Abstract
BackgroundHelium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons. Despite these biophysical advantages, raster-scanning 4He ion therapy remains poorly explored e.g., clinical translational is hampered by the lack of reliable and robust estimation of physical and radiobiological uncertainties. Therefore, prior to the upcoming 4He ion therapy program at the Heidelberg Ion-beam Therapy Center (HIT), we aimed to characterize the biophysical phenomena of 4He ion beams and various aspects of the associated models for clinical integration.MethodsCharacterization of biological effect for 4He ion beams was performed in both homogenous and patient-like treatment scenarios using innovative models for estimation of relative biological effectiveness (RBE) in silico and their experimental validation using clonogenic cell survival as the gold-standard surrogate. Towards translation of RBE models in patients, the first GPU-based treatment planning system (non-commercial) for raster-scanning 4He ion beams was devised in-house (FRoG).ResultsOur data indicate clinically relevant uncertainty of ±5–10% across different model simulations, highlighting their distinct biological and computational methodologies. The in vitro surrogate for highly radio-resistant tissues presented large RBE variability and uncertainty within the clinical dose range.ConclusionsExisting phenomenological and mechanistic/biophysical models were successfully integrated and validated in both Monte Carlo and GPU-accelerated analytical platforms against in vitro experiments, and tested using pristine peaks and clinical fields in highly radio-resistant tissues where models exhibit the greatest RBE uncertainty. Together, these efforts mark an important step towards clinical translation of raster-scanning 4He ion beam therapy to the clinic.
Highlights
Helium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons
For Rβ, we have introduced an linear energy transfer (LET)-dependent parameterization fitting the running averages of Rβ as function of LET:
For quantification of global difference in the target between the various models, equivalent uniform dose (EUD) calculations for the spread-out Bragg peak (SOBP) studied in silico are provided in Additional file 1: Table S2 and S3
Summary
Helium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons Despite these biophysical advantages, raster-scanning 4He ion therapy remains poorly explored e.g., clinical translational is hampered by the lack of reliable and robust estimation of physical and radiobiological uncertainties. Application of helium ions provides a distinct clinical advantage, i.e. favorable dose distributions with attributes such as a sharper Bragg peak and lateral penumbra (reduced range straggling and scattering) compared to protons, and similar potential for tumor control with a substantially reduced fragmentation tail compared to carbons ions [3, 4] With these characteristics, helium ions have been proposed as an ideal treatment option for radio-resistant diseases and delicate patient cases e.g. meningioma and pediatrics [5, 6]
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