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Page :APTSR 4 A CLINDCAL REVIEW OF 493 pATIENTS OF LONG CANCER (197G-:980) 34 .1 tSaterials 35 .2 Sex and age distribution 36 .3 Ristologic types 39 .4 Clinical features 43 .5 Chest radiological patterns 47 .6 tibreoptic bronohoecopic patterns 49 .7 Cigarette smoking (A) Cigarette amoking and lung cancer 53 (B) Cigarette sraoking pattern in our patients 57 .8 8urvivgls in untreatQd, inoperable disease 82 1.9 Conclusion 88' :x~~raa a A PLANNBa R6TROSpSCTIVS CLINICAL 8TU'nY OP $03 PATiaNTS Oa LUdiG CANCER (19a1- 1984) eg 5.1 }datesials 70 5.2 $sx and age distribution 70 5.3 Histologic types 73 5.4 Clinical features 77 S.S Chest radiolog:cal patterne 80 5.8 Pibreoptio broachoecopic patterns 82 5.7 Cigarette smoking pattern 86 5.8 Conclusion - 93 x1

CHAPT&R 6 SFF£CT OF CFi85QOT},*&nAPY ON SURVIVAL - A BTUDY OF TKRCB COld23INATIOh CH81d0TH8RAPY 8CH8MB3 IN 139 PATIENTS XITii INOPSRARLS LUNG CANCSR (1979- 1984) 6.1 (A) (3) (C) 1tmall cell carcinaes - HACC chemotheraqy Pxtienta ind 1eethode Results D1scuation 8.2 -Ron-sr.atll cel2 lung cancar (A) XACC ohesaotherapy 1. Patiente and Methods 2. Results (B) 2tivo FAY chemotherapy achecaee ia brcnchial adeaoc:rcinoma 1. Aa,tientc and ldetbode Z. Results (C) Diecus8ion 6.3 Conclusion 95 97 97 102 102 109 109 112 119 120 121 132 135 CiSAPTFsR 7 CABE-COltTRCL $TUDY OF 'PAS9IYE SMOKING, RaROSENB 8TOV8 t79XG3 XND R064E INC5N3E BURNING IN RSLATION TO Lt3NG CANCER IN NON-SldOKBR F81dAS.E' (1li81-1984) 136 7.1 2ntroductton .2 (A) (B) (C) Pxwsive smokin4 Keroaene atove cooking Incense burning at Aotne Patisnts and methods 7.3 Results 7.4 Discussion 7.5 Conclusion 137 137 138 13a 140 143 148 155 CIiAPTER 8 DIRECTIONS PC3R FIITURL* STUDIES 157 8.1 Bpidemio2ogioal tuAiea (A) In Bong Kong 159 (B) In collaboration With Guangzbow (Canton) 160 xii

8.2 Pathologic atudits: (A) Clinico-Pathologic study 161 (B) 8carring (tuberculoua) and lung cancer 181 8.3 lioat d.t.rminaatx t (A) Kistocompatibility (HLA) antitens and lung cancer 164 (8) Aryl fiydrocsrbon Hydroxy2Rgo (Aflti) iAducibility and luna asncer 165 8.4 • Epi; logue 167 aEFSA5NCS3 169

In Hona tong, lung cincer is the co=onest lethal malignant diseace in both aales aad tetaales. This theais represented the tirst major alinical study of luns cancer (197E3- 1954) in the loaa2 Chinese popstlation. The patients were those adaitted to the gnivaraity Departmant of Medicine, Queen ldary Bospital, Hong Kong, and all had histologically or cytoio:icaliy proven lung cincer. HistoloQical typing was based on the Tor1~d Health Orgazizat.on Claesitication (1981), with 4 major types of lung cancer, naMVly_. (1) squamous ceil carcinoma (SQ), (Z) ama2l cell carcinoma (SX), ~ (3) adenooaroinoms (aD), #.nd (4) large cell carcinoma (LA). f_ _ . . _ . . .. ... . -~- - A Drer.auiaits tor'a alinical •tudq of lun¢ oancer is acaurat• cell,tyDiag.,;Yq.phase-oae study wr.s to assess .' collaboratel ith th De t t o~ Qatholo the ooll t i I _ Y w a par m.n tF YD n8 i' =".accurscy of aytodlagnosla (broachoscoDlc aad sDutum) in our = hospital. 1n a tive-year studyYperiod (1978-1983) in 573 pstienta, for both bronchoscopio end sputum cytoxogic cell typing, accuracy wad highest in 8Q and SM (76-100x), followed by hD (80-88T.). That of LA wao much lower (< 67%), but the number ot patients was small. The mext phase io collecZion oS clinical data baae by a elinical review o2 493 yztients admitted trom 1976 to 1980. The mzle to leiaala sex ratio was low (1.87:1), reflecting the

