E7. The IASLC staging project: non-small cell lung cancer: a radiation oncologist's perspective

21 ,:,

E7. The IASLC staging project: non-small cell lung cancer: a radiation oncologist's perspective David L. Ball Peter MacCallum Cancer Centre, Departments uf Dlagnustlc Imaging and Radlatlun C>nculug.~,Melbuurne, Australia

In categurlslng malignant neuplasms, TNM stage is assigned tu the anatumical extent uf disease tu assist in ( 1 ) planning uf treatment, (2) estimating prugnusis, and (3) gruupmg patients intu prugnustlcally humugeneuus gruups tu alluw lntercumparlsun uf results Further, the 6th editiun uf the TNM classificatiun 11997 revisiun) states that a "classificatiun is needed whuse basic principles are applicable tu all sites regardless uf treatment" [1] In regard tu nun-small cell lung cancer (NSCLC) treated by radiutherapy, there are a number uf shurtcummgs in the 1997 classificatiun, buth in its ease uf applicatiun and m achieving the three aims stated abuve This presentatiun will review sume examples, and cunsider uppurtunities fur lmpruvement Ease of application: Nearlv all patients treated bv nun-surgical means are staged cllnlcallv and are therefure nut dlrectlv cumparable with surgical patients whu are pathulugically staged with greater precisiun. Clmlcallv staged patients appear tu have a different prugnusis stage fur stage if the staging algurithm includes FDG PET scanning cumpared with structural imaging alune [2] This is m part due tu the superiur sensltlvltv uf FDG PET fur the detectiun uf regiunal lymph nude invulvement 19qO.. versus 6qO.. fur CT) The 1997 revisiun separates nudal invulvement mtu 3 gruups N1 - lpsllateral hllar: N2 - lpsllateral medlastlnal and N3 - cuntralateral thuracic ur lpsllateral and cuntralateral scalene/supraclavlcular nudes The anatumical buundarv separating statiun lq~ (hllar, N l l frum statiun 4 (medlastlnal, N21 is the medlastmal pleural reflectiun, which cannut be distinguished radluluglcally, thus requiring uccasiunal guesswurk whether a cllnlcallv staged patient has N1 ur N2 disease Planning of treatment: T stag~ Increasing T stage reflects **increasing size and/ur lucal extent uf the primary tumuur'" The 1997 classificatlun [1] is based un patients treated between 1975 and 1988 During that perlud, there was httle evidence that chemutherapy and radlutherapy l m p r u ~ d survival uf patients with NSCLC, and the classificatlun favuured tumuur characteristics which predicted surgical resectabllltv Hence, T4 tumuurs are t~enerally unresectable un the basis uf anatomical loca~on and therefure can be, as fur T3, "w(,' s~c¢'" ~ t it is nut anatumical lucatiun, but tumuur size, which determines if a tuinuur can be radlcallv irradiated A pruspective studv uf the Trans Tasman Radiatiun CInculug~ Gruup

{TRC)G) cumpared T stage and primary tumur vulume in 212 patients with NSCLC [3] Althuugh there was a statlstlcallv significant trend {P -, q}q"q I fur tt~nuurs with a higher T stage tu have larger vulumes, sume T4 tumuurs were smaller than T1 tumuurs, and there was unlv a 5qO.. cuncurdance when tumuurs were categurlsed accurdmg tu T stage T~rsus vulume The T4 descriptur includes tumuurs which mav be technically treatable with radical radiutherapy as well as sume that are nut {malignant pleural effusiun) N stage Invulvement uf regiunal lymph nudes is nut unly prugnustic, but can alsu influence resectabllltv Thus N1 disease is technically resectable, N3 disease is nut The situatiun with N2 disease is less clear cut There are nu unlversallv agreed criteria differentiating resectable frum unresectable N2 disease, even thuugh this mav be impurtant in deciding whether a patient shuuld be treated bv mductlun therapy fulluwed by surgery, ur bv a nun-surgical appruach The current classificatiun dues nut take accuunt uf size, number ur fLxltv uf medlastlnal nudes, eT~n thuugh these mav have a cunsiderable bearing un resectabllltv Estimating prognosis: T stag~ When surgery was the unlv effective treatment mudalltv fur NSCLC, size may have been uf less cunsequence than resectabllltv Nuw that there is strung evidence that nun-surgical treatments radlutherapy and chemutherapy alune ur m cumbmatlun can lmpruve survival, it mav be necessarv tu re-evaluate the impurtance uf size, an lmpurtant radlubluluglcal determinant uf respunse Several recent repurts uf patients treated bv radiutherapy have fuund that tumur size is uf inure prugnustic significance than stage [4,5] Char gruup fuund nu effect uf T stage (as uppused tu size) un prugnusis in 243 patients treated bv nun-surgical means [6] TRC)G is currentlv perfurmmg a pruspective evaluatiun uf the influence uf vulume un survival in patients treated with radlutherapy fur NSCLC and has accrued uver 4q.~ uf a planned 5q.~ patients M stag~ Cumprehensive gruuping uf patients with metastatic disease, whether sulltarv ur multiple, using the single descriptur M1, mav nu lunger be apprupriate Patients with sulltarv metastases detected bv FDG PET appear tu h a ~ better survival than patients with multiple metastases [7] There is alsu evidence that particular subgruups with ullgumetastases [eg sulltarv brain] mav ubtain a survival benefit frum inure aggressive treatment

