White Michael G, Ayabe Reed I, Zeineddine Mohammad A, Zeineddine Fadl A, Yousef Abdelrahman M G, Yousef Mahmoud, Galbraith Norman J, Iorgulescu J Bryan, Scally Christopher, Fournier Keith, Newhook Timothy E, You Nancy Y, Willis Jason, Kopetz Scott, Chang George J, Shen John Paul, Uppal Abhineet
Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgery, University of California Irvine Medical Center, Orange, CA, USA.
Transl Oncol. 2025 May;55:102379. doi: 10.1016/j.tranon.2025.102379. Epub 2025 Apr 3.
Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) had CPM with extraperitoneal metastases. Patients with synchronous CPM and CLM had worse overall survival (HR 1.67 [95 %CI 1.26-2.22]). Mutations in ctDNA were noted in 110/145 (75.9 %) of CPM patients, with mutations in KRAS or PIK3CA ctDNA being associated with worse survival. Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly BRAF and KRAS, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.
结直肠腹膜转移（CPM）是结直肠癌转移扩散的第三大常见部位，与其他转移部位的疾病相比，其生存率更低。近年来，肿瘤循环肿瘤DNA（ctDNA）的突变状态在转移性结直肠癌患者的临床决策中得到了越来越多的应用，尽管其在CPM中的作用尚不清楚。在此，我们描述了不可切除CPM患者的标准治疗突变谱及相关结果，并与160例未切除的结直肠肝转移（CLM）患者进行了背景对比。在508例患者中，288例（57%）仅发生CPM，220例（43%）发生CPM并伴有腹膜外转移。同时发生CPM和CLM的患者总生存期更差（HR 1.67 [95%CI 1.26 - 2.22]）。在145例CPM患者中，110例（75.9%）检测到ctDNA突变，KRAS或PIK3CA ctDNA突变与较差的生存率相关。重要的是，肿瘤突变谱与生存率之间的关联因转移部位而异。特定突变（尤其是BRAF和KRAS）的预后意义在CPM和CLM患者中有所不同，这支持了这些转移部位的独特生物学特性，以及组织和循环基因组分析对于根据转移部位对这些患者进行风险分层的重要性。
