Building Evidence for Ablative Internal Radiation Therapy in Localized HCC Beyond the Up-To-7 Criteria

This prospective, multi-center, open-label, single-arm, phase II clinical trial aims to evaluate the efficacy and safety of ablative radioembolization in patients with hepatocellular carcinoma (HCC) that exceeds the up-to-seven (UT7) criteria but is confined to up to five geographically adjacent Couinaud segments. The primary endpoint is the objective response rate, assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

All patients will receive ablative radioembolization using Yttrium-90 glass microspheres with a personalized dosimetry approach targeting a tumor dose of 700 Gy (±50%). In cases of high tumor burden, a second radioembolization within 180 days of the initial procedure will be permitted at the operators' discretion, provided the cumulative lung dose remains below 50 Gy. Follow-up evaluations, including laboratory tests and dynamic imaging, will be performed at 4 weeks post-treatment and every 3 months thereafter for a total of 2 years. Efficacy data-including tumor response and survival-will be collected, with tumor responses evaluated by both site investigators and a blinded independent central review. Adverse events will be documented and graded according to the Common Terminology Criteria for Adverse Events v5.0. In addition, the incidence of radioembolization-induced liver disease and radiation pneumonitis will be monitored for 6 months following the procedure.

• ORR according to the RECIST 1.1 [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• ORR according to localized mRECIST and RECIST 1.1 [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Duration of response according to mRECIST, localized mRECIST, and RECIST 1.1 [Срок оценки: Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Overall survival rate [Срок оценки: Time of treatment up to participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Progression-free survival rates according to mRECIST, localized mRECIST, and RECIST 1.1 [Срок оценки: Time of treatment up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Time-to-progression according to mRECIST, localized mRECIST, and RECIST 1.1 [Срок оценки: Time of treatment up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled).]
• Major pathologic response rate (%) after surgical resection or liver transplantation [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Curative conversion rate [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Sustainable complete response rate according to mRECIST more than 1 year [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Locoregional treatment unsuitability rate [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Time to and reason for subsequent HCC treatment [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]
• Threshold tumor absorbed dose (Gy) to predict radiologic complete response and objective response as the best response by localized mRECIST [Срок оценки: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)]