1. Peritoneal metastases can be cured
Peritoneal metastases can be cured. Select the right patients and you will get good results.
Presented by Paul H. Sugarbaker, MD
Director, Program in Peritoneal Surface Malignancy
MedStar Washington Hospital Center
Washington, DC

2. Global Status of CRS/HIPEC for Peritoneal Metastases (PM)
Appendiceal – Standard of care (caution with aggressive histologies)
Peritoneal mesothelioma – Standard of care (consider use of NIPEC-LT)
Colorectal – Standard of care (follow NCCN guidelines)
Ovarian – Most common use of CRS/HIPEC (thousands of patients treated, >200 manuscripts, 7 RCTs in progress or published
Gastric – Selective use for prevention or PCI <6
Unusual malignancies with isolated PM – Select patients by quantitative prognostic indicators

3. Peritoneal Metastases
The panel currently believes that complete cytoreductive surgery and/or intraperitoneal chemotherapy can be considered in experienced centers for selected patients with limited peritoneal metastases for whom R0 resection can be achieved. The panel recognizes the need for (additional) randomized clinical trials that will address the risks and benefits associated with each of these modalities.

4. Standardized surgical technology to achieve a complete response:
Peritonectomy procedures
Anterior parietal
Right subphrenic
Left subphrenic
Pelvic
Omental bursa
Mesenteric
Visceral resections
Greater omentum
Spleen
Uterus and ovaries
Rectosigmoid colon
Right colon
Lesser omentum
Stomach

5. Standardized HIPEC for pseudomyxoma peritonei, adenocarcinoma from appendiceal and colonic cancer:
Dutch High Dose Mitomycin C Regimen: ‘Triple Dosing Regimen”
Add mitomycin C to 3 L 1.5% dextrose peritoneal dialysis solution
Add mitomycin C to the 1.5% peritoneal dialysis solution at a dose of 17.5 mg/m2 followed by 8.8 mg/m2 at 30 minutes and 8.8 mg/m2 at 60 minutes
Total dose of mitomycin C 35 mg/m2 for 90-minute HIPEC treatment
American Society of Peritoneal Surface Malignancy Low Dose Mitomycin C Regimen: ‘Concentration-Based Regimen”
Add mitomycin C to 3 L 1.5% dextrose peritoneal dialysis solution
Add mitomycin C to the 1.5% peritoneal dialysis solution at a dose of 30 mg/3 L followed by 10 mg at 60 minutes
Dose of mitomycin C 40 mg/3 L for 90-minute HIPEC treatment

6. Elias High Dose Oxaliplatin Regimen for Open HIPEC
Add oxaliplatin to 2 L/m2 5% dextrose solution
Dose of oxaliplatin is 460 mg/m2
30-minute HIPEC treatment at 43°C
Intravenous Component
Add 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 to separate bags of 250 mL normal saline. Begin rapid intravenous infusion of both drugs one hour before intraperitoneal chemotherapy.
Glehen Medium Dose Oxaliplatin Regimen for Closed HIPEC
Add oxaliplatin to 2 L/m2 5% dextrose solution
Dose of oxaliplatin is 400 mg/m2
30-minute HIPEC treatment at 43°C
Intravenous Component
Add 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 to separate bags of 250 mL normal saline. Begin rapid intravenous infusion of both drugs one hour before intraperitoneal chemotherapy .

7. Standardized HIPEC for sarcoma, gastric cancer, ovarian cancer, and peritoneal mesothelioma:
Sugarbaker Regimen
Add cisplatin to 2 L 1.5% dextrose peritoneal dialysis solution
Add doxorubicin to the same 2 L 1.5% peritoneal dialysis solution
Dose of cisplatin is 50 mg/m2 and doxorubicin is 15 mg/m2 for 90-minute HIPEC treatment
Intravenous Chemotherapy
Add ifosfamide 1300 mg/m2 to 1 L 0.9% sodium chloride. Begin continuous IV infusion over 90 minutes simultaneous with intraperitoneal chemotherapy
Add mesna disulfide 260 mg/m2 in 100 mL 0.9% sodium chloride to be given IV as a bolus 15 minutes prior to ifosfamide infusion
Add mesna disulfide 260 mg/m2 in 100 mL 0.9% sodium chloride to be given IV as a bolus 4 hours after ifosfamide infusion
Add mesna disulfide 260 mg/m2 in 100 mL 0.9% sodium chloride to be given IV as a bolus 8 hours after ifosfamide infusion

