Proton Beam Therapy Provides Longer Survival and Preserves Muscle Mass in Hepatocellular Carcinoma Compared to TACE+RFA.

[BACKGROUND] Proton beam therapy (PBT) provides excellent tumor control with minimal hepatic toxicity in patients with unresectable hepatocellular carcinoma (HCC), by minimizing radiation exposure to non-cancerous liver tissue. Progressive skeletal muscle loss, often seen in cirrhosis and HCC, can negatively impact treatment outcomes and survival. This study compared the efficacy and safety of PBT with transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in patients with unresectable HCC.

[METHODS] A total of 91 patients (PBT/TACE+RFA, = 41/50) ineligible for surgery or RFA alone were retrospectively analyzed, with propensity score matching applied to adjust for differences in baseline characteristics, resulting in matched groups of 33 patients each. The cross-sectional area of the psoas muscle at the third lumbar vertebra was assessed using computed tomography.

[RESULTS] PBT resulted in longer overall survival (OS) and fewer hepatic and systemic adverse events compared to TACE+RFA, with no grade 3 or higher toxicities observed in the PBT group. Importantly, psoas muscle size remained stable after PBT, even in patients with tumors ≥ 3 cm, whereas TACE+RFA led to significant muscle loss regardless of tumor size, which was associated with poorer prognosis. These findings suggest that, for patients with unresectable HCC not adequately controlled by RFA alone, PBT may improve OS and help preserve muscle mass, while offering lower toxicity and more favorable clinical outcomes than TACE+RFA.

[CONCLUSIONS] Overall, PBT may represent an effective strategy for managing unresectable HCC.