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Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma
Author(s) -
Welling Theodore H.,
Feng Mary,
Wan Shanshan,
Hwang Sin Ye,
Volk Michael L.,
Lawrence Theodore S.,
Zalupski Mark M.,
Sonnenday Christopher J.
Publication year - 2014
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.23757
Subject(s) - medicine , capecitabine , liver transplantation , transplantation , neoadjuvant therapy , tolerability , radiation therapy , chemoradiotherapy , adverse effect , surgery , cancer , colorectal cancer , breast cancer
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. Liver Transpl 20:81–88, 2014 . © 2013 AASLD.