8. National Cancer Institute Milan Regimen
15.25 mg/L of doxorubicin and 43 mg/L of cisplatin for 90-minute HIPEC treatment
Chemotherapy solution 4-6 liters based on capacity of the peritoneal space
Van der Speeten K et al. Pharmacokinetic study of perioperative intravenous ifosfamide. Int J Surg Oncol. 2011;2011:185092
Deraco M et al. Experience with peritoneal mesothelioma at the Milan National Cancer Institute. World J Gastrointest Oncol ;2:76-84
RENAPE – French HIPEC for Ovarian Cancer
Cisplatin 80 mg in 3 L 0.9% sodium chloride at 42°C for 60 minutes

9. Sugarbaker GEMCITABINE-BASED Regimen for resected pancreas cancer and cisplatin-resistant ovarian cancer
Add gemcitabine to 2 L 1.5% dextrose peritoneal dialysis solution, total chemotherapy solution 1.5 L/m2
Dose of gemcitabine is 1000 mg/m2 for 60-minute HIPEC treatment
Sugarbaker MELPHALAN-BASED Regimen for reoperative cytoreductive surgery and cisplatin-resistant ovarian cancer and rare diseases with isolated peritoneal metastases
Add melphalan to 2 L 1.5% dextrose peritoneal dialysis solution, total chemotherapy solution 1.5 L/m2
Dose of melphalan is mg/m2 for 60-minute HIPEC treatment

10. BIDIRECTIONAL ADJUVANT NORMOTHERMIC CHEMOTHERAPY (BANC) – Long-Term Cancer Chemotherapy for Peritoneal Metastases

15. Distribution of peritoneal metastases is dependent upon flow of peritoneal fluid
Gray’s Anatomy
41st Edition, 2016

16. Strategy for Treatment of Peritoneal Metastases
Goal for CRS – complete visible resection of all tumor from the abdomen and pelvis.
Goal for perioperative chemotherapy – preserve the surgical complete response by eradication of minimal residual disease.

17. Surgical Technology to Achieve a Complete Response
Peritonectomy Procedures
Visceral Resections
Anterior parietal
Right subphrenic
Left subphrenic
Pelvic
Omental bursa
Mesenteric
Greater omentum
Spleen
Uterus and ovaries
Rectosigmoid colon
Right colon
Lesser omentum
Stomach

20. Prognostic Indicators for Treatment of Peritoneal Metastases
Histopathology
Lymph node status
Abdominal-Pelvic CT
Peritoneal Cancer Index
Completeness of cytoreduction score
Prior surgical score

21. Survival by Histopathology – Appendiceal Mucinous Neoplasms

22. Product-Limit Survival Estimates – Appendiceal Cancer

23. Survival by Lymph Node Status – Colon Cancer

24. Influence of Tumor Volume on Sensitivity of CT Scan

25. Sugarbaker PH et al. Int J Hyperthermia, 2017

26. Predictive Value Score
Multivariate model of radiologic criteria predictive of suboptimal cytoreduction
Criteria OR
95% CI P
Predictive Value Score
Retroperitoneal lymph nodes above the renal hilum (including subdiaphragmatic) > 1 cm
1.59
1.58 – 1.6
<0.001 1
Diffuse small bowel adhesions/thickening
1.87
1.86 – 1.87
Perisplenic lesion > 1 cm
2.27
1.7 – 3.03 2
Small bowel mesentery lesion > 1 cm
2.28
1.08 – 4.8
0.03
Root of the superior mesenteric artery lesion > 1 cm
2.4
1.34 – 4.32
0.003
Lesser sac lesion > 1 cm
4.61
4.39 – 4.84 4
Suidan et al. Gynecol Oncol, 2014

28. Survival by PCI – Colon Cancer
Survival by PCI – Colon Cancer (N=416)
(Glehen et al. AFC monograph, 2008)
Survival by PCI – Colon Cancer

30. Survival by Completeness of Cytoreduction – Colon Cancer (N=416)
(Glehen et al. AFC monograph, 2008)

31. Survival by Prior Surgical Score – Ovarian Cancer

32. Survival by Prior Surgical Score – Colorectal Cancer

34. Recommendations for use of CRS and HIPEC
Clinical features suggesting a favorable outcome for use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases
General medical condition compatible with survival and recovery from the procedure.
Clinical information regarding the peritoneal metastases compatible with a complete or near complete cytoreduction from contrast-enhanced CT.
Relative sparing of the small bowel and colon.
Absence of disease outside the abdomen/pelvis.
If hepatic metastases are present, they are limited, compatible with wedge resection.
Absence of disease within the porta hepatis.
With high-grade malignancy, a low or moderate peritoneal cancer index.
Clinical features suggesting cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should not be recommended
Poor performance status.
Rapid progression of a high-grade disease process.
Low likelihood of a response to perioperative chemotherapy (extensive prior systemic chemotherapy)
One or more concerning radiologic features by CT.
Prior abdominal or pelvic radiation therapy.
Local control of the primary cancer is unlikely.