Biological dose representation for carbon-ion radiotherapy of unconventional fractionation

In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been common practice for effcient operation, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. Treatments are usually fractionated and treatment plans are evaluated with the total RBE-weighted dose; however, this is of limited relevance to the biological effect. In this study, we reformulate the biologically effective dose (BED) to normalize the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a reference cell line by a reference carbon-ion radiation. The BED distribution virtually represents the biological effect of a treatment regardless of radiation modality or fractionation scheme. We applied the BED formulation to simplistic model treatments and to a preclinical survey for hypofractionation based on an actual prostate cancer treatment with carbon ions. The proposed formulation was demonstrated to be practical and to give theoretical implications. For a prostate cancer treatment in 12 fractions, the distributions of BED and of RBE-weighted dose were very similar. With hypofractionation, while the RBE-weighted dose distribution varied signifcantly, the BED distribution was nearly invariant, implying that carbon-ion radiotherapy would be effectively insensitive to fractionation. However, treatment evaluation with such a simplistic biological dose is intrinsically limited and must be complemented in practice by clinical experience and biological experiments

Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams

Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction.Methods: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction.Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone.Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user\u27s specific system

Modeling of body tissues for Monte Carlo simulation of radiotherapy treatments planned with conventional x-ray CT systems

In the conventional procedure for accurate Monte Carlo simulation of radiotherapy, a CT number given to each pixel of a patient image is directly converted to mass density and elemental composition using their respective functions that have been calibrated speci cally for the relevant x-ray CT system. We propose an alternative approach that is a conversion in two steps: the rst from CT number to density and the second from density to composition. Based on the latest compilation of standard tissues for reference adult male and female phantoms, we sorted the standard tissues into groups by mass density and de ned the representative tissues by averaging the material properties per group. With these representative tissues, we formulated polyline relations between mass density and each of the following; electron density, stopping-power ratio and elemental densities. We also revised a procedure of stoichiometric calibration for CT-number conversion and demonstrated the two-step conversion method for a theoretically emulated CT system with hypothetical 80 keV photons. For the standard tissues, high correlation was generally observed between mass density and the other densities excluding those of C and O for the light spongiosa tissues between 1.0 g cm−3 and 1.1 g cm−3 occupying 1% of the human body mass. The polylines tted to the dominant tissues were generally consistent with similar formulations in the literature. The two-step conversion procedure was demonstrated to be practical and will potentially facilitate Monte Carlo simulation for treatment planning and for retrospective analysis of treatment plans with little impact on the management of planning CT systems

Predicting the Biological Effects of Human Salivary Gland Tumour Cells for Scanned 4He-, 12C-, 16O-, and 20Ne-Ion Beams Using an SOI Microdosimeter

Experimental microdosimetry along with the microdosimetric kinetic (MK) model can be utilized to predict the biological effects of ions. To predict the relative biological effectiveness (RBE) of ions and the survival fraction (SF) of human salivary gland tumour (HSGc-C5) cells, microdosimetric quantities measured by a silicon-on-insulator (SOI) MicroPlus-mushroom microdosimeter along the spread-out Bragg peak (SOBP) delivered by pencil beam scanning of 4He, 12C, 16O, and 20Ne ions were used. The MK model parameters of HSGc-C5 cells were obtained from the best fit of the calculated SF for the different linear energy transfer (LET) of these ions and the formerly reported in vitro SF for the same LET and ions used for calculations. For a cube-shaped target of 10 × 10 × 6 cm3, treatment plans for 4He, 12C, 16O, and 20Ne ions were produced with proprietary treatment planning software (TPS) aiming for 10% SF of HSGc-C5 cells over the target volume and were delivered to a polymethyl methacrylate (PMMA) phantom. Afterwards, the saturation-corrected dose-mean lineal energy derived based on the measured microdosimetry spectra, along with the physical dose at various depths in PMMA phantoms, was used for the estimation of the SF, RBE, and RBE-weighted dose using the MK model. The predicted SF, RBE, and the RBE-weighted dose agreed with what was planned by the TPS within 3% at most depths for these ions.publishedVersio

Effects of loading a magnetic field longitudinal to the linear particle-beam track on yields of reactive oxygen species in water

The effects of a magnetic field longitudinal to the ion beam track on the generation of hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) in water were investigated. A longitudinal magnetic field was reported to enhance the biological effects of the ion beam. However, the mechanism of the increased cell death by a longitudinal magnetic field has not been clarified. The local density of •OH generation was estimated by a method based on the EPR spin-trapping. A series of reaction mixtures containing varying concentrations (0.76‒2278 mM) of DMPO was irradiated by 16 Gy of carbon- or iron-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan) with or without a longitudinal magnetic field (0.0, 0.3, or 0.6 T). The DMPO-OH yield in the sample solutions was measured by X-band EPR and plotted versus DMPO density. O2-dependent and O2-independent H2O2 yields were measured. An aliquot of ultra-pure water was irradiated by carbon-ion beams with or without a longitudinal magnetic field. Irradiation experiments were performed under air or hypoxic conditions. H2O2 generation in irradiated water samples was quantified by an EPR spin-trapping, which measures •OH synthesized from H2O2 by UVB irradiation. Relatively sparse •OH generation caused by particle beams in water were not affected by loading a magnetic field on the beam track. O2-dependent H2O2 generation decreased and oxygen-independent H2O2 generation increased after loading a magnetic field parallel to the beam track. Loading a magnetic field to the beam track made •OH generation denser or made dense •OH more reactive