high incidence of lung cancer in women in Hong xong. In s.n, SQ was the predominant celi type (44%), followed by AD (23%), SM (13%) and LA (?%), but In women, the preponderance of AD (44%; SQ 31%; 8Y 10%; LA 2%) is noteworthy. Cigarette smoking wae a major tactar in•9Q and SM. The relative risk o: lung cancer in review study were confirmed. The pdalo to feroaie•ratio'was iow :- " (1.99:ij. A history of cigl,rette smoking wae strongly = , _ ___. . _. .. . - ; ~! Y._ . .~. . . . - .. .. ~ .diagnosis from January 1981 to April 1984. The findings of the smokers was 6.4 to 10.7 for SQ aad 8V, but was not cigaaficant ~ with AD or LA (C 1.8). SQ and 69, ~.Oing amoking-related, showed features of a centrally located tumour. Our AD, contrary to claseioal toachiag, also showed clinical, radiological and broaehoscopic teatures of a oentrally situated tumour. A three-yart study waa thea carried out in parallel from 1951 to 1984 : (i) :..-.Ciiaicsl dlta were eo2leoted from 503 patisnts upon associated with 8Q and SM. The relative risk of lunQ canaer In smokers was 5.5 with SQ aad 21 with 39 In men, and 10.5 with SQ and 33.9 with 8)d in women, but not excessive with AD aad LA (1 to 1.1). In women, AD was the predominant ceil type (58%), and 48% of a1l cases and E3% of AD were life-long non-smokers. Again, AD showed features of a predominantly centrally situated tumour. iii

(2) That our AD, usually in noti-etuoker females and centrally eituated, was intriguing. A caee-Ooptrol study of 183 temale patients and 185 iemaie eoetrols was carried out to compare their ezposure to three common eAvironmental, inhaled t •qIjAmi, Aw1 Y iw1 Yr wlrl ng Irarnronn nrrnrn finsn .t home incense burning. Analysis for non-smokero showed tbat kerosene stove and iaoenee burning were not coatributory factors (D ? 0.05). Paaeive scaoking wae with AD of the ceatral type, but also not shown to be aeaociated maf contribute to AD of the peripheral t3'pe (p C 0.05). (3). -The wedian survival oS our patieats:'with untreated,'. -e inoperable diseaae was zoor: beia¢ i tiontb tor small-l eall cancer Z, ~ yar+ • `.. I ' 3«S months ! or non•email celi •cancero. studied the '_ ~ _` ._._. . -,~ ~= sitect ot tbree eombiaation ehemotheraDy aohees@e on;surviv~tl of r : r._.-~--.'~ •te these patients. ~ Sst 43 patients oi smr~ll cell • carcinoma,- &CC ; (raetLotrexate, adriamycin, tyolophoaphamide and CCNU) :_ chemotherapy was etfective (21% complete and 33% partial response), and sisniticxntly improved overall patients survival (median survival 50 weflks). In ao,n•8mail cell cancers, hoMever, MACC aheraotherapy (in 42 patients) and luAX/FiAld schemes (Putrafui/S-rluorouraail, adriamycin, Mitoraycin-C, !n 44 patients of adeaooarcinoma), were ineft.ctive. Although partial response occurred in a-Z7% of patients, thore waa no overall survival benefit. - - Sv 2023512700 . i~y~'~

I XitD amore solid data base,.coilaborative atudios now bein.g iaitisted, including city-wtd. epidemio1o¢icsl studies, clinico-pstho2ogio ttudies, snd atudies ot host deteraiinants. are

iamilies, and should Lher.tore b. re-ezuain.d. C. Tncenee Burning at Home - Snrnin= of CLiaese ino.ase at . temples in vorship of idols or sods, a c:o=on scene in tourista books, is part of the trs.ditional Chinese oustoms still practised In gon8 ZooB. Eurnins of incense at hOIDe, eitber tor ancestor worshiD (traditional C2tinese tilial pietr) or deity worship, is also comon among the large non-Christian local population. Chinese incease smoke has been shown to contain carcinogens, (8choeatal i Oibbard, 1907) but to-date, oo studies have been undertaken to ezamine its relation to luaa cancer. • Given that (1) in SonB Zona, horae iacease ba.rniag In oommon, (2) that many sdnlt .flmen in EonR Zon8 are 6osssewives ebo sDend most ~ :.ot their tiw at home, inhalinj incenae smok. wbioh oontains + ~ oRroiaosens, k' (3) tlsat SonB 7[ons is overcrowded with *tap :"Saiailies .liwing 1ti bouses/tlats ot area 400 to 600 •Qaare teet ~ioh: woula -iaorease the lahaled dose oi any poteatial ~ . ~;" i,- ' - . . . . . . . . ;.° :,"tnhaied carciaoSea"., preseat In a small home area; it is coaceivable that inceasa smoke might well be important in the 9eaesis ot lung oancer In os:r womea wbo do not smoke. A study was thereiore carried out to examine whethsr passiw smoking, kerosenf itove cooking anct tncease buraing at home are liYely ozusatiee taotors in lua; aanoer in aon-smokin8 Chinesb women. This forms Part C of the 5981-1884 Iuat cancer 4

