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HIPEC in colorectal carcinomatosis 
Glehen olivier 
Surgical Oncology 
Hospices Civils de Lyon 
Centre Hospitalier Lyon Sud
Management of peritoneal carcinomatosis: 
EVOLUTION 
Before 1980 
PALLIATIVE TREATMENT 
1111999988880000-99995555:::: HHHHIIIIPPPPEEEECCCC,,,, 
EEEEPPPPIIIICCCC 
1995-2000: Cytoreductive surgery, 
phase II studies 
2000-2011: Registration, randomized study, 
Development of expert centers 
CURATIVE TREATMENT OF PC
Strong rational for locoregional 
treatment 
Peritoneal PPPeeerrriiitttooonnneeeaaalll ccccaaaarrrrcccciiiinnnnoooommmmaaaattttoooossssiiiissss 
LLLLooooccccoooorrrreeeeggggiiiioooonnnnaaaallll ddddiiiisssseeeeaaaasssseeee 
Treatment of macroscopic disease 
Cytoreductive surgery 
Peritonectomy procedures 
Treatment of microscopic disease 
Intraperitoneal chemotherapy
Peritonectomy 
procedures
Organ resections
Rational for Hyperthermic 
Intraperitoneal Chemotherapy 
1. Pharmacokinetic advantages of 
Intraperitoneal Chemotherapy 
2. - Cytotoxicity of hyperthermia 
(42,5°C) 
3. Synergistic effect « Hyperthermia - 
chemotherapy » 
4. Following surgical procedures 
- Avoid « cancer cells entrapment » 
- BUT « single shot » treatment
Improved efficiency of systemic chemotherapy 
fro metastatic colorectal cancers 
6 
12 12 
14 
15 
18 18 
21 21 
24 
25 
20 
15 
10 
5 
0 
BSC Bolus 
5FU-LV 
Xeloda LV5FU2 IFL Folfox Folfiri Folfox 
puis IRI 
Folfiri 
puis oxali 
Bevaciz + 
sequentiel 
5FU alone Sequentiel 
treatment 
Combined 
treatment 
Targeted therapy 
Median survival 
(months) 
0 
% 
23 
% 
21 
% 
36- 
59% 
34- 
56% 
60- 
72% 
45- 
72% 
Objective 
response
METASTATIC COLORECTAL CANCER Systemic Chemotherapy 
Author Year Journal IV Chemoregimen MFS 
(mths) 
Median 
(mths) 
Liver/Lung 
metastase 
PC 
Moertel 1989 JCO 5FU LV 6,2 14,7 ? 
DeGramont 2000 JCO 5FU LV 
OXALIPLATINE 
9,0 16,2 91% ? 
Saltz 2000 NEJM 5FU LV IRINOTECAN 7,0 14,8 662/683 ? 
Giachetti 2000 JCO 5FU chrono LV OXA 8,7 19,9 242/256 ? 
Douillard 2000 Lancet 5FU IRINOTECAN 6,7 17,4 367/387 20 ? 
Tournigand 2003 JCO FOLFIRI + FOLFOX 14,2 20,6 220/220 0 
Kabbinavar 2003 JCO 5FU LV Avastin 9,0 21,5 35 ? 
Hurwitz 2004 NEJM 5FU LV IRI 
Bevacizumab 
10,6 20,3 813 ? 
Goldberg 2006 JCO 5FU LV IRINOTECAN 9,7 19,0 305/305 0 
Masi 2006 Ann 
Oncol 
5FU LV OXA IRI 8,1 15,2 71/71 0 
TOTAL >4000 < 20
PC from colorectal origin Palliative systemic 
-Folprecht et al. 
Cancer Treat Res, 2007. 
chemotherapy 
Retrospective study 3825 patients. 
