Lung Cancer Cancer Lung Cancer

Document Sample
Lung Cancer Cancer Lung Cancer Powered By Docstoc
					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
•   85 % CB non à petites cellules
•   2 malades sur 3 forme étendue/métastatique
•   < 15 % malades guéris
•   1ére cause de mortalité par cancer pour les
    deux sexes confondus ; première cause chez
    la femme aux USA !
Survie en fonction du stade TNM
• % de survie à 5 ans (Mountain 1997)
                      cTNM      pTNM
    Stade IA            61        67
                 N0
    Stade IB            38        57

    Stade IIA           34        55
                 N1
    Stade IIB           24        39
                                        mN2 : 29
    Stade IIIA   N2     13        23    cN2 : 7

    Stade IIIB          5          -
    Stade IV     N3     1          -
             Traitements et stade TNM
     • Les standards thérapeutiques actuels
        Stades IA, IB (N0)
        Stade IIA, IIB (N1) Chirurgie*            + CT péri-opératoire
                                                    ± curage médiastinal
        Stade IIIA (N2)                             ± RT** post-op.
                                                    modes d’administration
        Stade IIIB (N3)                 CT-RT°    ±
                                                    doses, fractionnement

                                                    CT standards
        Stade IV (M1)                 CT(ddp)°°   ± CT de 2éme ligne/Tarceva®
                                                    BSC

*sauf inopérable, **toujours T3 pariétal, °sauf certains T4, IIIB pleurale et IRC,
°°sauf métastase cérébrale ou surrénale unique
J Clin Oncol 1997, 15:2996; SOR-FNLCC 2003
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 ?
            Excess of risk of LC in HIV
   • Increase in cancer-related death in HIV
                  Kaposi sarcoma
                                                       94
           Atypical mycobacteria                       98
        Non Hodgkin lymphoma
              P. carinii pneumonia
                    Liver disease
                   Coronaropathy
                          Cancer
                                     0   5   10   15   20 %


Louie, JID 2002
            Excess of risk of LC in HIV
   • Increase of LC in HIV hospitalized patients

                Kaposi sarcoma                           93-96
        Atypical mycobacteria                            96-99
          Bacterial pneumonia
       P. carinii pneumonia
Other opportunistic infection
                    Lung cancer
                                  0   5   10   15   20   30 %


Dufour, Lung 2004
        Excess of risk of LC in HIV
• Pre-HAART epidemiological studies
Author          n HIV         Study         Pre-            SIR*         Post-          SIR*
                                           HAART                        HAART
Frish          302,834           R            yes             4            no

Parker          26,181           R            yes            6.5           no

Grulich         31,616           R            yes            3.8           no

Dal Maso 60,421                  R            yes            2.4           no

Herida          77,025           P            yes             1           yes             2

Bower            8640            R            yes             1           yes           8.93
Reviewed in Lavolé, Lung Cancer 2005. *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
• Bias due to difference of
  smoking habits in HIV ?                       % of smokers
                                                    57
             risk factors for cardiovascular                  HIV
              disease                                          Non HIV

             age 35 to 44 years old                     33
             HIV patients, n=274
              (APROCO cohort)
             non HIV-persons, n=1038
              (WHO-MONICA project)
Savès, CID 2003
             Excess of risk of LC in HIV
      • Bias due to difference of smoking habits in
        HIV subgroups ?
       Groups                          Frish                Dal Maso        Herida
                                         SIR                      SIR        SIR

       All                               4.5                      2.4         1
       Men                               4.3                      2.2        1.13
       Women                             7.1                      8.7        1.08
       Homosexual                        3.7                       -         0.92
       IVDU                              6.8                      9.4        3.16
       Heterosexual                      4.2                       -         0.99
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
      expected number of LC in the general population if 100 %
       of the persons were smokers

                     40   SIR = 6.5                   40         SIR = 2.5


                                      Number of LC
      Number of LC




                     30                               30
                                                                        LC observed in HIV
                     20                               20                LC expected in HIV

                     10                               10

           0                                           0
      unknown % of smokers                           100 % of smokers

