Circulating Tumour DNA in Melanoma—Clinic Ready?

Abstract

Purpose of Review Liquid biopsies, including circulating tumour DNA (ctDNA), can inform a variety of clinical questions. This review examines the potential role of ctDNA as a clinical tool to inform clinical decision-making from early to late stage cutaneous melanoma. Recent Findings In pre-clinical studies, ctDNA has been shown to detect minimal residual disease and molecular relapse; predict and monitor response to therapy; and identify key resistance mechanisms. Here, we examine the potential utility of ctDNA and discuss its limitations for use in patients with melanoma. We present novel clinical trials, which are testing its value as a tool to augment clinical decision-making. Finally, we discuss the steps that are needed to ensure that ctDNA is used optimally in order to improve outcomes for patients with melanoma. Summary Preclinical studies have shown that ctDNA has huge potential to provide real-time information about disease status in patients with melanoma. It is now time to test it rigorously within clinical trials to assess how it can be optimally used to benefit patients in the clinic.

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma

“… 47 In a wider clinical context, ctDNA monitoring has the potential to become a commonly used tool to guide clinical decision-making in all melanoma patients, and future trials should include translational sub-studies to investigate the utility of this. 52 TebeMRD (NCT05315258) aims to establish whether treating uveal and CM patients who develop molecular relapsed disease after definitive treatment (assessed via serial measurements of ctDNA), can prevent or delay the appearance of macroscopic disease.…”

Case report: Real-world experience using a personalized cancer-specific circulating tumor DNA assay in different metastatic melanoma scenarios

“…Longitudinal analysis of ctDNA, as measured by ddPCR, was found to be predictive of disease relapse and response to adjuvant treatment in the absence of radiological findings in melanoma ( 9 , 19 ). Similarly, ctDNA monitoring of melanoma-associated somatic alterations was shown in a cohort of patients to predict disease progression ahead of radiological findings ( 10 ). Of note, the majority of the published studies in melanoma have used single mutation or limited targeted panel sequencing for ctDNA analysis ( BRAF , NRAS , KIT , and TERT ) ( 16 , 20 , 21 ).…”

“…Multiple platforms have been developed to analyze ctDNA in different cancers including single mutation detection by dropletdigital PCR (ddPCR), next-generation sequencing (NGS), or whole-exome sequencing (WES), which have been reviewed previously (7,8). Existing evidence on the clinical utility of ctDNA testing in melanoma has emerged recently in retrospective and prospective studies (9,10). The use of personalized and tumor-informed ctDNA testing has been shown in several studies to detect molecular residual disease (MRD), and serve as an important prognostic tool to predict relapse in colorectal, breast, lung and urothelial cancers (11)(12)(13)(14).…”

Potential of circulating tumor DNA to refine immunotherapy

“…Although this study is only an initial glimpse into the potential of ctDNA to impact on clinical practice, it seems likely that noninvasive disease assessment will have a major role in oncology moving into the future. Many studies across tumor types have now demonstrated ctDNA as a marker of tumor burden and cancer proliferation 2,3 . In addition, ctDNA has been shown to be predictive of treatment response across a variety of treatment modalities 4–7 .…”

“…Many studies across tumor types have now demonstrated ctDNA as a marker of tumor burden and cancer proliferation. 2,3 In addition, ctDNA has been shown to be predictive of treatment response across a variety of treatment modalities. [4][5][6][7] In adjuvant bladder cancer, reanalysis of an originally reported negative phase 3 trial suggests that ctDNA is highly predictive of benefit for atezolizumab versus observation.…”