Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma.

Background: Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence.
Patients and Methods: We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAF ^V600E -mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up.
Results: In 80 patients (stages ≤III), BRAF ^V600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003).
Conclusions: Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.
Competing Interests: Disclosure SGC is a current employee at Tempus Labs. FM-B has research support from Aileron Therapeutics, AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences, Curis, CytomX Therapeutics, Daiichi Sankyo Co., Debiopharm International, eFFECTOR Therapeutics, Genentech, Guardant Health, Klus Pharma, Takeda Pharmaceutical (formerly Millennium Pharmaceutical), Novartis, Puma Biotechnology, and Taiho Pharmaceutical; provided consulting role for AbbVie, Aduro BioTech, Alkermes, AstraZeneca, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche, Genentech, IBM Watson, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, OrigiMed, PACT Pharma, Parexel International, Pfizer, Samsung Bioepis, Seattle Genetics, Tyra Biosciences, and Xencor, Zymeworks; is on the advisory committee of Black Diamond, Eisai, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Mersana Therapeutics, Puma Biotechnology, Seattle Genetics, Silverback Therapeutics, Spectrum Pharmaceuticals, and Zentalis; received honoraria from Chugai Biopharmaceuticals, Mayo Clinic, and Rutgers Cancer Institute of New Jersey; and received travel-related support from Beth Israel Deaconess Medical Center. FJ has research support from Astex, Novartis, BioMed Valley Discoveries, Fore Bio, Deciphera, Bristol-Myers Squibb, Asana, Ideaya Biosciences, Sanofi, Merck, F-star, JSI Innopharm, Bioxcel, Lilly, Bicara, PureTech Health, FujiFilm Pharmaceuticals, Sotio, Synlogic, NextCure, and Hutchinson Medipharma; is on the Scientific Advisory Boards of Ideaya Biosciences, Synlogic, Sotio, Puretech Health, Deciphera, Crown Bioscience, Asana, Fore Bio, Novartis, Bicara, and PegaOne; is a paid consultant for Mersana Therapeutics, Flame Bio, Cardiff Oncology, MedinCell, and Immunomet; has ownership interests in Cardiff Oncology and Monte Rosa Therapeutics; and has the leadership position in Monte Rosa Therapeutics. The remaining authors have declared no conflicts of interest.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)