Predictors of toxicity after neoadjuvant chemoradiotherapy for locally advanced gall bladder cancer

Abstract

Background: The present study evaluated the correlation of hepatobiliary toxicity and radiation dose received in patients undergoing neoadjuvant chemoradiotherapy (NACRT) for locally advanced unresectable gall bladder cancers (LAGBC). Methods: Twenty-six patients with LAGBC, treated with NACRT (55–57 Gy/25 fractions/5 weeks and weekly gemcitabine 300 mg/m2) within a phase II study, were included. Whenever feasible, surgery was performed after NACRT. Acute and late hepatobiliary toxicity was recorded. Treatment scans were retrieved to delineate central porto-hepatobiliary system (CPHBS), resected liver surface, segment IV B and V, and duodenum. The doses received by these structures were recorded and correlated with toxicity. Results: Of 26 patients, 20 (77%) had partial or complete response and 12 (46%) had R0 resection. At the median follow-up of 38 months, overall survival was 38%. Eight (30%) patients had post-treatment toxicity, of which most common was biliary toxicity (30%). A correlation was observed between the biliary leak and V45Gy CPHBS >50 cm3 (P = 0.070). Higher toxicity was observed in those with metallic stents (P = 0.072). Conclusion: The incidence of the biliary leak was 46%. CPHBS dose was found to correlate with biliary leaks. Restricting V45Gy CPHBS <50 cm3 and using plastic stent may facilitate a reduction in hepatobiliary toxicity in patients undergoing NACRT and surgery.