230 - Pathological Complete Response and ctDNA Analyses Results from a Randomized Phase III Trial of Neoadjuvant Chemotherapy or Chemoradiotherapy plus Sintilimab vs. Chemoradiotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
Presenter(s)
J. Lv1, X. Leng2, L. Gong3, H. Wenwu2, Y. Chen4, W. Hu5, L. Xian6, T. Hu7, H. Zhou8, Y. Zheng9, I. Y. H. Wong10, W. Zhang11, F. Li12, Q. Li13, L. Xie14, X. Zheng1, H. Bai1, H. Qing4, Y. Zhou15, T. Lin16, P. Tang17, Y. Han18, and S. Zhang1; 1Department of Radiation Oncology, Sichuan Cancer Hospital& Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 2Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China Chengdu, chengdu, China, 3Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Chengdu, China, 4Sichuan Clinical Research Center for Cancer,Sichuan Hospital Cancer & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China, 5Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, wuhan, China, 6Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Guangxi Medical University, nanning, China, 7Department of Thoracic Surgery, The People's Hospital of Leshan in Sichuan Province, leshan, China, 8Department of Thoracic Surgery, Suining Central Hospital, suining, China, 9Department of Thoracic Surgery, General Hospital of Chengdu Military Region, chengdu, China, 10Department of Surgery, the University of Hong Kong, Hong Kong, Hong Kong, 11Tianjin Medical University Cancer Institute & Hospital, Tianjin, China, 12Genecast Biotechnology Co, beijing, China, 13Genecast Biotechnology Co., Ltd., Xishan District, Wuxi, China, 14Shanghai Jiao Tong University School of Medicine, shanghai, China, 15Department of Pathology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan province, China, 16Phase I Clinical Trial Ward of Medical Oncology Center, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan province, China, 17Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, tianjin, China, 18Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Purpose/Objective(s):
The SCIENCE trial is a multicenter, randomized, phase III study evaluating the efficacy of nCT plus Sintilimab, nCRT plus Sintilimab, and nCRT alone in LA-ESCC, with exploratory analysis of ctDNA dynamics as predictors of pathological response.Materials/Methods:
Locally advanced ESCC Patients with clinically stage cT1N2-3M0 or cT2-4aN0-3M0 were enrolled from multicenter across China. Participants were randomized by 1:1:1 to three neoadjuvant treatment groups: Group A: Sintilimab combined with nCT. Group B: Sintilimab combined with concurrent nCRT. Group C: Concurrent nCRT alone. Surgical resection was planned 4-8 weeks after neoadjuvant therapy. Co-primary endpoints were pathological complete response (pCR) and event-free survival (EFS). Exploratory endpoints included biomarker analyses, such as circulating tumor DNA (ctDNA) detection.Results:
Between November 2022 and August 2025, 307 patients were enrolled and randomly assigned to Group A (n=100), Group B (n=103), or Group C (n=104). Most patients were male (88.3%) and had clinical stage III disease (81.4%). All patients achieved R0 resection. pCR rates differed significantly comparing with Group A: 18.0% in Group A, 57.3% in Group B, and 49.0% in Group C. Compared with Group A, pCR was significantly higher in Group B (OR 6.1, 95% CI 3.3–11.9; p<0.0001) and Group C (OR 4.4, 95% CI 2.3–8.5; p<0.0001). The ctDNA cohort included 92 evaluable patients. CtDNA detectability declined from 96.7% at baseline to 48.9% preoperatively. Preoperative ctDNA positivity was significantly higher in Group A (78.6%) compared with Group B (40.0%) and Group C (32.4%) (p<0.001). Patients with ctDNA clearance achieved markedly higher pCR rates than those with persistent ctDNA (62.2% vs 9.1%, p<0.001). CtDNA clearance rates increased stepwise across pathological response categories: pCR (84.8%), major pathological response (48.1%), and non-responders (12.5%).Conclusion:
Interim results from SCIENCE demonstrate that neoadjuvant nCRT ± Sintilimab achieves superior pCR rates versus nCT + ICI in LA-ESCC. ctDNA clearance is significantly associated with pathological response, with early declines predictive of outcome. These findings support integrating ctDNA monitoring into future neoadjuvant strategies for ESCC. (NCT05244798)