Utilization Rate and Prognostic Impact of Brachytherapy for Bridging to Transplant in Intrahepatic Cholangiocarcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Intrahepatic cholangiocarcinoma (ICCA) patients who are dispositioned to liver transplant (LTX) can be bridged in the interim with any combination of systemic therapy and liver directed therapies such as radiotherapy (RT). The purpose of this study is to assess the utilization rate and prognostic impact of brachytherapy (BT) in a large national database. <h3>Materials/Methods</h3> The National Cancer Database (NCDB) was queried (2004-2017) for patients with ICCA who underwent LTX. Pearson chi-square testing was used to compare categorical frequencies between patients who received external beam RT without BT (EBRT alone) and patients who received BT. Propensity score matching (PSM) was performed to create a 1:1 matched cohort of patients who received EBRT alone v. BT. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which demographic and clinical factors were prognostic for OS. <h3>Results</h3> A total of 352 patients with median age 56 (IQR 49-62) were included in this study. A total of 212 (61%) received chemotherapy while 134 (39%) did not. A total of 216 (61%) received no RT, 92 (26%) received EBRT alone, and 44 (13%) received BT. RT began a median of 57 days (IQR 39- 89) after diagnosis. LTX occurred a median of 126 days (IQR 61- 202) after RT began. EBRT doses ranged from palliative doses of 20 Gy to definitive doses of 60 Gy (median 45 Gy, IQR 45- 45). BT doses were not available in >90% of cases. Surgical margins were negative in 298 (90%) patients, microscopically positive in 16 (5%) patients, & macroscopically positive in 18 (5%) patients. Within 30 days of LTX, 10 (5%) patients who received no RT died compared to 1 (1%) patient who received EBRT alone & 1 (3%) patient who received BT (p= 0.26). Compared to EBRT alone, patients who received BT were more likely diagnosed in 2012 or later (p= 0.02) and more likely grade 1 (p= 0.04). After PSM, there were no differences in demographic or clinical factors between patients who received EBRT alone v. BT. After PSM, the 4-year OS was 25% for EBRT alone & 62% for BT (p= 0.01). After PSM, on UVA BT (HR 0.36, p=0.02; 95% CI 0.16- 0.84) & insured status (HR 0.19, p=0.03; 95% CI 0.04- 0.86) were positive prognostic factors for OS while grade 3 disease (HR 4.0, p=0.04; 95% CI 1.07- 14.89) & positive surgical margin (HR 2.55, p=0.04; 95% CI 1.05- 6.18) were negative prognostic factors for OS. On MVA, over 50% of cases were dropped due to cumulative missing data and no factors remained prognostic. <h3>Conclusion</h3> The utilization rate of BT has increased as a bridging therapy for ICCA patients dispositioned to LTX. This study demonstrated a positive prognostic impact of BT relative to EBRT alone on UVA. This finding did not persist on MVA due to cumulative missing data from the various prognostic factors. A future prospective clinical trial should evaluate this.