Abstract 6412: Combination of liquid biopsy and PET/CT enhances prediction of pathological response to neoadjuvant immunochemotherapy in patients with esophageal squamous cell carcinoma

Abstract Background: Neoadjuvant immunochemotherapy (NICT) demonstrated remarkable efficacy in esophageal squamous cell carcinoma (ESCC) patients. An accurate evaluation of treatment response is critical before surgery. Therefore, this study aimed to explore and evaluate the use of non-invasive and clinical assessments to predict pathological response to NICT prior to surgery in these patients. Methods: A total of 71 ESCC patients who received NICT between March 2020 and February 2022 were recruited in this study. Clinicopathological characteristics and PET/CT assessment before and after NICT were evaluated. Peripheral blood mononuclear cells (PBMCs) were prospectively collected for genomic and T cell receptor (TCR) profiling using targeted next-generation sequencing and multiplex PCR, respectively. Univariate analysis was performed to identify features associated with pathological complete response (pCR) of primary tumor. Optimal predictive features were identified using the least absolute shrinkage and selection operator (LASSO) regression model. Subsequently, a prediction model was established using logistic regression, followed by receiver operating characteristic (ROC) analysis and internal validation. Results: Univariate analyses revealed significant associations between pCR and post-NICT features, including ctDNA, PET/CT parameters, and TCR clonality and diversity. Optimal predictive features were identified as post-NICT SUVmax, ctDNA positivity, and TCR clonotype clonality, and their area under the ROC curve (AUC) was 0. 784 (95%CI: 0. 644-0. 924), 0. 739 (95%CI: 0. 664-0. 813), and 0. 682 (95%CI: 0. 535-0. 829), respectively. The final prediction model integrating these three features achieved an AUC of 0. 918 (95%CI: 0. 849-0. 986), an accuracy of 0. 768 (95%CI: 0. 661-0. 875), a sensitivity of 1. 000 (95%CI: 1. 000-1. 000), and a specificity of 0. 705 (95%CI: 0. 568-0. 841), indicating excellent predictive performance. Conclusion: The combination of post-therapy ctDNA status, TCR clonality, and PET/CT assessments showed robust predictive power for assessing pathological response to NICT in ESCC, suggesting the potential to inform clinical decision-making for these patients. Future large-scale studies are warranted to strengthen and verify the findings from our study. Citation Format: Weixiong Yang, Zengli Fang, Xiaoyan Wang, Hui Luo, Shuishen Zhang, Bo Zeng, Zhenguo Liu, Chenxuan Wang, Qiuxiang Ou, Lingling Yang, Haimeng Tang, Sai-Ching J. Yeung, Chao Cheng. Combination of liquid biopsy and PET/CT enhances prediction of pathological response to neoadjuvant immunochemotherapy in patients with 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 (6Suppl): Abstract nr 6412.