-12% of peritoneal carcinomatosis 
-PC as strong prognostic factor 
-Patients with PC: median survival 7 to 18 months 
-Patients without PC: median survival 11 to 20 months
PC from colorectal origin Palliative systemic 
chemotherapy 
2095 patients 
Median survival 
•Patients with PC : 12.7 months 
•Patients without PC : 17.6 months
SYSTEMIC 
CHEMOTHERAPY 
PERITONEAL 
CARCINOMATOSIS 
from COLORECTAL CANCER 
Peritoneal carcinomatosis = metastatic disease 
BUT 
Different natural history and response to systemic 
chemotherapy from liver or lung metastasis 
5 months < median survival of colorectal PC ?? < 24 months 
Systemic chemotherapy should be considered 
as one important tool for the treatment of PC
COLORECTAL PC 
Randomized study 
Cytoreductive surgery+ HIPEC (MMC) 
+ 5FU-Leucovorin 
N=48 
 Colorectal PC 
5-FU-Leucovorin 
N=44 
43% (HIPEC) 
 2-year survival 
16% (control roup) 
P=0.001 
Verwaal et al. J Clin Oncol 2003, Ann Surg Oncol 2008
PERITONEAL 
CARCINOMATOSIS 
from COLORECTAL CANCER 
-Elias et al. 
J Clin Oncol 2008 
Retrospective study. 
Cytoreduction with HIPEC 
-48 Cytoreductions + HIPEC (oxaliplatin) versus 
48 « modern » systemic chemotherapy alone 
-Median follow-up  63 months 
-Better results for patients treated with HIPEC 
-51% of 5 year survival vs 13% (p0,05) 
-Median survival of 62 months vs 24 months
PERITONEAL 
CARCINOMATOSIS 
from COLORECTAL CANCER 
-Franco et al. 
Cancer 2010 
Prospective study. 
Cytoreduction with HIPEC 
-67 Cytoreductions + HIPEC versus 38 
« modern » systemic chemotherapy alone 
-Some patients had liver metastasis 
-Better results for patients treated with HIPEC 
-Median survival of 35 months vs 17 months
COLORECTAL 
CARCINOMATOSIS 
Cytoreductive surgery and 
intraperitoneal chemotherapy 
2222 Registres: national and international 
 500 patients 
1990 - 2007 
75 to 86 % : HIPEC 
54 to 85% de complete cytoreduction 
Mortality: 3 to 4% Morbidity:25 to 30% 
Median survival  30 months 
5 year survival  30% 
J Clin Oncol 2004 and 2010
Colorectal carcinomatosis 
Completeness of cytoreductive surgery 
CC-0 
CC-1 
J Clin Oncol 2010 
CC-2 ou 3 
CC-0
Colorectal carcinomatosis 
CCCCaaaarrrrcccciiiinnnnoooommmmaaaattttoooossssiiiissss EEEExxxxtttteeeennnntttt 
CC-0
Unresolved Questions 
Is synchronous liver 
metastasis a 
contraindication for 
curative treatment of 
carcinomatosis?
Survival according to the presence of associated 
Liver Metastases (n= 65) (p= NS)
Colorectal carcinomatosis 
and synchronous liver 
metastasis 
 Liver metastasis does not contitute an 
absolute contraindication for curative 
approach of carcinomatosis 
• Liver metastasis should be controlled by 
systemic chemotherapy 
• Extensive liver surgery combined to 
extensive peritoneal surgery should be 
avoided
Unresolved Questions 
Response to neoadjuvant 
systemic chemotherapy 
should be used for patient’s 
selection ?
Survival according to the use of neoadjuvant 
chemotherapy (n= 120 patients) 
P = 0.042 
Ann Surg 2012
Survival according to response to neoadjuvant 
chemotherapy (n= 120) (p= NS) 
P = NS Ann Surg 2012
Colorectal carcinomatosis and 
neoadjuvant chemotherapy 
 Progression with neoadjuvant systemic 
chemotherapy does not contitute an 
absolute contraindication for curative 
approach of carcinomatosis 
• Median survival more of 30 months may 
be obtained 
 The use of neoadjuvant systemic 
chemotherapy is important to exclude 
patients who will develop 
extraperitoneal disease 
Ann Surg 2012
2012 : Treatment of Peritoneal carcinomatosis : 
When and how to treat ? French national 
recommandations 
 Pseudomyxoma Peritonei. 
