Denise Bernhardt

Precise molecular characterization of glioblastoma (GB) is fundamental for accurate risk stratification and therapeutic planning. DNA methylation profiling reliably identifies key molecular features, including O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and specific molecular subtypes, such as receptor tyrosine kinase (RTK) I and II, and the mesenchymal (MES) subtype. In this study, we investigated the hypothesized correlation between these molecular profiles and preferential tumor locations, which could reveal a link to underlying tumor biology. We analyzed 227 GB patients characterized by DNA methylation profiling. To map significant clusters of tumor occurrence across subtypes and subcomponents, we performed voxel-wise analysis of differential involvement, utilizing 500 permutations to correct for multiple comparisons. While uncorrected frequency differential maps suggested localization tendencies for the RTK I, RTK II, and MES subtypes, stringent statistical correction revealed only one robust association: the non-enhancing component of MES tumors showed significant clustering in the left frontal lobe, the insula, and the temporal lobe. Contrary to prior literature, we observed no significant hemispheric preference regarding MGMT promoter methylation status. Our findings challenge prior assumptions regarding the spatial distinctiveness of GB subtypes and highlight the need to further elucidate the mechanisms governing tumorigenesis and spatial growth patterns.

Background: Evidence on the influence of eloquent brain areas on the effectiveness and side effects of radio-therapy (RT) remains limited. This study evaluated the relationship between eloquent brain regions, radiation dose, and tumor recurrence patterns in glioma patients. Methods: Preoperative navigated transcranial magnetic stimulation (nTMS) mapping of language and motor function, complemented by nTMS-based tractography, was performed. Magnetic resonance imaging of tumor recurrence was co-registered with RT treatment plans and functional nTMS data. Tumor growth direction, radiation dose to eloquent structures, and clinical outcomes were analyzed. Results: Seventy-two patients with glioblastoma, aged 57.7 ± 14.8 years, were included. Tumor recurrence toward eloquent brain areas, assessed either by volumetric or linear measurements, indicated growth affecting motor function in 68.1% and language function in 79.3% of patients. Following RT, new motor deficits occurred in 3/48 patients (6.3%) and language deterioration in 3/20 (15.0%). The mean dose to the corticospinal tract was 10.1 Gy in patients with motor decline versus 3.7 Gy in those without (P = .137). For language fiber tracts, corresponding doses were 34.1 Gy and 15.1 Gy (P = .073). Conclusions: Tumor recurrence toward eloquent brain areas was observed, with high radiation doses to eloquent brain areas being associated with higher rates of neurological deterioration. These findings create an ambiguous situation regarding the application of high radiation doses to the resection cavity facing eloquent brain areas while simultaneously ensuring optimal dose gradients to spare those.

Background/Objectives : Large-scale (epi)genomic studies have substantially advanced our understanding of the molecular landscape of meningiomas, most recently embedded in the cIMPACT-NOW update 8. As a result, molecular data are increasingly integrated into risk-adapted treatment algorithms. However, it remains uncertain to what extent non-invasive MRI can capture underlying molecular variation and risk. Methods: We assembled a large, single-institution cohort of 225 newly diagnosed meningiomas (WHO grades 1–3) with available preoperative MRI, as well as comprehensive epigenome-wide methylation and copy-number profiling. Tumors were segmented into core and edema regions using a state-of-the-art automated pipeline from the BraTS challenge. Radiomic features were extracted and used to train Random Forest classifiers to predict WHO grade, molecular risk, and specific alterations such as 1p loss in a hold-out test set. Results: Our models achieved accuracy above 91% for integrated molecular risk classification, 87.5% for 1p chromosomal status, and 76.8% for WHO grade prediction, with corresponding AUCs of 0.91, 0.90, and 0.89, underscoring the robustness of radiomic features in capturing histopathological and, especially, molecular characteristics. Conclusions: Preoperative MRI effectively captures the underlying molecular biology of meningiomas and may enable rapid molecular assessment to inform decision-making and prioritization of confirmatory testing. However, it is not yet ready for clinical use, showing lower accuracy for current WHO grade classification.

