Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma

Abstract

BackgroundWe examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma.MethodsThe clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.ResultsThe median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement.ConclusionsRelatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

Multimodality treatment of intrahepatic cholangiocarcinoma: A review

“…More recently, proton beam therapy (PBT) has been utilized in the treatment of unresectable and recurrent iCCA in small studies in an effort to deliver more effective, tumor‐specific doses of radiation . PBT has been used to treat cholangiocarcinoma in a group which contained a small number of iCCA patients (n = 6) . In this study, overall survival at 1 year was 49%, which is comparable to other radiation therapies.…”

Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review

“…Less OAR dose can translate to safer dose-escalation in various tumors, which has already been tested for other cancers (71). Aforementioned studies have also demonstrated improved LC with higher BED values (39). Additionally, as the treatment of GI tumors often requires concurrent or sequential multimodality therapy with surgery and/or chemotherapy, PBT may be an ideal RT modality for treating GI malignancies, as it may more safely allow for multimodality therapy (72).…”

“…Makita and colleagues examined 28 patients, 10 of which were locally or regionally recurrent (39). Of the 18 primary tumors, 6 each were intrahepatic and hilar, 3 distal extrahepatic, and 3 gallbladder.…”

Locoregional therapies in cholangiocarcinoma

“…Like SBRT, this results in significantly reduced doses to surrounding tissues [84]. A retrospective analysis in 28 patients with new or recurrent inoperable cholangiocarcinoma undergoing PBT reported 1-year PFS and OS of 29.5 and 49%, respectively [85]. However, toxicities were common; 29 grade I, 16 grade II and eight grade III toxicities were reported.…”