title: Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma.
abstract: Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically because of its anatomical location and its frequent association with primary sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node-negative patients has been advanced by select liver transplant centers for the treatment of patients with unresectable disease. This approach has most commonly used external-beam radiotherapy in combination with biliary brachytherapy and 5-fluorouracil-based chemotherapy. Our center recently embarked on a protocol using stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node-negative patients until liver transplantation. We, therefore, retrospectively determined the tolerability and pathological response in this pilot study. During a 3-year period, 17 patients with unresectable hilar CCA were evaluated for treatment under this protocol. In all, 12 patients qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5 fractions over the course of 2 weeks). After 1 week of rest, capecitabine was initiated at 1330 mg/m(2) /day, and it was continued until liver transplantation. During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplantation, and 6 patients received a liver transplant. The explant pathology of hilar tumors showed at least a partial treatment response in 5 patients, with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic indices and low proliferative indices were measured during histological examinations. Eleven transplant-related complications occurred, and the 1-year survival rate after transplantation was 83%. In this pilot study, neoadjuvant therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA demonstrated acceptable tolerability. Further studies will determine the overall future efficacy of this therapy.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Welling
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wan
authors.forename: Sin Ye
authors.initials: SY
authors.lastname: Hwang
authors.forename: Michael L
authors.initials: ML
authors.lastname: Volk
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sonnenday
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000069287:Capecitabine; D059248:Chemoradiotherapy; D018281:Cholangiocarcinoma / Q000628:therapy*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000628:therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009336:Necrosis / Q000473:pathology; D020360:Neoadjuvant Therapy; D016634:Radiosurgery; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil