Abstract 5208: Dynamic changes in circulating tumor DNA and T cell receptor repertoire predict disease progression in patients with unresectable esophageal squamous cell carcinoma

Abstract Background: Patients with unresectable esophageal squamous cell carcinoma (ESCC) showed variations in their response to treatments and experienced inevitable disease progression. The development of non-invasive and clinically viable biomarkers is urgently needed. Therefore, this study aimed to investigate prognostic value of circulating tumor DNA (ctDNA) and T cell receptor (TCR) repertoire in these patients. Methods: A total of 21 ESCC patients who underwent definitive chemoradiotherapy, radiotherapy, or immune checkpoint inhibitor (ICI)-combined therapy from October 2020 to March 2022 were retrospectively evaluated. Baseline tumor samples were collected for genomic profiling using targeted NGS. Baseline and post-therapy plasma were collected for genomic and TCR profiling. Results: We found that ctDNA detection rates were significantly reduced after treatment (P<0.001). Post-treatment ctDNA positivity were associated with worse local recurrence-free survival (P=0.001) and progression-free survival (P=0.001), but not overall survival. Moreover, TCR clonality was significantly increased after treatment, including CDR3 diversity (P=0.003), TCR clonotype (P=0.004), and VJ pairs (P=0.010), indicating an increased T cell expansion and complexity. Specifically, we identified two increased and four reduced VJ rearrangements after treatment, and the four reduced VJ rearrangements (Vβ12-2Jβ2-4, Vβ6-9Jβ1-5, Vβ6-7Jβ1-5, and Vβ6-9Jβ1-1) were significantly associated with worse progression-free survival. Conclusion: Our findings suggest the prognostic implication of plasma ctDNA and TCR profiles in patients with unresectable ESCC receiving definitive therapy, supporting the future development of non-invasive monitoring of disease progression in these patients. Citation Format: Baidong Zhang, Xiang Zhan, Qiang Li, Chenxuan Wang, Jiaohui Pang, Yaru Zhang, Song Wang, Qiuxiang Ou, Haimeng Tang, Alei Feng, Zhe Yang. Dynamic changes in circulating tumor DNA and T cell receptor repertoire predict disease progression in patients with unresectable esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5208.