Feasibility and dynamics of preoperative circulating tumor DNA in patients with gastroesophageal cancer receiving preoperative treatment.

Abstract

436 Background: Tumor-informed circulating tumor DNA (ctDNA) testing has shown high sensitivity and specificity for detecting molecular residual disease across solid tumors. However, the requirement of high-quality tissue specimens for upfront sequencing and designing of personalized ctDNA assays can be challenging using preoperative biopsy samples. There is a paucity of data on the feasibility of testing in preop tissue specimens in patients (pts) with gastroesophageal cancer (GEC) as well as its preop dynamics. Methods: We prospectively enrolled pts with locally advanced esophageal, gastroesophageal junctional (GEJ), or gastric cancer who were to receive preop treatment and surgery between 11/2021 and 07/2022. Tumor tissue was analyzed with next-generation sequencing to design a personalized, tumor-informed multiplex PCR assay (Signatera bespoke mPCR NGS assay) for each patient. Peripheral blood was collected for ctDNA analysis at baseline (before preoperative treatment), every 4 weeks until surgery, after surgery (before adjuvant therapy), and then every 4 weeks for patients who received adjuvant chemotherapy or every 3 months for patients who received adjuvant immunotherapy or no active treatment. Results: A total of 17 pts were enrolled, of which 7 had esophageal, 5 had GEJ, and 5 had gastric cancer. Tumor tissues from 14 (82.4%) pts passed quality control (QC), of which 11 were preoperative biopsy samples and 3 were surgically resected tissue. All 14 pts had detectable baseline ctDNA prior to preoperative treatment, with a median at 1.05 mean tumor molecules per mL of plasma (MTM/mL). Of these, 92.8% (13/14) of pts achieved ctDNA clearance by a median of 5 weeks from the start of preoperative treatment. Four pts opted for endoscopy surveillance, of whom 1 pt had transient ctDNA clearance at week 10, but had positive ctDNA at week 14, which persisted as of week 26. Conclusions: In our cohort, locally advanced GEC were ctDNA shedders. Preoperative tumor-informed ctDNA testing was feasible. Further studies to evaluate correlation between ctDNA dynamics and response to treatment are warranted. [Table: see text]