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

Abstract

<h3>Purpose/Objective(s)</h3> 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 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. <h3>Materials/Methods</h3> Consecutive patients treated with definitive-intent RT for a diagnosis of intrahepatic cholangiocarcinoma between 2016-2022 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). <h3>Results</h3> Twenty-five patients were identified. Two patients (7%) received prior surgery with local recurrence and 12 patients (48%) received chemotherapy prior to RT. RT was delivered by MRI-guidance in 16 patients (64%) and CT-guidance in the remaining 9 patients (36%). 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 24.8 months (range: 12.5 – 37.1), and 50.6 months (range: 39.7 – 62.5 months) respectively. Overall treatment was well tolerated. Most common side effects reported included grade 1 fatigue and grade 1 nausea seen in 8 (32%) and 5 (20%) patients respectively. One patient (4%) exhibited grade 3 abdominal pain and ascites requiring hospitalization. No grade 4 or 5 toxicities were observed. <h3>Conclusion</h3> 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 investigate this approach in a prospective setting.