Open AccessImpact of circulating tumor DNA mutant allele fraction on prognosis in RAS ‐mutant metastatic colorectal cancer
Author(s) -
Elez Elena,
Chianese Chiara,
SanzGarcía Enrique,
Martinelli Erica,
Noguerido Alba,
Mancuso Francesco Mattia,
Caratù Ginevra,
Matito Judit,
Grasselli Julieta,
Cardone Claudia,
Esposito Abate Riziero,
Martini Giulia,
Santos Cristina,
Macarulla Teresa,
Argilés Guillem,
Capdevila Jaume,
Garcia Ariadna,
Mulet Nuria,
Maiello Evaristo,
Normanno Nicola,
Jones Frederick,
Tabernero Josep,
Ciardello Fortunato,
Salazar Ramon,
Vivancos Ana
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12547
Subject(s) - hazard ratio , medicine , colorectal cancer , oncology , carcinoembryonic antigen , proportional hazards model , progression free survival , gastroenterology , confidence interval , cancer , chemotherapy
Despite major advances in the treatment of metastatic colorectal cancer (mCRC), the survival rate remains very poor. This study aims at exploring the prognostic value of RAS ‐mutant allele fraction (MAF) in plasma in mCRC. Forty‐seven plasma samples from 37 RAS ‐mutated patients with nonresectable metastases were tested for RAS in circulating tumor DNA using BEAMing before first‐ and/or second‐line treatment. RAS MAF was correlated with several clinical parameters (number of metastatic sites, hepatic volume, carcinoembryonic antigen, CA19‐9 levels, primary site location, and treatment line) and clinical outcome [progression‐free survival (PFS) and overall survival (OS)]. An independent cohort of 32 patients from the CAPRI‐GOIM trial was assessed for clinical outcome based on plasma baseline MAF. RAS MAF analysis at baseline revealed a significant correlation with longer OS [Hazard ratios (HR) = 3.514; P = 0.00066]. Patients with lower MAF also showed a tendency to longer PFS, although not statistically significant. Multivariate analysis showed RAS MAFs as an independent prognostic factor in both OS (HR = 2.73; P = 0.006) and first‐line PFS (HR = 3.74; P = 0.049). Tumor response to treatment in patients with higher MAF was progression disease ( P = 0.007). Patients with low MAFs at baseline in the CAPRI‐GOIM group also showed better OS [HR = 3.84; 95% confidence intervals (CI) 1.5–9.6; P = 0.004] and better PFS (HR = 2.5; 95% CI: 1.07–5.62; P = 0.033). This minimally invasive test may help in adding an independent factor to better estimate outcomes before initiating treatment. Further prospective studies using MAF as a stratification factor could further validate its utility in clinical practice.