Tinsley Nadina, O'Dwyer Sarah T, Nagaraju Raghavendar, Chakrabarty Bipasha, Braun Michael, Mullamitha Saifee, Kamposioras Konstantinos, Marti Marti F E, Saunders Mark, Clouston Hamish, Selvasekar Chelliah, Wild Jonathan, Wilson Malcolm, Renehan Andrew, Aziz Omer, Barriuso Jorge
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation Trust, Manchester, UK.
J Surg Oncol. 2024 Nov;130(6):1422-1432. doi: 10.1002/jso.27776. Epub 2024 Jul 16.
Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m, 90 min) or Oxaliplatin (368 mg/m, 30 min) heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response on preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versus NR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected by peritoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM.
PRODIGE-7提供的治疗指南推荐，对于结直肠癌腹膜转移（CRPM）患者，在进行减瘤手术（CRS）前进行围手术期全身化疗。多模式治疗的毒性需要进一步明确。化疗反应及其对生存的影响尚未见报道。我们评估了在CRS（术前）前接受全身奥沙利铂/伊立替康治疗，随后接受丝裂霉素C（35mg/m²，90分钟）或奥沙利铂（368mg/m²，30分钟）热灌注腹腔化疗（HIPEC）的CRPM患者。通过前瞻性数据库进行二次分析。比较化疗反应者（R）和无反应者（NR）的总生存期（OS）。通过不良事件（AE）发生率评估毒性。2005年4月至2021年4月，436例患者接受了CRS+HIPEC；125例（29%）接受了术前化疗。112例（90%）接受了奥沙利铂（64例，57%）或伊立替康（48例，43%）。R定义为术前影像学和/或术后组织学检查为完全缓解（CR）或部分缓解，71例（63%，53.8-72.3）出现R；16例（14%，8.4-22.2）为CR。R组与NR组的中位OS分别为43.7个月（37.9-49.4）和23.9个月（16.3-31.4），p=0.007，风险比（HR）为0.51（0.31-0.84）。OS多变量分析显示，经腹膜癌指数、减瘤评分完整性校正后，化疗反应的HR为0.48（0.25-0.95），p=0.03。CRS导致21%的3-4级AE，而术前化疗为4%。HIPEC的3-4级AE为0.5%。术前化疗反应是CRPM患者OS的独立预测因素。
