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Biophysical modeling and experimental validation of relative biological effectiveness (RBE) for 4He ion beam therapy

Mein, Stewart ; Dokic, Ivana ; Klein, Carmen ; Tessonnier, Thomas ; Böhlen, Till Tobias ; Magro, Guiseppe ; Bauer, Julia ; Ferrari, Alfredo ; Parodi, Katia ; Haberer, Thomas ; Debus, Jürgen ; Abdollahi, Amir ; Mairani, Andrea

In: Radiation Oncology, 14 (2019), Nr. 123. pp. 1-16. ISSN 1748-717X

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Download (4MB) | Lizenz: Creative Commons LizenzvertragBiophysical modeling and experimental validation of relative biological effectiveness (RBE) for 4He ion beam therapy by Mein, Stewart ; Dokic, Ivana ; Klein, Carmen ; Tessonnier, Thomas ; Böhlen, Till Tobias ; Magro, Guiseppe ; Bauer, Julia ; Ferrari, Alfredo ; Parodi, Katia ; Haberer, Thomas ; Debus, Jürgen ; Abdollahi, Amir ; Mairani, Andrea underlies the terms of Creative Commons Attribution 4.0

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Abstract

Background: 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. 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.

Methods: Characterization 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).

Results: Our 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.

Conclusions: Existing 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.

Item Type: Article
Journal or Publication Title: Radiation Oncology
Volume: 14
Number: 123
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 13 Aug 2019 10:41
Date: 2019
ISSN: 1748-717X
Page Range: pp. 1-16
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Medizinische Fakultät Heidelberg > Heidelberg Ion-Beam Therapy Center (HIT)
Subjects: 610 Medical sciences Medicine
Uncontrolled Keywords: Particle therapy, Helium ions, Relative biological effectiveness, Translational research
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