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.

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.

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes.

Aim: Data on the safety of moderately hypofractionated proton beam therapy (PBT) are limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT). Material and methods: We prospectively compared acute toxicity and QoL between patients treated with nPBT (dose per fraction 1.8-2.3 Gy, n = 90) and hPBT (dose per fraction 2.5-3.1 Gy, n = 49) in following locations: head and neck (H&N, n = 85), abdomen and pelvis (A&P, n = 43), and other soft tissue (ST, n = 11). The toxicities were grouped into categories-mucosal, skin, and other sites-and evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at baseline, treatment completion, and 3 months after PBT completion. QoL was evaluated with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 scale for all locations and additionally with EORTC QLQ-HN35 for H&N patients. Results: Overall, the highest toxicity grades of G0, G1, G2, and G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%), and 15 (10.8%) patients, respectively. According to organ and site, no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile as compared to nPBT with a higher frequency of G0 and G1 and a lower frequency of G2 and G3 events (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023), and full resolution of toxicities (87% vs 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except for loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (-8.33 vs -25, p = 0.016). Conclusion: Hypofractionated proton therapy offers non-inferior early safety and QoL as compared to normofractionated irradiation and warrants further clinical investigation.

Season of birth and population schizotypy: Results from a large sample of the adult general population.

Although the last years have seen an increasing interest in schizotypy and its pathogenesis, there exist only a handful of studies examining the possible interaction between season of birth (SOB) and schizotypic personality structure. Available research used differing screening instruments, rendering comparisons between studies difficult, and sample sizes in adult populations may have been too small to detect a mild effect. The current study examined the association between SOB and psychometric schizotypy in the so far single-largest sample from the adult general population (N=8114), balanced for men and women, and utilizing a valid and reliable instrument for the assessment of schizotypy. Using the 12 most informative items of the Schizotypal Personality Questionnaire Brief, we obtained evidence of a small, but significant, effect of late winter and early spring births (February/March) on psychometric schizotypy. The effect was not constrained to women, but affected men and women alike. The observed association between SOB and schizotypy appears compatible with seasonal variations of temperature and influenza prevalence, and with recent evidence on seasonal variability in the activity of the human immune system. Our findings lend support to the continuum hypothesis of schizotypy and schizophrenia, for which SOB effects have been previously established.