Abstract 3256: Circulating tumor DNA as a prognostic biomarker in locally advanced esophageal cancer

Introduction: The role of plasma circulating tumor DNA (ctDNA) as a prognostic biomarker in locally advanced esophageal cancer has not been well defined. We aim to evaluate the prognostic value of pre- and on-treatment ctDNA detection. Methods: In this retrospective single institution study, patients with esophageal cancer undergoing definitive local therapy via endoscopic resection (ER), esophagectomy, or definitive chemoradiation (CRT) underwent baseline and post-treatment ctDNA analysis utilizing a plasma-based tumor informed assay. ctDNA detection and quantification was annotated to clinicopathologic characteristics. Results: Between 2022 and 2024, 37 treatment-naïve esophageal cancer patients with stage I-IVA disease were analyzed. Overall, 28 underwent esophagectomy, 7 underwent definitive CRT, and 2 underwent ER. At baseline, ctDNA was detectable in 62% (23/37), with a mean 2.74 mean tumor molecules per milliliter of plasma (MTM/ml) (SD 6.37). Among those with detectable baseline ctDNA, 87% (13/15) achieved ctDNA clearance within a median of 45 days postoperatively. The rate of achievement of ctDNA clearance did not differ between the surgical or CRT groups (92% v. 83%, p>0.99). Of those patients who underwent surgery, 79% (22/28) had neoadjuvant therapy. Baseline ctDNA was detectable in 73% (16/22) of those patients, with a mean ctDNA level of 2.34 MTM/ml (SD 6.10). ctDNA remained detectable in 18% (3/17) after neoadjuvant therapy. Following surgery, 93% (14/15) achieved ctDNA clearance. When examining pathologic response among patients that had neoadjuvant therapy, 27% (6/22) had no residual disease at the time of resection. Patients with no residual disease had significantly lower ctDNA at baseline than those who did have residual disease (0.37 MTM/ml v 1.51 MTM/ml, p=0.005). Of the 14 patients that were detectable at baseline who achieved ctDNA clearance preoperatively, only 3 of those had no residual disease. Among the 28 esophagectomy patients, 11 had nodal metastases. While ctDNA detection rates at baseline were similar between pN0 and pN+ patients (58% v. 64%, p=0.70), patients with nodal metastases had significantly higher pre-treatment ctDNA levels (3.0 MTM/ml vs. 1.2 MTM/ml, p<0.001). Conclusion: Local therapy for esophageal cancer effectively clears ctDNA. Additionally, quantitative analysis of baseline ctDNA may be a useful prognostic indicator for patients likely to have nodal metastases and poor treatment response at the time of surgery. Citation Format: Marisa Sewell, Matthew Bott, Katherine Gray, Steve Maron, Yelena Janjigian, Hans Gerdes, Pari Shah, Abraham Wu, Bernard J. Park, David R. Jones, Daniela Molena. Circulating tumor DNA as a prognostic biomarker in locally advanced esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3256.