Definitive Ablative Radiation Therapy for Unresectable and Recurrent Intrahepatic Cholangiocarcinoma

Purpose: Treatment of intrahepatic cholangiocarcinoma (IHCC) remains a clinical challenge with noted short survival. Ablative doses of radiation may provide durable response in this setting. We hypothesized that dose escalated radiotherapy in the setting of IHCC would provide disease control and minimal toxicity. Here, we report the efficacy and safety of hypofractionated ablative radiotherapy (RT) in the setting of IHCC from a single institution.

Methodology: Consecutive patients treated with definitive-intent RT for unresectable or recurrent, of IHCC between 2016 and 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 with median follow-up of 50.6 months. Six patients (16%) received prior surgery with local recurrence and 19 patients (50%) received chemotherapy prior to RT. RT was delivered under 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 (range: 0.8 – 49.4) and 24 (range: 1.6 – 98.3) months, respectively. Overall, treatment was well tolerated. Two patients (5%) experienced grade 3 toxicities: one patient (2.6%) exhibited abdominal pain and ascites requiring hospitalization and another patient (2.6%) exhibited fatigue which resolved after common bile duct stent exchange. No grade 4 or 5 toxicities were observed.

Conclusions: Dose escalation in the setting of IHCC appears to be safe and effective. 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.

References: 1. Tao R, Krishnan S, Bhosale PR, et al. Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis. J Clin Oncol. 2016;34(3):219-226.
2. Smart AC, Goyal L, Horick N, et al. Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2020;27(4):1122-1129.