University of Manchester, Manchester, United Kingdom;
Nadina Tinsley , Raghavendar Nagaraju , Sarah O'Dwyer , Michael Braun , Saifee Mullamitha , Konstantinos Kamposioras , Omer Aziz , Jorge Barriuso
Background: The role of heated intraperitoneal chemotherapy (HIPEC) in colorectal cancer peritoneal metastases (CRPM) is confounded by cytoreductive surgery (CRS) or receipt of peri-operative systemic anticancer therapy (SACT). Following Prodige-7, the role of Oxaliplatin HIPEC in addition to CRS has been debated. We evaluated a patient series undergoing CRS with Oxaliplatin (368mg/m2 for 30 mins) or Mitomycin C (MMC) (35mg/m2 for 90 mins) HIPEC stratified by extent of CRS and SACT. Methods: Data collected retrospectively from a prospective database of CRPM patients undergoing CRS +/- HIPEC at a single UK Peritoneal Tumour Centre included sex, primary tumour detail: site, TNM stage, SACT: adjuvant, peri-operative, operation details: peritoneal cancer index (PCI), cytoreductive score (CC), HIPEC agent, molecular profile: RAS, BRAFV600E, PIK3CA, microsatellite status, date of last follow-up or recurrence/death to 1st July 2022. Univariable and multivariable (MVA) analysis were performed for overall survival (OS) and recurrence free survival (RFS). Outcomes were compared among three patient groups: 1. all comers (all patients who underwent CRS +/- HIPEC), 2. CC0-1 (those who achieved CC0-1) and 3. SACT naïve (CC0-1 and no SACT pre-CRS, adjuvant SACT post primary resection allowed if completed > 6 months). Results: From April 2005 to April 2021, 409 patients received HIPEC: 271 (66%) MMC, 138 (34%) Oxaliplatin; 395 patients (97%) had CRPM (all comers); 336 (85%) achieved CC0-1; 187 (47%) were SACT naïve. Median OS for all comer, CC0-1 and SACT naïve groups were 39, 44 and 47 months respectively. MMC vs Oxaliplatin HIPEC median OS was 44 (95% CI 38-49) vs 50 (95% 40-60) months, p=0.3 in CC0-1. Median OS in SACT naïve was 46 (95% CI 34-58) vs 60 (95% CI 38-82) months, p=0.3. Oxaliplatin HIPEC showed a trend to benefit PCI <15 and SACT naïve (table). OS MVA in CC0-1 and SACT naïve showed Oxaliplatin HIPEC was comparable to MMC HR: 0.85, 95% CI (0.60-1.19) p=0.3, HR: 0.83, 95% CI (0.51-1.35) p=0.5, respectively. Oxaliplatin HIPEC had a significant benefit on local RFS in CC0-1 (MMC vs Oxaliplatin RFS 9 vs 12 months p=0.01; distant RFS 10 vs 12 months p=0.5, local and distant RFS 6 vs 8 months p=0.3). Local RFS MVA showed a HR: 0.64, 95% CI (0.41-0.99), p=0.04 for Oxaliplatin HIPEC when corrected by PCI, N stage and grade. Conclusions: The study shows a trend to better OS with Oxaliplatin HIPEC in selected patients with low volume CRPM not requiring SACT. CRS with Oxaliplatin HIPEC is beneficial in local RFS, suggesting there is a role for local control in CRPM with Oxaliplatin HIPEC. This needs to be further explored in clinical trials.
Median OS (95% CI) months | |||
---|---|---|---|
CC0-1 | SACT naïve | ||
PCI <11 | MMC | 47 (33-60) | 61 (38-83) |
Oxaliplatin | 70 (49-91) | Not reached | |
PCI 11-15 | MMC | 29 (26-33) | 32 (15-49) |
Oxaliplatin | 40 (19-61) | 35 (23-46) | |
PCI >15 | MMC | 31 (19-44) | 31 (22-40) |
Oxaliplatin | 26 (6-43) | 32 (10-55) | |
p=0.2 | p=0.2 |
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