Proton Beam Therapy for Unresectable Cholangiocarcinoma

Abstract

To evaluate the treatment outcome and patterns of failure in patients with unresectable cholangiocarcinoma undergoing proton beam therapy (PBT). We retrospectively analyzed 22 patients with pathologically confirmed cholangiocarcinoma who were treated with definitive PBT from November 2015 to August 2017. Four-dimensional computer tomography (4D-CT) with and without intravenous contrast-enhancement was acquired with 2.5 mm slide thickness. A clinical target volume expansion of 5-10 mm was used. The internal target volume was generated based on the 4D-CT images, and respiratory gaiting was adopted in patients with tumor motion >10 mm. Treatment-related toxicities were recorded according to Common Terminology Criteria for Adverse Event version 4.0 (CTCAE v4.0). The study included 11 male and 11 female participants, with a median age of 68 years (range, 46-88 years). Intrahepatic, perihilar and distal extrahepatic, and gallbladder tumors were recorded in 12 (54%), 7 (32%), 1 (5%) and 2 (9%), respectively. The median tumor dimension was 7.0 cm (range, 3.8-18.2 cm). Stage IV, III and II was documented in 15 (68%), 5 (23%) and 2 (9%) patients, respectively. Tumor vascular invasion was observed in 5 (23%) patients, and 19 (86%) patients demonstrated biliary tract obstruction. The median PBT dose was 72.6 cobalt gray equivalent (CGE) (range, 39.6-72.6 CGE). Gemcitabine-based concomitant chemotherapy was administered in 15 (68%) patients. After a median follow-up of 14.3 months, the 1-year overall survival rate was 75%. Fifteen (68%) patients developed disease progression. Among them, one (5%) patients experienced in-field local failure, whereas 4 (18%) patients developed intrahepatic out-field recurrence. Distant metastasis (N = 10, 45%) was the predominant form of treatment failure. The 1-year local control and progression-free survival rates were 100% and 42%, respectively. Among the 19 patients who presented obstructive jaundice, normalization of total bilirubin level was recorded in 14 (74%) patients after PBT with or without biliary drainage. Grade 3 dermatitis and grade 4 duodenal ulcer occurred in 2 (9%) and 2 (9%) patients, respectively. PBT could lead to an excellent local control probability, sustainable relief of biliary tract obstruction and a favorable survival outcome in patients with unresectable cholangiocarcinoma. However, distant recurrence remains the primary reason of failure after PBT.