Combined Radiation and Immune Checkpoint Inhibitor Therapy for Metastatic or Recurrent Hepatocellular Carcinoma: A Real-World Study of 108 Patients

Yirui Zhai¹Yefan Zhang²Fan Wu²Jianguo Zhou²Ling-Xia Xin³Feng Ye⁴Wei Sun⁵Huiying Zeng⁵Yan Song⁶Yongkun Sun⁶Wen Zhang⁶Shu-Lian Wang³Yuan Tang³Hui Fang³Pan Zhao³Yueping Liu³Ning-Ning Lu³Shunan Qi³Hao Jing³Wenwen Zhang³Yongwen Song³Ye-Xiong Li³Liming Wang³Bo Chen^1*

• ¹Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
• ²Department 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, China
• ³Department 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, China
• ⁴Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
• ⁵Department 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, China
• ⁶Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Beijing Municipality, China

The 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 Methods: Patients 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. Results: From 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 14.8% of patients. Conclusion: The ICI and radiotherapy combination was effective and welltolerated in real-world patients, providing a new multimodality therapy for patients with recurrent and metastatic HCC.