Cell biological basis for combination radiotherapy using carbon-beam and photon

Purpose: Carbon-beam therapy is a promising cancer treatment with superb biological effects and excellent dose distribution. Efficacy of carbon-beam therapy has been shown in the clinical trials. A combined therapy of carbon-beam and photon may be a more useful strategy with photon for clinical target volume and with carbon-beam for gross tumor volume. The aim of this study is to clarify whether these different LET radiations can act simple additive way when the doses are expressed with GyE (Gray equivalent) unit and to assess that this combination could be a promising strategy. Materials and Methods: A 290-MeV/nucleon carbon-beam with 6 cm spread-out Bragg peak (SOBP) and a 60Co gamma-ray were used. Cultured cells from human salivary gland cancer (HSG cells) in logarithmic growth seeded on 25 cm2 plastic flasks were irradiated with a single source of carbon-beam or gamma-ray, or with a combination (carbon-beam followed by gamma-ray, or gamma-ray followed by carbon-beam). Fraction intervals were set for 0.5, 1.5, 3, 6, and 24 hours to observe the influence of damage repair. Cell survivals were assessed by clonogenic assay and survival curves were fitted by using linear-quadratic (LQ) model. Effects of combining carbon-beam and gamma-ray were predicted by the method built on the ideas of Zaider and Rossi (1980). Results: In all fraction interval conditions, survival curves for cells irradiated with carbon-beam showed the steepest curves with the smallest shoulders, gamma-ray-irradiated cells showed the gentlest curves, and combined-beam-irradiated cells showed intermediate curves. The difference of cell survival in the irradiation sequence of carbon-ion and gamma-ray was not significant. No influence of damage repair on the shapes of survival curves was observed. The analyses of prediction of combined-beam effect showed that there was no synergistic interaction between carbon-beam and gamma-ray, and they acted additively without regard to fraction interval. This means the effect of combining them is described by a simple addition of gamma-ray dose and carbon-beam dose based on biological equivalent dose (GyE). Conclusions: A combination of carbon-beam and gamma-ray acts additively regardless of fraction interval in vitro. When we employ GyE as the indication of therapeutic dose, the effects can be explained with simple additive way in the treatment plan.ASTRO\u27s 46th Annual Meetin