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Infection VIH et Cancer Bronchique Le cancer bronchique en France 25 000 nouveaux cas par an 5 hommes/1 femme; age moyen 60 ans > 80 % cas liés au tabac.

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Presentation on theme: "Infection VIH et Cancer Bronchique Le cancer bronchique en France 25 000 nouveaux cas par an 5 hommes/1 femme; age moyen 60 ans > 80 % cas liés au tabac."— Presentation transcript:

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2 Infection VIH et Cancer Bronchique

3 Le cancer bronchique en France nouveaux cas par an 5 hommes/1 femme; age moyen 60 ans > 80 % cas liés au tabac 85 % CB non à petites cellules 2 malades sur 3 forme étendue/métastatique < 15 % malades guéris 1 ére cause de mortalité par cancer pour les deux sexes confondus ; première cause chez la femme aux USA !

4 % de survie à 5 ans (Mountain 1997) Stade IA Stade IB Stade IIA Stade IIB Stade IIIA Stade IIIB Stade IV N0 N1 N2 cTNM pTNM N3 mN2 : 29 cN2 : 7 Survie en fonction du stade TNM

5 Les standards thérapeutiques actuels Stades IA, IB (N0) Stade IIA, IIB (N1) Stade IIIA (N2) Stade IIIB (N3) Stade IV (M1) Chirurgie* CT péri-opératoire ± curage médiastinal ± RT** post-op. *sauf inopérable, **toujours T3 pariétal, °sauf certains T4, IIIB pleurale et IRC, °°sauf métastase cérébrale ou surrénale unique CT-RT° ± modes d’administration doses, fractionnement ± CT standards CT de 2 éme ligne/Tarceva® BSC J Clin Oncol 1997, 15:2996; SOR-FNLCC 2003 CT(ddp)°° Traitements et stade TNM +

6 Which questions to be answered ? Is there an excess of risk ? Is there a specific clinical presentation ? Is there a particular histological type ? Is there a poorer prognosis ? Is there a particular therapeutic management ?

7 Increase in cancer-related death in HIV % Coronaropathy Liver disease P. carinii pneumonia Non Hodgkin lymphoma Atypical mycobacteria Kaposi sarcoma Cancer Louie, JID 2002 Excess of risk of LC in HIV

8 Increase of LC in HIV hospitalized patients Dufour, Lung Lung cancer Bacterial pneumonia Other opportunistic infection P. carinii pneumonia Atypical mycobacteria Kaposi sarcoma % Excess of risk of LC in HIV

9 SIR*Post- HAART SIR*Pre- HAART Studyn HIVAuthor Reviewed in Lavolé, Lung Cancer *SIR is defined by the number of LC observed in the HIV- population/number of LC expected in the general population matched for age Excess of risk of LC in HIV Pre-HAART epidemiological studies 8.93yes1 R8640Bower 2yes1 P77,025Herida no3.8yesR31,616Grulich no6.5yesR26,181Parker no4yesR302,834Frish no2.4yesR60,421Dal Maso

10 Savès, CID HIV Non HIV % of smokers  risk factors for cardiovascular disease  age 35 to 44 years old  HIV patients, n=274 (APROCO cohort)  non HIV-persons, n=1038 (WHO-MONICA project) Excess of risk of LC in HIV Bias due to difference of smoking habits in HIV ?

11 Frish, JAMA 2001, Dal Maso, Brit J Cancer 2003; Herida, J Clin Oncol 2003 Excess of risk of LC in HIV Bias due to difference of smoking habits in HIV subgroups ? Groups All Men Women Homosexual IVDU Heterosexual Frish SIR Dal Maso SIR Herida SIR

12 Parker, Chest 1998 SIR = % of smokersunknown % of smokers LC observed in HIV LC expected in HIV Bias due to difference of smoking habits in HIV  expected number of LC in the general population if 100 % of the persons were smokers Bias due to difference of smoking habits in HIV  expected number of LC in the general population if 100 % of the persons were smokers Excess of risk of LC in HIV Number of LC SIR = 2.5

13 SIR*Post- HAART SIR*Pre- HAART Studyn HIVAuthor Reviewed in Lavolé, Lung Cancer *SIR is defined by the number of LC observed in the HIV- population/number of LC expected in the general population matched for age Excess of risk of LC in HIV Pre-HAART epidemiological studies 8.93yes1 R8640Bower 2yes1 P77,025Herida no3.8yesR31,616Grulich no6.5yesR26,181Parker no4yesR302,834Frish no2.4yesR60,421Dal Maso

