Unique brain injury patterns after proton vs photon radiotherapy for WHO grade 2-3 gliomas

Sebastian F Winter; Melissa M Gardner; Philipp Karschnia; Eugene J Vaios; Clemens Grassberger; Marc R Bussière; Katarina Nikolic; Thanakit Pongpitakmetha; Felix Ehret; David Kaul; Wolfgang Boehmerle; Matthias Endres; Helen A Shih; Michael W Parsons; Jorg Dietrich

doi:10.1093/oncolo/oyae195

Unique brain injury patterns after proton vs photon radiotherapy for WHO grade 2-3 gliomas

Oncologist. 2024 Aug 10:oyae195. doi: 10.1093/oncolo/oyae195. Online ahead of print.

Authors

Sebastian F Winter^{1

2

3}, Melissa M Gardner^{1

4}, Philipp Karschnia^{1

5}, Eugene J Vaios⁶, Clemens Grassberger⁷, Marc R Bussière⁷, Katarina Nikolic⁸, Thanakit Pongpitakmetha^{9

10}, Felix Ehret^{7

11

12}, David Kaul^{11

12}, Wolfgang Boehmerle², Matthias Endres^{2

13

14

15

16

17}, Helen A Shih^{1

7}, Michael W Parsons^{1

4}, Jorg Dietrich¹

Affiliations

¹ Division of Neuro-Oncology, Mass General Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
² Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
³ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, 10117 Berlin, Germany.
⁴ Department of Psychiatry, Psychology Assessment Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
⁵ Department of Neurosurgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.
⁶ Department of Radiation Oncology, Duke Cancer Institute, Durham, NC 27710, United States.
⁷ Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
⁸ Department of Neurology, Universitätsklinikum St. Pölten, 3100 Sankt Pölten, Austria.
⁹ Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, 10330 Bangkok, Thailand.
¹⁰ Chula Neuroscience Center, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, 10330 Bangkok, Thailand.
¹¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, 13353 Berlin, Germany.
¹² German Cancer Consortium (DKTK), Partner Site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
¹³ Center for Stroke Research Berlin, 10117 Berlin, Germany.
¹⁴ ExcellenceCluster NeuroCure, 10117 Berlin, Germany.
¹⁵ German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, 10117 Berlin, Germany.
¹⁶ German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10117 Berlin, Germany.
¹⁷ German Centre for Mental Health (DZPH), Partner Site Berlin, 10117 Berlin, Germany.

PMID: 39126664
DOI: 10.1093/oncolo/oyae195

Abstract

Background: Central nervous system (CNS) injury following brain-directed radiotherapy remains a major challenge. Proton radiotherapy (PRT) minimizes radiation to healthy brain, potentially limiting sequelae. We characterized CNS radiotoxicity, including radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), in glioma patients treated with PRT or photons (XRT).

Patients and methods: Thirty-four patients (19 male; median age 39.6 years) with WHO grade 2-3 gliomas treated with partial cranial radiotherapy (XRT [n = 17] vs PRT[n = 17]) were identified and matched by demographic/clinical criteria. Radiotoxicity was assessed longitudinally for 3 years post-radiotherapy via serial analysis of T2/FLAIR- (for RIL), contrast-enhanced T1- (for TN), and susceptibility (for CMB)-weighted MRI sequences. RIL was rated at whole-brain and hemispheric levels using a novel Fazekas scale-informed scoring system.

Results: The scoring system proved reliable (ICC > 0.85). Both groups developed moderate-to-severe RIL (62%[XRT]; 71%[PRT]) within 3 years; however, XRT was associated with persistent RIL increases in the contralesional hemisphere, whereas contralesional hemispheric RIL plateaued with PRT at 1-year post-radiotherapy (t = 2.180; P = .037). TN rates were greater with PRT (6%[XRT] vs 18%[PRT]; P = ns). CMB prevalence (76%[XRT]; 71%[PRT]) and burden (mean #CMB: 4.0[XRT]; 4.2[PRT]) were similar; however, XRT correlated with greater contralesional hemispheric CMB burden (27%[XRT]; 17%[PRT]; X2 = 4.986; P = .026), whereas PRT-specific CMB clustered at the radiation field margin (X2 = 14.7; P = .002).

Conclusions: CNS radiotoxicity is common and progressive in glioma patients. Injury patterns suggest radiation modality-specificity as RIL, TN, and CMB exhibit unique spatiotemporal differences following XRT vs PRT, likely reflecting underlying dosimetric and radiobiological differences. Familiarity with such injury patterns is essential to improve patient management. Prospective studies are needed to validate these findings and assess their impacts on neurocognitive function.

Keywords: complications; glioma; neurotoxicity; protons; radiation injury.

Abstract

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