Post-Hoc Analysis Shows Dose-Escalated Radiation is Safe and Efficacious in Intrahepatic Cholangiocarcinoma

Hari Menon, MD

Dose escalation of radiation therapy was safe and elicited similar efficacy rates with previously published data in terms of local control rates in patients with intrahepatic cholangiocarcinoma, according to results from a post-hoc analysis of patients treated at Carbone Cancer Center and the University of Wisconsin School of Medicine and Public Health in Madison.¹

At a median follow-up of 46.2 months, patients treated with definitive radiation (n = 40) achieved a median progression-free survival (PFS) of 9.3 months (range, 1.67-48.57). The median overall survival (OS) was 24.8 months (range, 6.70-84.30), and the median local control rate was 49.37 months with a 3-year control rate of 71.1%. Patients received radiation therapy in the form of MRI guidance (62%) or CT guidance (28%), and doses were a median of 67.5 Gy (range, 50-70) in 5 to 25 fractions, which investigators noted was for a median biological equivalent dose (BED) of 90.17 Gy (range, 87.31-113.73).

Based on prior data suggesting ablative doses of radiation of more than 80.5 Gy BED may lead to durable responses, investigators conducted this analysis. Previous data revealed that patients with intrahepatic cholangiocarcinoma treated with a median dose of 58.05 Gy (range, 37.5-67.5) hypofractionated proton or photon radiation therapy delivered in 15 daily fractions achieved a 2-year local control rate of 84% and a 2-year OS rate of 58%.²

“We report dose-escalated radiation therapy in the setting of unresectable intrahepatic cholangiocarcinoma is safe with minimal grade 3 toxicities, and no reported grade 4 or 5 toxicities,” lead study author Hari Menon, MD, a radiation oncology resident in the Department of Human Oncology at the University of Wisconsin School of Medicine and Public Health, and colleagues, wrote in a poster presentation. “Overall, treatment was well tolerated with 2 patients exhibiting grade 3 abdominal pain requiring hospitalization.”

Additional adverse effects occurring at grade 1 and 2 included fatigue (grade 1, 32%; grade 2, 4%), nausea (20%; 12%), and chills (4%; 0%). Grade 1 and 2 malaise, anorexia, fever, dyspepsia, diarrhea, and abdominal pain occurred in 4% and 4% of patients, respectively.¹

“Treatment of unresectable intrahepatic cholangiocarcinoma remains a clinical challenge with noted short survival, [and] the general treatment paradigm for unresectable intrahepatic cholangiocarcinoma has largely included chemotherapy with limited survival advantages. The utility of radiation therapy has been a topic of great interest in this otherwise difficult disease,” study authors noted.

Investigators conducted this post-hoc analysis from an institutional database including consecutive patients with intrahepatic cholangiocarcinoma from 2016 to 2024. Those with non-intrahepatic cholangiocarcinoma diagnoses and a BED of less than 80 Gy were not eligible for the analysis.

The median age of patients was 71 years (range, 45-90) and the median cycles of chemotherapy received was 4. Most patients were male (52%) and had a Karnofsky performance status of more than 80 (58%). Prior therapies received for less than 6 months included surgery (15%) as well as chemotherapy (45%), and patients had stage I (20%), II (28%), III (30%), or IV (22%) disease. Additionally, 15% of patients received prior surgery with local recurrence, and 45% of patients received chemotherapy prior to radiation therapy.¹

Moreover, OS and PFS were assessed via Kaplan Meier analysis, and toxicities were evaluated based on Common Terminology Criteria for Adverse Events 5.0 criteria.

“Further studies are warranted to investigate this approach in a prospective manner, especially in the setting of evolving systemic treatment options,” the study authors concluded.

References

1. Menon H, Basree M, Bassetti M. Dose-escalated ablative radiotherapy as definitive treatment for unresectable and recurrent intrahepatic cholangiocarcinoma. Presented at: 2024 ACRO Annual Meeting; March 13-16, 2024; Orlando, FL.
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. doi:10.1245/s10434-019-08142-9.