14 Louie, JID 2002 Increase of LC since the use of HAART  bias due to dramatic decrease in AIDS-related mortality Increase of LC since the use of HAART  bias due to dramatic decrease in AIDS-related mortality Excess of risk of LC in HIV % Coronaropathy Liver disease P. carinii pneumonia Non Hodgkin lymphoma Atypical mycobacteria Kaposi sarcoma Cancer

15 Hérida, J Clin Oncol 2004, Remontet, Resp 2003 Dramatic increase of LC in HIV-women since the use of HAART SIR of LC MaleFemale % % Years Incidence Bias due to smoking epidemic in women ? Excess of risk of LC in HIV

16 Cadranel, Respiration 1999; Bower, AIDS 2004 Hypothesies for causal factors…  increased frequency of smoking in HIV population, but intensity and duration not different  HIV status seems probable, but the mechanisms remain unknown : degree of immune deficiency duration of immune deficiency oncogenic role of HIV per se other oncogenic virus role of HAART Excess of risk of LC in HIV

17 3p LOH, microsatellite alterations 9p21 LOH telomerase upregulation, MYC over expression 8p21-23 LOH neoangiogenesis, loss of FHIT, P53 mutations, aneuploidy, methylation 5q21 APC-MCC LOH, K-ras 12 mutation Wistuba, JAMA 1997 Excess of risk, which mechanisms NormalDysplasiaHyperplasiaMetaplasiaCarcinoma Smoking Increase of genomic instability ? + HIV + ID + HAART…

18 . quantity. duration % smoker % male age n py Lavolé 40 cig/dy Tirelli 30 py Vyzula 60 py Sridhar Alshafie Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004 Clinical presentation of LC in HIV Epidemiological characteristics py Spano

19 . quantity. duration % smoker % male age n py Lavolé 40 cig/dy Tirelli 30 py Vyzula 60 py Sridhar Alshafie Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004 Clinical presentation of LC in HIV Epidemiological characteristics py Spano

20 . quantity. duration % smoker % male age n py Lavolé 40 cig/dy Tirelli 30 py Vyzula 60 py Sridhar Alshafie Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004 Clinical presentation of LC in HIV Epidemiological characteristics py Spano

21 Histological type Clinical presentation of LC in HIV Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol SCC Other LC SC ADC AlshafieSridharVyzulaTirelliLavolé % of total Spano

22 No ADC predominance compared to controls Br J Sur 1984; Chest 1992; Cancer 2000; Lung Cancer Non HIV HIV AlshafieVyzulaTirelliLavolé % of adenocarcinoma Clinical presentation of LC in HIV

23 Extensive disease at presentation Clinical presentation of LC in HIV

24 Clinical TNM staging at presentation Clinical presentation of LC in HIV Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol Stage I Stage II Stage III Stage IV AlshafieSridharVyzulaTirelliLavolé % of total Spano

25 % of stage IIIB-IV similar as controls AlshafieSridharVyzulaTirelliLavolé Non HIV HIV % of stadge III-IV Clinical presentation of LC in HIV Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003

26 Almost all heavy smokers Male predominance (but also male predominance in HIV population of industrialized countries) Similar to LC in the general population matched for age Characteristics of LC in HIV-patients are those observed in young people  adenocarcinoma predominance  extensive disease at diagnosis Clinical presentation of LC in HIV

27 Alshafie VIH/non VIH 4/7 mo. p= /20% 0/8% Sridhar VIH/non VIH 3/10 mo. p= /32% 0/0% Vyzula VIH/non VIH 8/12.5 mo. p= /50% 0/18% Tirelli VIH/non VIH 5/10 mo. p= /48% 0/25% Lavolé VIH/non VIH 9/13 mo. p= /55% 13/34% Median 1-yr survey 2-yr survey Survival of LC in HIV Clinical studies on survival Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Br J Cancer 2003 Powles VIH/non VIH 4/4 mo. ns 11/22% -

28 Classical factors… Other factors ? ? TNM: RR=2.2 IC95% [ ] PS: RR=11 IC95% [3.6-34] HIV: RR=1.7 IC95% [1-2.9] Lavolé, in press 2004 Prognostic factors on survival

