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Mitigating Radiotoxicity in the Central Nervous System: Role of Proton Therapy

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Opinion statement

Central nervous system (CNS) radiotoxicity remains a challenge in neuro-oncology. Dose distribution advantages of protons over photons have prompted increased use of brain-directed proton therapy. While well-recognized among pediatric populations, the benefit of proton therapy among adults with CNS malignancies remains controversial. We herein discuss the role of protons in mitigating late CNS radiotoxicities in adult patients. Despite limited clinical trials, evidence suggests toxicity profile advantages of protons over conventional radiotherapy, including retention of neurocognitive function and brain volume. Modelling studies predict superior dose conformality of protons versus state-of-the-art photon techniques reduces late radiogenic vasculopathies, endocrinopathies, and malignancies. Conversely, potentially higher brain tissue necrosis rates following proton therapy highlight a need to resolve uncertainties surrounding the impact of variable biological effectiveness of protons on dose distribution. Clinical trials comparing best photon and particle-based therapy are underway to establish whether protons substantially improve long-term treatment-related outcomes in adults with CNS malignancies.

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Funding

S.F.W. and F.E. are participants in the BIH Charité Junior Clinician Scientist Program funded by the Charité -Universitätsmedizin Berlin and the Berlin Institute of Health at Charité (BIH). E.J.V. is funded by an NIH/NCI R38 Award (1R38CA245204) at the Duke Cancer Institute. M.E. received funding from DFG under Germany´s Excellence Strategy – EXC-2049 – 390688087, Collaborative Research Center ReTune TRR 295-424778381, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq. J.D. received funding from the American Cancer Society, American Academy of Neurology, the Amy Gallagher foundation, and the Derrick Wong Family foundation.

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Authors and Affiliations

  1. Department of Neurology and MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Sebastian F. Winter MD, PhD & Jorg Dietrich MD, PhD

  2. Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany

    Sebastian F. Winter MD, PhD, Wolfgang Boehmerle MD & Matthias Endres MD

  3. Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, 10117, Berlin, Germany

    Sebastian F. Winter MD, PhD & Felix Ehret MD

  4. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    Eugene J. Vaios MD, MBA

  5. Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Helen A. Shih MD, MS, MPH & Clemens Grassberger PhD

  6. Department of Psychiatry, Psychology Assessment Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Michael W. Parsons PhD & Melissa M. Gardner MA

  7. Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353, Berlin, Germany

    Felix Ehret MD & David Kaul MD

  8. Charité – Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Felix Ehret MD & David Kaul MD

  9. Center for Stroke Research Berlin, Berlin, Germany

    Matthias Endres MD

  10. ExcellenceCluster NeuroCure, Berlin, Germany

    Matthias Endres MD

  11. German Center for Neurodegenerative Diseases (DZNE), partner site Berlin, Berlin, Germany

    Matthias Endres MD

  12. German Centre for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany

    Matthias Endres MD

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S.F.W. and J.D. conceptualized and designed the paper. S.F.W. and E.J.V. performed the literature research and wrote the first draft. All authors critically revised previous versions and approved the final version of this manuscript.

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Correspondence to Sebastian F. Winter MD, PhD.

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Winter, S.F., Vaios, E.J., Shih, H.A. et al. Mitigating Radiotoxicity in the Central Nervous System: Role of Proton Therapy. Curr. Treat. Options in Oncol. 24, 1524–1549 (2023). https://doi.org/10.1007/s11864-023-01131-x

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  • DOI: https://doi.org/10.1007/s11864-023-01131-x

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