A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada.

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19-99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.

Predictive and Prognostic Properties of Human Equilibrative Nucleoside Transporter 1 Expression in Gemcitabine-Treated Pancreatobiliary Cancer: A Meta-Analysis.

PURPOSE: Gemcitabine, the primary drug for the treatment of pancreatobiliary cancer (PBC), requires human equilibrative nucleoside transporter 1 (hENT1) to enter cells. High tumoral hENT1 expression has been linked with improved survival among patients with PBC treated with gemcitabine; however, this finding has been inconsistent, and studies used different expression assays. METHODS: Databases were reviewed for studies that examined hENT1 and clinical outcome in PBC. Of 307 publications, 34 studies were found that used immunohistochemistry (IHC) with one of eight anti-hENT1 antibody assays. Five studies were excluded for redundancy, and 29 studies underwent detailed review. RESULTS: On average, 51% of tumor samples had high hENT1 expression (range, 7% to 92%). Among studies that examined hENT1 expression and overall survival (OS), 58% (15 of 26 studies) showed an association between high tumoral hENT1 and improved OS for gemcitabine-treated patients. Among 10D7G2 antibody studies, 88% (seven of eight studies) demonstrated this association. Studies with other antibodies-in particular, SP120 (two of nine studies)-were less consistent. The ability to detect an association between improved OS and high hENT1 was antibody dependent (χ2 P = .0237). An association between high tumoral hENT1 expression and improved disease-free/progression-free survival (DFS/PFS) was demonstrated in 71% of studies (15 of 21 studies). Pooled hazard ratio (HR) analyses of all antibody studies demonstrated a link between high hENT1 tumor expression and improved OS (HR, 0.674; 95% CI, 0.509 to 0.893; P = .006) and DFS/PFS (HR, 0.740; 95% CI, 0.517 to 0.1.059; P = .10). This signal was stronger among studies that used the 10D7G2 antibody in comparison to those in which another antibody was used, with HRs of 0.488 (95% CI, 0.396 to 0.602; P < .001) and 0.410 (95% CI, 0.280 to 0.599; P < .001), respectively. CONCLUSION: High tumoral hENT1 expression on IHC with 10D7G2 is a strong and reproducible prognostic marker for improved outcome among gemcitabine-treated patients with PBC.