Preservation of Neurocognition after Proton Beam Radiation Therapy for Intracranial Tumors: First Results from REGI-MA-002015.

PURPOSE: Proton beam radiation therapy reduces dose to healthy brain tissue and thereby decreases the risk of treatment-related decline in neurocognition. Considering the paucity of prospective data, this study aimed to evaluate neurocognitive performance in an adult patient population with intracranial tumors. METHODS AND MATERIALS: Between 2017 and 2021, patients enrolled in the MedAustron registry study and irradiated for intracranial tumors were eligible for neurocognitive assessment. Patients with available 1-year follow-up data were included in the analysis. The test battery consisted of a variety of standardized tests commonly used in European Organization for Research and Treatment of Cancer trials. Scores were transformed into z scores to account for demographic effects, and clinically relevant change was defined as a change of ≥1.5 standard deviations. Binary logistic regression analysis and the χ2 test were conducted for clinical parameters and dosimetric hippocampal parameters to evaluate the relationship with overall cognitive decline and changes in memory. RESULTS: One hundred twenty-three patients with mostly nonprogressive, extra-axial tumors and neurocognitive assessment at baseline and treatment end as well as 3, 6, and 12 months after completion of proton beam radiation therapy were analyzed. Overall, 7 test scores revealed stability in neurocognitive function with minimal positive changes 1 year after treatment completion (statistically significant in 6 of 7 tests), whereas the majority had no or minimal baseline deficits. At 1-year follow-up, 89.4% of all patients remained stable in their overall cognitive functioning without clinically relevant deterioration in 2 or more tests. None of them showed disease progression. Of the patients, 8.1% presented with radiation-induced brain lesions and exhibited a higher percentage of overall cognitive deterioration without reaching statistical significance. Multivariate binary logistic regression analysis revealed higher age at baseline as the only independent parameter to be associated with an overall clinically relevant cognitive decline. There was no significant correlation of hippocampal doses and memory functioning. CONCLUSIONS: One year after proton therapy, we observed preservation of cognitive functioning in the vast majority of our patients with intracranial tumors.

Meningioma WHO I with involvement of the optical structures-does proton therapy lead to changes in quality of life with regard to subjective visual performance?

BACKGROUND: In addition to local tumor control, the aim of any curative radio-oncological treatment is to maintain quality of life. In the treatment of patients with meningioma with a close relationship to optical structures, the preservation of visual performance is a particular challenge. Use of proton therapy can reduce the dose burden to organs at risk immediately adjacent to the tumor. The aim of this study was to score the subjective assessment of visual performance in patients with meningioma involving the optical structures before and after proton therapy. METHODS: All proton-treated patients with meningioma WHO I whose planning target volumes (PTV) included parts of the optic nerve and/or chiasm were included in this study. Subjective assessment of visual performance was evaluated using the Visual Disorder Scale (VDS) of the EORTC QLQ-BN20 questionnaire. This scale includes values from 0 to 100, whereby high values reflect a high degree of subjective symptom burden and thus subjective visual impairment. The visual acuity in externally performed eye tests at baseline and follow-ups (FU) was also evaluated. The timepoints for testing were before the start of radiotherapy, at the end of treatment, and 3, 6, 12, and 24 months in FU (times t1-t6). All patients with at least the first annual postradiation FU at the time of the evaluation were included. The correlation between VDS changes and potential influencing factors such as previous therapies, dosimetric data, initial tumor volume, and tumor shrinkage 1 year after treatment was assessed. RESULTS: A total of 56 patients (45 female/11 male) aged 24-82 years (mean ± SD = 53.9 ± 13.3) treated between March 2017 and September 2019 were included in the analysis. The prescription dose was 54.0 Gy (RBE) with active scanned proton therapy. The mean/D2% dose ± SD for the optic chiasm and ipsilateral optic nerve was 43.4 ± 8.9 Gy (RBE)/49.9 ± 7.1 Gy (RBE) and 35.6 ± 11.7 Gy (RBE)/51.7 ± 4.8 Gy (RBE); the mean/D2% dose ± SD of the contralateral optic nerve was 18.8 ± 12.1 Gy (RBE)/42.4 ± 14.6 Gy (RBE), respectively. A total of 302 data collections were available (t1/t2/t3/t4/t5/t6: n = 56/56/48/56/52/34). Median observation time was 23.6 months. Mean symptom burden decreased over time (mean VDS: t1 29.8 ± 27.9; t2 25.0 ± 27.9; t3 21.8 ± 26.0; t4 22.2 ± 26.0; t5 21.4 ± 26.2; t6 17.3 ± 23.6) with statistically significant improvement at 3­ and 6­month FU as well as 1 year after proton therapy (p = 0.0205; p = 0.0187; p = 0.0054). Objective eye tests available in 41/52 patients confirm the trend towards improved visual acuity (97.5% stable/improved until 24-month FU). However, no potential predictor for VDS changes was revealed. CONCLUSION: Proton treatment of patients with meningioma WHO I with involvement of optical structures does not impair subjective visual performance. After treatment, there is a significant improvement in perceived visual performance.