Zhuo Song,1,* Xuan Zheng,1,* Hongzhi Wang,1,* Dezuo Dong,1 Xianggao Zhu,1 Jianhao Geng,1 Shuai Li,1 Maxiaowei Song,1 Rongxu Du,1 Yangzi Zhang,1 Zhiyan Liu,1 Yong Cai,1 Yongheng Li,2 Weihu Wang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 2State 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, 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihu Wang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Email wangweihu88@163.comPurpose: This study explored the efficacy and safety of combining systemic therapy with stereotactic body radiotherapy (SBRT) for oligoprogressive (OP) and oligometastatic (OM) hepatocellular carcinoma (HCC).Patients and Methods: From January 2017 to June 2023, 37 HCC patients (28 OP, 9 OM) receiving systemic therapy and SBRT were identified. OP is defined as up to 5 progressive lesions with others stable after systemic therapy and OM as newly identified metastatic disease with up to 5 metastatic lesions. SBRT was delivered in fractions of 5 Gy or more to all lesions. Clinical outcomes and toxicity were evaluated.Results: The median follow-up was 32.8 months. The objective response rates (ORRs) were 47.2%, 44.4%, and 55.5% for overall, OP, and OM cohorts. SBRT treated 48 OP and 17 OM lesions, achieving an ORR of 64.7%. For overall, OP, and OM cohorts, the 2-year local failure rates were 3.0%, 4.0%, and 0%, with median progression-free survival (PFS) of 11.2, 11.2, and 10.2 months, and median overall survival (OS) of 34.9 months, 32.6 months, and not reached (NR), respectively. In the OP cohort, 12 patients switched to next-line systemic therapy (OP-N) and 16 remained on current therapy (OP-C). Median PFS and OS were 11.6 months and NR for OP-N versus 16.5 months and 32.6 months for OP-C (P=0.89 and 0.47). Grade 3 acute and late treatment-related adverse events occurred in 40.5% and 5.4% of patients.Conclusion: Systemic therapy combined with SBRT was effective and safe for OP and OM HCC. SBRT may delay next-line systemic therapy by blocking OP.Plain Language Summary: Combining systemic therapy with stereotactic body radiotherapy (SBRT) represents a promising treatment strategy for oligoprogressive (OP) and oligometastatic (OM) hepatocellular carcinoma.This study demonstrates that SBRT combined with systemic therapy may offer favorable short-term response and long-term outcomes while maintaining a good safety profile.OP patients who continue their current systemic therapy while receiving SBRT may block OP status and achieve outcomes comparable to those who switch therapies, highlighting the potential of this approach to delay treatment changes and improve outcomes.Keywords: oligoprogressive, oligometastatic, hepatocellular carcinoma, stereotactic body radiotherapy, efficacy, safety
