title: Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer.
abstract: OBJECTIVE
  To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival.
  
  
  METHODS
  Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m(2) under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined.
  
  
  RESULTS
  Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m(2). The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m(2)) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively.
  
  
  CONCLUSIONS
  Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.
authors.affiliation: Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: shinoto@saga-himat.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shinoto
authors.affiliation: Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Terashima
authors.affiliation: Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shioyama
authors.affiliation: Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honda
authors.affiliation: Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kamada
authors.affiliation: Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Tsujii
authors.affiliation: Department of Internal Medicine and Clinical Oncology, Kaken Hospital, Chemotherapy Research Institute, Chiba, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saisho
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine