COLON CANCER PERITONEAL CARCINOMATOSIS TREATMENT Prof. Annibale Donini

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1 UNIVERSITY OF PERUGIA Department of General and Emergency Surgery Chief: Prof. Annibale Donini COLON CANCER PERITONEAL CARCINOMATOSIS TREATMENT Prof. Annibale Donini

2 COLON CANCER IS A HIGHLY FREQUENT NEOPLASIA From IARC Cancer Base 2013

3 MORTALITY REMAINS RATHER HIGH ALTHOUGH SCREENING AND MODERN CHEMOTHERAPY DRUGS From IARC Cancer Base 2013

4 4

5 CC PERITONEAL CARCINOMATOSIS EPIDEMIOLOGY Retrospective analysis of a prospective database with a literature review COLON CANCER POPULATION STAGE IV AT DIAGNOSIS: 20% LIVER METASTASES 74,5% PERITONEAL CARCINOMATOSIS 24% PC AND OTHER 55% ONLY PC 45%

6 CC PERITONEAL CARCINOMATOSIS EPIDEMIOLOGY CC PERITONEAL CARCINOMATOSIS 3-28% SYNCRONOUS CC PC 7-10% METACHRONOUS CC PC 4-44% *High Variability for the difficult diagnosis of PC

7 Prognostic Factors of PC Occurence

8 Prognostic Factors of PC Occurence

9 Peritoneal Carcinomatosis Metastasis? Are the benefits of sistemic chemotherapy alone so great that Cytoreductive Surgery and perioperative chemotherapy is not needed? 9

10 10

11 11

12 5Y-OS AND DFS IN PTS WITH CC PC TREATED WITH CRS AND CH-TR Median Survival: 12,6 months Median DFS: 7 months

13 Overall Survival in patients with PC compared to other metastatic sides

14 5-FU; Leucovorin; Oxaliplatin 5-FU; Leucovorin; Irinotecan Conclusion: - Shorter OS and DFS when PC - 5-y survival with Folfox (all pts: 4%) Oxaliplatin; Irinotecan

15 PC is a LOCAL REGIONAL PROGRESSION that represent the natural hystory of all GI Cancer IP CHEMOTHERAPY IV CHEMOTHERAPY

16 16

17 Journal of Clinical Oncology 2004 Median Survival: 22,4 (HIPEC) vs 12,6 (control) monnths

18 Retrospective Analysis: 2009 Median Survival: 62,7 (HIPEC) vs 23 (CONTROL) months

19 Retrospective Analysis: 2010 Median Survival: 34,7 (HIPEC) vs 16,8 (CONTROL)months

20 5y-OS: 35% 5y-DFS: 16%

21 PRODIGE 7: FRENCH RANDOMIZED TRIAL Waiting for final results Accruiment of 264pts PERITONEAL CARCINOMATOSIS CITOREDUCTIVE SURGERY; PCI<24 RANDOMIZATION NO HIPEC HIPEC WITH OXALIPLATIN ADJUVANT CHEMOTHERAPY 6 FOLFOX CYCLES Kindly provided by Prof Glehen

22

23 VERY DIFFICULT PTS ACCRUIMENT!

24 Median Survival: 25 (HIPEC) vs 18 (CONTROL) months P<0.04

25

26 5y-PFS: 17%(HIPEC) vs 0% (CONTROL) months P<0.04

27 Completeness of Cytoreduction Score Peritoneal Cancer Index 27

28 CC SCORE IS A STRONG INDICATOR OF SURVIVAL (P<0.001)

29 PCI IS A STRONG INDICATOR OF SURVIVAL (P<0.001)

30 30

31 31

32 32

33 How much does it cost?

34 Analysis of 26 series of patients affected by CC PC treated with CRS and HIPEC POST-SURGICAL OUTCOMES: MORBIDITY II-IV according to Clavien Dindo: 12-48% PROCEDURE RELATED MORTALITY: 1-5,8% COMPARABLE TO THAT OF MAJOR GI SURGICAL PROCEDURES (WHIPPLE PROCEDURE)