 Peritoneal Mesothelioma. 
 PC from colorectal, small bowel 
adenocarcinoma and 
appendiceal cancers. 
Patient in good general status 
When optimal cytoreductive 
surgery (R0 – R1) is achievable. 
Strict patient selection. 
Experienced multidisciplinary 
center. 
 PC from gastric cancer. 
 PC from ovarian cancer. 
PC from pancreas, bile duct, 
gallblader, breast, …. 
Highly recommended 
Under evaluation 
Ongoing trial inclusion 
Probably not ???
PERITONEAL 
CARCINOMATOSIS 
RECOMMENDATIONS TO 
GENERAL SURGEONS 
AND ONCOLOGISTS
For current practice 
1ST Message 
Curative treatment of peritoneal 
carcinomatosis must be 
considered at the time of 
diagnosis 
Not after failure of palliative treatment (surgery – 
systemic chemotherapy)
How to select patients for 
treatment with curative intent? 
Which PATIENTS ?? 
AN AGGRESSIVE THERAPEUTIC 
APPROACH 
Mortality 4% 
Morbidity 34% 
Evaluation of general status
How to manage patients for treatment 
with curative intent? 
Cytoreductive surgery and perioperative 
intraperitoneal chemotherapy should be 
performed in expert centers in peritoneal 
surface malignancy 
 Complex, costly, long procedures 
 Better patients selection 
 Lower complications rates 
 Higher rate of complete cytoreduction 
Smeenk, Br J Surg 2007 
AFC 2008 
WHERE ??? 
Expert center should be contacted at the time of 
diagnosis
How to select patients for 
treatment with curative intent? 
WHICH carcinomatosis ??? 
Indications 
• Patients with no extraabdominal disease 
 Body-scan 
 Pet-scan 
• POSSIBILITY of COMPLETE CYTOREDUCTIVE 
SURGERY +++ 
 Preoperative assessment: CT-scan, MRI 
 Peroperative assessment ++++ 
• Laparoscopy 
• Detailed operative report
For current practice 
SECOND Message 
Precise description of 
carcinomatosis distribution and 
extension must be performed
How to manage patients for 
treatment with curative intent? 
IN ALL CASES 
• POSSIBILITY of COMPLETE 
CYTOREDUCTIVE SURGERY +++ 
• PRECISE ASSESSMENT OF 
CARCINOMATOSIS EXTENT ++++ 
Description of small bowel, hepatic pedicula, 
bladder involvement 
 Photos or films 
Help expert centers for selection 
Avoid useless explorative laparotomy
Precise description during laparotomy or laparoscopy 
of carcinomatosis that are not evaluable on 
morphologic exams 
Mesenteric retraction Diffuse small tumoral nodules
For current practice 
THIRD Message 
Respect peritoneum !! 
Respect parietal wall!!
Respect peritoneum and 
parietal wall 
 Peritoneum is the first-line of defense 
 “Cancer cells entrapment” 
Curative procedure more complex and less 
efficient 
No extensive peritonectomies or cytoreductive surgery 
without perioperative intraperitoneal chemotherapy
Respect peritoneum and 
parietal wall 
Clinical situations: carcinomatosis suspected on 
preoperative exams 
• Explorative laparoscopy (trocarts on middle line) 
• Diagnostic biopsy
Respect peritoneum and 
parietal wall
Respect peritoneum and 
parietal wall 
Clinical situations: Carcinomatosis is 
discovered peroperatively 
No resection of primary tumor 
• Rectosigmoïd tumors (ureters) 
Stomia for occlusive tumor 
 Exception for hemorrhagi tumors 
Avoiding drainage into flank 
The prognosis depend on the treatment of the metastatic 
disease and not on the primary tumor
Respect peritoneum and 
parietal wall 
 What should we do with scars or 
intraperitoneal nodules or anastomoses 
following previous surgery? 
