Circulating tumor DNA in conjunctival melanoma: landscape and surveillance value

Abstract

PurposeTo evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM). DesignRetrospective, observational case series. MethodsFrom July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases. We employed a 437-gene panel containing common mutations in CoM and common drug-sensitive mutations using next-generation sequencing (NGS) technology to analyze ctDNA mutations in plasma. Clinical and radiological records were used to assess tumor status. The relationship between ctDNA characteristics, tissue gene mutations, and clinical manifestations were explored. ResultsCoM-related driver mutations were detected in ctDNA of 11 patients with distant metastasis. The ctDNA were highly consistent with tissue sequencing, mutual driver mutation including BRAF, NRAS, KRAS, NF1, CTNNB1, and TP53 mutation. those with a higher VAF had shorter progression-free survival (PFS, p=0.0475) and overall survival (OS, p=0.0043). The ctDNA variant allele fraction (VAF) was not correlated with the sum of the longest diameters (SLD, p=0.8192) in distant metastasis patients. ConclusionsPositive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients.