Traitement n©o(adjuvant) du cancer de l’“sophage

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Traitement néo(adjuvant) du cancer de l’œsophage. Christophe Mariette. Service de chirurgie digestive et générale CHRU Lille. 0,0,0,0,0,0,0,0,0,0. Item 1 Item 2 Item 3 Item 4 Item 5 Item 6 Item 7 Item 8 Item 9. 274,1,2,1,0,1,1,1,1,1,1,1,1,0. Tumeurs T1 – T2. - PowerPoint PPT Presentation

Text of Traitement n©o(adjuvant) du cancer de l’“sophage

  • Service de chirurgie digestive et gnraleCHRU Lille

  • 0,0,0,0,0,0,0,0,0,0Item 1Item 2Item 3Item 4Item 5Item 6Item 7Item 8Item 9

    274,1,2,1,0,1,1,1,1,1,1,1,1,002040608010001224364860stade 0stade Istade IIAstade IIBstade III100%84%49%27%17%Chirurgie seule : Survie 5 ans Mariette Eur J Surg Oncol 2004

  • Surgery alone vs. chemoradiotherapy followed by surgery for localized esophageal cancer: analysis of a randomized controlled phase III trial FFCD 9901 C. Mariette, JF Seitz, E Maillard, F Mornex, PA Thomas, JL Raoul, V Boige, D Pezet, C Genet, L BedenneFdration Franaise de Cancrologie Digestive

    Dpt of digestive and oncological surgery, University Hospital - Lille - FRANCE

  • Study design

    Neoadjuvant CRT + surgery group (CRT+S group, n=97)45Gy/25F/5 weeks with 2 courses of concomitant CT 5FU 800mg/m2/day D1-D4 + cisplatin 75mg/m2 D1 or D2

    Surgery alone group (S group, n=98)Transthoracic approach with two-field lymphadenectomy

    R SURGERY SURGERY4 to 6 weeksMariette ASCO 2010

  • Postoperative course Mariette ASCO 2010

    CRT + S groupN=84S groupN=91P30-day postop mortality6 (7.1%)1 (1.1%)0.054Postoperative morbidity37 (44.1%)45 (49.5%)0.18Mean nb of resected nodes17.723.9

  • Overall survivalMariette ASCO 2010

    CRT + S groupS groupPHRMedian survival (months)31.8 [25.2-72.5]44.5 [29.8-59.1]0.680.92[0.63-1.35]3-year survival48.6%55.2%

  • 0,0,0,0,0,0,0,0,0,0Item 1Item 2Item 3Item 4Item 5Item 6Item 7Item 8Item 9

    274,1,2,1,0,1,1,1,1,1,1,1,1,002040608010001224364860stade 0stade Istade IIAstade IIBstade III100%84%49%27%17%Chirurgie seule : Survie 5 ans Mariette Eur J Surg Oncol 2004

  • Thirion P., Michiels S., Le Matre A., Tierney J. The MetaAnalysis of Chemotherapy in Esophagus Cancer Collaborative Group Thirion, ASCO 2008

  • Thirion, ASCO 2008

  • Analyse en intention de traiterQueen Mary48/7439/73-4.28.9Italy37/4835/48-1.04.5MRC EO-02233/400215/402-9.649.5RTOG 8911144/233138/234-3.328.0MD Anderson13/1716/190.71.4Scandinavia 223/5616/50-2.46.2Scandinavia 2R28/5320/58-5.16.9Oeso-235/5840/640.77.3Total561/939519/948-24.2112.7EtudeChimio propNo. Evts / No. inclusTmoinsO-EVarianceOdds ratioOR (95% CI)Effet chimio prop p = 0,02Test dhtrognit: p = 0,740,81 [0,67-0,97]Chimio prop meilleure| Tmoin meilleur0.00.51.01.52.0

  • Thirion P., Maillard E., Pignon J.P.

