Impact of First-line Chemoimmunotherapy with or without Radiotherapy on the Prognosis of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Multicenter, Real-World, Retrospective Cohort Study from China (NCT06478355)

Xinyi Liu¹Jingyuan Wen¹Yaowen Zhang²Chenyu Wang²Yatian Liu³Pudong Qian³Jianzhong Cao⁴Qing Hou⁴Yuanji Xu⁵Zhongmei Lin⁵Xianghua Ye⁶Min Hou⁷Yan Gui⁷Lulu Wang⁸WEI Zhouwei978978@163.com⁸Zhimin Zeng⁹Yaqi Song¹⁰Honglei Luo¹⁰Jiahua Lyu¹¹Wenbin Shen^1*

• ¹Fourth Hospital of Hebei Medical University, Shijiazhuang, China
• ²Anyang Tumor Hospital, Anyang, China
• ³Jiangsu Cancer Hospital, Nanjing, China
• ⁴Shanxi Cancer Hospital, Taiyuan, China
• ⁵Fujian Provincial Cancer Hospital, Fuzhou, China
• ⁶The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
• ⁷Affiliated Hospital of North Sichuan Medical College, Nanchong, China
• ⁸Chongqing University Cancer Hospital, Chongqing, China
• ⁹Nanchang University Second Affiliated Hospital, Nanchang, China
• ¹⁰Huaian First People's Hospital, Huaian, China
• ¹¹Sichuan Cancer Hospital and Institute, Chengdu, China

Background: This research aims to evaluate whether first-line chemoimmunotherapy combined with radiotherapy improves outcomes and safety in patients who suffer from locally advanced and metastatic ESCC. Methods: A total of 664 patients who suffer from locally advanced or metastatic ESCC going through first-line chemoimmunotherapy with or without radiotherapy at China’s 11 large cancer centers from Jan. 2019 to Dec. 2022 were retrospectively explored. Each patient received first-line chemoimmunotherapy, and the specific program was determined by the investigator. Regarding the radiotherapy group, each patient went through radiotherapy with a dose of ≥30 Gy to the primary lesion. The possible biases were minimized through performing the PSM. Results: The research enrolled 664 patients in total, of which 438 received radiation therapy and 226 received immunotherapy combined with chemotherapy alone. Compared to those in the ICT group, the median OS and median PFS in the ICRT group were significantly longer(mOS,33 versus 20 months, P < 0.001;mPFS, 15 versus 12 months, P < 0.001). To reduce the effect of bias, the two groups went through a 1:1 PSM analysis. The study assessed 334 patients, in which a total of 167 patients in every subgroup. The analysis demonstrated that adding radiotherapy significantly improved the median OS (mOS, 34 versus 20 months, P=0.015) and PFS (mPFS, 16 versus 12 months, P=0.008), consistent with the pre-match results. According to the multivariate COX regression analysis, radiotherapy served as one of the independent prognostic factors that impact OS (HR=0.67,95%CI:0.50-0.89, P=0.006) and PFS (HR=0.68,95%CI:0.53-0.89, P=0.004). There were prolonged both OS (HR=0.58,95%CI:0.41-0.81, P=0.002) and PFS(HR=0.61,95%CI:0.44-0.82, P=0.001) after radiotherapy within patients that just had regional lymph node metastasis. Concerning patients not going through immune maintenance therapy (number of immune cycles>6), radiotherapy significantly reduced not only mortality (HR=0.66,95%CI:0.49-0.90, P=0.009) but also recurrence (HR=0.72,95%CI:0.54-0.97, P=0.028). In terms of security, ICRT group esophagitis (22.8% versus 3.6%; P<0.001), esophageal fistula (5.4% versus 0.0%; P=0.003), and pneumonia (10.8% versus 3.0%;P=0.008) all exhibited a higher incidence. Conclusion: According to the research, adding radiotherapy into systemic chemotherapy integrated with immune checkpoint inhibitors improves the prognosis of patients in China who suffer from locally advanced or metastatic ESCC.