Abstract 2281: The role of baseline and early dynamics of ctDNA in predicting response and prognosis of early and advanced gastroesophageal adenocarcinomas
Authors: Ali Abdulnabi Suwaidan, Mark R. Openshaw, Barbara Ottolini, David Guttery, Daniel Fernandez Garcia, Cathy J. Richards, Jacqui A. Shaw, Anne L. Thomas
Journal: Cancer Research (2019)

Abstract Background: Circulating tumor DNA (ctDNA) is emerging as a valuable less-invasive adjunct to tissue biopsy for real time monitoring and personalization of cancer treatment. This study aimed to determine the prognostic value of baseline ctDNA in both early and advanced gastroesophageal adenocarcinoma (GEA) and establish whether dynamic changes in ctDNA provides useful response and prognosis information. Patients and Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue DNA and serial plasma cell-free DNA (cfDNA) were obtained from 36 patients (23 early stage (63.9%), 13 advanced stage (36.1%)) undergoing treatment for GEA. Tumor DNA was analyzed by targeted next generation sequencing (NGS) (custom ampliseq six gene panel) and Nanostring™ nCounter® technology (87 gene panel). In each patient, selected mutations and gene amplifications were profiled in serial cfDNA samples using a combination of NGS, droplet digital PCR and real-time quantitative PCR. Results: Mutations and/or gene amplifications were identified in tumor DNA of 33/36 patients (91.7%). Patient specific profiling detected ctDNA in 19/33 patients (57.6%) at baseline: 9/22 with early stage disease (40.9%) and 10/11 with advanced stage disease (90.9%). Objective Response Rate (ORR) by RECIST 1.1 criteria was 71.4% (10/14) for patients who were ctDNA negative at baseline (group A) and 52.9% (9/17) for patients with detectable ctDNA at baseline (group B). Multivariate Cox regression analysis, adjusted for stage of disease and patient performance status, showed presence of ctDNA at baseline was associated with both reduced progression free survival (PFS) and overall survival (OS) [hazard ratio (HR) of 6.2 (95% CI 1.9-19.8, P = 0.002) and 7.3 (CI 1.9-28.2, P = 0.004), respectively]. The median PFS was 34.7 months and 12.1 months and median OS was not reached and 14.5 months for group A and B, respectively (Mantel-Cox Log Rank P = 0.008 and P &amp;lt; 0.001, respectively). ctDNA was detected before relapse in 3/22 (13.6%) early stage patients and before progression in 5/11 (45.5%) advanced stage patients, with an overall median lead-time of 6.3 weeks before radiological evidence of relapse or progression. Conclusion: This pilot study suggests that presence of ctDNA at baseline and recurrence during treatment are poor prognostic biomarkers both in early and advanced GEA. Citation Format: Ali Abdulnabi Suwaidan, Mark R. Openshaw, Barbara Ottolini, David Guttery, Daniel Fernandez Garcia, Cathy J. Richards, Jacqui A. Shaw, Anne L. Thomas. The role of baseline and early dynamics of ctDNA in predicting response and prognosis of early and advanced gastroesophageal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2281.