Proton Beam Therapy for Unresectable Perihilar Cholangiocarcinoma

Background: The outcomes of chemotherapy for patients with perihilar cholangiocarcinoma (PHC) are unsatisfactory, and photon therapy for unresectable PHC reportedly results in improved outcomes. Proton beam therapy (PBT) can be a treatment option for these patients; however, the role of PBT in these patients is poorly defined as PHC is rare. Herein, we evaluated the efficacy and safety of PBT for unresectable PHC.Methods: This observational retrospective cohort study conducted at a single institution included patients with unresectable PHC who received definitive PBT. Patients who had nodal metastasis at presentation or those who underwent surgery or other radiation therapies before PBT were excluded. To compare different dose fractionations, biologically equivalent doses with α/β=10 [BED10] were calculated.Results: Overall, 26 patients were eligible. The commonly prescribed doses were 67.5 Gy (relative biological effectiveness [RBE]) in 25 fractions or 70.2 Gy (RBE) in 26 fractions. The median follow-up period was 19.4 months (range, 4.2-137.4 months). The Kaplan–Meier estimates of the 1-, 2-, and 5-year overall survival (OS) rates were 72.9%, 47.7%, and 17.4%, respectively, and the median survival time was 23.7 months. The multivariate analysis demonstrated that Child–Pugh classification B was a significant prognostic factor for unfavorable OS (hazard ratio [HR] 4.92; p=0.009) and that a mean gross tumor volume dose of ≥79.2 Gy (RBE) [BED10] was a significant prognostic factor for favorable OS (HR 0.19; p=0.025). Grade ≥3 late adverse events were observed in seven patients (26.9%).Conclusions: We demonstrated that definitive PBT for patients with unresectable PHC might improve the prognosis. Further large-scale prospective studies are warranted to validate our findings.