 More extensive will be previous 
surgery, more difficult, extensive and 
less curative will be the curative 
treatment
Unresolved Questions 
What is the exact role of 
HIPEC into therapeutic 
management ?
PRODIGE 7 (F Quenet) 
RANDOMIZED FRENCH STUDY 
Colorectal carcinomatosis 
Complete cytoreductive 
No HIPEC 
surgery 
RANDOMIZATION 
HIPEC oxaliplatin 
Perioperative systemic 
chemotherapy for 6 months 
RANDOMIZATION
Prevention 
Interest of 2nd look for 
patients at risk of 
carcinomatosis 
development?
Patients et Methods (1) 
 From 1999 to 2009, 47 patients with a high risk to develop a PC 
(without clinical, radiologic or biologic symptoms), underwent a 
second look, 12 months after their first surgery. 
 Selected: 3 groups of high-risk patients: 
• 28 who presented a minimal macroscopic PC synchronous to the 
primary (and which was completely resected during the same session) 
• 8 who presented synchronous ovarian metastases, 
• 11 who presented a perforation of their primary tumour. 
 All these patients received the adjuvant standard treatment after the 
first surgery: 6 months of systemic chemotherapy (Folfox or Folfiri)
Patients et Methods (2) 
 Careful exploration of the whole abdominal cavity 
 Mean duration of surgery: 6 hours 
47 patients 
23 with PC (49%) 24 without PC (51%) 
23 Cytoreduc Surg + HIPEC 
Mean peritoneal index: 7 No HIPEC = 6 (PC- H-) 
(PC+ H+) HIPEC = 18 (PC- H+)
Follow-up: 45 months (mean) 
Nb Recurrence IP recurrence Died 
PC+ H+ 23 12 (52%) 6 3 (13%) 
PC - H + 18 2 (11%) 1 0 
PC – H - 6 4 (75%) 3 3 (50%) 
Only one prognostic factor: HIPEC (p = 0.02) 
Among the 41 pts with HIPEC: only 7 (17%) 
presented a peritoneal recurrence
Conclusion (1) 
 A second-look, performed 1 year after the resection of the primary, 
in a selected high-risk group of patients, allowed to found and treat 
an early and minimal PC in 50% of the patients. 
 This new therapeutical approach seems benefit for the patients 
who initialy presented a minimal PC or ovarian metastasis. 
 These encouraging preliminary results lead to initiate a prospective 
randomized trial, with the aim to definitely prove this benefit.
French randomized multicentric study 
(Prophylochip) 
Patients at risk of carcinomatosis 
development 
(Perforated tumors, localized carcinomatosis 
removed, isolated ovarian metastasis) 
Adjuvant FOLFOX (6 months) 
or systemic chemotherapy 
(Negative workshop) 
Randomization 8 months) 
Follow-up 
2nd look and 
prophylactic HIPEC

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O. Glehen - HIPEC in colorectal carcinomatosis

  • 1. HIPEC in colorectal carcinomatosis Glehen olivier Surgical Oncology Hospices Civils de Lyon Centre Hospitalier Lyon Sud
  • 2. Management of peritoneal carcinomatosis: EVOLUTION Before 1980 PALLIATIVE TREATMENT 1111999988880000-99995555:::: HHHHIIIIPPPPEEEECCCC,,,, EEEEPPPPIIIICCCC 1995-2000: Cytoreductive surgery, phase II studies 2000-2011: Registration, randomized study, Development of expert centers CURATIVE TREATMENT OF PC
  • 3. Strong rational for locoregional treatment Peritoneal PPPeeerrriiitttooonnneeeaaalll ccccaaaarrrrcccciiiinnnnoooommmmaaaattttoooossssiiiissss LLLLooooccccoooorrrreeeeggggiiiioooonnnnaaaallll ddddiiiisssseeeeaaaasssseeee Treatment of macroscopic disease Cytoreductive surgery Peritonectomy procedures Treatment of microscopic disease Intraperitoneal chemotherapy
  • 6. Rational for Hyperthermic Intraperitoneal Chemotherapy 1. Pharmacokinetic advantages of Intraperitoneal Chemotherapy 2. - Cytotoxicity of hyperthermia (42,5°C) 3. Synergistic effect « Hyperthermia - chemotherapy » 4. Following surgical procedures - Avoid « cancer cells entrapment » - BUT « single shot » treatment
