Cytoreductive surgery and perioperative intraperitoneal chemotherapy for Rare Peritoneal Disease. Results of the French multicentric database

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1 Cytoreductive surgery and perioperative intraperitoneal chemotherapy for Rare Peritoneal Disease Results of the French multicentric database Université Lyon 1 Centre Hospitalo-Universitaire Lyon-Sud EA 3738 O.GLEHEN D.ELIAS FN.GILLY

2 Primary Peritoneal carcinomatosis or carcinomatosis from digestive origin REGISTRATION from french speaking centers ( ) 1344 procedures combining cytoreductive surgery and perioperative intraperitoneal chemotherapy (EPIC or HIPEC) 1290 patients

3 25 centers : - 20 France - 2 Canada - 2 Belgium - 1 Swisserland

4 Incidence of patient s inclusions

5 Methods carcinomatosis extent STAGES CARCINOMATOSIS Stage 1 < 5 mm, one part Stage 2 < 5mm, diffuse Stage 3 5mm to 2 cm Stage 4 Large malignant cakes

6 Methods carcinomatosis extent Milan consensus 2006 P.Sugarbaker

7 Methods completeness of cytoreduction Milan consensus 2006

8 Primary Peritoneal carcinomatosis or carcinomatosis from digestive origin etiology Etiology Colorectal Cancer Pseudomyxoma Peritonei Gastric Cancer Peritoneal Mesothelioma Appendiceal cancer Small intestinal cancer Primary perioneal serous carcinoma Peritoneal Sarcomatosis Other Total Number % 40.5% 23.3% 12.3% 6.8% 3.9% 3.5% 2.5% 2.2% 5%

9 Overall survival according to etiology

10 Pseudomyxoma Peritonei Population ( , 18 centers) N = 301 patients 190F 111M Median age: 52 ans 52 ans Origin appendix: : 91%

11 Pseudomyxoma Peritonei Population ( , 18 centers) Cytoreductive surgery CC-0: 73% CC-1: 21% CC-2 ou 3: 6% HIPEC: 90% - EPIC 10% Open :79% Oxaliplatin: : 62% Mitomycin C: 38% Systemic chemotherapy: 13%

12 Mortality: : 4.4% Pseudomyxoma Peritonei Population ( , 18 centers) Morbidity : 41% (grade III or IV) Digestive fistula: : 8% Aplasia grade III-IV: IV: 20% Factors with significant influence: Institution (p<0.001) Disease extent (p=0.002)

13 Pseudomyxoma Peritonei Population ( , 18 centers) Overall survival Median survival: : NR 5 year survival: 73% 10 year survival: 55%

14 Pseudomyxoma peritonei prognostic factors Institution P<0.001

15 Pseudomyxoma peritonei prognostic factors Disease extent (PCI) P=0,002, RR de 1,08

16 Pseudomyxoma peritonei prognostic factors Completeness of cytoreduction P=NS

17 Pseudomyxoma peritonei prognostic factors Lymph node involvement P=0,02, RR=0.4

18 Pseudomyxoma peritonei prognostic factors Type of intraperitoneal chemotherapy P=0,04, RR=4.7

19 Pseudomyxoma peritonei prognostic factors Clinicopathologic grade P=0,014, RR=0.28

20 Pseudomyxoma peritonei prognostic factors Disease free survival Year s experience of institutions P=0.006

21 Confirmations Pseudomyxoma peritonei Conclusions Complete Cytoreductive surgery + HIPEC may achieve 5-year and 10-year survival rates of more than 75% and 50%, respectively. Strong prognostic factors: New concepts Institution (year s experience) Clinicopathologic grades Lymph node involvement Strong prognostic influence of disease extent > completeness of cytoreduction HIPEC > EPIC

22 Carcinomatosis from appendiceal adenocarcinoma Population ( , 13 centers) N = 49 patients 30F 19M CC-0: 83% HIPEC: 83% Mortality: 4% Morbidity: 35%

23 Carcinomatosis from appendiceal adenocarcinoma Overall survival Median survival: : 77 months Population ( , 13 centers)) 1 year survival: 78% 5 year survival: 56%

24 Carcinomatosis from appendiceal adenocarcinoma Prognostic factors Sexe PCI P=0.001 P=0.04

25 Carcinomatosis from appendiceal adenocarcinoma Prognostic factors Completeness of cytoreduction Lymph node involvement P=0.006 P=0.04

26 Carcinomatosis from appendiceal adenocarcinoma Conclusions Prognosis of carcinomatosis from appendiceal adenocarcinoma is close than grade 3 pseudomyxoma peritonei: 5-year survival rates: 56% vs 48% Should we compile both groups in future studies? Prognostic factors: Sexe? Carcinomatosis extent Completeness of cytoreduction Lymph node involvement

27 Perioneal Mesothelioma Population ( , 13 centres) N = 83 patients 39F 49M Median age: 47 years Difficult diagnosis Laparoscopy: : 31% Abdominal pain: 32% Ascitis:24% Asthenia: : 12%

28 Perioneal Mesothelioma Population ( , 13 centres) Completenes of cytoreduction CC-0: 52% CC-1: 36% CC-2 ou 3: 12% 3: 12% HIPEC: 96% Open technic :65% Oxaliplatin: : 50% Cisplatin: 43% Adjuvant chemotherapy: 25%

29 Peritoneal Mesothelioma Population ( , 13 centres) 4 pathologic groups Multicystic (8%) Papillary (28%) Epithelial (47%) Biphasic or sarcomatoïd (6%)

30 Peritoneal Mesothelioma Population ( , 13 centres) Mortality: : 1,1% Morbidity : 33% (grade III or IV) Digestive fistula: : 5% Aplasia grade III-IV: IV: 17% Factors with significant influence: Institution s s expérience (p=0,01)

31 Peritoneal Mesothelioma Population ( , 13 centres) Overall survival Median: : 45 months 5-year survival: 44% Strongest prognostic factor: INSTITUTION

32 Peritoneal Mesothelioma Prognostic factors Sexe Female Male P=0,011, RR de 0,28

33 Peritoneal Mesothelioma Prognostic factors Completeness of cytoreduction CC-0 CC-1 CC-2 ou 3 P=0,03, RR de 2,07

34 Peritoneal Mesothelioma Prognostic factors Pathologic groups Multicystic Papillary Epithelial P=0,013

35 Peritoneal Mesothelioma Conclusions Cytoreductive surgery with HIPEC may achieve 5-year survival rate of 68% for peritoneal mesothelioma. Median survival not reached for female Strongest prognostic factors Completeness of cytoreduction Institution Several pathologic types with prognostic influence

36 Other rare peritoneal disease Primary peritoneal serous carcinoma (33 patients) Median survival not reached (5-year survival rate of 58%) Only one prognostic factor: pathologic differentiation Peritoneal sarcomatosis (28 patients) Median survival of 21 months (5-year survival rate of 22%) One prognostic factor: completeness of cytoreduction Prolonged survival for desmoplastic carcinomatosis

37 Conclusions Registrations or large multicentric retrospective studies Provide information on a a large population: reference Only way to identify prognostic indicators for rare disease Confirmation of the major influence of institution s experience in the management of rare peritoneal surface malignancies Mortality morbidity Survival results We should move to other cooperative studies trying to identify new prognostic factors (molecular or genetic) to establish new targeted therapy