29 Difference in TNM staging at presentation AlshafieSridharVyzulaTirelliLavolé Non HIV HIV % of stadge III-IV Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003

30 Difference in PS at presentation Prognostic factors on survival PS < 2 PS 2-4 p < 0,01 Non HIV HIV % of patients Maybe at cause ? Lavolé, in press 2004

31 Prognostic factors on survival Impact of HIV-status  severity of immune deficiency, not demonstrated  duration of immune deficiency, not evaluated  role of HAART, not evaluated  surmortality due to HIV-related mortality ?  impact of LC treatment ? Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003

32 AlshafieTirelliLavolé Others HIV Lung cancer Prognostic factors on survival Surmortality due to HIV-related mortality… Chest 1992; Br J Sur 1984; Lung Cancer 2003 % of total mortality HAART Very unprobable ?

33 Massera, Lung Cancer 2000; Lavolé, in press; Cooper, JAMA 1984; Costleigh, AmJGastro 1995; Vallis, Lancet 91 Therapeutic management Surgical management  absence of large series  similar indications that for the general population, but surgery is less frequently performed in HIV-patients because of poorer PS (64 % vs 100 %, p<0.04)  absence of post-operative surmortality Radiation management  few case-reports  increase frequency of radiation esophagitis ?

34 Therapeutic management Medical management  absence of prospective studies evaluating efficiency or toxicity of chemotherapy for LC in HIV-patients  indications and drugs similar as for the general population, but CT is less frequently performed in HIV-patients because of poorer PS (71 % vs 100 %, p=0.009)  disease control is less frequent (25 % vs 50 %, p<0.01) and grade III hematological toxicities more comon (75 % vs 25 %, p=0.02) Lavolé, Lung Cancer 2005

35 CYP450 Antiproteases RT, SQ, IND Anthracyclines Alcaloïdes Taxanes Cyclophosphamide Etoposide Carboplatine Taxanes NRTI ddc, ddi, d4T neuropathy Cisplatine Vinorelbine NRTI AZT anemia neutropenia Washington, J AIDS Hum Retrovirol 1998; Flexner NEJM 1998; Scagliotti JCO 2002 Interactions between CT and HAART Therapeutic management

36 HIV-related Lung Cancer How to improve these results ?  to better inform the HIV-population and to encourage smoking cessation  to propose a chest X ray in very large clinical situations and maybe to include HIV- populations in CT-scan screening studies  to open a national database on HIV-related LC  to perform prospective clinical studies evaluating effectiveness and toxicity of chemotherapy in HIV-patients

37 HIV-related Lung Cancer… a Growing Concern… Jacques Cadranel and Armelle Lavolé Service de Pneumologie et Réanimation Respiratoire UPRES EA3493 Hôpital Tenon, Paris - Université Paris VI

38 Cadranel, Respiration 1999 Kaposi’s sarcoma. RR = 177. Role of HHV8 Lymphoma. RR = Role of EBV Lung carcinoma. RR = ?. Oncogenic virus ? Lung tumors in HIV

39 Pre-test : question #1 Which of the following statements are true concerning the epidemiology of lung cancer in the HIV-population ?  A. LC is more frequent in the HIV-population  B. Increase of LC is more obvious in HIV-women than men  C. LC in the HIV-population is as frequent as in the non HIV-population matched for age  D. LC in HIV-population is as frequent as in non HIV-population matched for smoking habits  E. LC has increased in the HIV-population since the use of HAART

40 Pre-test : question #2 Which of the following statements are true concerning the clinical presentation of lung cancer in HIV-patients ?  A. Adenocarcinoma is the most frequent histology  B. One third of patients are non smokers  C. Most patients are PS < 2  D. Disease is most frequently diagnosed at stage I-IIIA  E. Immunodeficiency is usually severe

41 Pre-test : question #3 Which of the following statements are true concerning the prognosis and treatment of lung cancer in HIV-patients ?  A. Prognosis is poorer than in non HIV-patients  B. Poorer prognosis is related to more extensive disease  C. Poorer prognosis is related to the use of less optimal treatment compared with non HIV-patients  D. Chemotherapy is less effective in HIV-patients  E. Post-operative mortality is increased in HIV-patients


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