A Phase I study of high-dose-rate intraluminal brachytherapy as palliative treatment in extrahepatic biliary tract cancer

Purpose: To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachytherapy (HDR-192Ir-ILBT) as a palliative treatment of extrahepatic biliary tract cancer. Methods and Materials: Patients with non-metastatic extrahepatic biliary cancer with age <80 years, unsuitable for surgical resection or radiochemotherapy for comorbidities or Eastern Cooperative Oncology Group (ECOG) ≥2 or patients with age ≥80 years were included. They were undergone to implantation of metal stents by endoscopic retrograde cholangiopancreatography followed by HDR-192Ir-ILBT. The initial dose of HDR-192-Ir-ILBT was 15Gy. Three levels of dose were planned. At each dose level almost three patients were treated, and if no Grade 3-4 toxicity (considering as dose-limiting toxicity) was recorded, dose escalation was applied with 5Gy increments until the maximum tolerated dose was established. A high dose Iridium-192 after loading system was used (Nucletron Microselectron HDR). Results: From May 2007 to January 2010, 18 patients underwent HDR-192Ir-ILBT, with one catheter in 12 patients and two catheters in six patients. Three levels of dose were planned: 15Gy in three patients, 20Gy in nine patients, and 25Gy in six patients with daily dose of 500cGy per fraction. One patient at Dose Level II experienced acute toxicity (cholangitis) related to brachytherapy procedure, so the cohort was expanded. No patient of Level III had a dose-limiting toxicity and we stopped at this dose level waiting to assess the late toxicity that has not yet appeared at the time of the analysis. Six months and 1 year overall survival was 77% and 59%, respectively, with a median of 12 months. Conclusions: The recommended dose was defined as 25Gy in five fractions. It will be used in a Phase II study to better evaluate tumor and symptom control in patients with extrahepatic biliary tract cancer.