  • 7. Improved efficiency of systemic chemotherapy fro metastatic colorectal cancers 6 12 12 14 15 18 18 21 21 24 25 20 15 10 5 0 BSC Bolus 5FU-LV Xeloda LV5FU2 IFL Folfox Folfiri Folfox puis IRI Folfiri puis oxali Bevaciz + sequentiel 5FU alone Sequentiel treatment Combined treatment Targeted therapy Median survival (months) 0 % 23 % 21 % 36- 59% 34- 56% 60- 72% 45- 72% Objective response
  • 8. METASTATIC COLORECTAL CANCER Systemic Chemotherapy Author Year Journal IV Chemoregimen MFS (mths) Median (mths) Liver/Lung metastase PC Moertel 1989 JCO 5FU LV 6,2 14,7 ? DeGramont 2000 JCO 5FU LV OXALIPLATINE 9,0 16,2 91% ? Saltz 2000 NEJM 5FU LV IRINOTECAN 7,0 14,8 662/683 ? Giachetti 2000 JCO 5FU chrono LV OXA 8,7 19,9 242/256 ? Douillard 2000 Lancet 5FU IRINOTECAN 6,7 17,4 367/387 20 ? Tournigand 2003 JCO FOLFIRI + FOLFOX 14,2 20,6 220/220 0 Kabbinavar 2003 JCO 5FU LV Avastin 9,0 21,5 35 ? Hurwitz 2004 NEJM 5FU LV IRI Bevacizumab 10,6 20,3 813 ? Goldberg 2006 JCO 5FU LV IRINOTECAN 9,7 19,0 305/305 0 Masi 2006 Ann Oncol 5FU LV OXA IRI 8,1 15,2 71/71 0 TOTAL >4000 < 20
  • 9. PC from colorectal origin Palliative systemic -Folprecht et al. Cancer Treat Res, 2007. chemotherapy Retrospective study 3825 patients. -12% of peritoneal carcinomatosis -PC as strong prognostic factor -Patients with PC: median survival 7 to 18 months -Patients without PC: median survival 11 to 20 months
  • 10. PC from colorectal origin Palliative systemic chemotherapy 2095 patients Median survival •Patients with PC : 12.7 months •Patients without PC : 17.6 months
  • 11. SYSTEMIC CHEMOTHERAPY PERITONEAL CARCINOMATOSIS from COLORECTAL CANCER Peritoneal carcinomatosis = metastatic disease BUT Different natural history and response to systemic chemotherapy from liver or lung metastasis 5 months < median survival of colorectal PC ?? < 24 months Systemic chemotherapy should be considered as one important tool for the treatment of PC
  • 12. COLORECTAL PC Randomized study Cytoreductive surgery+ HIPEC (MMC) + 5FU-Leucovorin N=48 Colorectal PC 5-FU-Leucovorin N=44 43% (HIPEC) 2-year survival 16% (control roup) P=0.001 Verwaal et al. J Clin Oncol 2003, Ann Surg Oncol 2008
  • 13. PERITONEAL CARCINOMATOSIS from COLORECTAL CANCER -Elias et al. J Clin Oncol 2008 Retrospective study. Cytoreduction with HIPEC -48 Cytoreductions + HIPEC (oxaliplatin) versus 48 « modern » systemic chemotherapy alone -Median follow-up 63 months -Better results for patients treated with HIPEC -51% of 5 year survival vs 13% (p0,05) -Median survival of 62 months vs 24 months
  • 14. PERITONEAL CARCINOMATOSIS from COLORECTAL CANCER -Franco et al. Cancer 2010 Prospective study. Cytoreduction with HIPEC -67 Cytoreductions + HIPEC versus 38 « modern » systemic chemotherapy alone -Some patients had liver metastasis -Better results for patients treated with HIPEC -Median survival of 35 months vs 17 months
  • 15. COLORECTAL CARCINOMATOSIS Cytoreductive surgery and intraperitoneal chemotherapy 2222 Registres: national and international 500 patients 1990 - 2007 75 to 86 % : HIPEC 54 to 85% de complete cytoreduction Mortality: 3 to 4% Morbidity:25 to 30% Median survival 30 months 5 year survival 30% J Clin Oncol 2004 and 2010
  • 16. Colorectal carcinomatosis Completeness of cytoreductive surgery CC-0 CC-1 J Clin Oncol 2010 CC-2 ou 3 CC-0
  • 18. Unresolved Questions Is synchronous liver metastasis a contraindication for curative treatment of carcinomatosis?
