title: Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using the tumor growth delay and crypt survival assays.
abstract: OBJECTIVE
  The aim of the study was to evaluate the therapeutic gain of carbon ion (C-ion) radiotherapy using a mouse model.
  
  
  METHODS
  Transplanted fibrosarcoma (NFSa) growing in C3H/He mice and murine small intestine were irradiated with 290 MeV/nucleon C-ion beams (C-ions) in 1-12 fractions separated by 4h. The cell killing efficiencies of C-ions were measured using jejunum crypt survival and tumor growth delay (TGD) assays.
  
  
  RESULTS
  The equieffect dose for crypt survival and TGD increased with increasing number of fractions after X-rays and 20 keV/μm C-ions, whereas TGD after 77 keV/μm C-ions rather decreased. Crypts showed stronger LET-dependent increase in α terms than the tumor while β terms less depended on LET irrespective of tissues. Therapeutic gain factor, i.e., a ratio of tumor RBE over crypt RBE, of 77 keV/μm C-ions was more than unity at any doses while that of 20 keV/μm C-ions increased with an increase in dose per fraction.
  
  
  CONCLUSIONS
  These specific data imply that use of large dose per fraction would be suitable for C-ion radiotherapy irrespective of LET from the point of view of therapeutic gain, though small dose per fraction by high-LET radiation decreases total dose for tumor.
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Japan. Electronic address: yyukari@gunma-u.ac.jp.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshimoto
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Musha
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Kawamura
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Koike
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Uzawa
authors.affiliation: Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Japan; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D005354:Fibrosarcoma / Q000532:radiotherapy*; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D007414:Intestinal Neoplasms / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Carbon-ion beam; Crypt; Fraction; RBE; Survival parameters; Tumor growth delay