Carcinoses Péritonéales d origine Colorectale F.Quénet CRLC Val d Aurelle Montpellier
Toward curative treatment of peritoneal carcinomatosis from digestive or primitive origin. A multi-institutional study of 290 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy Glehen Olivier, MD, PhD, Gilly François Noel, MD, PHD,2 Boutitie Florent,3 Bereder Jean Marc, MD, 4 Quénet François, MD, 5 Sideris Lucas, MD,6 Mansvelt Baudouin, MD,7 Lorimier Gérard, MD, 8 Msika Simon, MD, PhD,9 Elias Dominique, MD, PhD, and Association Française de Chirurgie Hospices Civils de Lyon, Surgical Oncology Department, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite cedex. Equipe Accueil 3738, Université Lyon, France. 2 Hospices Civils de Lyon, Service de Biostatistique, UMR 5558, CHU de Lyon, France. 3 Hopital de l Archet, CHU Nice, France. 4 CLCC Val d Aurelle, Montpellier, France 5 Hopital Maisonneuve-Rosemont, Montréal, Canada 6 Hopital de Jolimont, Haine St Paul, Belgium 7 CLCC Paul Papin, Angers, France 8 Hopital Louis Mourier, Collombes, France 9 Institut Gustave Roussy, Villejuif, France
Pour Quelles Pathologies Carcinoses Primitives ou Secondaires Mais surtout : Maladies Rares du Péritoine Pseudomyxomes Mésothéliomes Carcinomes séreux primitifs Psammocarcinomes Et : Carcinoses Secondaires fréquentes Carcinome ovarien Carcinome gastrique Carcinome Colique ou Rectal
Morbidité & Mortalité Mortalité globale 4.%, Parmis les 6 patients décédés, 4 patients avaient un PCI of >20 Morbidité globale 47.2%. Plus basse dans le groupe ox que dans le groupe ox-irino 34.9% vs. 52.4%, (p=0.05) Le taux de neutrpoénie expliquait cette difference ox-irino (37.9% vs. 2.3%, p= 0.00) En analyse multivariée anastomose colorectale (OR=3.67, 95%CI.68-7.98, p=0.00) Anastomose ureterale (OR=4.39, 95%CI.07-7.85, p=0.039) Sexe féminin (OR=2.43, 95%CI.4-5.8, p=0.02) Le taux de complications intra-abdominales pas significativement différent (8.6% in ox-alone vs. 9.4% in ox-irino, p=0.67)
Survival Results Dutch Trial : 05 patients Complete cytoreduction : median survival - 42.9 months After an 8 years follow up : The 5-year survival was 45% for R (V.Verwaal, Ann Surg Oncol. 2005 Jan;2():65-7 / Ann. Surg. Oncol. Vol. 5, No. 9, 2008) French multicentric study 523 patients Median overall survival: 33 months 5 years overall survival: 4, 27% (D.Elias & al JCO 200)
Survival Results 2 Groups of patients retrospectively selected 48 underwent CRS & HIPEC with oxaliplann 48 treated by systemic chemotherapy. HIPEC: Median overall survival: 62 months Standard: Median overall survival: 23 months (D.Elias JCO 2008) 4 patients treated by oxaliplatin alone & oxali-irinotecan Follow-up 48 months Median OS 6 months Median RFS 4 months (F.Quénet submitted)
In HIPEC procedures, which is the determining factor in improving survival?
