RASmutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61RAS-mutated mCRC. Fifty patients with codon 61RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61RASwild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61RAS-mutated mCRC compared to codon 61RASwild-type (54 vs. 28.5%), non-codon 61RAS-mutated (35.6%),BRAFV600E-mutated (25%), andRAS/BRAFwild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61RAS-mutated patients was significantly shorter compared toRAS/BRAFwild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61RAS-mutated andBRAFV600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61RASmutations and metastatic involvement of the peritoneum and ovary.
在转移性结直肠癌（mCRC）中，涉及密码子61的RAS突变较为罕见，仅占1-4%，但近期研究发现，在对表皮生长因子受体抑制剂（抗EGFRs）产生继发性耐药患者的循环肿瘤DNA（ctDNA）中，此类突变出现频率较高。本项回顾性单中心研究旨在探讨密码子61RAS突变型mCRC的临床表型及预后特征。研究纳入2013年1月至2021年12月期间在本机构接受治疗的50例密码子61RAS突变型mCRC患者，并以648例密码子61RAS野生型mCRC患者作为对照数据集。预后评估的主要终点为总生存期（OS）。与密码子61RAS野生型（28.5%）、非密码子61RAS突变型（35.6%）、BRAFV600E突变型（25%）及RAS/BRAF野生型（20.5%）队列相比，密码子61RAS突变型mCRC患者的腹膜或卵巢转移发生率显著更高（54%）。在中位随访96.2个月后，密码子61RAS突变型患者的中位OS较RAS/BRAF野生型患者显著缩短（26.9个月 vs 36.0个月，HR 0.56），但与非密码子61RAS突变型及BRAFV600E突变型患者相比无显著差异。本研究证实密码子61RAS突变具有负面预后影响，且与腹膜及卵巢转移存在统计学显著相关性。
Focus onRASCodon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis
肿瘤(癌症)患者之家