Lung Cancer
Pleural Fluid Cytology
If uid is present, tap it
For tissue diagnosis and assists in staging
Only 50% are cytologically positive
Direct invasion is not the only mechanism
If cytology is negative in 2 taps
Proceed to thoracoscopy
Blind biopsy improves recovery by only 8%
D|agnos|s of Lung Cancer
8lopsy of posslble meLasLauc slLes
Supraclavlcular nodes
Llver Leslons
Adrenal LnlargemenL
noL only makes Lhe dlagnosls buL also sLages as lv
Stag|ng
1nM sysLem
LsumaLe prognosls
SelecL LreaLmenL opuons
8eporL ouLcomes
7
Lh
edluon of Lhe 1Mn Classlcauon of MallgnanL
1umors
ubllshed ln !uly 2009

Internanona| Stag|ng System Changes
1 componenL (Slze mauers)
Subclasslfy 11
11a, lf < 2cm
11b, lf beLween 2 and 3 cm
Subclasslfy 12
12a, lf beLween 3 and 3 cm
12b, lf beLween 3 and 7 cm
8eclasslfy 12 > 7 cm
now 13
Old T2
New T2
T2b
T3
T2 T2
3.1 cm 6.8 cm
13 cm
now to make a 13
tumor
8e very large (>7 cm)
lnvade someLhlng
noL lung
noL essenual
Pave a second Lumor ln
Lhe same lobe
Cause aLelecLasls of a
whole lung
IASLC Staging Handbook in Thoracic Oncology
now to make a 14
tumor
lnvade someLhlng
LhaL surgeons canL
(or prefer noL Lo)
remove
CeL a second Lumor
lpsllaLeral lung
ulerenL lobe
IASLC Staging Handbook in Thoracic Oncology
1 descr|ptors: What changed?
lurLher subdlvlde 11 and
12 Lumors
8ecognlzed Lhe poorer
prognosls for very large
prlmarles (>7 cm)
8ecognlze Lhe beuer
prognosls for lpsllaLeral
lung nodules
8ecognlze Lhe poor
prognosls assoclaLed wlLh
mallgnanL pleural
euslons
Internanona| Stag|ng System Changes
n componenL
no changes

Internanona| Stag|ng System Changes
M componenL
M1a = ConLralaLeral nodules or pleural
dlssemlnauon
M1b = ulsLanL meLasLases

M descr|ptors
What has changed?
8ecognluon LhaL.
noL all meLasLases are creaLed equal
MeLasLases Lo dlsLanL organs carry a worse
prognosls Lhan Lo Lhe conLralaLeral lung
MallgnanL pleural euslons confer a
prognosls LhaL ls as poor as meLasLauc
dlsease
Stage I
11a and 11b
n0 M0 ls lA
12a
n0 M0 ls l8
Stage II
12b
n0 M0 ls llA
11a or 11b
n1 M0 ls llA
12a
n1 M0 ls llA
12b
n1 M0 ls ll8
13
n0 M0 ls ll8

Stage IIIA
lpsllaLeral medlasunal nodes (n2)
Also 13 n1,2 M0
Also 14 n0,1 M0
noL recognlzed by A!CC, buL lllA may be funcuonally
dlvlded lnLo:
lllA1 = + nodes found ln speclmen
lllA2 = + nodes found aL surgery
lllA3 = + nodes found durlng pre-op w/u
lllA4 = 8ulky + nodes found durlng pre-op w/u

Stage III8
ConLralaLeral medlasunal nodes (n3)
Also, 14 n2 M0
Stage IV
Any 1 or n wlLh an M1a or M1b
kev|sed S year Surv|va|
Stage Clinical Pathologic
IA 50% 73%
IB 47% 58%
IIA 36% 46%
IIB 26% 36%
IIIA 19% 24%
IIIB 7% 9%
IV 2% 13%
Sma|| Ce|| Lung Cancer - Stag|ng
SCLC may be sLaged uslng Lhe revlsed 1nM sysLem