    The MetaAnalysis of Chemotherapy in Esophagus Cancer Collaborative Group Thirion ESTRO 2008

  • Thirion, ESTRO 2008

  • Analyse en intention de traiter

  • Sjoquist et al Lancet Oncol 2011

  • Adnocarcinome

    CT noadjuvante

    RCT noadjuvanteT3 N1 T4N0N1 M0 TNCD

  • T3 carcinome pidermoideESSAI GECSG Population :Epidermodessophage thoracique 1/3 sup et moyenOprables T3 N 0/1 Schma :

    CT induction FLEP x 3 puis RT 40Gy + EP + ChirCT induction FLEP x 3 puis RT >65Gy + EP Hypothse :

  • ESSAI GECSG: Survie globaleSurvie 2 ansBras A : RCT+chir 40%Bras B : RCT 35%

  • Bras A RCT+chir (n=27) survie 3 ans 58% Bras B RCT (n=25) survie 3 ans 55% ESSAI GECSG: Survie globale chez les rpondeurs la CT dinduction

  • ESSAI GECSG: RcidiveContrle loco-rgionale 2 ansBras A : RCT+chir 66%Bras B : RCT 35%P = 0,003p = 0,003

  • ESSAI FFCD 9102 Population :Epidermodes 90%/Adksophage thoracique, oprables T3 N 0/1 Schma :

    RT+ 5 FU-CDDP x 2 Chirurgie si rponse objective RT + 5 FU-CDDP x 3 Hypothse :

  • ESSAI FFCD 9102 : survie globaleSurvie 2 ansBras A : RCT+chir 34%Bras B : RCT 40%p = 0,44 NSBedenne J Clin Oncol 2007

    Chirurgie

    RT-CT

    p

    Geste palliatif contre la dysphagie

    24 %

    46 %

    < 0,0005

    Mortalit 3 mois

    9 %

    1%

    < 0,005

    Dure d'hospitalisation

    68 jours

    52 jours

    < 0,05

  • 34% (bras chir) vs 43% (bras RCT+C)39% (bras chir) vs 29% (bras RCT+C)P=0,04 A 2 ansESSAI FFCD 9102 : rcidiveBedenne J Clin Oncol 2007

    RLbras

    00

    1.87.1

    17.934.5

    31.939

    33.643

    36.144.9

    36.147.2

    39.147.2

    39.147.2

    44.955.4

    44.955.4

    chir

    RT-CT

    2-YEAR RECURRENCE RATE 56% vs 59% (arm B)

