结直肠癌在10%的病例中导致腹膜转移（CRPM）。采用细胞减灭手术联合腹膜内超温化疗（CRS-HIPEC）可以提高生存率。原发肿瘤的位置和RAS、BRAF以及错配修复/微卫星稳定性（MMR/MSI）异常可能会影响CRS-HIPEC术后生存率，但存在研究结果不一致的情况。我们评估原发肿瘤部位和基因改变对CRS-HIPEC术后生存率的影响。本回顾性队列研究包括了2001年至2020年在高强度中心接受针对CRPM的CRS-HIPEC病例。通过下一代测序和微卫星测试定义RAS、BRAF和MMR/MSI基因型。使用多变量Cox比例危险模型对肿瘤侧向和基因组学对生存的调整效应进行了评估。我们分析了这些变量对无进展生存期的影响以及免疫检查点抑制剂的影响。总共250名患者接受了CRS-HIPEC手术并进行了RAS、BRAF和MMR/MSI检测；50.8%的患者有RAS突变，12.4%有BRAF突变，6.8%的患者MMR/MSI缺陷-高（dMMR/MSI-H）。基因组变异在右侧癌症中占优势。在考虑并发症、肿瘤学和围手术期变量影响的调整后，直肠起源（危险比（HR）1.9，p=0.01）、RAS突变（HR 1.6，p=0.01）和BRAF突变（HR 1.7，p=0.05）均与较差的生存有关。RAS突变还与较短的无进展生存期（手术后6个月HR 1.6，P=0.01）有关，而dMMR/MSI-H状态则与较好的生存（两年HR 0.3，P=0.01）有关。dMMR/MSI-H患者接受免疫检查点抑制剂，则趋向于有更好的生存率。对于CRPM患者，直肠起源、RAS突变和BRAF突变均与CRS-HIPEC术后较差的生存相关。具有CRPM和dMMR/MSI-H状态的患者则有更好的生存。进一步的研究应该评估这个亚组的免疫检查点抑制剂的益处。©2023年外科肿瘤学会。

Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor location and abnormalities in RAS, BRAF, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival.This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the RAS, BRAF, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables' effects on progression-free survival and the effects of immune checkpoint-inhibitors.A total of 250 patients underwent CRS-HIPEC with testing for RAS, BRAF, and MMR/MSI; 50.8% of patients were RAS-mutated, 12.4% were BRAF-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities and oncological and perioperative variables, rectal origin [hazard ratio (HR) 1.9, p = 0.01], RAS mutation (HR 1.6, p = 0.01), and BRAF mutation (HR 1.7, p = 0.05) were associated with worse survival. RAS mutation was also associated with shorter progression-free survival (HR 1.6, p = 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3, p = 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival.Rectal origin, RAS mutations, and BRAF mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup.© 2023. Society of Surgical Oncology.