Dose-Escalated Ablative Radiotherapy as Definitive Treatment for Unresectable and Recurrent Intrahepatic Cholangiocarcinoma

Summary: Purpose/Objective: Treatment of intrahepatic cholangiocarcinoma remains a clinical challenge with noted short survival. Ablative doses of radiation may provide durable response in this setting. We hypothesized that the dose escalated radiotherapy in the setting intrahepatic cholangiocarcinoma would provide disease control and minimal toxicity. Here, we report the efficacy and safety of hypofractionated ablative radiotherapy (RT) in the setting of intrahepatic cholangiocarcinoma from a single institution. Methods: Consecutive patients treated with definitive-intent RT for a diagnosis of intrahepatic cholangiocarcinoma between 2016-2023 were identified. Clinical and dosimetric data were retrospectively collected. Patients treated with a biological equivalent dose (BED10) of less than 80 Gy were excluded. Toxicities were evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Kaplan Meier analysis was utilized to calculate progression free survival (PFS) and overall survival (OS). Results: Thirty-eight patients were identified. Six patients (16%) received prior surgery with local recurrence and 19 patients (50%) received chemotherapy prior to RT. RT was delivered by MRI-guidance in 28 patients (74%) and CT-guidance in the remaining 10 patients (26%). RT doses ranged between 50 to 75 Gy (median 67.5 Gy) in 5 to 25 fractions (median 15) for a median BED10 of 90.2 (range: 87.3 - 113.7 Gy). Median PFS and OS for all patients were 14.4 months (range: 0.8 – 49.4), and 24 months (range: 1.6 – 98.3 months) respectively. Overall treatment was well tolerated. Two patients (5%) exhibited grade 3 toxicities: one patient (2.6%) exhibited grade 3 abdominal pain and ascites requiring hospitalization and one patient (2.6%) exhibited grade 3 fatigue which resolved after common bile duct stent exchange. No grade 4 or 5 toxicities were observed. Conclusions: Dose escalation in the setting of intrahepatic cholangiocarcinoma appears to be a safe and effective treatment. Prolonged survival with definitive-intent ablative radiotherapy is possible in appropriately selected patients. Further studies are warranted to evaluate patients who would most benefit from this approach in a prospective setting.