Circulating tumor DNA analysis for outcome prediction in localized esophageal cancer.

Abstract

4055 Background: Blood-based biomarkers are not used in routine clinical practice in patients with esophageal carcinomas (ECs). Circulating tumor DNA (ctDNA) is an attractive biomarker that could be applied to ECs. We performed a study to explore pre- and post-treatment ctDNA analysis using the next generation sequencing-based CAPP-Seq method as a prognostic biomarker for localized EC. Methods: We prospectively enrolled 29 patients with localized EC treated with chemoradiotherapy (CRT) between June 2011 and October 2015. 12 (43%) patients were treated with CRT alone and 17 (57%) were treated with CRT followed by esophagectomy. Our cohort included patients with stage IB (1; 3.4%), II (7; 24.1%), and III (21; 72.4%) disease. Eight (27.6%) harbored squamous cell carcinoma (SCC) and 21 (72.4%) adenocarcinoma (AC). All patients received pre-treatment evaluation by thoracic CT, PET/CT, and esophagoduodenoscopy. ctDNA levels were quantitated in pre-treatment and post-treatment plasma samples using CAPP-Seq. Results: Median follow-up time was 21 months. We detected ctDNA pre-treatment in 72.4% of cases (N = 21) with a median concentration of 2.69 haploid genome equivalents per mL (hGE/mL; range 0.34-107.3). Pre-treatment ctDNA concentrations were strongly correlated with metabolic tumor volumes (MTV; R2= 0.74; p = 1.7e-07) and were significantly higher in SCC than AC patients (28.2 vs. 2.1 mean hGE/mL; p = 0.002). Overall survival (OS) at 2 years for pretreatment ctDNA+ vs. ctDNA- patients was 47% vs. 86% (HR = 6.0; 95% CI = 0.74-49.2; p < 0.05) and trended toward significance when accounting for stage, histology, and age (p = 0.09). A single post-treatment plasma sample was collected within 3 months of treatment and was available for 19 patients. Post-treatment ctDNA was detected in 3 (15.7%) patients with a median concentration of 11.5 hGE/mL (range 2.2–11.9). Post-treatment ctDNA detection was strongly predictive of poor event-free survival (p < 0.0001) and time to distant metastasis (p < 0.0001). Conclusions: Our data suggest that pre- and post-treatment ctDNA levels may be prognostic for patients with localized EC and could potentially guide risk-adapted adjuvant therapy approaches.