Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis

Abstract

Purpose: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC.

Patients and methods: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy).

Results: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities.

Conclusion: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.

Trial registration: ClinicalTrials.gov NCT02200042.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

Radiation treatment plan illustrating the simultaneous integrated boost/simultaneous integrated protection (SIP) technique. A dose of 100 Gy in 25 fractions is delivered to the center of the tumor (dark blue contour) while the gross tumor volume (GTV) receives 75 Gy in 25 fractions (red contour). The GTV does not overlap with the planning risk volume (PRV) created by a 5-mm expansion of adjacent organs at risk for SIP. For treatment planning, the organ at risk is the priority constraint over the planning target volume (PTV). A microscopic dose of 45 Gy, which is within the tolerance of the gastric mucosa, is delivered to the whole tumor with margin as the PTV 45 Gy (light blue contour).

Fig 2.

Effect of radiation dose of local control (LC) and overall survival (OS) from the time of diagnosis. Kaplan-Meier estimates of (A) LC and (B) OS according to a biologic equivalent dose (BED) less than 80.5 or 80.5 Gy or greater illustrate the superiority of the higher dose. BED analyzed as a continuous variable also had a dose-response effect on (C) LC and (D) OS.

Fig A1.

No correlations were found between radiation dose and (A) tumor size and (B) duration of follow-up.