3565 - Feasibility of Serial Tumor-Informed ctDNA Testing to Assess Response to Chemoradiation in Esophageal Cancer

Purpose/Objective(s): Concurrent chemoradiation (CRT) can serve as definitive therapy for esophageal cancer (EC). However, it remains uncertain whether an apparent CRT response will result in durable disease remission without surgery, particularly for adenocarcinoma (AC). Circulating tumor DNA (ctDNA) assays could aid in measuring CRT response and residual disease, potentially serving as a clinical decision tool for surgery after CRT and facilitating a larger role for CRT as nonsurgical management. We obtained serial tumor-informed ctDNA measurements in EC pts undergoing definitive CRT, using a commercially available assay.

Materials/Methods: 12 pts treated with definitive-intent CRT for EC in 2024 underwent serial ctDNA testing using a personalized tumor-informed assay 8 pts (67%) had squamous cell carcinoma (SCC) and 4 had AC. All were prescribed =50.4Gy. ctDNA was measured before, during, and approximately 4 weeks post-CRT, then every three months for up to a year. ctDNA results were correlated to clinical and pathological responses (based on PET, endoscopy, and/or surgery) and recurrence-free survival.

Results: 11 (92%) of 12 pts (8 with SCC, 4 with AC) successfully underwent ctDNA testing; one pt lacked sufficient tumor material to perform the assay. ctDNA was detectable in all 11 pts with a median pre-CRT value of 9.84 mean tumor molecules (MTM)/ml (range 0.05-51.2). Median followup was 9 months (range 4-12) from CRT start. Substantial ctDNA reduction was seen during CRT in all pts (mean reduction 78.6%, range 9.6-100%). Of 10 pts with available post-CRT data, 9 achieved ctDNA clearance following CRT; the one pt (with SCC) with persistent post-CRT ctDNA (0.06 MTM/mL) had negative biopsy 6 weeks post-CRT but recurred 4 months later. One pt (with AC) had post-CRT surgery and had pathologic complete response corresponding to undetectable pre-surgery ctDNA. 7 (78%) of the 9 pts with initially undetectable post-CRT ctDNA remain without evidence of disease. The other two pts subsequently developed detectable ctDNA and were later confirmed to have clinically recurrent disease.

Conclusion: Serial tumor-informed ctDNA testing using a commercially available assay is feasible in EC pts undergoing CRT and qualitatively correlates with CRT response and disease recurrence. Post-CRT ctDNA was detectable prior to all recurrences, suggesting a role for post-CRT ctDNA monitoring. All pts with sustained ctDNA clearance remained clinically disease-free within this short followup period, suggesting a role for ctDNA in predicting and guiding potential non-surgical management after CRT. However, recurrence occurred in two pts despite initially undetectable post-CRT ctDNA, indicating a need for continued monitoring, and for continued improvement and validation of ctDNA assays before they can be used to select patients for nonsurgical management after CRT.