From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real‐world setting. Issue 10 (8th September 2018)

• Record Type: Journal Article
• Authors: Rowe, Steven P.; Luber, Brandon; Makell, Monique; Brothers, Patricia; Santmyer, JoAnn; Schollenberger, Megan D.; Quinn, Hannah; Edelstein, Daniel L.; Jones, Frederick S.; Bleich, Karen B.; Sharfman, William H.; Lipson, Evan J.
• Is Part Of: Molecular oncology. Volume 12:Issue 10(2018)
• Page Start: 1661
• Page End: 1672
• Publication Date: 2018-09-08
• Subjects: circulating tumor DNA -- ctDNA -- melanoma; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12373
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Melanoma currently lacks a reliable blood‐based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high‐risk resected melanoma. Patients were prospectively accrued into ≥ 1 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data. Cohorts B and C: patients with BRAF‐ or NRAS‐mutant melanoma who had either undergone surgical resection of high‐risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ctDNA measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ctDNA assay were 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ctDNA. In two patients in cohort A, ctDNA test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In four of 30 patients with advanced melanoma, ctDNA assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25, and 38 weeks, respectively. CtDNA was detectable in three of these four patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ctDNA data in managing patients with melanoma in a real‐world setting. Abstract : We investigated the clinical utility (i.e, impact on outcomes) of measuring circulating tumor DNA (ctDNA) in patients with metastatic or high‐risk resected melanoma. CtDNA interrogation revealed targetable mutations where tumor testing did not, allowing for treatment with (and anti‐tumor response to) targeted therapy. Additionally, ctDNA revealed evidence of melanoma activity in patients with no radiographic evidence of tumor. Image is of a 5cm hypermetabolic metastasis (arrowhead) within a fibroid uterus representing progressive melanoma, presaged months earlier by ctDNA.