Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients.
Cancer
; 129(11): 1723-1734, 2023 06 01.
Article
em En
| MEDLINE
| ID: mdl-36869646
ABSTRACT
BACKGROUND:
Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment.METHODS:
A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease.RESULTS:
In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression.CONCLUSION:
Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Tumoral Circulante
/
Melanoma
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer
Ano de publicação:
2023
Tipo de documento:
Article