E~ rev,te,t .45 "~,~ r. Prognostic homogeneity: T stage A w i d e r a n g e o f five year survival data (6-32°.) have been reported for p a t i e n t s w i t h s t a g e T1 N ~ a n d T 2 N ~ N S C L C t r e a t e d b v r a d i o t h e r a p y [8] B e f o r e a t t r i b u t i n g a n y o f t h e s e o u t c o m e s to the effects o f radiotherapy, the influence o f other prognostic factors, especially serious c o - m o r b i d i t y i n a n o n - s u r g i c a l population, needs to be taken mto account Hence. i n a Japanese series o f patients w i t h stage I N S C L C treated bv s t e r e o t a c t l c i r r a d i a t i o n . 5-year s u r v i v a l w a s a p p r o x i m a t e l y 8~O,, i n p a t i e n t s w h o w e r e m e & c a i N o p e r a b l e b u t r e f u s e d s u r g e r y , c o m p a r e d w i t h 3~O,, i n p a t i e n t s w h o w e r e m e & c a i N

i n o p e r a b l e [9] Stage g r o u p T h e h e t e r o g e n e l . t y w i t h i n s t a g e I I I A ( N 2 ) was demonstrated in a review of surgical outcomes m w h i c h 5-vear s u r v i v a l w a s o n l v 20,, i f it w a s k n o w n b e f o r e s u r g e r y t h a t p a t i e n t s h a d N 2 d i s e a s e , c o m p a r e d w i t h 3~O,, i f n o d e i n v o l v e m e n t w a s f o u n d m c l d e n t a l l v at s u r g e r y [1~] Similar discrepancies have been observed m studies of

c h e m o r a d l o t h e r a p y for stage III N S C L C I n one recent r a n d o m l s e d trial m v o l v l n g patients w i t h stage IIIA and B disease, t h e m e d i a n s u r v i v a l i n o n e a r m w a s o n l v 11 4 m o n t h s [11]. w h i l e m a s i n g l e a r m s t u d v i n c l u d i n g o n l y p a t i e n t s w i t h I I I B disease, it w a s 2 6 m o n t h s [12] A l t h o u g h these differences have b e e n attributed to variations i n the t r e a t m e n t p r o t o c o l s u s e d . d i f f e r e n c e s o f t h i s m a g n i t u d e are s e l d o m s e e n i n r a n d o m l s e d t r i a l s , a n d t h e v are m o r e h k e l v t o b e r e l a t e d t o c h a r a c t e r i s t i c s o f t h e p o p u l a t i o n s or o t h e r e n v i r o n m e n t a lfactors not accounted for b v stage Conclusion: From the perspective of the radiation oncologlst, t h e r e are i m p o r t a n t s h o r t c o m m g s m t h e 1997 r e v i s i o n o f t h e TNNI c l a s s i f i c a t i o n T h e s e c a n r e s u l t m d e m o n s t r a b l e h e t e r o g e n e i t y w l t h m s t a g e c a t e g o r i e s w i t h t h e p o t e n t i a l to mask the true benefits of therapeutic mterxentlon Studies of prognostic factors m large cohorts of patients treated bv n o n - s u r g i c a l m e a n s are u r g e n t l y r e q u i r e d t o a d d r e s s t h e s e deficiencies

