Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

Christin Glowa; Maria Saager; Lisa Hintz; Rosemarie Euler-Lange; Peter Peschke; Stephan Brons; Michael Scholz; Stewart Mein; Andrea Mairani; Christian P Karger

doi:10.1016/j.phro.2024.100581

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

Phys Imaging Radiat Oncol. 2024 Apr 20:30:100581. doi: 10.1016/j.phro.2024.100581. eCollection 2024 Apr.

Authors

Christin Glowa^{1

2

3}, Maria Saager^{1

2}, Lisa Hintz^{1

2

4}, Rosemarie Euler-Lange^{1

2

5}, Peter Peschke^{1

2}, Stephan Brons^{2

6}, Michael Scholz⁷, Stewart Mein^{2

6

8}, Andrea Mairani^{2

6

9}, Christian P Karger^{1

2}

Affiliations

¹ Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
³ Department of Radiation Oncology and Radiotherapy, University Hospital Heidelberg, Germany.
⁴ Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
⁵ Department of Radiooncology/Radiobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.
⁷ Department of Biophysics, Helmholtz Center for Heavy Ion Research (GSI), Darmstadt, Germany.
⁸ Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹ National Centre of Oncological Hadrontherapy (CNAO), Medical Physics, Pavia, Italy.

Abstract

Background and purpose: Ion beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord.

Materials and methods: The spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses. Dose-response curves were established for the endpoint paresis grade II and based on ED₅₀ (dose at 50 % effect probability), the RBE was determined and compared to model predictions.

Results: When LET increased from 26 to 98 keV/µm, ED₅₀ decreased from 17.2 ± 0.3 Gy to 13.5 ± 0.4 Gy for single and from 21.7 ± 0.4 Gy to 15.5 ± 0.5 Gy for split doses, however, at 141 keV/µm, ED₅₀ rose again to 15.8 ± 0.4 Gy and 17.2 ± 0.4 Gy, respectively. As a result, the RBE increased from 1.43 ± 0.05 to 1.82 ± 0.08 (single dose) and from 1.58 ± 0.04 to 2.21 ± 0.08 (split dose), respectively, before declining again to 1.56 ± 0.06 for single and 1.99 ± 0.06 for split doses at the highest LET. Deviations from RBE-predictions were model-dependent.

Conclusion: This study established first RBE data for the late reacting central nervous system after single and split doses of oxygen ions. The data was used to validate the RBE-dependence on LET and dose of three RBE-models. This study extends the existing data base for protons, helium and carbon ions and provides important information for future patient treatments with oxygen ions.

Keywords: Late normal tissue effects; Linear energy transfer (LET); Local effect model (LEM); Modified microdosimetric kinetic model (mMKM); Myelopathy; Oxygen ion radiotherapy; Rat spinal cord; Relative biological effectiveness (RBE).