  • 19. Survival according to the presence of associated Liver Metastases (n= 65) (p= NS)
  • 20. Colorectal carcinomatosis and synchronous liver metastasis Liver metastasis does not contitute an absolute contraindication for curative approach of carcinomatosis • Liver metastasis should be controlled by systemic chemotherapy • Extensive liver surgery combined to extensive peritoneal surgery should be avoided
  • 21. Unresolved Questions Response to neoadjuvant systemic chemotherapy should be used for patient’s selection ?
  • 22. Survival according to the use of neoadjuvant chemotherapy (n= 120 patients) P = 0.042 Ann Surg 2012
  • 23. Survival according to response to neoadjuvant chemotherapy (n= 120) (p= NS) P = NS Ann Surg 2012
  • 24. Colorectal carcinomatosis and neoadjuvant chemotherapy Progression with neoadjuvant systemic chemotherapy does not contitute an absolute contraindication for curative approach of carcinomatosis • Median survival more of 30 months may be obtained The use of neoadjuvant systemic chemotherapy is important to exclude patients who will develop extraperitoneal disease Ann Surg 2012
  • 25. 2012 : Treatment of Peritoneal carcinomatosis : When and how to treat ? French national recommandations Pseudomyxoma Peritonei. Peritoneal Mesothelioma. PC from colorectal, small bowel adenocarcinoma and appendiceal cancers. Patient in good general status When optimal cytoreductive surgery (R0 – R1) is achievable. Strict patient selection. Experienced multidisciplinary center. PC from gastric cancer. PC from ovarian cancer. PC from pancreas, bile duct, gallblader, breast, …. Highly recommended Under evaluation Ongoing trial inclusion Probably not ???
  • 26. PERITONEAL CARCINOMATOSIS RECOMMENDATIONS TO GENERAL SURGEONS AND ONCOLOGISTS
  • 27. For current practice 1ST Message Curative treatment of peritoneal carcinomatosis must be considered at the time of diagnosis Not after failure of palliative treatment (surgery – systemic chemotherapy)
  • 28. How to select patients for treatment with curative intent? Which PATIENTS ?? AN AGGRESSIVE THERAPEUTIC APPROACH Mortality 4% Morbidity 34% Evaluation of general status
  • 29. How to manage patients for treatment with curative intent? Cytoreductive surgery and perioperative intraperitoneal chemotherapy should be performed in expert centers in peritoneal surface malignancy Complex, costly, long procedures Better patients selection Lower complications rates Higher rate of complete cytoreduction Smeenk, Br J Surg 2007 AFC 2008 WHERE ??? Expert center should be contacted at the time of diagnosis
  • 30. How to select patients for treatment with curative intent? WHICH carcinomatosis ??? Indications • Patients with no extraabdominal disease Body-scan Pet-scan • POSSIBILITY of COMPLETE CYTOREDUCTIVE SURGERY +++ Preoperative assessment: CT-scan, MRI Peroperative assessment ++++ • Laparoscopy • Detailed operative report
  • 31. For current practice SECOND Message Precise description of carcinomatosis distribution and extension must be performed
  • 32. How to manage patients for treatment with curative intent? IN ALL CASES • POSSIBILITY of COMPLETE CYTOREDUCTIVE SURGERY +++ • PRECISE ASSESSMENT OF CARCINOMATOSIS EXTENT ++++ Description of small bowel, hepatic pedicula, bladder involvement Photos or films Help expert centers for selection Avoid useless explorative laparotomy
  • 33. Precise description during laparotomy or laparoscopy of carcinomatosis that are not evaluable on morphologic exams Mesenteric retraction Diffuse small tumoral nodules
  • 34. For current practice THIRD Message Respect peritoneum !! Respect parietal wall!!
