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This is a prospective, single-arm Phase II study designed to evaluate the safety and efficacy of carbon ion radiotherapy in patients with hepatocellular carcinoma (HCC) who demonstrate residual or recurrent disease after prior transarterial radioembolization (TARE). Carbon ion radiotherapy delivers highly conformal, high-linear energy transfer radiation, enabling dose escalation to hepatic tumors while minimizing exposure to surrounding normal tissues.
Eligible patients will receive carbon ion radiotherapy to target lesions, and clinical outcomes including objective response rate, progression-free survival, overall survival, and treatment-related toxicity will be systematically assessed. The study aims to determine whether carbon ion radiotherapy can provide effective local tumor control and acceptable safety in this population, thereby establishing evidence to guide its therapeutic role following TARE.
This prospective, single-arm Phase II study evaluates the safety and efficacy of carbon ion radiotherapy in patients with hepatocellular carcinoma (HCC) who have residual or recurrent disease after prior transarterial radioembolization (TARE). Although TARE is an important locoregional treatment, some patients exhibit incomplete response or local progression and have limited subsequent therapeutic options.
Carbon ion radiotherapy provides highly conformal dose distribution and increased biological effectiveness, enabling escalation of tumoricidal doses while sparing surrounding liver tissue and adjacent gastrointestinal organs. Eligible patients will undergo baseline assessments and multidisciplinary review to confirm suitability for treatment. Carbon ion radiotherapy will be delivered using hypofractionated regimens individualized based on tumor characteristics and organ-at-risk constraints.
Patients will be followed with scheduled imaging, laboratory tests, and toxicity assessments. Efficacy will be measured through tumor response, local control, progression-free survival, and overall survival. Safety will be evaluated according to CTCAE criteria. The study aims to determine whether carbon ion radiotherapy can serve as an effective and feasible salvage treatment for TARE-refractory or recurrent HCC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carbon Ion Radiotherapy | Experimental | Participants will receive carbon ion radiotherapy targeting residual or recurrent hepatocellular carcinoma following prior transarterial radioembolization (TARE). Treatment will be delivered using hypofractionated high-linear energy transfer radiation, with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk constraints. The intervention aims to provide effective local tumor control while maintaining acceptable safety in patients who have limited subsequent treatment options after TARE. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carbon Ion Radiotherapy | Radiation | Carbon ion radiotherapy will be delivered to residual or recurrent hepatocellular carcinoma in patients previously treated with transarterial radioembolization (TARE). Treatment will be administered using hypofractionated high-linear energy transfer radiation, with dose and fractionation individualized based on tumor size, tumor location, and organ-at-risk constraints. The aim of the intervention is to achieve enhanced local tumor control while minimizing toxicity to surrounding normal tissues |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | Objective response rate is defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to mRECIST criteria. Tumor response will be assessed through scheduled imaging studies within 6 months after carbon ion radiotherapy. | Up to 6 months after completion of carbon ion radiotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | PFS is defined as the time from the start of carbon ion radiotherapy to the first documented disease progression or death from any cause, or to the date of last follow-up. | Up to 3 years after initiation of carbon ion radiotherapy |
| Overall Survival (OS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yonsei University Health System, Severance Hospital | Recruiting | Seoul | South Korea |
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All enrolled participants will receive carbon ion radiotherapy as a single-arm interventional treatment. Outcomes will be evaluated prospectively to assess safety and efficacy in patients with hepatocellular carcinoma previously treated with TARE.
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This is an open-label study; no blinding will be applied to participants, investigators, or outcome assessors.
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OS is defined as the time from the start of carbon ion radiotherapy to death from any cause, or to the last follow-up date for censored patients. |
| Up to 3 years after initiation of carbon ion radiotherapy |
| Time to overall tumor progression (TTP) | TTP is defined as the time from the start of carbon ion radiotherapy to progression of any target or non-target lesion, or the appearance of new intrahepatic or extrahepatic lesions. | Up to 3 years after initiation of carbon ion radiotherapy |
| Time to local progression | Time to local progression is defined as the interval from the start of carbon ion radiotherapy to radiologic progression within the treated liver area. | Up to 3 years after initiation of carbon ion radiotherapy |
| Treatment-related toxicity | Toxicity will be evaluated and graded according to CTCAE version 5.0. Toxicity follow-up continues from treatment initiation until confirmation of study completion or until the earliest start of subsequent therapy. | From treatment initiation through 30 days post-treatment, or until the next alternative therapy |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000230 | Adenocarcinoma |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| D063193 | Heavy Ion Radiotherapy |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
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