The Impact of Ablative Doses on Survival for Patients Treated with Definitive Radiotherapy for Intrahepatic Cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (IHCC) is a rare malignancy with a rising incidence. Prognosis is poor, especially for patients who are surgically inoperable. A recent single institution retrospective study demonstrated improved local control and overall survival for patients treated with biologically effective dose (BED)>80.5 Gy, compared to those with BED ≤80.5 Gy. The purpose of this study is to investigate the impact of ablative radiotherapy doses on survival using a large cancer database registry. The National Cancer Database was queried (2004-2015) for patients with histologically-confirmed, localized IHCC treated with definitive external beam radiotherapy with or without chemotherapy. Patients treated with palliative radiotherapy dose fractionation schemes were excluded (BED <40). Patients were divided into two cohorts based on BED: BED>80.5 Gy and BED ≤80.5 Gy. Kaplan-Meier analysis evaluated overall survival (OS). Significance of Kaplan-Meier estimates of OS was determined by log-rank testing. Multivariable Cox Proportional Hazards Regression Analysis (coxph) was used to establish factors associated with OS, with BED as a continuous variable. A total of 579 patients met the inclusion criteria; median BED was 60 Gy. 481 (83%) of patients received BED ≤80.5 Gy, whereas 98 (17%) received BED >80.5 Gy. Median follow-up was 11.8 and 13.8 months for the BED ≤80.5 Gy and BED>80.5 Gy groups, respectively. Median OS was 12.5 months for the BED ≤80.5 Gy group and 14.65 months for the BED>80.5 Gy groups (log-rank p = 0.035). Coxph results can be found in Table 1. Older age, more advanced T and N stage, and lower BED as a continuous variable were significantly associated with worse OS (p<0.05 for all). Sex, presence of comorbidities and the receipt of chemotherapy were not significantly with OS. This is the largest study to do date looking at the effect of dose escalation on outcomes of definitive radiotherapy for patients treated for IHCC. Higher BED was significantly associated with better OS using both Kaplan Meier (BED ≤80.5 Gy verses BED>80.5 Gy) and as a continuous variable on coxph. Chemotherapy was not significantly associated with OS. The retrospective nature of this analysis is recognized as a limitation. Further prospective studies are warranted to confirm these findings.Abstract 3516; TableMultivariable Cox Proportional Hazards Regression Analysis ResultsHazard Ratio95% CIp-valueAge1.0151.007-1.023<0.0005Sex0.9020.750-1.0840.2713BED0.9940.990-0.9990.0108T stage1.1421.035-1.2600.0083N stage1.4601.193-1.7860.0002Chemotherapy0.8720.701-1.0850.2204No comorbidities1.0360.8445-1.2710.7355 Open table in a new tab