May be sLaged uslng an older vA Lung Cancer SLudy
group sysLem
LxLenslve SLage
LlmlLed SLage
Sma|| Ce|| Lung Cancer
LlmlLed SLage (30)
1umor ls conned Lo one hemlLhorax, Lhe medlasunum, or
Lhe supraclavlcular nodes
All Lumor ls encompassed ln a slngle x81 porL
noL conLralaLeral hllar or supraclavlcular
LxLenslve SLage (70)
Cllnlcally deLecLable dlsLanL meLasLases
lncludlng (+) pleural and perlcardlal euslons
MosL commonly = 8one, Llver, CnS, Adrenal
D|agnos|s - Now what?
1wo Maln Cuesuons:
ls Lhe Lumor resecLable (sLaglng)?
no beneL from debulklng
Answerable from work-up

ls Lhe pauenL operable (genl healLh)?
Can Lhe pL wlLhsLand Lhe sLress of surgery?
uo Lhe poLenual beneLs ouLwelgh Lhe rlsks?

D|agnos|s - Now what?
1wo Maln Cuesuons
ls Lhe Lumor resecLable?
8aslcally, a search for meLasLauc dlsease
Pas Lhe Lumor spread beyond LhaL whlch ls
resecLable?

re-1reatment Lva|uanon - n|story
WelghL loss
SkeleLal paln, ChesL paln
Peadache
Syncope
Selzure
LxLremlLy Weakness
MenLal SLaLus Change
re-1reatment Lva|uanon - hys|ca| Lxam
LymphadenopaLhy
Poarseness
SvC Syndrome
8one Lenderness
PepaLomegaly
local neurologlc slgns
apllledema
So ussue mass
re-1reatment Lva|uanon - 1esnng
C8C
LlecLrolyLes and Creaunlne
Calclum and Alkallne hosphaLase
AS1, AL1, and 1oLal 8lllrubln
Cx8
C1 down Lhrough Lhe adrenal glands
Stag|ng for Lung Cancer
Non-|nvas|ve Stag|ng
Invas|ve Stag|ng
C1
L1
Non-surg|ca| Surg|ca|
LUS
L8US
Med|asnnoscopy
Anter|or
Med|asnnotomy
(Chamber|a|n
procedure)
VA1S
Why Do Invas|ve Stag|ng?
Accuracy of C1 and L1 Stag|ng
Med|asnna| Lymph Nodes
Sensitivity Specificity
CT
N=7,368
55% 81%
PET
N=4,105
80% 88%

Summary of 43 (C1) and 4S (L1) tr|a|s
Silvestri et al. CHEST 2013; 143(5)(Suppl):e211Se250S
Methods of Cbta|n|ng 1|ssue
Medlasunoscopy
MedlasunoLomy
1horacoscopy
1rans bronchlal needle asplraLe
LuS wlLh lnA
L8uS wlLh lnA
Conhrmanon of Intrathorac|c Stage
Extensive Infiltration
Discrete N2, 3 enlargement
CT neg. but central, adeno, N1
Peripheral clinical stage I
Accuracy of Stag|ng 1ests |n Lung Cancer
anents
rocedure Number
of
Stud|es
N Sens Spec
Med|asnnoscopy 3S 10,648 81 100
LUS 26 2,443 89 100
L8US 26 2,7S6 89 100
L8US]LUS 7 811 91 100
S||vestr| et a|. !"#$% '()*+ ),*-./-$0112/34'))$54'.($
kecommendanons
ACC guldellnes 2007: Many lnvaslve Lechnlques for Lhe
conrmauon of Lhe n2,3 node sLaLus are suggesLed as reasonable
approaches (eg, medlasunoscopy, LuS-nA, 18nA, L8uS-nA, or
11nA)
ACC guldellnes 2013: ln pauenLs wlLh hlgh susplclon of n2,3
lnvolvemenL, elLher by dlscreLe medlasunal lymph node
enlargemenL or L1 upLake (and no dlsLanL meLasLases), a needle
Lechnlque (L8uS- nA, LuS- nA or comblned L8uS/LuS - nA) ls
recommended over surglcal sLaglng as a besL rsL LesL

ueuerbeck l eL al. ACC 2 guldellnes ChesL 2007
SllvesLrl eL al. !"#$% '()*+ ),*-./-$0112/34'))$54'.($