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BackgroundIDH-wild-type glioblastoma (GBM) is a disease with devastating prognosis. First-line therapy consists of gross total resection and adjuvant radiotherapy with concomitant temozolomide. Several clinical parameters have been identified to provide prognostic value. We investigated whether peri-operative overall neurological performance could also be used to evaluate patients’ prognosis.MethodsAll patients with histologically diagnosed GBM between 2014 and 2017 over 18 years and MRI within 72 h after surgery were reviewed. To quantify neurological performance, the medical research council neurological performance score (MRC-NPS) was used. Univariate analysis with Kaplan–Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression.ResultsOne hundred thirty-nine patients were included. In univariate analysis, survival decreased with increasing post-operative MRC-NPS scale. Moreover, post-operative MRC-NPS of 4 was statistically significant associated with reduced overall survival when analyzed for complete (p = 0.027) and partial resection (p = 0.002) as well as unilobar (p = 0.003) and multilobar tumor location (p < 0.0005). In multivariate analysis, extent of resection (hazard ratio (HR) 3.142), adjuvant therapy regimen (HR 3.001), tumor location (HR 2.005), and post-operative MRC-NPS (HR 2.310) had significant influence on overall survival.ConclusionWe propose the post-operative neurological performance as an independent prognostic factor for GBM patients.

Glioneural tumors are primary brain tumors that consist of both neural and glial neoplastic cells, often presenting with seizures and primarily affecting children and young adults. Specifically, gangliogliomas are composed of neoplastic ganglion and glial cells, accompanied by other characteristic histological features such as lymphoid cuffing, eosinophilic granular bodies, and Rosenthal fibers. Oncogenic driver mutations and gene fusions have been shown to be of prognostic significance in gangliogliomas and can offer potential therapeutic targets. Typical molecular alterations are mitogen-activated protein kinase (MAPK) pathway activations with BRAF p.V600E being the most frequent one. Here, we report for the first time a gene fusion between epidermal growth factor receptor ( EGFR ) and vesicular, overexpressed in cancer, prosurvival protein 1 ( VOPP1) as a potential oncogenic driver in a glioneuronal tumor morphologically resembling ganglioglioma. VOPP1::EGFR fusion associated with the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling. Furthermore, we provide histological and epigenetic findings and clinical outcome. The case expands the known molecular spectrum of oncogenic drivers in glioneuronal tumors and provides a link to potentially prognostic and therapeutically relevant alterations.

Background/Objectives: Positron emission tomography (PET) imaging with radiolabeled amino acids is increasingly used in glioma patients for biopsy planning, tumor delineation, prognostication, and therapy response assessment. This study investigated whether baseline amino acid PET imaging could identify regions at risk of future tumor recurrence. Methods: Retrospective case series of 14 patients with high-grade glioma. Contrast-enhanced magnetic resonance imaging (MRI) data of tumor recurrence and baseline imaging (PET-MRI) were co-registered. Volumes of interest (VOIs) of the high-grade glioma were derived from contrast-enhanced MRI at baseline and follow-up and from amino acid PET at baseline. The Dice similarity coefficient (DSC) was used to assess the overlap between VOIs. Furthermore, dynamic and static PET parameters were compared between the VOIs derived from contrast-enhanced MRI at follow-up and from the region of increased amino acid transport at baseline. Results: Regions of tumor recurrence in high-grade glioma patients overlap significantly more with baseline regions of increased amino acid transport on PET compared to regions of contrast enhancement on baseline MRI (p < 0.001). However, the static and dynamic PET statistics did not differentiate between regions that would later develop tumor recurrence and other areas of increased amino acid transport at baseline. Conclusions: These findings reaffirm the ability of amino acid PET to visualize the infiltrative components of gliomas not detected by contrast-enhanced MRI. Also, this study supports the role of amino acid PET in visualizing glioma infiltration beyond the MRI-visible tumor, but also indicates that accurately predicting the specific regions of recurrence based on baseline PET remains limited.

Single-session, multiparametric [¹⁸F]FET PET/MRI is used to detect tumor recurrence in high-grade glioma, but its prognostic value for overall survival remains uncertain. This study evaluated whether biological tumor volume, tumor-to-background ratio (TBRmax), cerebral blood volume (rCBVmax), and choline/NAA ratio (Cho/NAA) could predict survival in recurrent high-grade glioma.BACKGROUND AND PURPOSESingle-session, multiparametric [¹⁸F]FET PET/MRI is used to detect tumor recurrence in high-grade glioma, but its prognostic value for overall survival remains uncertain. This study evaluated whether biological tumor volume, tumor-to-background ratio (TBRmax), cerebral blood volume (rCBVmax), and choline/NAA ratio (Cho/NAA) could predict survival in recurrent high-grade glioma.Twenty-six patients with histopathologically confirmed tumor progression underwent simultaneous [¹⁸F]FET PET/MRI. PET-derived biological tumor volume and TBRmax, MRI-derived rCBVmax, and Cho/NAA ratio were analyzed. A Cox proportional hazards model assessed associations with overall survival, adjusting for the number of lesions and treatment strategy.MATERIALS AND METHODSTwenty-six patients with histopathologically confirmed tumor progression underwent simultaneous [¹⁸F]FET PET/MRI. PET-derived biological tumor volume and TBRmax, MRI-derived rCBVmax, and Cho/NAA ratio were analyzed. A Cox proportional hazards model assessed associations with overall survival, adjusting for the number of lesions and treatment strategy.Biological tumor volume (hazard ratio = 2.22, 95%-CI: 1.035-4.762, p = 0.041) and the number of lesions (hazard ratio = 1.03, 95%-CI 1.00-1.06, p = 0.036) were significantly associated with survival. TBRmax (p = 0.089), rCBVmax (p = 0.088), and Cho/NAA ratio (p = 0.734) were not predictive. Treatment strategy after tumor recurrence diagnosis did not significantly impact overall-survival (HR = 0.208, p = 0.649). PET/MRI interaction terms did not enhance survival prediction.RESULTSBiological tumor volume (hazard ratio = 2.22, 95%-CI: 1.035-4.762, p = 0.041) and the number of lesions (hazard ratio = 1.03, 95%-CI 1.00-1.06, p = 0.036) were significantly associated with survival. TBRmax (p = 0.089), rCBVmax (p = 0.088), and Cho/NAA ratio (p = 0.734) were not predictive. Treatment strategy after tumor recurrence diagnosis did not significantly impact overall-survival (HR = 0.208, p = 0.649). PET/MRI interaction terms did not enhance survival prediction.Biological tumor volume is a significant prognostic imaging biomarker in recurrent high-grade glioma, emphasizing tumor burden over metabolic activity or perfusion of individual lesions. Volume-based PET metrics may offer better survival prediction than traditional PET or MRI parameters. Prospective multicenter studies are needed to validate these findings and explore automated segmentation and machine learning approaches for improved prognostication.CONCLUSIONBiological tumor volume is a significant prognostic imaging biomarker in recurrent high-grade glioma, emphasizing tumor burden over metabolic activity or perfusion of individual lesions. Volume-based PET metrics may offer better survival prediction than traditional PET or MRI parameters. Prospective multicenter studies are needed to validate these findings and explore automated segmentation and machine learning approaches for improved prognostication.