Parker, Chest 1998
        Excess of risk of LC in HIV
• Pre-HAART epidemiological studies
Author          n HIV         Study         Pre-            SIR*         Post-          SIR*
                                           HAART                        HAART
Frish          302,834           R            yes             4            no

Parker          26,181           R            yes            6.5           no

Grulich         31,616           R            yes            3.8           no

Dal Maso 60,421                  R            yes            2.4           no

Herida          77,025           P            yes             1           yes             2

Bower            8640            R            yes             1           yes           8.93
Reviewed in Lavolé, Lung Cancer 2005. *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
   • Increase of LC since the use of HAART
          bias due to dramatic decrease in AIDS-related mortality

                  Kaposi sarcoma                           94
           Atypical mycobacteria                           98
        Non Hodgkin lymphoma
              P. carinii pneumonia
                    Liver disease
                   Coronaropathy
                          Cancer
                                     0   5   10    15     20 %
Louie, JID 2002
                  Excess of risk of LC in HIV
    • Dramatic increase of LC in HIV-women since
      the use of HAART
                                                      25000
              7
                                                      20000   16395                         23152
                                                                                            + 41 %

                                          Incidence
              5
  SIR of LC




                                                      15000


                                                      10000                                  4591
                                                                                            + 182 %
              3                                       5000     1629

                                                         0

              1                                                1980   1985   1990    1995    2000
                                                                             Years
                  Male   Female
                                     Bias due to smoking epidemic in women ?

Hérida, J Clin Oncol 2004, Remontet, Resp 2003
            Excess of risk of LC in HIV

 • 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
Cadranel, Respiration 1999; Bower, AIDS 2004
 Excess of risk, which mechanisms

     Smoking + HIV + ID + HAART…

        Normal       Hyperplasia       Metaplasia       Dysplasia       Carcinoma



    3p LOH, microsatellite alterations
        9p21 LOH
                    telomerase upregulation, MYC over expression
                                                  8p21-23 LOH
                                                    neoangiogenesis, loss of FHIT, P53
                                                    mutations, aneuploidy, methylation
Increase of genomic instability ?                                5q21 APC-MCC LOH,
                                                                     K-ras 12 mutation
Wistuba, JAMA 1997
   Clinical presentation of LC in HIV
   • Epidemiological characteristics
                 Alshafie Sridhar Vyzula                     Tirelli        Lavolé           Spano
 n                   11            19            16            36               44            44
 age                49.7           48           44.5           38               42            42
 % male              82           100            94            89               93            93
 % smoker            90            84           100            94              100            100
 . duration           -             -             -             -               28            28
 . quantity           -          60 py         30 py       40 cig/dy         30 py           30 py
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
                 Alshafie Sridhar Vyzula                     Tirelli        Lavolé           Spano
 n                   11            19            16            36               44            44
 age                49.7           48          44.5            38               42            42
 % male              82           100            94            89               93            93
 % smoker            90            84           100            94              100            100
 . duration           -             -             -             -               28            28
 . quantity           -          60 py         30 py       40 cig/dy         30 py           30 py
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
                 Alshafie Sridhar Vyzula                     Tirelli        Lavolé           Spano
 n                   11            19            16            36               44            44
 age                49.7           48           44.5           38               42            42
 % male              82           100            94            89               93            93
 % smoker            90            84           100            94              100            100
 . duration           -             -             -             -               28            28
 . quantity           -          60 py         30 py       40 cig/dy         30 py           30 py
Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004
   Clinical presentation of LC in HIV
   • Histological type
                      100

                       80                                                              SCC
         % of total




                       60                                                              Other
                                                                                       LC
                       40
                                                                                       SC
                       20                                                              ADC

                        0
                            Alshafie Sridhar   Vyzula   Tirelli   Lavolé   Spano

Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004
   Clinical presentation of LC in HIV
   • No ADC predominance compared to controls
                                       50
                 % of adenocarcinoma




                                                                                 Non HIV
                                       25                                        HIV




                                        0
                                            Alshafie Vyzula   Tirelli   Lavolé

Br J Sur 1984; Chest 1992; Cancer 2000; Lung Cancer 2003
Clinical presentation of LC in HIV

