Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model

Abstract

BackgroundTo determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations.Material and methodsThe rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV).ResultsAt six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range.ConclusionsThis study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.

Carbon Ion Radiobiology

“…The RBE drop at high dose/fraction in Figure 9 has been confirmed by clinical data in lung cancer patients [ 98 ] and in several animal experiments on rat spinal cord [ 99 , 100 , 101 , 102 , 103 , 104 ], with a more significant fractionation effect in the entrance channel than in the SOBP, consistent with the LET dependence of the sparing effect ( Figure 2 ). Acute skin reactions in mice-bearing tumors also support the RBE variation shown in Figure 9 , i.e., higher RBE in tumor control than for skin reaction is observed in hypofractionation [ 105 ].…”

Carbon Ion Radiobiology

“…The RBE drop at high dose/fraction in Figure 9 has been confirmed in several animal experiments on rat spinal cord [96][97][98][99][100][101], with a more significant fractionation effect in the entrance channel than in the SOBP, consistent with the LET dependence of the sparing effect ( Figure 2). Acute skin reaction in mice-bearing tumor also support the RBE variation shown in Figure 9, i.e.…”

Characterizing Radiation Effectiveness in Ion Beam Therapy Part I: Introduction and Biophysical Modeling of RBE Using the LEMIV

“…LEM IV has been demonstrated to accurately represent experimental data in-vitro over a larger range of different ion species from protons to oxygen ions [22,[31][32][33]. Furthermore, besides in-vitro experiments also RBE for in-vivo experiments, e.g., the tolerance of the rat spinal cord, can be modeled with LEM IV [34,35]. Interestingly, the concept of damage classification that has been developed for the LEM IV has been shown to be applicable also to other radiation qualities, and several key aspects like LQ-shape of survival curves, rejoining kinetics, dose rate effects and cell cycle effects are consistently modeled by this approach [36][37][38].…”