Immediate postoperative minimal residual disease detection with MAESTRO predicts recurrence and survival in head and neck cancer patients treated with surgery

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Purpose While circulating tumor DNA (ctDNA) is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed accurate MRD at clinically-relevant timepoints. Ultrasensitive immediately after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics poorly understood. Experimental Design We applied MAESTRO, whole-genome, tumor-informed, mutation-enrichment sequencing assay, pooled testing format called MAESTRO-Pool, to plasma samples from HNSCC patients collected during surveillance. evaluated whether predict outcomes. Results Among 24 predominantly HPV-independent (95.8%) patients, rapid clearance occurred by the first postoperative sample (1-3 days postoperatively) 9 without an event (recurrence or death). 13/15 with were MRD+ (PPV = 92.9%; NPV 80%) median fraction (TFx) of 54 ppm (range 6-1,177 ppm). In last immediate window, 8/13 10/13 had TFx below 100 ppm, respectively, limit leading commercial assays. Early correlated worse overall survival (HR 8.3; 95% CI: 1.1-66.1; P 0.02) event-free 27.4; 3.5-214.5; < 0.0001) independent high-risk pathology. Conclusions Immediate MAESTRO was predictive recurrence death. Given ultralow TFxs observed, ultrasensitive will be essential reliable timepoints enable personalized decision-making HNSCC.

Language: Английский

Differential methylation of circulating free DNA assessed through cfMeDiP as a new tool for breast cancer diagnosis and detection of BRCA1/2 mutation

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 15, 2024

Recent studies have highlighted the importance of cell-free DNA (cfDNA) methylation profile in detecting breast cancer (BC) and its different subtypes. We investigated whether plasma cfDNA methylation, using Methylated Immunoprecipitation High-Throughput Sequencing (cfMeDIP-seq), may be informative characterizing patients with BRCA1/2 germline mutations for early detection response to therapy.

Language: Английский