Uncovering the molecular landscape of meningiomas and the impact of perioperative steroids on patient survival.

BACKGROUND: The current literature on meningioma reveals a gap in knowledge regarding the impact of genetic factors on patient survival. Furthermore, there is a lack of data on the relationship between the perioperative use of corticosteroids and patient survival in meningioma patients. Our study aims to overcome these gaps by investigating the correlation between genetic factors and overall survival and the effect of postoperative corticosteroids and other clinical characteristics on patient outcomes in meningioma patients. METHODS: A retrospective analysis of the medical records of 85 newly diagnosed meningioma patients treated from 2016 to 2017 with follow-up until December 2022 was performed. RESULTS: NF2 mutations occurred in 60% of tumors, AKT1 mutations in 8.2%, and TRAF7 mutations in 3.6%. Most tumors in the parasagittal region had the NF2 mutation. On the other hand, almost all tumors in the sphenoid ridge area did not have the NF2 mutation. AKT-1-mutated meningiomas had more frequent peritumoral edema. Patients who received steroids perioperatively had worse overall survival (OS) than those without steroids (p = 0.034). Moreover, preoperative peri-meningioma edema also was associated with worse OS (p < 0.003). Contrarily, NF2 mutations did not influence survival. CONCLUSIONS: The combination of clinical, pathomorphological, and genetic data allows us to characterize the tumor better and assess its prognosis. Corticosteroids perioperatively and peri-meningioma edema were associated with shorter OS, according to our study. Glucocorticoids should be used judiciously for the shortest time required to achieve symptomatic relief.

Dural sinus thrombosis after resection of vestibular schwannoma using suboccipital retrosigmoid approach-thrombosis classification and management proposal.

Dural sinus thrombosis is one of the complications after posterior fossa surgery. However, that topic is not described well with regard to vestibular schwannoma surgery using the unique suboccipital retrosigmoid approach. We analyzed retrospectively medical records and radiological investigations of 116 patients. The including criteria were histopathologically confirmed vestibular schwannoma operated on using the retrosigmoid approach, preoperative and postoperative contrast-enhanced MRI, and at least 1-year follow-up. The patient group included 36% males and 64% females. The average age was 47.3 ± 13.9 years. Sixty percent of the tumors were classified as T4b according to the Hannover scale and their mean volume was 13.73 ± 10.28 cm3. There were no signs of thrombosis preoperatively. Postoperative changes in the dural sinuses were found in 26 (22%) cases. In 7 (27%) cases, there was an external compression by the hemostatic agent, and in 19 (73%) cases, a thrombus was visualized in the sinus lumen. The size of the sinus, age, and the tumor size were not risk factors for thrombosis, whereas an intraoperative sinus injury was a statistically significant risk factor (p = 0.0012). All of the patients diagnosed with thrombosis were in good clinical condition in long-term follow-up, except one fatal case. Complete recanalization was observed in 58% of cases after 1-year follow-up. Postoperative changes in the dural venous sinuses are a frequent finding after vestibular schwannoma surgery using the suboccipital retrosigmoid approach. Intraoperative dural injury is a risk factor for thrombosis. Thrombosis in that group of patients is usually asymptomatic and does not influence the prognosis.

Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes.

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.

Coated Blade Spray-Mass Spectrometry as a New Approach for the Rapid Characterization of Brain Tumors.

Brain tumors are neoplasms with one of the highest mortality rates. Therefore, the availability of methods that allow for the quick and effective diagnosis of brain tumors and selection of appropriate treatments is of critical importance for patient outcomes. In this study, coated blade spray-mass spectrometry (CBS-MS), which combines the features of microextraction and fast ionization methods, was applied for the analysis of brain tumors. In this approach, a sword-shaped probe is coated with a sorptive material to enable the extraction of analytes from biological samples. The analytes are then desorbed using only a few microliters of solvent, followed by the insertion of the CBS device into the interface on the mass spectrometer source. The results of this proof-of-concept experiment confirmed that CBS coupled to high-resolution mass spectrometry (HRMS) enables the rapid differentiation of two histologically different lesions: meningiomas and gliomas. Moreover, quantitative CBS-HRMS/MS analysis of carnitine, the endogenous compound, previously identified as a discriminating metabolite, showed good reproducibility with the variation below 10% when using a standard addition calibration strategy and deuterated internal standards for correction. The resultant data show that the proposed CBS-MS technique can be useful for on-site qualitative and quantitative assessments of brain tumor metabolite profiles.

Endoscopic versus stereotactic biopsies of intracranial lesions involving the ventricles.

