Circulating tumor DNA (ctDNA) analysis for improved treatment response assessment and prediction of clinical outcomes in patients with esophageal cancer.

Abstract

4077 Background: Despite curative-intent treatment, patients with esophageal cancer experience a high risk of recurrence, and optimal patient management is limited by poor risk stratification and treatment response assessment strategies. ctDNA has demonstrated value as a prognostic biomarker in esophageal cancer; however, improved analytical and clinical performance of ctDNA analysis is necessary to reliably support patient management decisions in clinical practice. Methods: Between September 2017 and June 2023, plasma samples were collected from patients with esophageal cancer before, during, and after standard of care treatment in the routine care setting. In this retrospective analysis, ctDNA testing was performed on a subset of patients using a next-generation tumor-informed assay interrogating up to 50 personalized variants (Haystack MRD, Quest Diagnostics). Results: ctDNA was assessed in 149 samples from 51 patients with stage I-III esophageal adenocarcinoma (n= 40) or squamous cell carcinoma (n= 11). Fifteen patients with clinical follow-up (FU) available at the time of analysis had at least one sample collected after curative-intent treatment [neoadjuvant chemoradiotherapy (nCRT) and surgery (n=10) or definitive CRT (n=5)]. ctDNA was detected (ctDNA+) following curative-intent treatment in 5/15 (33%) patients, all 5 (100%) of whom experienced disease recurrence or were deceased at FU (median time from ctDNA+ result to FU: 14.4 months, range: 0.1-24.5). Of the 10 (67%) patients with no ctDNA detected (ctDNA-) following curative-intent treatment, 7 (70%) were disease-free at FU (median time from ctDNA- result to FU: 46.7 months, range: 6.3-65.5). In the neoadjuvant setting, paired pre- and post-nCRT samples were evaluated in 18 patients, demonstrating ctDNA detection in 18/18 (100%) patients prior to nCRT versus 8/18 (44%) following nCRT. ctDNA positivity following nCRT was strongly associated with poor pathological response (p=0.0026), and ctDNA dynamics observed longitudinally during nCRT served as a robust indicator of response. Of note, one patient experienced metastatic progression during nCRT, discovered at surgery, and ctDNA levels in this patient increased 550-fold while on nCRT. Conclusions: Evaluation of ctDNA using a next-generation tumor-informed platform supports improved response assessment to nCRT as well as accurate risk stratification following curative-intent treatment in patients with esophageal cancer. ctDNA positivity following curative-intent treatment predicted disease recurrence with a lead time of up to 22 months. Additional analyses are ongoing to further validate these findings.