Association of Chronological Age and Comorbidity Burden with Outcomes After Proton Beam Therapy for Hepatocellular Carcinoma

Background/Objectives: The prognostic relevance of chronological age versus comorbidity burden in patients with hepatocellular carcinoma (HCC) undergoing proton beam therapy (PBT) is unclear. This study evaluated whether comorbidity burden provides prognostic information beyond age. Methods: We retrospectively analyzed 269 patients with HCC treated with PBT between December 2009 and March 2015. Patients were classified as elderly (≥75 years, n = 105) or non-elderly (<75 years, n = 164). Overall survival (OS), local control (LC), progression-free survival (PFS), and treatment-related adverse events were assessed. Comorbidity burden was evaluated using the Charlson Comorbidity Index (CCI). Multivariable Cox regression analyses were performed for OS and PFS. Results: The 3-year OS rates were 65.9% in the elderly group and 56.9% in the non-elderly group (p = 0.20), while the corresponding LC rates were 86.7% and 90.5% (p = 0.24) and PFS rates were 30.3% and 29.9% (p = 0.81), respectively. In multivariable analyses, age ≥ 75 years was not significantly associated with OS (HR, 1.25; 95% CI, 0.89–1.74; p = 0.198) or PFS (HR, 1.15; 95% CI, 0.86–1.54; p = 0.331). In contrast, CCI ≥ 3, compared with CCI 0, was independently associated with poorer OS (HR, 3.31; 95% CI, 1.54–7.15; p = 0.002), while its association with PFS did not reach statistical significance (HR, 1.87; 95% CI, 0.98–3.58; p = 0.057). No significant age × CCI interaction was observed for OS or PFS. Conclusions: Chronological age was not independently associated with OS or PFS in patients with HCC treated with PBT, whereas a high comorbidity burden was independently associated with poorer OS. These findings suggest that comorbidity burden should be considered in addition to chronological age when estimating prognosis after PBT.