In HIPEC procedures, which is the determining factor in improving survival? French Multicentric Study 523 patients 46 patients treated by CRS + HIPEC OX-Irinotecan compared to Ox alone (F.Quénet, D.Goéré, D.Elias. Submitted)
CHIPOXIRI: Survie Globale Il n y avait pas de différence significative entre : Median OS oxali seule 4 months, (95%CI 29 6) Median OS ox-iri 47 months, (95%CI 32-6) (p=0.94)
CHIPOXIRI : Survie sans récidive Median RFS Dans le groupe oxali 6.8 mois (95%CI -25) Dans le groupe ox-iri 5.7 mois (95%CI -8) (p=0.93)
CHIPOXIRI : Survie Globale Analyse univariée Métastases ganglionnaires Brèche diaphragmatique Nombre de régions touchées PCI Colectomie totale Nombre d organes réséqués En analyse multivariée Métastases ganglionnaires PCI OS à 5 ans : 65% pour PCI<0 26% pour PCI -9 8% pour PCI 20
in HIPEC procedures, which is the determining factor in improving survival? French Multicentric Study 523 patients No difference between Hipec with or without Oxaliplatin Good results with Oxaliplatin And good (not so bad?) results with Mitomycin C Does HIPEC really depend on the drug used?
R 6 months Before Interval After
Prodige 7 : Statistical Framework Primary endpoint : overall survival Secondary endpoints : PFS Treatment safety At first Intermediate analysis : Survival NA Mortality & Morbidity in accordance with expected figures Morbidity : There doesn t seem to be a big difference between the 2 arms Duration 44 months Number of patients 264 st intermediate analysis 2 d intermediate analysis Final analysis At 5 events, 34 months At 02 events, 50 months At 54 events, 7 months Power of test 80 HR 0.625
City Institution Investigators Number of patients registered Number of patients randomized LYON Hôpital Lyon Sud Olivier GLEHEN MONTPELLIER Centre Val d'aurelle François QUENET VILLEJUIF Institut Gustave Roussy Dominique ELIAS PARIS (Tenon) Hôpital Tenon Valéria LOI ANGERS Centre Paul Papin Gérard LORIMER PARIS (Lariboisière) Hôpital Lariboisière Marc POCARD DIJON CHU du Bocage Patrick RAT Centre René NANTES Gauducheau Jacques PAINEAU LYON Centre Léon Bérard Pierre MEEUS Centre Hospitalier TOULOUSE Purpan Guillaume PORTIER STRASBOURG Hôpital de Hautepierre Cécile BRIGANT NICE Hôpital de l'archet 2 Jean-Marc BEREDER 5 3 36 24 8 9 4 3 3 3 3 3 9 3 4 2 2 2 TOTAL 34 82
Multicenter phase III trial Comparing Standard Follow-up with Laparotomy plus HIPEC in Patients at High Risk of Developing a Peritoneal Carcinomatosis after Surgical Resection and Adjuvant Chemotherapy for Primary Colorectal Cancer. PROPHYLOCHIP PI : Dominique Elias
Preoperative assesment Patients at risk of developing a carcinomatosis Group : Synchronous minimal macroscopic PC Group 2 : Synchronous ovarian metastases Group 3 : Perforation of primary tumour Group 4 : Iatrogenic tumor perforation at first laparotomy 2nd look surgery CT scan : Se 60-79% Pet-Scan : Se 57% Under-estimation of the extent of desease Sensitivity < 30% if < 0,5mm Jacquet et al. Cancer 993 De Bree et al. J S urg Oncol 2004 Dromain et al. Abdom Imaging 2008
Results A macroscopic PC was found and treated in 6/29 (55%) patients, G Initial PC G2 Ovarian Metastasis G3 Perforation 0/6 (63%) 3/4 (75%) 3/9 (33%) Morbidity (grade III/IV) was 4%. Mean hospital stay was 6 days (Elias D et al. Ann Surg 2008; 247: 445-450)
2nd look - Results 25% Elias et al. Ann Surg 2008
ProphyloCHIP : Design N = 30 (overall) Patients at risk of developping PC Primary end point : PFS at 3 years Secondary end points : OS at 5 years Peritoneal recurrent free survival at 5 years Morbidity of 2nd look laparotomy & Toxicity of HIPEC Registration Randomization Standard Arm 6 months Systemic Chemo Experimental Arm Follow-up 2 nd Look + HIPEC
Conclusion Deux essais thérapeutiques En cours : ACCORD 5 PRODIGE 7 A venir : PROPHYLOCHIP