Symptom burden and surgical outcome in non-skull base meningiomas.

Purpose: Non-skull base meningiomas (NSBM) are a distinct entity and frequently present with focal neurological deficits. This study was designed to analyze functional and oncological outcome following microsurgical tumor resection in patients with NSBM. Patients and methods: An analysis of 300 patients that underwent NSBM resection between 2003 and 2013 was performed. Assessment measures for functional outcome were Karnofsky Performance Scale (KPS), Medical Research Council - Neurological Performance Scale (MRC-NPS), and improvement rates of focal deficits and seizures. The extent of resection; recurrence-free survival (RFS) and tumor-specific survival (TSS) were also determined. Results: Impaired KPS and MRC-NPS were present in 73.3% and 45.7%, respectively. Focal neurological deficits were recorded in 123 patients (41.0%), with hemiparesis (21.7%) and aphasia (9.3%) the most prevalent form of impairment. Most meningiomas were localized at the convexity (64.0%), followed by falcine tumors (20.3%). Both KPI and MRC-NPS scores were significantly improved by surgical resection. Postoperative improvement rates of 96.6%, 89.3%, 72.3%, 57.9%, and 27.3% were observed for aphasia, epilepsy, hemiparesis, cranial nerve, and visual field deficits, respectively. Long-term improvement was achieved in 83.2%, 89.3%, 80.0%, 68.4% and 54.6% of patients, respectively. Gross total resection (GTR) over subtotal resection (STR) significantly improved preoperative seizures and visual field deficits and correlated with reduced risk of new postoperative hemiparesis. Poor Simpson grade was the only significant prognostic factor in multivariate analysis for long-term functional deficit, which occurred in 7.3%. Median RFS was 45.9 months (6.0 - 151.5 months), while median TSS was 53.7 months (3.1 - 153.2 months). Both WHO grade (p= 0.001) and Simpson classification (p= 0.014 and p= 0.031) were independent significant prognostic factors for decreased RFS and TSS by multivariate analysis, respectively. Furthermore, tumor diameter > 50 mm (p= 0.039) significantly correlated with decreased TSS in multivariate analysis. Conclusion: Surgical resection significantly and stably improves neurological deficits in patients with NSBM.

Validation Study for Non-Invasive Prediction of IDH Mutation Status in Patients with Glioma Using In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning.

The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinical routine, however, non-invasive determination of IDH mutation status is desirable in cases where tumor biopsy is not possible and for monitoring neuro-oncological therapies. In a previous publication, we presented reliable prediction of IDH mutation status employing proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 Tesla (T) scanner and machine learning in a prospective cohort of 34 glioma patients. Here, we validated this approach in an independent cohort of 67 patients, for which 1H-MR spectra were acquired at 1.5 T between 2002 and 2007, using the same data analysis approach. Despite different technical conditions, a sensitivity of 82.6% (95% CI, 61.2-95.1%) and a specificity of 72.7% (95% CI, 57.2-85.0%) could be achieved. We concluded that our 1H-MRS based approach can be established in a routine clinical setting with affordable effort and time, independent of technical conditions employed. Therefore, the method provides a non-invasive tool for determining IDH status that is well-applicable in an everyday clinical setting.

Breakouts-A Radiological Sign of Poor Prognosis in Patients With Brain Metastases.

Purpose: Brain metastases (BM) can present a displacing or infiltrating growth pattern, independent of the primary tumor type. Previous studies have shown that tumor cell infiltration at the macro-metastasis/brain parenchyma interface (MMPI) is correlated with poor outcome. Therefore, a pre-therapeutic, non-invasive detection tool for potential metastatic cell infiltration at the MMPI would be desirable to help identify patients who may benefit from a more aggressive local treatment strategy. The aim of this study was to identify specific magnetic resonance imaging (MRI) patterns at the MMPI in patients with BM and to correlate these patterns with patient outcome. Patients and Methods: In this retrospective analysis of a prospective BM registry, we categorized preoperative MR images of 261 patients with BM according to a prespecified analysis system, which consisted of four MRI contrast enhancement (CE) patterns: two with apparently regularly shaped borders (termed "rim-enhancing" and "spherical") and two with irregular delineation (termed "breakout" and "diffuse"). The primary outcome parameter was overall survival (OS). Additionally analyzed prognostic parameters were the Karnofsky Performance Index, tumor size, edema formation, extent of resection, and RPA class. Results: OS of patients with a breakout pattern was significantly worse than OS of all other groups. Conclusion: Our data show that BM with a breakout pattern have a highly aggressive clinical course. Patients with such a pattern potentially require a more aggressive local and systemic treatment strategy.

Current standards and new concepts in MRI and PET response assessment of antiangiogenic therapies in high-grade glioma patients.

Despite multimodal treatment, the prognosis of high-grade gliomas is grim. As tumor growth is critically dependent on new blood vessel formation, antiangiogenic treatment approaches offer an innovative treatment strategy. Bevacizumab, a humanized monoclonal antibody, has been in the spotlight of antiangiogenic approaches for several years. Currently, MRI including contrast-enhanced T1-weighted and T2/fluid-attenuated inversion recovery (FLAIR) images is routinely used to evaluate antiangiogenic treatment response (Response Assessment in Neuro-Oncology criteria). However, by restoring the blood-brain barrier, bevacizumab may reduce T1 contrast enhancement and T2/FLAIR hyperintensity, thereby obscuring the imaging-based detection of progression. The aim of this review is to highlight the recent role of imaging biomarkers from MR and PET imaging on measurement of disease progression and treatment effectiveness in antiangiogenic therapies. Based on the reviewed studies, multimodal imaging combining standard MRI with new physiological MRI techniques and metabolic PET imaging, in particular amino acid tracers, may have the ability to detect antiangiogenic drug susceptibility or resistance prior to morphological changes. As advances occur in the development of therapies that target specific biochemical or molecular pathways and alter tumor physiology in potentially predictable ways, the validation of physiological and metabolic imaging biomarkers will become increasingly important in the near future.

Surgical resection of brain metastases-impact on neurological outcome.

Brain metastases (BM) develop in about 30% of all cancer patients. Surgery plays an important role in confirming neuropathological diagnosis, relieving mass effects and improving the neurological status. To select patients with the highest benefit from surgical resection, prognostic indices (RPA, GPA) have been formulated which are solely focused on survival without considering neurological improvement. In this study we analyzed the impact of surgical resection on the neurological status in addition to overall survival in 206 BM patients. Surgical mortality and morbidity was 0.0% and 10.3% respectively. New neurologic deficits occurred in 6.3% of all patients. The median overall survival was 6.3 months. Poor RPA class and short time interval between diagnosis of cancer and the occurrence of BM were independent factors predictive for poor survival. Improvement of neurological performance was achieved in 56.8% of all patients, with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis. Notably, the neurological benefits were independent from RPA class. In conclusion, surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival. Considering the low mortality and morbidity rates, resection should be considered as a valid option to increase neurological function and quality of life for patients with BM.