Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma

Abstract

To evaluate outcomes for patients with unresectable/locally recurrent intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008-18. 51 patients had intrahepatic disease only, and 15 patients had extrahepatic disease at time of RT but received RT for biliary control. Median age at RT was 76 years (range: 30-92), including 27 patients (41%) ≥ 80 years. Median RT dose was 58.05 Gy (range: 37.5-67.5), all delivered in 15 daily fractions. 32 patients received proton RT, and 34 patients received photon RT. Rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the Cox proportional hazards method. For multivariate analyses, variables with p < 0.5 on univariate analysis were evaluated by backwards selection. Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, 5 patients (7.6%) developed local failure. Only 1 patient developed isolated local failure. The 2-yr outcomes were 93% LC, 37% PFS, and 55% OS. Among the 51 patients treated with definitive intent, the 2-yr LC was 96%, PFS 35%, OS 60%. Receipt of protons was significantly associated with younger age (p = 0.02), but not gender, race, ECOG status, metastatic disease at presentation, mean liver dose, cumulative GTV, or number of lesions. There were no significant predictors of LC or PFS, including RT dose. On UVA for OS, younger age, female gender, prior chemotherapy, and prior surgery were significantly associated with improved OS (p < 0.05). On MVA, female gender (HR: 0.33, p = 0.001), prior chemotherapy (HR: 0.38, p = 0.002), and proton vs. photon RT (HR: 0.50, p = 0.05) remained significantly associated with OS. The rate of overall Grade 3+ toxicity was 11%. Radiation-induced liver disease (RILD) was documented in 1 patient who underwent glucocorticoid treatment. HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC. HF-RT is well tolerated and should be considered as a treatment option for elderly patients who are considered medically inoperable. Proton RT and chemotherapy may further improve outcomes.