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World J Gastroenterol. Jan 21, 2027; 33(3): 123331
Published online Jan 21, 2027. doi: 10.3748/wjg.123331
Anlotinib plus radiotherapy or chemoradiotherapy in locally advanced or advanced esophageal squamous cell carcinoma: A multicohort, real-world study
Guo-Jie Feng, Cheng-Rui Fu, Fan Wang, Jian-Cheng Li, Yue Jiang, Xin-Yi Wang, Bai-Hua Yang, Wen-Cai Xu, Yao-Wen Zhang, Xin-Yu Cheng, Xiao-Lin Ge, Xiao-Jie Xia, He-Ming Xi, Xue-Song Zhao, Hong-Bing Ma, Xi-Xi Zhao, Xin Wang, Bao-Sheng Li
Guo-Jie Feng, Xin Wang, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, China
Cheng-Rui Fu, Bao-Sheng Li, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250000, Shandong Province, China
Fan Wang, Xin-Yi Wang, Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Jian-Cheng Li, Bai-Hua Yang, Department of Radiation Oncology, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
Yue Jiang, Wen-Cai Xu, Department of Radiation Oncology, Henan Cancer Hospital, Zhengzhou 450000, Henan Province, China
Yao-Wen Zhang, Xin-Yu Cheng, Department of Radiation Oncology, Anyang Tumor Hospital, Anyang 455001, Henan Province, China
Xiao-Lin Ge, Xiao-Jie Xia, Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
He-Ming Xi, Xue-Song Zhao, Department of Radiation Oncology, Anyang People’s Hospital, Anyang 455002, Henan Province, China
Hong-Bing Ma, Xi-Xi Zhao, Department of Radiation Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University (Xibei Hospital), Xi’an 710004, Shaanxi Province, China
Co-first authors: Guo-Jie Feng and Cheng-Rui Fu.
Co-corresponding authors: Xin Wang and Bao-Sheng Li.
Author contributions: Feng GJ and Fu CR contributed equally to this article, they are the co-first authors of this manuscript; Feng GJ, Fu CR, Wang F, Li JC, Jiang Y, Wang XY, Yang BH, Xu WC, Zhang YW, Cheng XY, Ge XL, Xia XJ, Xi HM, Zhao XS, Ma HB, and Zhao XX input and interpreted the data, and wrote the first draft of the paper; Feng GJ, Fu CR, Wang F, Li JC, Jiang Y, Wang XY, Yang BH, Xu WC, Zhang YW, Cheng XY, Ge XL, Xia XJ, Xi HM, Zhao XS, Ma HB, Zhao XX, Wang X, and Li BS contributed to data collection and interpretation, participated in the critical review and revision of the manuscript, and approved the final version for submission; Wang X and Li BS designed the study; they contributed equally to this article; they are the co-corresponding authors of this manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, approval No. 24/429-4709.
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The sponsor will provide access to individual de-identified patients' data from the present study, upon request by qualified researchers whose proposals are approved.
Corresponding author: Xin Wang, MD, Professor, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuannanli, Chaoyang District, Beijing 100000, China.
beryl_wx2000@163.com
Received: May 15, 2026
Revised: July 8, 2026
Accepted: July 28, 2026
Published online: January 21, 2027
Processing time: 183 Days and 10.9 Hours
BACKGROUND
Although standard treatments have been established for patients with locally advanced or advanced esophageal squamous cell carcinoma (ESCC), the outcomes remain suboptimal.
AIM
To investigate the effectiveness and safety of anlotinib plus radiotherapy (RT)/chemoradiotherapy (CRT) in locally advanced or advanced ESCC.
METHODS
This multicenter, multicohort, real-world study included patients with unresectable locally advanced ESCC (cohort 1) or advanced ESCC (cohort 2) treated with anlotinib and RT/CRT between June 2018 and June 2024. A 1:2 propensity score matching (PSM) analysis was performed in locally advanced ESCC (cohort 1) to compare anlotinib plus RT/CRT (cohort1_psm) with CRT [control group (CG_psm)]. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated.
RESULTS
Overall, 154 patients were included (112 in cohort 1; 42 in cohort 2). In cohort 1, median OS was 34.5 months [95% confidence interval (CI): 26.2-not estimable] and median PFS was 16.7 months (95%CI: 11.5-25.7). The ORR and DCR were 44.6% and 97.3%, respectively. For cohort 2, the median OS and PFS were 22.7 months (95%CI: 14.9-61.8) and 8.5 months (95%CI: 4.7-14.9), respectively. The ORR and DCR were 47.6% and 88.1%, respectively. Notably, the majority of patients received concurrent immune checkpoint inhibitors (cohort 1, 61.6%; cohort 2, 71.4%), yet no significant differences were observed in PFS or OS between the immunotherapy and non-immunotherapy subgroups. The safety profile was manageable, with grade ≥ 3 treatment-emergent adverse events occurring in 15.2% and 16.7% of patients in cohort 1 and cohort 2, respectively. Following PSM, 51 patients in cohort1_psm and 102 patients in CG_psm were analyzed, with significantly improved OS in cohort1_psm compared to CG_psm (median: Not reached vs 26.4 months; P = 0.02).
CONCLUSION
Anlotinib combined with RT/CRT demonstrated potential survival benefits and a manageable safety profile in patients with locally advanced or advanced ESCC.
Core Tip: Despite established standard treatments for locally advanced or advanced esophageal squamous cell carcinoma, patient survival and disease control remain suboptimal. This multicenter, real-world, retrospective study observed that anlotinib combined with radiotherapy or chemoradiotherapy (CRT) was associated with encouraging overall survival and disease control, with manageable toxicity. Propensity score matching analysis was further conducted to explore potential differences in efficacy between this regimen and standard CRT. These hypothesis-generating findings provide real-world evidence for anlotinib plus radiotherapy or CRT in this population and warrant further prospective investigation.
