Comparing Acute Toxicities of Patients With Unresectable Hepatocellular Carcinoma Treated With Definitive Proton vs. Photon-Based Radiotherapy

Purpose/Objective(s) Radiation therapy (RT) remains a critical treatment modality for unresectable hepatocellular carcinoma (HCC), with proton beam therapy (PBT) being widely utilized due to its decreased exit dose compared to photon-based RT. We hypothesize that patients with HCC receiving definitive PBT would experience decreased acute toxicity when compared to those receiving photon-based RT. Materials/Methods Electronic medical records were retrospectively reviewed at a single institution for patients diagnosed with unresectable HCC and treated with definitive RT between 1/2011 and 12/2020. Patients treated with prior surgery or radiofrequency ablation were excluded. Progress notes and treatment summaries were reviewed to determine baseline characteristics including age at diagnosis, Child-Pugh classification (CPC), AJCC 8th edition T stage, performance status, and RT dose. Acute treatment toxicities were evaluated using Common Terminology Criteria for Adverse Events v5.0. Descriptive statistics were quantified for baseline characteristics. Odds ratios (OR) with 95% confidence intervals (CI) were generated to determine the association between PBT vs. photon therapy and acute radiation toxicities in bivariate and multivariate logistic regression models. Results Forty-six patients were included in the analysis. 24 (52%) patients received PBT while 22 (48%) received photon-based RT. Median age for the PBT and photon-based RT groups were 67 (interquartile range (IQR): 58.6 to 72.5) and 65.5 years (IQR: 61.0 to 73.0), respectively (P = 0.991). 50% of patients who received PBT had a T stage greater than T2, compared to 71% of patient in the photon group (P = 0.148). 42% of the PBT group had CPC B or worse, compared to 38% in the photon group (P = 0.813). Performance status and total dose did not significantly differ between groups (P = 0.351 and P = 0.773, respectively). PBT was associated with higher odds of any grade radiation dermatitis (RD) (OR = 6.00, 95% CI: 1.13 to 31.9) and lower odds of any grade anorexia (OR = 0.21, 95% CI 0.05 to 0.91). Odds of any grade diarrhea and fatigue, did not significantly differ between groups (P = 0.086 and P = 0.958, respectively). After controlling for performance status, total dose, T stage, CPC, and age at diagnosis, PBT was still associated with higher odds of RD (OR = 11.07, 95% CI: 1.14 to 107.71) and lower odds of anorexia (OR = 0.14, 95% CI: 0.02 to 0.93). Conclusion This study provides evidence that although PBT appears to have a superior safety profile in regard to acute anorexia, patients treated with PBT have higher odds of acute RD; these effects persist even after controlling for relevant confounding factors. PBT may result in fewer GI toxicities at the cost of greater skin toxicity.