Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients

BackgroundThe prognosis of metastatic or recurrent hepatocellular carcinoma (HCC) remains poor, and new treatment strategies are warranted. Despite promising preclinical results demonstrating that radiation primes the immune system and produces a synergistic antitumor response for long-term disease...

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Main Authors: Yirui Zhai, Yefan Zhang, Fan Wu, Jianguo Zhou, Lingxia Xin, Feng Ye, Wei Sun, Huiying Zeng, Yan Song, Yongkun Sun, Wen Zhang, Shu-Lian Wang, Yuan Tang, Hui Fang, Pan Zhao, Yueping Liu, Ningning Lu, Shunan Qi, Hao Jing, Wenwen Zhang, Yongwen Song, Ye-Xiong Li, Liming Wang, Bo Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594577/full
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author Yirui Zhai
Yefan Zhang
Fan Wu
Jianguo Zhou
Lingxia Xin
Feng Ye
Wei Sun
Huiying Zeng
Yan Song
Yongkun Sun
Wen Zhang
Shu-Lian Wang
Yuan Tang
Hui Fang
Pan Zhao
Yueping Liu
Ningning Lu
Shunan Qi
Hao Jing
Wenwen Zhang
Yongwen Song
Ye-Xiong Li
Liming Wang
Bo Chen
author_facet Yirui Zhai
Yefan Zhang
Fan Wu
Jianguo Zhou
Lingxia Xin
Feng Ye
Wei Sun
Huiying Zeng
Yan Song
Yongkun Sun
Wen Zhang
Shu-Lian Wang
Yuan Tang
Hui Fang
Pan Zhao
Yueping Liu
Ningning Lu
Shunan Qi
Hao Jing
Wenwen Zhang
Yongwen Song
Ye-Xiong Li
Liming Wang
Bo Chen
author_sort Yirui Zhai
collection DOAJ
description BackgroundThe prognosis of metastatic or recurrent hepatocellular carcinoma (HCC) remains poor, and new treatment strategies are warranted. Despite promising preclinical results demonstrating that radiation primes the immune system and produces a synergistic antitumor response for long-term disease control, limited clinical data are available. Therefore, in this study, we investigated the efficacy and safety of combining radiotherapy with immune checkpoint inhibitors (ICIs) for patients with metastatic and recurrent HCC in a real-world setting.Materials and methodsPatients with stage IV or recurrent HCC who received sequential or concurrent radiotherapy and ICIs in our institution were enrolled in this study. Data regarding clinicopathological characteristics, treatment protocols, response rates, toxicities, and survival were collected.ResultsFrom January 2018 to December 2021, 108 patients were included. Extra-hepatic metastasis and portal vein tumor thrombosis were recorded in 58 (53.7%) and 69 patients (63.9%), respectively. A median radiation dose of 55 Gy was administered, and ICIs were administered for 3 weeks until disease progression or limiting toxicities occurred. After treatment, the overall response rate was 75.0%, and the median follow-up duration was 18.8 months. Median overall survival and progression-free survival were 17.0 and 12.6 months, respectively. Only one patient experienced in-field recurrence. Grade ≥3 adverse events were observed in 30.6% of patients. Dermatitis was the most common toxicity-related event and thrombocytopenia was the most common grade ≥3 adverse event, occurring overall in 17.6% of patients.ConclusionThe ICI and radiotherapy combination was effective and well-tolerated in real-world patients, achieving more favorable results compared with historical ones and providing a new multimodality therapy for patients with recurrent and metastatic HCC.
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spelling doaj-art-8645d12a4c4e4d949f17f0a49b41129b2025-08-20T03:00:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.15945771594577Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patientsYirui Zhai0Yefan Zhang1Fan Wu2Jianguo Zhou3Lingxia Xin4Feng Ye5Wei Sun6Huiying Zeng7Yan Song8Yongkun Sun9Wen Zhang10Shu-Lian Wang11Yuan Tang12Hui Fang13Pan Zhao14Yueping Liu15Ningning Lu16Shunan Qi17Hao Jing18Wenwen Zhang19Yongwen Song20Ye-Xiong Li21Liming Wang22Bo Chen23Department 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, ChinaDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment 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, ChinaDepartment of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaBackgroundThe prognosis of metastatic or recurrent hepatocellular carcinoma (HCC) remains poor, and new treatment strategies are warranted. Despite promising preclinical results demonstrating that radiation primes the immune system and produces a synergistic antitumor response for long-term disease control, limited clinical data are available. Therefore, in this study, we investigated the efficacy and safety of combining radiotherapy with immune checkpoint inhibitors (ICIs) for patients with metastatic and recurrent HCC in a real-world setting.Materials and methodsPatients with stage IV or recurrent HCC who received sequential or concurrent radiotherapy and ICIs in our institution were enrolled in this study. Data regarding clinicopathological characteristics, treatment protocols, response rates, toxicities, and survival were collected.ResultsFrom January 2018 to December 2021, 108 patients were included. Extra-hepatic metastasis and portal vein tumor thrombosis were recorded in 58 (53.7%) and 69 patients (63.9%), respectively. A median radiation dose of 55 Gy was administered, and ICIs were administered for 3 weeks until disease progression or limiting toxicities occurred. After treatment, the overall response rate was 75.0%, and the median follow-up duration was 18.8 months. Median overall survival and progression-free survival were 17.0 and 12.6 months, respectively. Only one patient experienced in-field recurrence. Grade ≥3 adverse events were observed in 30.6% of patients. Dermatitis was the most common toxicity-related event and thrombocytopenia was the most common grade ≥3 adverse event, occurring overall in 17.6% of patients.ConclusionThe ICI and radiotherapy combination was effective and well-tolerated in real-world patients, achieving more favorable results compared with historical ones and providing a new multimodality therapy for patients with recurrent and metastatic HCC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594577/fullhepatocellular carcinomaradiotherapyimmunotherapyimmune checkpoint inhibitorPD-1/PD-L1 inhibitor
spellingShingle Yirui Zhai
Yefan Zhang
Fan Wu
Jianguo Zhou
Lingxia Xin
Feng Ye
Wei Sun
Huiying Zeng
Yan Song
Yongkun Sun
Wen Zhang
Shu-Lian Wang
Yuan Tang
Hui Fang
Pan Zhao
Yueping Liu
Ningning Lu
Shunan Qi
Hao Jing
Wenwen Zhang
Yongwen Song
Ye-Xiong Li
Liming Wang
Bo Chen
Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
Frontiers in Immunology
hepatocellular carcinoma
radiotherapy
immunotherapy
immune checkpoint inhibitor
PD-1/PD-L1 inhibitor
title Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
title_full Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
title_fullStr Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
title_full_unstemmed Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
title_short Combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma: a real-world study of 108 patients
title_sort combined radiation and immune checkpoint inhibitor therapy for metastatic or recurrent hepatocellular carcinoma a real world study of 108 patients
topic hepatocellular carcinoma
radiotherapy
immunotherapy
immune checkpoint inhibitor
PD-1/PD-L1 inhibitor
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594577/full
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