245. CLINICAL UTILITY OF CTDNA IN LONGITUDINAL MONITORING OF TREATMENT RESPONSES AND RELAPSE IN METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Esophageal squamous cell carcinoma (ESCC) is a deadly cancer frequently diagnosed only at advanced stages, contributing to high mortality. In this study, circulating tumor DNA (ctDNA), which is DNA shed from the tumor into the bloodstream, was utilized for real-time monitoring of treatment response and early detection of relapse using next-generation sequencing. The clinical utility of ctDNA as a biomarker for monitoring disease burden and treatment response was evaluated. A total of 72 metastatic ESCC patients, who received palliative chemotherapy, were recruited. Blood was collected from the patients before, during, and at the end of treatment. ctDNA was extracted from plasma and the mutation profiles were determined by targeted-capture sequencing using the Roche AVENIO ctDNA expanded 77-genes kit. Mutations or amplification detected in the ctDNA were validated by Sanger sequencing or digital PCR. Mutations in the tumors were validated using formalin-fixed paraffin-embedded (FFPE) tissue with the Roche AVENIO Tumor tissue expanded 77-genes kit. Single nucleotide variations (SNVs) were detected in 92% and copy number variations (CNVs) were detected in 22% of the metastatic ESCC patients. The most frequently mutated genes were TP53, NFE2L2 and PIK3CA. The presence of TP53 mutations at pre-cycle III treatment was associated with poor progression-free survival and overall survival. Longitudinal ctDNA analysis showed good concordance between mutant allele frequency (MAF) and tumor burden and the change in MAF preceded the radiographic relapse with an average of 46 days. ctDNA also demonstrated the ability to capture inter-tumor heterogeneity in the primary tumor and lymph node metastasis. Using the 77-gene panel, mutations were detected in ctDNA of metastatic ESCC patients; the change in MAF reflected the tumor burden. Serial analysis of ctDNAs indicates the usefulness of ctDNA as a prognostic and predictive biomarker for real-time non-invasive monitoring to assess tumor burden and to predict treatment efficacy, disease relapse, and patient survival. Mutation profiles in ctDNA may also be useful in guiding personal targeted therapy.