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

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).

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.

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).

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.