1870P - Developing the liquid biopsy in gastroesophageal adenocarcinoma: Disease monitoring and detection of minimal residual disease

Abstract

Background: Gastroesophageal adenocarcinoma (GOA) is a molecularly defined group of cancers with shared genetic alterations, poor overall survival and no routine blood based biomarker. The liquid biopsy, including circulating tumour DNA (ctDNA) is a promising technology that may improve our ability to monitor disease and enhance survival. This study aimed to determine the utility of ctDNA in GOA. Methods: A pilot study of 37 patients with GOA were recruited. These comprised 24 patients treated with curative intent and 13 palliative patients. Tumour DNA was sequenced using a custom ampliseq six gene targeted next generation sequencing (NGS) panel. Tumours from patients treated with curative intent with no detectable somatic mutation were also analysed for gene amplification via Nanostring™ nCounter. Plasma from blood samples taken at multiple time points were analysed by NGS and digital droplet PCR to detect ctDNA. Results: Somatic mutations at > 5% allele frequency were identified in 30 of 37 (81%) tumours, most commonly in TP53. Gene amplification was detected in a further three. In 11 of 13 (85%) palliative patients that had a detectable somatic mutation ctDNA was detected in 9 (82%). These ctDNA levels were dynamic, falling with treatment response and rising with disease progression, often prior to clinical relapse. 22 of 24 (92%) patients treated with curative intent had a detectable somatic mutation or gene amplification. 9 of these 22 (41%) relapsed during follow-up. CtDNA was detected prior to relapse in 7 of 22 (31%) patients and predicted poor survival (median PFS 298 vs > 1000 days, HR = 11.8, p < 0.001). In 4 patients, ctDNA was detected in the postsurgical blood test, of these 3 have relapsed and one remains disease free at 5 months (median PFS 203 vs > 1000 days, HR = 9.6, p = 0.004). This patient will be followed up for evidence of relapse as these ctDNA positive post surgical bloods suggest detection of minimal residual disease. Conclusions: Tracking of ctDNA in patients with GOA provides valuable clinical information regarding disease progression and response, and presence of ctDNA is generally a poor prognostic sign. In addition, ctDNA may define patients with minimal residual disease who are at high risk of relapse after surgery. Legal entity responsible for the study: University of Leicester. Funding: HOPE against Cancer Experimental Cancer Medicine Centres Network. Disclosure: B. Ottolini: Previous employee: DiaDx; Holding patents: DiaDx. C.J. Richards: Honoraria: MSD. J.A. Shaw: Travel, accommodation, expenses reimbursements: Thermofisher. A. Thomas: Honoraria: Amgen, Servier, BMS. All other authors have declared no conflicts of interest.