Stereotactic biopsies of ventricular lesions may be less safe and less accurate than biopsies of superficial lesions. Accordingly, endoscopic biopsies have been increasingly used for these lesions. Except for pineal tumors, the literature lacks clear, reliable comparisons of these two methods. All 1581 adults undergoing brain tumor biopsy from 2007 to 2018 were retrospectively assessed. We selected 119 patients with intraventricular or paraventricular lesions considered suitable for both stereotactic and endoscopic biopsies. A total of 85 stereotactic and 38 endoscopic biopsies were performed. Extra procedures, including endoscopic third ventriculostomy and tumor cyst aspiration, were performed simultaneously in 5 stereotactic and 35 endoscopic cases. In 9 cases (5 stereotactic, 4 endoscopic), the biopsies were nondiagnostic (samples were nondiagnostic or the results differed from those obtained from the resected lesions). Three people died: 2 (1 stereotactic, 1 endoscopic) from delayed intraventricular bleeding and 1 (stereotactic) from brain edema. No permanent morbidity occurred. In 6 cases (all stereotactic), additional surgery was required for hydrocephalus within the first month postbiopsy. Rates of nondiagnostic biopsies, serious complications, and additional operations were not significantly different between groups. Mortality was higher after biopsy of lesions involving the ventricles, compared with intracranial lesions in any location (2.4% vs 0.3%, p = 0.016). Rates of nondiagnostic biopsies and complications were similar after endoscopic or stereotactic biopsies. Ventricular area biopsies were associated with higher mortality than biopsies in any brain area.

Prognostic and Predictive Biomarkers in Gliomas.

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.

Profiling of Carnitine Shuttle System Intermediates in Gliomas Using Solid-Phase Microextraction (SPME).

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detection and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography-high-resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed the presence of two separate clusters: short-chain and long-chain carnitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher-malignancy tumor samples (high vs. low grade) and in those samples with worse projected clinical outcomes (without vs. with IDH mutation; without vs. with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.

Biomarker concordance between molecular stereotactic biopsy and open surgical specimens in gliomas.

AIMS: To compare 1p/19q codeletion, MGMT promoter methylation, and IDH mutation status in stereotactic biopsy and open craniotomy specimens. CLINICAL RATIONALE: The latest WHO classification of gliomas requires assessment of the expression of molecular markers. Samples can be obtained for molecular assays via open craniotomy or molecular stereotactic biopsy (MSB). However, there is uncertainty as to whether MSB is representative of the entire tumour, and therefore how reliable it is for treatment planning. PATIENTS AND METHODS: We examined 11 patients diagnosed with brain tumours suspicious of glioma who underwent open craniotomy after stereotactic biopsy and in whom multiple biomarkers were assessed in both sets of samples by methylation-specific multiplex ligation-dependent probe amplification. Institutional Review Board ethical approval was granted (KB 694/2018). RESULTS: The initial histopathological grade as determined by stereotactic biopsy was the same as in the samples obtained by open surgery. Further, the marker profile used here was valid in both high- and low-grade gliomas. CONCLUSION AND CLINICAL IMPLICATION: MSB is a reliable way to obtain material for precision medicine approaches.

Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.

The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months) had a better prognosis than those with MGMT methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n = 7) with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

Beyond conventional imaging: Advancements in MRI for glioma malignancy prediction and molecular profiling.

This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. The paper underscores the importance of integrating modern MRI modalities, such as diffusion-weighted imaging and perfusion MRI, which are essential for assessing glioma malignancy and predicting tumor behavior. Special attention is given to the 2021 WHO Classification of Tumors of the Central Nervous System, emphasizing the integration of molecular diagnostics in glioma classification, significantly impacting treatment decisions. The review also explores radiogenomics, which correlates imaging features with molecular markers to tailor personalized treatment strategies. Despite technological progress, MRI protocol standardization and result interpretation challenges persist, affecting diagnostic consistency across different settings. Furthermore, the review addresses MRI's capacity to distinguish between tumor recurrence and pseudoprogression, which is vital for patient management. The necessity for greater standardization and collaborative research to harness MRI's full potential in glioma diagnosis and personalized therapy is highlighted, advocating for an enhanced understanding of glioma biology and more effective treatment approaches.

Preliminary results of linac-based radiosurgery in arteriovenous malformations and cerebral tumours in the Oncology Centre in Bydgoszcz.

