title: Radiochemotherapy with Gemcitabine in Unresectable Extrahepatic Cholangiocarcinoma: Long-term Results of a Phase II Study.
abstract: OBJECTIVE
  To evaluate the outcome of patients affected by unresectable extrahepatic cholangiocarcinoma treated with radiotherapy (ERT) and concurrent gemcitabine-based chemotherapy with or without intraluminal brachytherapy (BT).
  
  
  METHODS
  Twenty-seven patients underwent weekly gemcitabine (100 mg/m(2)) as a 24-h infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor and 39.6 Gy to the nodes). Among them, certain patients received a boost of intraluminal high-dose rate (HDR) brachytherapy with 192 Ir. The outcome of patients was evaluated in terms of response to therapy, local control (LC), overall survival (OS) and toxicity.
  
  
  RESULTS
  We analyzed a total of 27 patients with the diagnosis of unresectable, non-metastatic adenocarcinoma of the extrahepatic biliary ducts, treated with radiochemotherapy with gemcitabine. After a dose of 50 Gy, a boost of HDR intraluminal brachytherapy was administered in 6 patients (22%): 4 patients received 15 Gy and 2 patients 20 Gy. With a median follow-up of 16 months (range=3-52 months), for the entire group, 2-year LC was 29% (median=12 months), 2-year MFS was 36% (median 16 months). Two-year and three-year OS were 27% and 7% respectively, with a median of 14 months. Toxicities were acceptable. Median OS in patients treated with brachytherapy boost was 21 months versus 14 months for the group treated with gemcitabine-based radiochemotherapy only; 2-year LC was 53% versus 25%, respectively.
  
  
  CONCLUSIONS
  Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it shows encouraging tumor response. Moreover, patients treated with a boost of brachytherapy after radiochemotherapy seem to have a better local control with an acceptable toxicity. Further investigation is warranted to confirm these data and define the optimal combined treatments.
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Rosa
authors: R
authors: Autorino
authors: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy gcmattiucci@gmail.com.
authors: Gian Carlo
authors: GC
authors: Mattiucci
authors: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors: Francesco
authors: F
authors: Ardito
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Mario
authors: M
authors: Balducci
authors: Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.
authors: Francesco
authors: F
authors: Deodato
authors: Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.
authors: Gabriella
authors: G
authors: Macchia
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Giovanna
authors: G
authors: Mantini
authors: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors: Vincenzo
authors: V
authors: Perri
authors: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors: Andrea
authors: A
authors: Tringali
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Maria Antonietta
authors: MA
authors: Gambacorta
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Luca
authors: L
authors: Tagliaferri
authors: Digestive Endoscopy Unit, Department of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
authors: Felice
authors: F
authors: Giuliante
authors: Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.
authors: Alessio Giuseppe
authors: AG
authors: Morganti
authors: Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Vincenzo
authors: V
authors: Valentini
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D001918:Brachytherapy / Q000009:adverse effects / Q000401:mortality; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D018281:Cholangiocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Cholangiocarcinoma; gemcitabine; radiotherapy