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'))$54'.($