511

References

[1] &,bin LH and ~rittelr.in,i ,- TNM, l ~ i f l , lti,,n ,,t m~li~nant n_m~,,ur.Wiley-Liaa, New 7; ,rl:. 21,12 [2] M~ Manna MP. et ~1 F-18 fiu,,r,,,te,,:.:¢glu,,,ae p,,a:tr,,n em:aa:,,n t,,m,,~ ml're aN:rig m r~h, :1 r~,h,,th_~y, an,t:,t~e a w:th n,,n-cm~ll , ell lung, at, :n,,m: p,,w_~tul, ,,rrel~:,,nw:th~'t~v:v~lan,t h:~h m,p~, t ,,n tre~rnent ,: an, _~ 21,11.~2 88~-8~5 [,3] B,dl E,. et ,d Ttm,,,r v,,ltm, e , ,,rrel'~ea p,,,,rl;¢ w~th ,t~ae',~e at~,e m n,,n-m,~ll , ell lun~ , an, _~ prelm, mary an~l:ea~a ,,t the TranaI~m, an R ~ h ~ , , n ,-,n, ,,1,,g;¢ ,3r,,up ~ - ~ 5 ,t~c,~ae Lun~ ,-an, _~ [4] ,-lam,,n ,3. et ~1 R ~,h,,aena~t~W~,,nw~th, ~rb,,pl~m t,,r p ~ e n t a w~th urtreae,t~ole a~eIIIn,,n-m*~ll,ell lung, an, _~ ~ph~eIIItn~l,,t the ,-an, _~ and Leukem~ ,3r,,up B and the E~:t~n ,-,,,,p_~~ree ,-n, ,,1,,g;¢ ,Trr,,up J,,um~l ,4 ,-lm~, ~1 ,-~n,,,1,,g;¢ 1 ~ . 7 4-11 [5] ~,tle;¢ J. et "d ,3r,,~'~"am,,,r v,,ltm,< ,nh, al pr,,gn,,a~, t~,t,,r m p ~ e n t a tre~e,t w~th three-,tm, ena~,,n~l , ,,nt,,rm~l r~h~h,,n th_~p;¢ t,,r n,,n-m,~ll-, ell lung, ~r, m,,m~. Int~r~t~,,n~l J,,urn~l ,,t R ~,h'~-~,,n ,-n,, ,1,,g:¢B~,,1,,g:¢Pl'r/a~,a fi~"~fi.Sfi 4~--57 [~'] B'dl L' et "d F'alure ,,t T a ~ e t,, pre, h, t ~'t~-el-¢'d m p'~lent a with n, ,n-cm~ll , ell lun~ , an, _~ tre~e,t 1:,7 r~tl, ,th_~p;¢ with , ,r with, ,ut , ,,n, ,,mlranr, hem,,th_~y Int J R ~t1~1,,n ,-n, ,,1 BI,,1 Pk¢a 211112.54 111117-11117 [7] M~ Manu~"MR. et ,d FL,,3-PET-,tete,ted e:~tr~rm111 m e t ~ t ~ l : m p ~henr~-w~rhn, ,n-m, ~11,ell lung, an, _erun, t_~g,,rag a ~ m g },,r aUrg_ery ,,r r~tl, ~1 r~tl,,th~n:e-~'t~vr¢~l , ,,rrelctea with metc.'tCtl, ,tlaet~e bur,ten A, t¢ ,:~n,,,1,,~1, ¢ 2~,~,3.42 48-54 [8] ~?lble:¢,3 R ~tl,,ther~n:¢},¢ pZtlenta with me, h, ~11:¢m,,p~ole at~e I n,,n-m:¢ll,ell lun~, an, ~ ,: an, er 1~8 82 4,3,3-4,38 [~] ,:~n1~1H. et ¢1 ~?t~e,,t~ tl, hl~h ,t, ,ae trr ~t1¢tl,,n },,r a¢~e I n, ,n-retell , ell lun~ , at, ln,,m¢ Pr,,, A~?,:,:, 2~,~4 ~,14

[111] ~?hlel,ta TW The al~nlfl, an, e ,4 lpallZt~.l me,hc.'tln~l 1Fmph n,,,te met ¢.'t~1a [N2 ,tlae~e] m n, ,n-rot ~11, ell, at, m, ,m ¢, ,} the lun~ J, ,urn~l ,,t Th,,r~, 1, and ,: ~r,t>,v',~,u l ~ bUrg_er;¢ I'~'~L'~'~48-5,3 [11] V,,kea E. et ¢1 In,tu, t~,,n ,hem,,th_~pv t,,ll,,we,t 1:,7 ,,,n,,,nntant , hem,,r~,h,,th_er~p;¢-¢_erma , hem,,r~,h,,th_er~p;¢ "d,,ne },,r reg__~,,n,dl;¢ ~,t-¢an,e,t urtreae, tcble n,,n-m,¢ll , ell lun~ , an, _~ Pr,,, Ab,-,-, [lfi] ,3an,tare E, et ~1 ,-,,na,,h,t~,,n ,t,,, eta.el ~t_~ , ,,n, urrent ,hem,,r~h,,th_~pv m a ~ e IIIB n,,n-m,~ll, ell l u n g , m, _~ J ,-lm ,-~n, ,,1 21111,321211114-211111