Neoadjuvant chemotherapy for resectable oncologically high-risk biliary tract cancers

Abstract

Presenter: Kelvin Allenson MD | Moffitt Cancer Center Background: Surgical resection for biliary tract cancers (BTC) remains the only curative therapy, yet recurrence rates following resection remain high. Prior retrospective studies have identified clinicopathologic features that are associated with high risk of recurrence. A neoadjuvant chemotherapy (NAC) approach for high-risk BTC may select patients with more favorable tumor biology, treat micrometastatic disease and decrease the risk of recurrence, although this approach has not yet been examined in prospective clinical trials. The purpose of this study was to evaluate the safety and outcomes of a NAC approach in resectable oncologically high-risk BTC. Methods: A hepatobiliary disease-site-specific multidisciplinary tumor board was created at a major comprehensive cancer center in November 2015. Diagnosis, stage, pertinent imaging findings and treatment recommendations are prospectively recorded. Tumor board records were reviewed from November 2015-May 2020 to identify patients with resectable, oncologically high-risk BTC for whom a NAC approach was recommended. These patients were cross-referenced with the prospectively maintained hepatobiliary surgery database to ensure that all patients were captured. Patients who underwent abdominal exploration/aborted surgical resection prior to initiation of chemotherapy were excluded. Patients who met the inclusion criteria composed the intention-to-treat (ITT) cohort, while those patients who met the inclusion criteria and received NAC, composed the NAC cohort. Results: Fifteen patients were identified who had resectable oncologically high-risk BTC and recommended to undergo NAC. Three (20%) patients were lost to follow-up, and to the best of authors’ knowledge never started NAC, while the remaining 12 (80%) received NAC. The mean age of the ITT cohort was 64 years old, 12 (80%) had a Charlson Comorbidity Index of 2-3. Nine (60%) patients had intrahepatic cholangiocarcinoma (IHCC) and 6 (40%) had gallbladder cancer (GBC). In the NAC cohort, the median number of chemotherapy cycles was 4; 11 patients received gemcitabine/cisplatin and 1 received FOLFOX. Ten of 12 patients underwent oncologic resection, while the other 2 patients (1 IHCC and 1 GBC) had evidence of disease progression on re-staging imaging. One of 10 patients who underwent surgical resection had a Clavien-Dindo grade 3/4 complication (percutaneous drain for a seroma). On final surgical pathology, 2 IHCC patients had pathologic upstaging, while 3 of 4 gallbladder cancer patient had no residual disease. Eight of 10 patients who underwent surgical resection received additional postoperative chemotherapy. With a median follow up of 19.9 months, the median progression free (PFS) and overall survival (OS) in the ITT cohort was 11.7 and 16.9 months, respectively. In the NAC cohort, PFS and OS was 15.8 and 20 months respectively. Conclusion: In this retrospective study of NAC in resectable oncologically high-risk BTC, 67% and 83% of the ITT and NAC cohorts received NAC and surgical resection. Only 1 significant perioperative complication was observed. Although NAC for BTC remains investigational, it was well tolerated, did not appear to increase surgical morbidity and resulted in reasonable oncologic outcome (median OS 20 months). Randomized trials investigating a NAC approach for oncologically high-risk BTC are warranted.