Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer

PRIMARY OBJECTIVE: I. To determine if overall survival (OS) is different for hepatocellular carcinoma patients treated with protons compared to photons. SECONDARY OBJECTIVES: I. To determine the difference in progression-free-survival (PFS) in patients with hepatocellular carcinoma (HCC) treated with protons compared to patients with HCC treated with photons. II. To determine the difference in local progression (LP) in patients with HCC treated with protons compared to patients with HCC treated with photons. III. To determine differences in toxicity in patients with HCC treated with protons versus photons. IV. To determine differences in fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue in patients with HCC treated with protons, versus photons; as well as quality-adjusted survival, if the primary endpoint is met. V. To determine if there are correlations between the baseline values of hepatocyte growth factor (HGF) and outcomes (OS/PFS/fatigue). EXPLORATORY OBJECTIVES: I. To determine differences in overall quality of life, measured by Functional Assessment of Cancer Therapy-Hepatobiliary Cancer (FACT-Hep) in patients with HCC treated with protons. II. Biospecimen collection for future correlative science projects. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. ARM II: Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.