Induction sintilimab and chemotherapy followed by concurrent chemoradiotherapy for locally advanced esophageal cancer: a proof-of-concept, single-arm, multicenter, phase 2 trial

作者：Dashan Ai, Shengnan Hao, Wenbin Shen, Qibing Wu, Shengjian Zhang, Yun Chen, Qi Liu, Jiaying Deng, Hongcheng Zhu, Ke Chen, Miao Mo, Dayong Gu, Yatian Liu, Zhi Zhang, Guoren Zhou, Jingwen Hu, Zhen Zhang, Jinjun Ye, Kuaile Zhao · 发表于：EClinicalMedicine · 年份：2024 · DOI：10.1016/j.eclinm.2024.102471 · 被引用次数：34 · 研究领域：Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research

Background: Concurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control. Methods: We did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046). Findings: Seventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3-35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%-90.7%), which wa...