R. Du1, J. Geng1, Z. Liu1, X. Sui1, S. Li1, L. Tang2, Z. Wang3, X. Zhang4, Y. Yan5, A. Wu6, Z. Li7, Y. Li8, W. Wang1, and Z. Li9; 1Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China, Beijing, China, 2Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Imaging, Peking University Cancer Hospital & Institute, Beijing 100142, China, Beijing, China, 3Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Imaging, Peking University Cancer Hospital & Institute, Beijing 100142, China, beijing, China, 4State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China, 5State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Endoscopy Center, Peking University Cancer Hospital & Institute, Beijing, China, 6State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department 3 of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China, 7Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China, Beijing, China, 8State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China, 9Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China
Purpose/Objective(s): Neoadjuvant chemoradiotherapy combined with surgery has been recommended in the treatment of locally advanced adenocarcinoma of the esophagogastric junction (AEG), while the tumor response still remained suboptimal. In this study, we hypothesized that neoadjuvant Toripalimab (PD-1 inhibitor) plus chemoradiotherapy would improve the tumor response and toxicity would be tolerable. Materials/
Methods: cT3-T4/N+M0 AEG patients with resectable Siewert type II/III tumors were enrolled in this prospective, phase ?, clinical trial. Patients accepted neoadjuvant radiotherapy (50Gy/45Gy/25f), with 5 cycles of weekly capecitabine and oxaliplatin concurrently and 4 cycles of immunotherapy (Toripalimab), followed by radical surgery. The primary endpoints of this study were major pathologic response (MPR) rate and toxicity, with disease-free survival (DFS), overall survival (OS) as secondary endpoints. Pathologic results after surgery were evaluated with National Comprehensive Cancer Network (NCCN) Tumor Regression Score system, and adverse events were assessed according to Common Terminology Criteria for Adverse Event (CTCAE) v5.0. Survival analysis was performed with the Kaplan–Meier method. Results: Between August 2019 and July 2023, 43 patients were enrolled, all of whom have completed neoadjuvant chemoradiotherapy and immunotherapy. 29 patients underwent radical surgery, while 13 patients failed to accept curative resection due to progress of primary tumors, treatment-related complications or personal reasons, five of whom had stable lesions demonstrated by imaging examination and biopsy, and had been alive without recurrences until the latest follow-up. And there was 1 patient died of acute internal disease before surgery. In the surgery population, R0 resection rate was 100%, 21 patients (72.4%) achieved MPR, and pathologic complete response (pCR) rate was 37.9%. In terms of safety, one elderly patient died of severe pneumonitis during the neoadjuvant treatment, 5 cases of grade 3 hematologic toxicity, 9 cases of grade 2 radiation esophagitis and 13 cases of grade 1 radiation pneumonitis were reported. Post-surgery chest and abdominal infection and anastomotic fistula were main reasons of prolonged hospitalization. During a median follow-up period of 24.1 months (IQR 18.0-33.4), 2-year OS was 86.0%, 2-year DFS for surgery patients was 89.7%. Conclusion: For locally advanced AEG patients, neoadjuvant Toripalimab combined with chemoradiotherapy is effective in improving the tumor response, without increase of treatment-related complications.