    %

    FFCD 9102 - RECURRENCE RATE ACCORDING TO RANDOMISATION ARM

    metabras

    00

    64.8

    25.219.9

    33.925.9

    39.129

    43.530.8

    43.533.3

    43.536.3

    43.536.3

    43.536.3

    43.536.3

    P=0,21

    Chirurgie

    Chimiothrapie

    Mois

    %

    Mtastatique

    RLttrec

    00

    26.5

    15.835

    27.542.1

    27.547.3

    30.249.1

    30.251.2

    33.751.2

    33.751.2

    33.762.6

    33.762.6

    chir

    RT-CT

    mois

    %

    Risque de rcidive locale selon le traitement reu

    metattrec

    00

    55.8

    26.120.3

    36.125.7

    39.830.1

    44.531.9

    44.534.5

    44.537.5

    44.537.5

    44.537.5

    44.537.5

    Surgery

    chemo XRT

    mois

    %

    Risque de mtastases selon le traitement reu

    REbras

    00

    7.811.1

    34.447

    51.154

    55.558.5

    60.961.1

    60.964.3

    6366.1

    6366.1

    66.571.4

    66.571.4

    chir

    RT-CT

    mois

    %

    Risque de reprise volutive selon le bras de randomisation

    REttrec

    00

    711.6

    33.247.5

    48.656.6

    51.961.8

    57.964.3

    57.967.4

    60.369.1

    60.369.1

    60.376.3

    60.376.3

    chir

    RT-CT

    mois

    %

    Risque de reprise volutive selon le traitement reu

    Feuil1

    RL en brasmta en brasRL en tt reumta en tt reuRE en brasRE entt reu

    chirRT-CTChirurgieChimiothrapiechirRT-CTChirurgieChimiothrapiechirRT-CTchirRT-CT

    000000000000000000

    61.87.1664.8626.5655.867.811.16711.6

    1217.934.51225.219.91215.8351226.120.31234.4471233.247.5

    1831.9391833.925.91827.542.11836.125.71851.1541848.656.6

    2433.6432439.1292427.547.32439.830.12455.558.52451.961.8

    3036.144.93043.530.83030.249.13044.531.93060.961.13057.964.3

    3636.147.23643.533.33630.251.23644.534.53660.964.33657.967.4

    4239.147.24243.536.34233.751.24244.537.5426366.14260.369.1

    4839.147.24843.536.34833.751.24844.537.5486366.14860.369.1

    5444.955.45443.536.35433.762.65444.537.55466.571.45460.376.3

    6044.955.46043.536.36033.762.66044.537.56066.571.46060.376.3

    Feuil2

    Feuil3

    RLbras

    00

    1.87.1

    17.934.5

    31.939

    33.643

    36.144.9

    36.147.2

    39.147.2

    39.147.2

    44.955.4

    44.955.4

    Locorgionale

    Chirurgie

    Chimiothrapie

    %

    metabras

    00

    64.8

    25.219.9

    33.925.9

    39.129

    43.530.8

    43.533.3

    43.536.3

    43.536.3

    43.536.3

    43.536.3

    p=0,21

    Surgery

    Chemo XRT

    Months

    %

    FFCD 9102 - METASTATIC RECURRENCE RATE ACCODING TO RANDOMISATION ARM

    RLttrec

    00

    26.5

    15.835

    27.542.1

    27.547.3

    30.249.1

    30.251.2

    33.751.2

    33.751.2

    33.762.6

    33.762.6

    chir

    RT-CT

    mois

    %

    Risque de rcidive locale selon le traitement reu

    metattrec

    00

    55.8

    26.120.3

    36.125.7

    39.830.1

    44.531.9

    44.534.5

    44.537.5

    44.537.5

    44.537.5

    44.537.5

    Surgery

    chemo XRT

    mois

    %

    Risque de mtastases selon le traitement reu

    REbras

    00

    7.811.1

    34.447

    51.154

    55.558.5

    60.961.1

    60.964.3

    6366.1

    6366.1

    66.571.4

    66.571.4

    chir

    RT-CT

    mois

    %

    Risque de reprise volutive selon le bras de randomisation

    REttrec

    00

    711.6

    33.247.5

    48.656.6

    51.961.8

    57.964.3

    57.967.4

    60.369.1

    60.369.1

    60.376.3

    60.376.3

    chir

    RT-CT

    mois

    %

    Risque de reprise volutive selon le traitement reu

    Feuil1

    RL en brasmta en brasRL en tt reumta en tt reuRE en brasRE entt reu

    ChirurgieChimiothrapieSurgeryChemo XRTchirRT-CTSurgerychemo XRTchirRT-CTchirRT-CT

    000000000000000000

    61.87.1664.8626.5655.867.811.16711.6

    1217.934.51225.219.91215.8351226.120.31234.4471233.247.5

    1831.9391833.925.91827.542.11836.125.71851.1541848.656.6

    2433.6432439.1292427.547.32439.830.12455.558.52451.961.8

    3036.144.93043.530.83030.249.13044.531.93060.961.13057.964.3

    3636.147.23643.533.33630.251.23644.534.53660.964.33657.967.4

    4239.147.24243.536.34233.751.24244.537.5426366.14260.369.1

    4839.147.24843.536.34833.751.24844.537.5486366.14860.369.1

    5444.955.45443.536.35433.762.65444.537.55466.571.45460.376.3

    6044.955.46043.536.36033.762.66044.537.56066.571.46060.376.3

    Feuil2

    Feuil3

  • T3 carcinome pidermode rpondeurs RCT2 essais RCT exclusive vs RCT + chir

    Pas de diffrence significative en termes de survie globale chez les patients rpondeurs la RCT/CT dinduction Meilleur contrle loco-rgional en cas de chirurgie Dcs prcoces plus frquents dans le bras chirurgical

    Stahl J Clin Oncol 2005 - Bedenne J Clin Oncol 2005

  • Etude prospective controlle incluant seulement patients T3 N0-N1 80 chirurgie seule144 RCT + chirurgie

    R0: 48% vs 74.3% (p < 0.001)Downstaging significatif :16% pCRSurvie 5 ans 17% vs 37% (p = 0.002)Survie 2 ans RCT+chir 55%RCT: facteur indpendant de survie RR 2.1 IC 1.5 to 2.9, P < 0.001

    Mariette Br J Surg 2006

  • T3 carcinome pidermode rpondeurs RCT2 essais RCT exclusive vs RCT + chir

    Pas de dif