title: A Phase I study of high-dose-rate intraluminal brachytherapy as palliative treatment in extrahepatic biliary tract cancer.
abstract: OBJECTIVE
  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
  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 15 Gy. 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 5 Gy 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: 15 Gy in three patients, 20 Gy in nine patients, and 25 Gy in six patients with daily dose of 500 cGy 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 25 Gy 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.
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Mattiucci
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: rosa_autorino@yahoo.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Autorino
authors.affiliation: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tringali
authors.affiliation: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Perri
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Balducci
authors.affiliation: Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Gambacorta
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantini
authors.affiliation: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tagliaferri
authors.affiliation: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mutignani
authors.affiliation: Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.
authors.forename: Alessio Giuseppe
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D017734:Bile Ducts, Extrahepatic; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D007496:Iridium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D015996:Survival Rate
chemical_list: D007496:Iridium Radioisotopes
keywords: Brachytherapy; Colangiocarcinoma; Endoscopy; Metal stents; Neoplasm