Purpose: We have previously reported that RBE values of carbon-ion beams for skin reaction and tumors increases with an increase of fractionation in a different way so that therapeutic gain is maximally obtained at around 4 fractions. Purpose of present study is to compare survivals of crypts and tumor cells after multiple 1 Gy per fraction followed by top-up doses. Materials and Methods: C3H male and female mice at age 8-12 week old were used. NFSa fibrosarcoma was subcutaneously transplanted to ventral skin of male mice 10 days before irradiation. Carbon ions with 290 MeV/u were accelerated by HIMAC synchrotron, and LET of 20 keV/micrometer at entrance plateau of a Spread-Out Bragg peak (6 cm width) was used. Mice were immobilized by placing in Lucite holders without anesthesia, and received horizontal beams every 4 hr. Tumors were removed shortly after final irradiation, and preceded to single cell preparation. Cell suspensions were intravenously injected to recipient mice that were pretreated with cyclophosphamide, and lung colony assay was conducted. Jejunum of female mice was removed 3.5 days after final irradiation and served for histology preparation. Results: Survival curves for crypts and tumor cells were obtained after single doses, 1 Gy x 5 fractions plus top-up doses and 1 Gy x 11 fractions plus top-up doses. The NFSa tumor showed biphasic curves after single doses, suggesting oxic and hypoxic cells included. Slopes of survival curves fit by single hit model were not significantly different between single doses and fractionated doses, even though single doses showed a lightly shallower curve than the fractionated doses. Crypt survivals plot against total doses clearly shifted to the right after fractionated doses: 1 Gy x 5 fractions moved survival curves parallel to single doses while 1 Gy x 11 fraction not only moved further to the right but also showed a shallower slopes that either single or 1 Gy x 5 fractions. Conclusion: Repair of damage caused by 1 Gy of low-LET carbon ions was different between the NFSa tumor and gut crypts. Therapeutic gain was apparently larger for 11 fractions than 5 fractions.
Koichi Ando1, Sachiko Koike2, Akiko Uzawa3, Ryoichi Hirayama2, Yoshitaka Matsumoto3, Yoshiya Furusawa3, Nobuhiko Takai4, Takeshi Fukawa5, Yukari Yoshida1, 1Gunma University, Maebashi, Japan, 2Natl Inst.Radiol.Sci., Chiba, Japan, 3Natl.Inst.Radiol.Sci., Chiba, Japan, 4Nagasaki International University, Sasebo, Japan, 5Josai International University, Togane, Japan
