S.J. Buskirk

External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma

PURPOSE/OBJECTIVE Review survival, prognostic factors, and patterns of failure in patients with extrahepatic bile duct (EHBD) carcinoma treated with external beam irradiation (EBRT) and transcatheter iridium. METHODS AND MATERIALS The charts of 24 patients with EHBD cancer treated with EBRT and transcatheter boost were reviewed. All patients had transhepatic biliary tubes or endoprostheses placed. Two patients underwent hemihepatectomy with hepaticojejunostomy formation but had residual disease. Two patients had biopsy proven adenopathy. Five patients had Grade 1 adenocarcinoma, nine Grade 2, six Grade 3, and one Grade 4 disease. Median EBRT dose was 50.4 Gy delivered in 1.8 Gy/day fractions. Median transcatheter boost at 1 cm radius was 20 Gy. Nine patients received concomitant 5-Fluorouracil (5-FU) during EBRT. RESULTS Median survival was 12.8 months (range 7.5 months to 9 years). Overall 2- and 5-year survival rates were 18.8 and 14.1%, respectively (three disease-free survivors > or =5 years). One patient is still alive without relapse 10 years from diagnosis and 5 years after liver transplantation for liver failure (no cancer in specimen, underlying sclerosing cholangitis). Two additional long-term survivors had no evidence of relapse 6.9 and 8.2 years after diagnosis. Histologic grade, lymph node status, cystic, hepatic, common hepatic or common bile duct involvement, surgical resection, radiation therapy dose, and chemotherapy did not significantly effect survival due to the number of patients analyzed. There was a trend towards improved survival with the addition of 5-FU chemotherapy (5-year survival in two of nine patients, or 22%). Eight of 24 patients (33%) demonstrated radiographic evidence of local recurrence. Distant metastases developed in 6 of 24 (25%) patients. The most common complications were tube related cholangitis (50%) and gastric/duodenal ulceration or bleeding (42%). CONCLUSION External beam irradiation combined with a transcatheter boost can result in long-term survival of patients with EHBD cancer. Both distant metastases and local recurrence develop in 25-30% of patients despite irradiation. Survival may be improved by using chemotherapy in combination with EBRT to impact disease relapse (local and distant). Because there may be a dose response with irradiation, survival may also be improved by increasing the dose of radiation delivered by transcatheter boost. A Phase II trial is being developed using a combination of 45-50 Gy EBRT with concomitant 5-FU delivered by protracted venous infusion followed by a 25-30 Gy transcatheter boost.