Focus on Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis.

mutations 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 61 -mutated mCRC. Fifty patients with codon 61 -mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 wild-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 61 -mutated mCRC compared to codon 61 wild-type (54 vs. 28.5%), non-codon 61 -mutated (35.6%), V600E-mutated (25%), and / wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 -mutated patients was significantly shorter compared to / wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 -mutated and V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 mutations and metastatic involvement of the peritoneum and ovary.