Relative Biological Effectiveness of 290 MeV/u Carbon Ions for the Growth Delay of a Radioresistant Murine Fibrosarcoma

Abstract

The relative biological effectiveness (RBE) for animal tumors treated with fractionated doses of 290 MeV/u carbon ions was studied. The growth delay of NFSa fibrosarcoma in mice was investigated following various daily doses given with carbon ions or those given with cesium gamma-rays, and the RBE was determined. Animal tumors were irradiated with carbon ions of various LET (linear energy transfer) in a 6-cm SOBP (spread-out Bragg peak), and the isoeffect doses; i.e. the dose necessary to induce a tumor growth delay of 15 days were studied. The iso-effect dose for carbon ions of 14 and 20 keV/microm increased with an increase in the number of fractions up to 4 fractions. The increase in the isoeffect dose with the fraction number was small for carbon ions of 44 keV/microm, and was not observed for 74 keV/microm. The alpha and beta values of the linear-quadratic model for the radiation dose-cell survival relationship were calculated by the Fe-plot analysis method. The alpha values increased linearly with an increase in the LET, while the beta values were independent of the LET. The alpha/beta ratio was 129 +/- 10 Gy for gamma-rays, and increased with an increase in the LET, reaching 475 +/- 168 Gy for 74 keV/microm carbon ions. The RBE for carbon ions relative to Cs-137 gamma-rays increased with the LET. The RBE values for 14 and 20 keV/microm carbon ions were 1.4 and independent of the number of fractions, while those for 44 and 74 keV/microm increased from 1.8 to 2.3 and from 2.4 to 3.0, respectively, when the number of fractions increased from 1 to 4. Increasing the number of fractions further from 4 to 6 was not associated with an increase in the RBE. These results together with our earlier study on the skin reaction support the use of an RBE of 3.0 in clinical trials of 80 keV/microm carbon beams. The RBE values for low doses of carbon beams were also considered.

Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays

“…This finding is in agreement with a previous report that heavy-ion irradiation inhibits in vitro angiogenesis (29). Several previous studies reported that the in vivo RBE values for high LET carbon-ion beams ranged from 2.0 to 3.1 (30,31). In the present study, the in vivo RBE was calculated as 3.05 to 3.25 from the slope of the dose-response curve for tumor growth suppression by carbon ions relative to X-rays, which is almost in line with previous reports (30,31).…”

“…Several previous studies reported that the in vivo RBE values for high LET carbon-ion beams ranged from 2.0 to 3.1 (30,31). In the present study, the in vivo RBE was calculated as 3.05 to 3.25 from the slope of the dose-response curve for tumor growth suppression by carbon ions relative to X-rays, which is almost in line with previous reports (30,31). It is known that RBE is a complex quantity, depending on many factors such as particle type, dose per fraction, and LET, as well as on biological factors like cell or tissue type and the selected biological endpoint.…”

“…Cells were irradiated with 2, 4, 6, or 8 Gy of X-rays or 1, 2, 4, or 6 Gy carbon ions. Transplanted xenograft tumors were irradiated with various doses of X-rays (15,30, and 60 Gy) or carbon-ions (5, 15, and 30 Gy).…”

Change in fibroblast growth factor 2 expression as an early phase radiotherapy‐responsive marker in sequential biopsy samples from patients with cervical cancer during fractionated radiotherapy

“…The difference between the tumor growth time for the treatment group and for a nonirradiated control group was defined as the tumor growth delay. 36 Tumor growth delay induced by radiation treatment was used as a parameter to measure treatment effect.…”

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness

“…It is assumed that the RBE systematics found for in vitro and in vivo also remain true for clinical data, thus permitting the use of these estimates as surrogate of the 'clinical RBE' to predict the clinical treatment outcome. Following the linear-quadratic (LQ) formalism, the initial RBE (α/α X ) after ion beam irradiation mainly depends on the α X /β X ratio for the reference radiation (Koike et al 2002, Friedrich et al 2012b. The reduction of the required input information to the α X /β X ratios also increases the range of applicability, since this ratio is known for many tumor and normal tissues.…”