Overview

Recent years have seen significant advancements in the treatment landscape of advanced hepatocellular carcinoma (HCC), with the emergence of targeted and immunotherapy strategies reshaping first-line therapy. Sorafenib, a multi-targeted tyrosine kinase inhibitor, initially set the standard, followed by approvals for lenvatinib, regorafenib, cabozantinib, and ramucirumab. Immunotherapy, particularly combinations like atezolizumab with bevacizumab, has shown superior efficacy over sorafenib. Despite these advances, second-line therapies offer limited progression-free survival (mPFS: 2-3 months), necessitating new approaches. Radiotherapy, bolstered by technological advancements, has shown promise. Techniques like stereotactic body radiotherapy (SBRT) combined with PD-1 inhibitors achieve significant response rates and survival benefits. Combining radiotherapy with targeted immunotherapy has also demonstrated improved outcomes. Radiotherapy, especially in oligometastatic HCC, is increasingly favored due to its ability to enhance local control without increasing toxicity. These developments underscore the evolving landscape of HCC treatment towards personalized and multimodal approaches.

Eligibility

Inclusion Criteria:

• Obtain written informed consent before implementing any trial-related procedures.
• Male or female, aged 18 years or older, and 75 years or younger.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Histological or cytological confirmation of primary hepatocellular carcinoma (HCC), or diagnosed according to the Clinical Diagnosis and Treatment Guidelines for Primary - Liver Cancer (2019 edition) issued by the National Health Commission of the People's Republic of China.
• Tumor staged as BCLC stage C; patients have ≤5 lesions (≤3 affected organs) with oligometastasis or oligoprogression.
• Liver function assessed by Child-Pugh score ≤7 points.
• Availability of tumor samples for biomarker assessment.
• Stable disease with systemic therapy for ≥3 months and an anticipated survival period of ≥6 months.

Exclusion Criteria:

• Diagnosis of malignancy other than liver cancer within 3 years before enrollment (excluding curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma).
• Currently participating in interventional clinical research treatment, or received other investigational drugs or investigational device therapy within the past 4 weeks before enrollment.
• Received traditional Chinese medicine or immunomodulatory drugs with anti-tumor indications within 2 weeks before enrollment (including thymosin, interferon, interleukin, except for local use to control pleural effusion).
• Experienced active autoimmune diseases requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressive agents) within 2 years before enrollment. Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Received radiotherapy within 2 weeks before enrollment.
• HIV +
• Active untreated hepatitis B (defined as HBsAg positive with HBV-DNA copy number exceeding the upper limit of normal value in the laboratory of the participating center).
• Pregnant or lactating women.