• Extensive disease at presentation
   Clinical presentation of LC in HIV
   • Clinical TNM staging at presentation
                     100

                      80
                                                                                   Stage I
        % of total




                      60
                                                                                   Stage II
                      40                                                           Stage III

                      20                                                           Stage IV

                       0
                           Alshafie Sridhar   Vyzula   Tirelli   Lavolé   Spano


Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Med Oncol 2004
   Clinical presentation of LC in HIV
   • % of stage IIIB-IV similar as controls
                                  100

                                   80
             % of stadge III-IV




                                   60                                                  Non HIV
                                                                                       HIV
                                   40

                                   20

                                    0
                                        Alshafie Sridhar   Vyzula   Tirelli   Lavolé

Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003
Clinical presentation of LC in HIV
• 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
                     Survival of LC in HIV

 • Clinical studies on survival
                 Alshafie       Sridhar          Vyzula           Tirelli       Lavolé         Powles
                 VIH/non VIH    VIH/non VIH     VIH/non VIH     VIH/non VIH    VIH/non VIH VIH/non VIH

Median            4/7 mo.       3/10 mo. 8/12.5 mo.             5/10 mo.       9/13 mo. 4/4 mo.
                   p=0.003       p=0.002         p=0.003         p=0.0001        p=0.01          ns

1-yr survey        0/20%         0/32%          10/50%           10/48%         33/55%         11/22%

2-yr survey         0/8%          0/0%           0/18%            0/25%         13/34%           -




Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003; Br J Cancer 2003
        Prognostic factors on survival


    Classical factors…     Other factors ?
      TNM: RR=2.2
         IC95% [1.3-3.9]

         PS: RR=11                 ?
          IC95% [3.6-34]

       HIV: RR=1.7
           IC95% [1-2.9]

Lavolé, in press 2004
        Prognostic factors on survival
   • Difference in TNM staging at presentation
                                   100

                                    80
              % of stadge III-IV




                                    60                                                  Non HIV
                                                                                        HIV
                                    40

                                    20

                                     0
                                         Alshafie Sridhar   Vyzula   Tirelli   Lavolé

Br J Sur 1984; Chest 1992; Lung Cancer 1996; Cancer 2000; Lung Cancer 2003
        Prognostic factors on survival
   • Difference in PS at presentation
                                                    p < 0,01
                                    100

                                    75
                    % of patients




                                                                         PS < 2
                                    50
                                                                         PS 2-4

                                    25

                                     0
                                          Non HIV              HIV
                                                                     Maybe at cause ?
Lavolé, in press 2004
        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
        Prognostic factors on survival
   • Surmortality due to HIV-related mortality…



                                                          HAART
                                             100
                      % of total mortality


                                             75
                                                                                Others
                                             50                                 HIV
                                                                                Lung cancer
                                             25

                                              0
                                                   Alshafie Tirelli   Lavolé
                                                                               Very unprobable ?
Chest 1992; Br J Sur 1984; Lung Cancer 2003
               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 ?
Massera, Lung Cancer 2000; Lavolé, in press; Cooper, JAMA 1984; Costleigh, AmJGastro 1995; Vallis, Lancet 91
            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
               Therapeutic management
    • Interactions between CT and HAART
            NRTI                          Antiproteases                            NRTI
         ddc, ddi, d4T                        RT, SQ, IND                            AZT




                                                                                   anemia
         neuropathy                             CYP450
                                                                                 neutropenia

                                           Anthracyclines
                                             Alcaloïdes
        Carboplatine                                                             Cisplatine
                                              Taxanes
         Taxanes                                                                 Vinorelbine
                                         Cyclophosphamide
                                             Etoposide
Washington, J AIDS Hum Retrovirol 1998; Flexner NEJM 1998; Scagliotti JCO 2002
     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
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
                       Lung tumors in HIV




 Kaposi’s sarcoma            Lymphoma        Lung carcinoma
 . RR = 177                  . RR = 44-77    . RR = ?
 . Role of HHV8              . Role of EBV   . Oncogenic virus ?


Cadranel, Respiration 1999
            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
             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
              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

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:8
posted:9/17/2012
language:French
pages:40