Glioneural tumors are primary brain tumors that consist of both neural and glial neoplastic cells, often presenting with seizures and primarily affecting children and young adults. Specifically, gangliogliomas are composed of neoplastic ganglion and glial cells, accompanied by other characteristic histological features such as lymphoid cuffing, eosinophilic granular bodies, and Rosenthal fibers. Oncogenic driver mutations and gene fusions have been shown to be of prognostic significance in gangliogliomas and can offer potential therapeutic targets. Typical molecular alterations are mitogen-activated protein kinase (MAPK) pathway activations with BRAF p.V600E being the most frequent one. Here, we report for the first time a gene fusion between epidermal growth factor receptor (EGFR) and vesicular, overexpressed in cancer, prosurvival protein 1 (VOPP1) as a potential oncogenic driver in a glioneuronal tumor morphologically resembling ganglioglioma. VOPP1::EGFR fusion associated with the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling. Furthermore, we provide histological and epigenetic findings and clinical outcome. The case expands the known molecular spectrum of oncogenic drivers in glioneuronal tumors and provides a link to potentially prognostic and therapeutically relevant alterations. Keywords: VOPP1, EGFR, Ganglioglioma, Gene fusion, NFκB

ObjectiveFeasibility and value of non-invasive transcranial magnetic brain stimulation (TMS MAGVENTURE® MagPro R30 Denmark) for preoperative diagnosis and surgical planning of brain tumor operations in everyday clinical practice.MethodsA prospective monocentric study was conducted, which included preoperative neurological and electrophysiological examination, TMS, and display of functional data in the navigation system (LOCALITE® TMS Navigator Germany). During surgery, the TMS data were correlated with the intraoperative monitoring (IOM). Twenty-four hours to 96 h and after at least 3 months, follow-ups with neurological, electrophysiological examinations and TMS stimulation were performed.ResultsTwenty-five patients with tumors in or near by the primary motor cortex region were included in the study. Twenty-one patients completed preoperative and first postoperative TMS and the neurological examination. Eight of 21 patients showed slight worsening of primary motor cortex function, 8 patients had an unchanged state, and 4 patients showed an improvement early after surgery. The changes of the electrophysiological examination like significant delay of the latency and/or reduced amplitudes matched well with the postoperative neurological outcome: if patients showed a worsening of the SEP’s and MEP’s, the postoperative results revealed deterioration.ConclusionA preoperatively performed TMS using the MAGVENTURE® MagPro R30 and the LOCALITE® TMS Navigator could be established in our clinical daily practice and allowed a safe and reliable mapping of the primary motor cortex in order to minimize the risk of postoperative neurological deficits and improve the neurological outcome of the patients.

BackgroundDistress impacts the daily life of glioma patients. This study explored its course over time and the usage of psychosocial care.MethodsA consecutive sample of glioma patients completed the Hospital Anxiety and Depression Scale to assess distress levels at admission to the hospital (t1), before discharge (t2), after 3 months (t3), and after 6 months (t4). They were interviewed with the Structured Clinical Interview for DSM-IV to ascertain psychiatric disorders at t2. Psycho-oncological care in the hospital was determined with the Hospital Information System, and the use of outpatient treatment was evaluated with the Health Care Usage Questionnaire at t4. We compared the percentages of elevated distress, psychiatric co-morbidity, and care usage between men and women.ResultsDuring the study period, 37 patients were enrolled. Nineteen percent of the patients were diagnosed with a psychiatric disorder. The percentages of patients with elevated distress were 56, 59, 39, and 40% at t1, t2, t3, and t4, respectively. Participants who did not survive the 6 months presented with higher levels of distress. In the hospital, 14% of those with elevated distress were visited by a psycho-oncologist. In the outpatient setting, 43% of those with elevated distress visited a neuro-psychiatrist, and 14% went to a psychotherapist. There was no evidence for an effect of gender on psychiatric co-morbidity, distress, or care use.ConclusionsA significant proportion of glioma patients report elevated distress during the hospital stay and thereafter. Only a fraction of them receive mental health care.