  • 35. Respect peritoneum and parietal wall Peritoneum is the first-line of defense “Cancer cells entrapment” Curative procedure more complex and less efficient No extensive peritonectomies or cytoreductive surgery without perioperative intraperitoneal chemotherapy
  • 36. Respect peritoneum and parietal wall Clinical situations: carcinomatosis suspected on preoperative exams • Explorative laparoscopy (trocarts on middle line) • Diagnostic biopsy
  • 37. Respect peritoneum and parietal wall
  • 38. Respect peritoneum and parietal wall Clinical situations: Carcinomatosis is discovered peroperatively No resection of primary tumor • Rectosigmoïd tumors (ureters) Stomia for occlusive tumor Exception for hemorrhagi tumors Avoiding drainage into flank The prognosis depend on the treatment of the metastatic disease and not on the primary tumor
  • 39. Respect peritoneum and parietal wall What should we do with scars or intraperitoneal nodules or anastomoses following previous surgery? More extensive will be previous surgery, more difficult, extensive and less curative will be the curative treatment
  • 40. Unresolved Questions What is the exact role of HIPEC into therapeutic management ?
  • 41. PRODIGE 7 (F Quenet) RANDOMIZED FRENCH STUDY Colorectal carcinomatosis Complete cytoreductive No HIPEC surgery RANDOMIZATION HIPEC oxaliplatin Perioperative systemic chemotherapy for 6 months RANDOMIZATION
  • 42. Prevention Interest of 2nd look for patients at risk of carcinomatosis development?
  • 43. Patients et Methods (1) From 1999 to 2009, 47 patients with a high risk to develop a PC (without clinical, radiologic or biologic symptoms), underwent a second look, 12 months after their first surgery. Selected: 3 groups of high-risk patients: • 28 who presented a minimal macroscopic PC synchronous to the primary (and which was completely resected during the same session) • 8 who presented synchronous ovarian metastases, • 11 who presented a perforation of their primary tumour. All these patients received the adjuvant standard treatment after the first surgery: 6 months of systemic chemotherapy (Folfox or Folfiri)
  • 44. Patients et Methods (2) Careful exploration of the whole abdominal cavity Mean duration of surgery: 6 hours 47 patients 23 with PC (49%) 24 without PC (51%) 23 Cytoreduc Surg + HIPEC Mean peritoneal index: 7 No HIPEC = 6 (PC- H-) (PC+ H+) HIPEC = 18 (PC- H+)
  • 45. Follow-up: 45 months (mean) Nb Recurrence IP recurrence Died PC+ H+ 23 12 (52%) 6 3 (13%) PC - H + 18 2 (11%) 1 0 PC – H - 6 4 (75%) 3 3 (50%) Only one prognostic factor: HIPEC (p = 0.02) Among the 41 pts with HIPEC: only 7 (17%) presented a peritoneal recurrence
  • 46. Conclusion (1) A second-look, performed 1 year after the resection of the primary, in a selected high-risk group of patients, allowed to found and treat an early and minimal PC in 50% of the patients. This new therapeutical approach seems benefit for the patients who initialy presented a minimal PC or ovarian metastasis. These encouraging preliminary results lead to initiate a prospective randomized trial, with the aim to definitely prove this benefit.
  • 47. French randomized multicentric study (Prophylochip) Patients at risk of carcinomatosis development (Perforated tumors, localized carcinomatosis removed, isolated ovarian metastasis) Adjuvant FOLFOX (6 months) or systemic chemotherapy (Negative workshop) Randomization 8 months) Follow-up 2nd look and prophylactic HIPEC