Survival Outcomes of Patients With Unresectable Hepatocellular Carcinoma Secondary to Viral vs. Non-Viral Etiologies Treated with Definitive Radiotherapy.

Purpose/Objective(s) Radiation therapy (RT) is a critical modality for the treatment of unresectable hepatocellular carcinoma (HCC). Little is known about how the etiology of HCC impacts overall and progression free survival (OS and PFS) in patients treated with definitive RT. We hypothesize that patients treated with definitive RT for HCC secondary to hepatitis B and hepatitis C viruses (viral group) would have favorable OS and PFS when compared to patients with HCC secondary to other etiologies (non-viral group). Materials/Methods 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 were reviewed to determine date of last follow-up, progression, and death. Notes were also assessed to determine the etiology of HCC, age at diagnosis, Child-Pugh classification (CPC), AJCC 8th edition T stage, RT strategy, and planning target volume (PTV). Descriptive statistics were quantified for baseline characteristics. Survival curves were estimated via Kaplan-Meier method; statistical difference was determined using the log-rank test. Multivariate (MVA) Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. Results Forty-six patients were included in the analysis. 30 (65%) patients were in the viral group, while 16 (35%) patients were in the non-viral group. Median ages at diagnosis for the viral and non-viral groups were 64 (interquartile range (IQR): 60 to 69) and 71 years (IQR: 66.5 to 76.5), respectively (P = 0.014). Treatment with hypofractionated RT (P = 0.559), proton therapy (P = 0.686), performance status (P = 0.222), CPC (P = 0.270), T stage (P = 0.639), and PTV (P = 0.472) were not different between groups. There was a trend toward improved Median OS for the viral group compared to the non-viral group: 17.9 months (95% confidence interval (CI): 9.7 to not-reached (NR)) vs. 8.8 months (95% CI: 6.1 to NR) (P = 0.072). Similarly, PFS was not different between viral and non-viral groups: 9.3 (95% CI: 7.4 to 19.0) vs. 8.0 (95% CI: 4.0 to 10.3), P = 0.314. However, after controlling for confounding factors with MVA Cox proportional hazards models, the viral group had superior OS (HR = 4.20, 95% CI: 1.47 to 12.02, P = 0.008); the viral group also had superior PFS (HR = 2.48, 95% CI: 1.06 to 5.81, P = 0.037). Conclusion Our retrospective review of patients with unresectable HCC treated with definitive RT provides evidence that viral etiologies of HCC may fare better in OS and PFS when compared to non-viral etiologies. The etiology of HCC development for virally vs non-virally mediated tumors may have implications for treatment and response in the setting of radiation therapy.