Comparing radiotherapy with early switch to second-line therapy for oligoprogressive HCC

Inclusion Criteria:

* 1\. Histological or cytological confirmation of primary hepatocellular carcinoma (HCC), or diagnosis based on the Clinical Diagnosis and Treatment Guidelines for Primary Liver Cancer (2024 edition) issued by the National Health Commission of the People's Republic of China.
* 2\. BCLC stage C at the time of first-line systemic treatment.
* 3\. Oligoprogression must be confirmed by imaging or histopathology during first-line systemic therapy (FLST). The number of oligoprogressive lesions is limited to 1-5, involving no more than 1-3 organs or systems. These lesions may represent either new metastatic sites or progression of pre-existing lesions. In addition, they must fit one of the two classifications defined in the ESTRO-EORTC consensus on oligometastases: repeat oligoprogression or induced oligoprogression. Oligoprogression may occur within intrahepatic lesions. In the case of lymph node progression, each lymphatic drainage region is considered a separate lesion. For example, the para-aortic lymph nodes (number 16a and number 16b) are each counted as separate lymph node regions.
* 4\. Patients must have experienced oligoprogression while receiving their current FLST and must not have previously received any other FLST that resulted in disease progression. Additionally, the current FLST must have maintained disease stability (SD) for at least three months prior to the occurrence of oligoprogression. Furthermore, the expected survival time must be ≥6 months.
* 5\. Oligoprogressive lesions must be eligible for radiotherapy and should have at least one measurable lesion that meets RECIST v1.1 criteria; Bone metastases without soft tissue formation are eligible but are considered non-measurable lesions; Bone metastases with soft tissue formation that meet RECIST v1.1 measurable criteria are considered measurable lesions.
* 6\. Liver function must be assessed as Child-Pugh score ≤7 points.
* 7\. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1.
* 8\. Participants must be able to understand and voluntarily sign a written informed consent prior to the initiation of any study-specific procedures and must agree to comply with the treatment and follow-up requirements of the study.
* 9\. Male or female patients between 18 and 75 years of age.
* 10\. Availability of tumor and blood samples for biomarker assessment.

Exclusion Criteria:

* 1\. Patients who received FLST as adjuvant treatment after curative surgery for HCC.
* 2\. Tumor progression occurring within 3 months after initiation of FLST.
* 3\. Patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC)
* 4\. History of grade ≥3 serious adverse events due to FLST.
* 5\. Presence of brain, peritoneal or omental metastases with bleeding after FLST.
* 6\. Previous radiation therapy to the site of the oligoprogressive lesion.
* 7\. Active untreated hepatitis B, defined as HBsAg positive with HBV DNA levels above the upper limit of normal in the participating center's laboratory.
* 8\. Oligoprogressive lesions not amenable to radiotherapy.
* 9\. Alpha-fetoprotein (AFP) level ≥10,000 ng/mL at the time of oligoprogression.
* 10\. Diagnosis of malignancy other than liver cancer within 3 years prior to enrollment (excluding curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or carcinoma in situ).
* 11\. Currently participating in any interventional clinical research treatment or having received any other investigational drug or investigational device therapy within the last 4 weeks prior to enrollment.
* 12\. Presence of autoimmune disease or other conditions requiring long-term steroid use.
* 13\. Severe impairment of the heart, lungs, kidneys, or other vital organs, active infections (other than viral hepatitis), or other serious comorbidities that render the patient unable to tolerate treatment.
* 14\. known or suspected allergy to any study drug or to any drug related to this study.
* 15\. History of organ transplantation
* 16\. Pregnant or breastfeeding women
* 17\. Any other factor that the investigator believes may affect the enrollment of patients or the evaluation of study results.