Year: 2021
Type: article
Abstract: Objective To evaluate the prognostic significance of detectable circulating cell-free DNA (cfDNA) BRAF V600E/K mutations in patients with advanced melanoma enrolled in a clinical trial without BRAF -targeted therapy. Patients and Methods BRAF V600E/K mutation status was determined on archived tissue and pretreatment stored plasma from 149 patients with unresectable stage IV melanoma who were enrolled between May 5, 2010 and May 2, 2014 in the North Central Cancer Treatment Group/Alliance N0879 randomized phase 2 clinical trial. Results were reported as presence or absence of cfDNA BRAF V600E/K detection of assay vs tissue. Progression-free survival (PFS) and overall survival (OS) were assessed for patients with and without detectable BRAF mutation. Results In total, 63 of 149 (42.3%) patients had BRAF V600E/K results for tissue and blood, and 20 of 63 (31.7%) patients had tissue-diagnosed mutant BRAF . Of these, 11 of 20 (55.0%) patients had detectable plasma cfDNA BRAF . Among patients with tissue-mutant BRAF V600E/K, PFS and OS were shorter for those with corresponding cfDNA mutations (PFS, 5.8 vs 12.0 months; P =.051; OS, 9.2 vs 27.1 months; P =.054). Our assay demonstrated sensitivity of 55% (95% CI, 0.322 to 0.768), specificity of 97.7% (95% CI, 0.932 to 1.000), positive predictive value of 91.7% (95% CI, 0.760 to 1.000), and negative predictive value of 82.4% (95% CI, 0.719 to 0.928). Conclusion In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF -mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials. Trial Registration: clinicaltrials.gov Identifier: NCT00976573
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: Alliance Statistics and Data Management Center, G1784070713, Sanford Community Cancer Program of the North Central Plains (NCORP), Naional Cancer Institute, Naitonal Clinical Trials Network U10 Lead Academic Site, Metro-Minnesota Community Oncology Research Consortium (MMCORC), North Central Cancer Treatment Group, Alliance for Clinical Trials in Oncology Operations Center, Mayo Clinic Comprehensive Cancer Center Support Grant, The Alliance NCTN Biorepository and Biospecimen Resource
OpenAlex ID: W3205791037