35

36 MORBIDITY: GRADE III-IV CHEMOTHERAPY ARM: 50% SURGERY ARM: 42% GRADE V O% IN BOTH ARMS

37

38

39 GRADE RACCOMMANDATION B

40 UNSOLVED PROBLEM:ME TACHRONOUS PC PATIENT IS KILLED BY WHAT THE SURGEON DOESN T SEE P. H. SURGARBAKER

41 Clinical and intraoperative histophatologic features of the primary cancer as an estimate of the incidence of Subsequent metacronous peritoneal metastases CLINICAL FEATURES 1. PERITONEAL NODULES OVARIAN METASTASES PERFORATION 50 INCIDENCE OF PERITONEAL METASTASES DURING FOLLOW-UP (%) 4. INVASION OF ADJACENT ORGAN OR STRUCTURES SIGNET REING HISTOLOGY FISTULA 20 Prophylactic HIPEC or second look 7. OBSTRUCTION 20 HYSTOPATHOLOGIC FEATURE 8. POSITIVE MARGIN RESECTION POSITIVE PERITONEAL LAVAGE LYMPHNODES POSITIVE AT MARGIN OF RESECTION T3/T4 MUCINOUS CANCER 40 Kindly provided by Prof Sugarbaker

42 PC and Second-look Rational : For minimal PCI HIPEC could be the most efficient approach. But early detection of minimal PC is not possible neither with clinical signs neither with imaging studies. THUS It is logical to propose a second-look to asymptomatic patients presenting high risks to develop a PC, with the aim to treat PC at an early stage. 42

43 ETHICAL PERSPECTIVE IN PATIENTS AT HIGH RISK OF PC - THE COST OF PROPHYLACTIC HIPEC MINIMAL COST, ACCEPTABLE MORBIDITY - COST OF NOT USING PROPHYLACTIC HIPEC-DEATH FROM PERITONEAL METASTASIS -IN THE FUTURE THERE MUST BE A MULTI-ISTITUTIONAL CLINICAL TRIAL. I WILL ENCOURAGE MY PATIENTS TO ENTER. UNTIL MORE DATA BECOMES AVAILABLE I WILL R OUTINELY USE PROPHYLACTIC HIPEC IN SELECTED PRIMARY GASTROINTESTINAL CANC ER PATIENTS Kindly provided by Prof Sugarbaker

44 5Y-DFS (%): 90 (EXP) VS 60 (CONTROL) 5Y-OS (%): 85 (EXP) VS 55 (CONTROL)

45 OVERALL SURVIVAL 5YOS (%): 90 (EXP) VS 40 (CONTROL)

46 treated patients 46

47 OUR EXPERIENCE FROM 2007 TO DATE: Primary Tumor Distribution 47

48 Colon Cancer OUR EXPERIENCE from colon cancer surgically treated 28 (5%) pts with peritoneal carcinomatosis 74% synchronous PC 26% metachronous PC 23 CRS + HIPEC 5 CRS Patients Features Mean Age 59yo Mean PCI 4,5 Side Right Colon 43,5% Left Colon 52,5% Rectum 4% Mmytomicin plus Cisplatin 43,5% Oxaliplatin 56,5%

49 OUR EXPERIENCE from 2008 RESULTS (1) 5y-OS: 45%; MEDIAN SURVIVAL 60 MONTHS vs 28 months (only CRS)

50 OUR EXPERIENCE from 2008 RESULTS (2)

51 OUR EXPERIENCE from 2008 RESULTS (3) MORBIDITY: GRADE III-IV 4.3% GRADE V 4,3%

52 Conclusion 52

53 ONCOLOGIST SURGEONS

54 AN AGREEMENT BETWEEN ONCOLOGISTS AND SURGEONS IS NEAR Int J Clon Onc 2015

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