Medical image segmentation rapidly shifts toward vision(-language) foundation models that unify diverse modalities and tasks within a single framework. In this work, we systematically benchmark high-impact vision-language and segment-anything-based architectures across multiple clinically relevant CT and MRI tasks. We show that while these models achieve strong performance, each comes with specific (dis)advantages. Non-3D models are highly flexible but require substantial user guidance and are prone to over- or under-detection. 3D architectures offer overall more reliable volumetric consistency, but can still have detection problems. Vision-language models appear sensitive to the coverage of training data, whereas click-prompted SAM-based models are more universal, with a, though limited, ability to address zero-shot targets. When tested with more complex text prompts, most vision-language models exhibit missing semantic language understanding. Overall, these models hold considerable promise but still express limitations. Our work highlights key areas where future research is needed to advance vision(-language) foundation models.

Background: The impact of surgical resection on the survival and functional outcomes of patients with multiple brain metastases remains a critical question in neuro-oncology. Methods: This retrospective study involved 160 patients who underwent surgical resection of brain metastases from 2017 to 2020. Patients were classified by the number of metastases—single, oligometastatic, or multiple—and whether complete removal of the main symptomatic lesion was achieved. Outcomes such as survival rates, complications, and functional status were assessed. Results: Among the patients, 48.1% had a single metastasis, 21.9% were oligometastatic, and 30% had multiple metastases. Survival did not differ by number of metastases when the main lesion was completely resected and remaining lesions were radiated (p = 0.6172). Complete resection increased mean survival to 15.74 months compared with 4.5 months without it. Additionally, patients who underwent complete resection experienced fewer seizures (16.2% vs. 32.6%, p = 0.019), implying a lower seizure risk. Functional independence was maintained post-surgery. Conclusions: While multiple brain metastases are generally associated with poor outcomes, a trend toward longer survival was observed after complete resection of the index metastasis, though this was not statistically significant. Radiation of residual lesions remains important to support prognosis. Reducing the tumor volume is key to lowering seizure risk. This study supports the role of aggressive surgical interventions, paired with radiation, to potentially enhance outcomes in patients with multiple brain metastases.

Background: Postoperative radiotherapy improves local control after brain metastasis (BM) resection. Whole-brain radiotherapy (WBRT) reduces recurrence risk but impairs neurocognition. Hypofractionated stereotactic radiotherapy of the cavity (HFSRT) may offer equivalent tumor control with reduced toxicity. ESTRON is the first randomized trial comparing post-operative HFSRT and WBRT. Methods: This single-center phase 2 trial randomized 56 patients with resected BM to receive HFSRT (35 Gy in 7 fractions) or WBRT (30 Gy in 10 fractions). Patients could have ≤ 10 additional unresected BMs. The primary endpoint was intracranial progression-free survival (ic-PFS). Secondary endpoints included local control (LC), overall survival (OS), leptomeningeal disease (LMD), and toxicity. Results: Fifty-four patients were evaluable (n = 27 per arm). At 24.7 months median follow-up, 12-month ic-PFS was 44.4% (HFSRT) versus 59.3% (WBRT) (HR 1.72, P = .080). Median ic-PFS was 4.7 versus 15.0 months. LC at 24 months was 94.1% (HFSRT) versus 85.4% (WBRT) (HR 0.41, P = .433). One-year OS was 63.0% (HFSRT) versus 77.8% (WBRT), with no significant difference in median OS (17.8 vs 27.0 months; HR 1.09, P = .336). One-year risk of LMD was 27.0% (HFSRT, predominantly outside the irradiated field) versus 8.7% (WBRT) (log-rank P = .03). Treatment-related adverse events were more frequent with WBRT (115 vs 54 events), including 19% versus 11% grade 3 events, and poorer neurocognitive performance. Conclusions: Survival was similar for HFSRT and WBRT, while WBRT trended toward better ic-PFS. HFSRT showed substantially lower toxicity and better neurocognitive preservation, however, a higher risk of LMD. Risks and benefits should be weighed individually when determining post-operative treatment for BM.