study, (soe Cbapter 5, pp a0). 7.2 ?atieots & Methods This is a Case-control study. Tbo cases weru all of t1,u Chioose iemale patients who •oro admitted to the University D.p4rtment of Nedioine, Queon Mary BosDital, i3oag 1Cona, bet.oon Jauurry 1981 aad April 1984, .with htstolodioaliy and/or oytologioa11y confirmed carcinoma of the lung of the four major cell types (Types 1-4, 1f.8.0. Classification, 19a1).- Oreat cars •. was taken to exciude saoondary carciooma oi ths iuna (seo pp 18- :.- ;"_ 18) but otherwise all Chinese temale patients were included with ;, no other selection oriterir. , Compc~rison p~tieAts (/ooatrols)z: c .:._ , .: . . . - - . r~.. - a. .~ ~ i. -'ti •• . .. .- - ._... _-1 , .. .. . ~ wdre Chincsa iemsile patients admitted to the'OrtdoDaidic`.vardi ' . .. -=:r I n Mu..n 1/s rv tln.rwf ta l Aut+4 w• t}.Ab ..ar4 wA I 9A 2-t ARd i• w..m n,. w.1.T ....,~. . _ . ..r-. . . ' to.lunr canosr patisuts in a8o and sociai class -•both cases and '`yi, =~ s`-~ ~.1':- . , . w-. . . . . . ~...... . . , _ ~ . .. , . ~ ~. .... . . i:: . t.. _ ~ . coatrol• were'patisnts ol the thirl class aeneral wards and voru ~ oostly from thu lower inaoioe group. Patients with Dathological : tractures due to smokidt-related msli8nanoia, and periphoral=''.,', ; vasoular d,isoase-rel,eted orthopaedio coaditioaa xore sxcluded. it is oonsiclervd that our ortDop.odio coatrols should not be biased toeards swkin6-aasooLwted disaases. AI1 aasQS .rore interviewed by aysoll, and the oontrols by myself or Kiaa Ciudy Lina, our technician and research assistRnt, rlto was tralnecd for this invevtl6ation anQ thoroughly -140- N . C N C1t F-~ N ~ O W 4

, famS.liar with locul culture. Z'be Questiono'aovor4d dialect group, oocnpation, smokiag habits, pascivo smokina, domestic cooking including kvrosons stove, and home incense burning, in tUrm o! a standardixW questionnaire (Fig. 7.1). nor vary ill p..tidnts, or for pr.tients wllo spoke & dialect other than Ckntoaose or 8atidarin, arraagemont would then be made for their next-ot-kin to be interviewed with the patienta as ieterpreter. Attempts at quantitation ot passivo smoking Aas boen ' _ _,~ __.. . _ . . . . ::recogniwed as difeioult (2oyal ColleBo ot Physicians, 1983; Yeiss at s.l, 1883).:~ 8ideetroan smoke, ; to which the passive ~~-~-smoko r is esflasoA.-is Qiiutvd by room air'to a variable'extsnt. ' ~'~`.5`Ite :TUa room air itaelI also oontains sa,oks which Kas been iahaled _ AC' and tt~dn exhaled into tbe air.~ lmount and duration of smoke ,, expo aure,- tho smokers'.g srnaking habit,'siso and veatilation of rcwrns otc. are all importunt variabi.s, and the amouotof the" various components ot tobaoco smoke breatbod by the non-smoker from a smoky atmoaphere are therefore extrwaely vartablo and unpredictable, anA there aro no agrood standards for expressinII the oxtunt of pollution of indoor atmocDhorus by tobacco saoko. Ttro same problwr applies to Quantitatioa ot einosure to kerosone sto'vu cooking tuioes and burning of incense at home. 2 bad the opportuqity o! Qisouseire this with air Richard Doll during his visit to the University Deptrtment of tlodicino, fiong lConB, in