colon cancer peritoneal carcinomatosis treatmentmedia.aiom.it/.../slide/20160116pg_5c_donini.pdf ·...
TRANSCRIPT
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UNIVERSITY OF PERUGIA
Department of General and Emergency Surgery
Chief: Prof. Annibale Donini
COLON CANCER
PERITONEAL CARCINOMATOSIS
TREATMENT
Prof. Annibale Donini
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COLON CANCER IS A HIGHLY FREQUENT NEOPLASIA
From IARC Cancer Base 2013
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From IARC Cancer Base 2013
MORTALITY REMAINS RATHER HIGH ALTHOUGH SCREENING AND MODERN CHEMOTHERAPY DRUGS
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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%
ONLY PC 45%
PC AND OTHER 55%
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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
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Prognostic Factors of PC Occurence
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Prognostic Factors of PC Occurence
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Peritoneal Carcinomatosis ? Metastasis
Are the benefits of sistemic chemotherapy alone so great that Cytoreductive Surgery and perioperative chemotherapy is not needed ?
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5Y-OS AND DFS IN PTS WITH CC PC TREATED WITH CRS AND CH-TR
Median Survival: 12,6 months Median DFS: 7 months
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Overall Survival in patients with PC compared to other metastatic sides
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5-FU; Leucovorin; Oxaliplatin
5-FU; Leucovorin; Irinotecan
Oxaliplatin; Irinotecan
Conclusion: - Shorter OS and DFS when PC
- 5-y survival with Folfox (all pts: 4%)
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PC is a LOCAL REGIONAL PROGRESSION that represent the natural hystory
of all GI Cancer
IP CHEMOTHERAPY
IV CHEMOTHERAPY
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Median Survival: 22,4 (HIPEC) vs 12,6 (control) monnths
Journal of Clinical Oncology 2004
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Median Survival: 62,7 (HIPEC) vs 23 (CONTROL) months
Retrospective Analysis: 2009
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Median Survival: 34,7 (HIPEC) vs 16,8 (CONTROL)months
Retrospective Analysis: 2010
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5y-OS: 35% 5y-DFS: 16%
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PRODIGE 7: FRENCH RANDOMIZED TRIAL Waiting for final results Accruiment of 264pts
PERITONEAL CARCINOMATOSIS
CITOREDUCTIVE SURGERY; PCI<24
HIPEC WITH OXALIPLATIN
ADJUVANT CHEMOTHERAPY 6 FOLFOX CYCLES
NO HIPEC
RANDOMIZATION
Kindly provided by Prof Glehen
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VERY DIFFICULT PTS ACCRUIMENT!
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Median Survival: 25 (HIPEC) vs 18 (CONTROL) months P<0.04
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5y-PFS: 17%(HIPEC) vs 0% (CONTROL) months P<0.04
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Completeness of Cytoreduction Score
Peritoneal Cancer Index
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CC SCORE IS A STRONG INDICATOR OF SURVIVAL (P<0.001)
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PCI IS A STRONG INDICATOR OF SURVIVAL (P<0.001)
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How much does it cost ?
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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)
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MORBIDITY: GRADE III-IV • CHEMOTHERAPY ARM: 50% • SURGERY ARM: 42% GRADE V • O% IN BOTH ARMS
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GRADE RACCOMMANDATION B
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UNSOLVED PROBLEM:ME
TACHRONOUS PC
“PATIENT IS KILLED BY WHAT THE SURGEON DOESN’T SEE”
P. H. SURGARBAKER
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Clinical and intraoperative histophatologic features of the primary cancer as an estimate of the incidence of
Subsequent metacronous peritoneal metastases
CLINICAL FEATURES INCIDENCE OF PERITONEAL
METASTASES DURING
FOLLOW-UP (%)
1. PERITONEAL NODULES 70
2. OVARIAN METASTASES 60
3. PERFORATION 50
4. INVASION OF ADJACENT ORGAN OR
STRUCTURES 20
5. SIGNET REING HISTOLOGY 20
6. FISTULA 20
7. OBSTRUCTION 20
HYSTOPATHOLOGIC FEATURE
8. POSITIVE MARGIN RESECTION 80
9. POSITIVE PERITONEAL LAVAGE 40
10. LYMPHNODES POSITIVE AT MARGIN
OF RESECTION 20
11. T3/T4 MUCINOUS CANCER 40
Prophylactic HIPEC or second look
Kindly provided by Prof Sugarbaker
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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.
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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 ROUTINELY USE PROPHYLACTIC HIPEC IN SELECTED PRIMARY GASTROINTESTINAL CANCER PATIENTS
Kindly provided by Prof Sugarbaker
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5Y-OS (%): 85 (EXP) VS 55 (CONTROL)
5Y-DFS (%): 90 (EXP) VS 60 (CONTROL)
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OVERALL SURVIVAL
5YOS (%): 90 (EXP) VS 40 (CONTROL)
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2007 2015
65 treated patients
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OUR EXPERIENCE FROM 2007 TO DATE: Primary Tumor Distribution
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Colon Cancer OUR EXPERIENCE from 2008 650 colon cancer surgically treated 28 (5%) pts with peritoneal carcinomatosis 74% synchronous PC 26% metachronous PC
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%
23 CRS + HIPEC 5 CRS
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OUR EXPERIENCE from 2008
RESULTS (1)
5y-OS: 45%; MEDIAN SURVIVAL 60 MONTHS vs 28 months (only CRS)
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OUR EXPERIENCE from 2008
RESULTS (2)
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MORBIDITY: GRADE III-IV • 4.3% GRADE V • 4,3%
OUR EXPERIENCE from 2008
RESULTS (3)
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Conclusion
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SURGEONS
ONCOLOGIST
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AN AGREEMENT BETWEEN ONCOLOGISTS AND SURGEONS IS NEAR
Int J Clon Onc 2015