Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation

Background: Stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT) generally are safe and effective for non-operative hepatocellular carcinoma (HCC). To date, data comparing the two modalities are limited. We aimed to identify the practice patterns and outcomes of nonsurgical HCC cases treated definitively with either SBRT or PBT. Methods: We queried the National Cancer Database for T1-2N0 HCC patients receiving PBT or SBRT from 2004 to 2015. Patients were excluded for any treatment other than non-palliative external beam radiotherapy. A multivariable binomial regression model identified patterns of SBRT/PBT use, and propensity-matched multivariable Cox regression assessed correlates of survival. Results: A total of 71 patients received PBT and 918 patients received SBRT (median follow-up 45 months). SBRT was used in 1.8% of nonoperative early stage HCC cases in 2004 and 4.2% of cases in 2015, whereas PBT was used in 0.1-0.2% of cases every year. The median biologically effective dose (BED) for SBRT and PBT was 100 Gy10 and 98 Gy10, respectively (OR =0.70, P=0.17). Factors predictive of receiving PBT included: white race, higher comorbidity score, higher education, metropolitan residence, tumors >5 cm and recent treatment (all P<0.05). Both PBT (HR =0.48, 95% CI: 0.29-0.78) and BED >= 100 Gy10 (HR =0.61, 95% CI: 0.38-0.98) were independent predictors for longer survival. Conclusions: Although not implying causation and requiring prospective corroboration, PBT was independently associated with longer survival than SBRT, despite being delivered to HCC patients with multiple poor prognostic factors. PBT may also allow for safer BED escalation, which also independently associated with outcomes.