Proton Beam Therapy for Large Localized Hepatocellular Carcinomas in Western Patients

Area of Science:

• Oncology
• Radiation Oncology
• Hepatology

Background:

• Management of large, unresectable hepatocellular carcinoma (HCC) is challenging.
• Proton beam therapy (PBT) offers potential dosimetric advantages for liver tumors.
• Limited data exists on PBT outcomes in Western HCC populations.

Purpose of the Study:

• To evaluate clinical outcomes, toxicity, and failure patterns in Western patients with large HCC treated with PBT.
• To assess the efficacy of PBT for unresectable HCC.
• To identify predictors of survival and toxicity.

Main Methods:

• Retrospective analysis of 51 Western patients with HCC tumor ≥ 5 cm treated with PBT.
• Exclusion of patients with extrahepatic metastases or concurrent systemic therapy.
• Assessment of local failure (LF), overall survival (OS), progression-free survival (PFS), and radiation-induced liver disease (RILD) using competing risk and Kaplan-Meier methods.

Main Results:

• High-risk features present: BCLC stage C (45%), Child-Pugh B/C (26%), vascular invasion (39%), median tumor size 9.2 cm.
• Excellent 1-, 2-, and 3-year local failure rates of 4%, 13%, and 13%.
• 1-, 2-, and 3-year OS rates of 65%, 46%, and 30%; tumor size predicted OS. Non-classic RILD occurred in 15% (6% CP-A vs. 43% CP-B+).

Conclusions:

• Dose-escalated PBT provides excellent local control and acceptable toxicity for large HCC in Western patients.
• Patients with preserved liver function (CP-A) benefit most; CP-B patients face higher hepatotoxicity risks.
• Out-of-field intrahepatic and distant failures suggest combining PBT with systemic therapy is crucial.