Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma

Abstract

Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically given its anatomical location and its frequent association with primary sclerosing cholangitis (PSC). Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node negative patients has been advanced by select liver transplant centers for treatment of patients with unresectable disease. This approach has most commonly used external beam radiotherapy combined with biliary brachytherapy and 5-FU based chemotherapy. Our center has recently embarked on a protocol utilizing stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node negative patients until liver transplantation. We therefore retrospectively determined tolerability and pathologic response in this pilot study. Over a three 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, 3–5 fractions over two weeks). Following one week of rest, capecitabine was initiated at 1330 mg/m2/day and continued until liver transplantation. During neoadjuvant therapy, there were a total of 35 adverse events with cholangitis and palmar/plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplant and 6 patients received a liver transplant. Explant pathology of hilar tumors showed at least a partial treatment response in five patients with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic and low proliferative indices were measured on histological examination. Eleven transplant-related complications occurred, and one-year survival after transplant 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.

Positioning high-dose radiation in multidisciplinary management of unresectable cholangiocarcinomas: Review of current evidence

“…Other centers have also reported smaller cohorts with the use of brachytherapy and external beam radiotherapy [18,19]. Recently, combination of SBRT and chemotherapy in the neoadjuvant setting before liver transplantation reported a 1-year survival of 83 % [20]. Furthermore, unlike gallbladder cancers, a vast majority of patients with cholangiocarcinoma present with local recurrence as a primary site of failure.…”

Management of liver cancer. The Surgeon's point of view

“…Several centres have published encouraging results with 70% free-disease survival at 5 years, namely with SBRT and Capecitabine. 27 A very similar protocol has been recently published in the case of IHCC. 28 …”

Radiation therapy for hepatobiliary malignancies

“…The University of Michigan is currently exploring a similar method of treatment for unresectable hilar CC with SBRT (50). Twelve patients with unresectable hilar CC were treated with 50-60 Gy in 3-5 fractions followed by maintenance capecitabine until liver transplantation.…”