AIM OF THE STUDY: Efficacy of stereotactic radiosurgery (SRS) in the treatment in cerebral AVM's, mennigiomas, metastases, acoustic neuromas and recurrent anaplastic gliomas is well documented. The object of this work was the analysis of the results of the treatment of AVM and selected cerebral lesions with linear accelerator-based stereotactic radiosurgery. MATERIAL AND METHODS: THE LESIONS INCLUDED: 12 AVMs, 2 cavernomas, 27 meningiomas, 16 metastases, 5 acoustic neuromas, 16 gliomas in 78 patients. A mean radiation dose of 16Gy was delivered to the tumour or AVM margin and 12Gy to the tumours located in a ponto-cerebellar angle. Follow-up was 18 months. RESULTS: Control of tumour growth or AVM was achieved in all cases after 6 months and radiological regression was observed in 20 cases after 12 months. The best results were noted in AVM's, meningiomas and neuromas.There were no new permanent deficits nor complications after radiosurgery requiring medicamentation. CONCLUSIONS: Organization of SRS in Oncological Center in Bydgoszcz involving close co-operation of radiotherapist, neurosurgeon and physicist in the process of qualification and treatment planning is based on the best global standards. Preliminary results of treatment are consistent with the literature data. A longer follow-up is required to determine the long term efficacy and the toxicity of this treatment in our institution.

Current and promising treatment strategies in glioma.

Gliomas are the most common primary central nervous system tumors; despite recent advances in diagnosis and treatment, glioma patients generally have a poor prognosis. Hence there is a clear need for improved therapeutic options. In recent years, significant effort has been made to investigate immunotherapy and precision oncology approaches. The review covers well-established strategies such as surgery, temozolomide, PCV, and mTOR inhibitors. Furthermore, it summarizes promising therapies: tumor treating fields, immune therapies, tyrosine kinases inhibitors, IDH(Isocitrate dehydrogenase)-targeted approaches, and others. While there are many promising treatment strategies, none fundamentally changed the management of glioma patients. However, we are still awaiting the outcome of ongoing trials, which have the potential to revolutionize the treatment of glioma.

Combining amino acid PET and MRI imaging increases accuracy to define malignant areas in adult glioma.

Accurate determination of the extent and grade of adult-type diffuse gliomas is critical to patient management. In clinical practice, contrast-enhancing areas of diffuse gliomas in magnetic resonance imaging (MRI) sequences are usually used to target biopsy, surgery, and radiation therapy, but there can be discrepancies between these areas and the actual tumor extent. Here we show that adding 18F-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) to MRI sequences accurately locates the most malignant areas of contrast-enhancing gliomas, potentially impacting subsequent management and outcomes. We present a prospective analysis of over 300 serial biopsy specimens from 23 patients with contrast-enhancing adult-type diffuse gliomas using a hybrid PET-MRI scanner to compare T2-weighted and contrast-enhancing MRI images with FET-PET. In all cases, we observe and confirm high FET uptake in early PET acquisitions (5-15 min after 18F-FET administration) outside areas of contrast enhancement on MRI, indicative of high-grade glioma. In 30% cases, inclusion of FET-positive sites changes the biopsy result to a higher tumor grade.

Functional State and Rehabilitation of Patients after Primary Brain Tumor Surgery for Malignant and Nonmalignant Tumors: A Prospective Observational Study.

The aim of this study was to compare the pre- and postoperative function of patients qualifying for resection of malignant and nonmalignant primary brain tumors to determine the relationship among tumor type, function, and the course of rehabilitation after surgery. This single-center, prospective, observational study recruited 92 patients requiring prolonged postoperative rehabilitation during their inpatient stay, who were divided into a nonmalignant tumor group (n = 66) and a malignant tumor group (n = 26). Functional status and gait efficiency were assessed using a battery of instruments. Motor skills, postoperative complications, and length of hospital stay (LoS) were recorded and compared between groups. The frequency and severity of postoperative complications, the time needed to attain individual motor skills, and the proportion of patients losing independent gait (~30%) were similar between groups. However, paralysis and paresis were more frequent in the malignant tumor group before surgery (p < 0.001). While nonmalignant tumor patients deteriorated more according to all scales after surgery, patients with malignant tumors were still characterized by worse ADL, independence, and performance at discharge. Worse functional outcomes in the malignant tumor group did not affect LoS or rehabilitation. Patients with malignant and nonmalignant tumors have similar rehabilitation needs, and patient expectation-especially those with nonmalignant tumors-should be appropriately managed.

Application of intraoperative computed tomography in a neurosurgical operating theatre.

BACKGROUND AND PURPOSE: The authors describe their own experience in use of intraoperative computed tomography (CT) with the Siemens SOMATOM Sensation in 125 cases. MATERIAL AND METHODS: Intraoperative CT of the head was most often used in functional neurosurgery for stereotactic planning in 32 cases and for control of deep brain stimulation electrode placement in 18 cases. In spine surgery, CT was used most often in spine stabilization to control the placement of implants. RESULTS: The implant had to be corrected in 7 cases (17% of 41 procedures), and in those cases the need for a revision procedure was therefore avoided. Intraoperative CT was also widely used in emergency procedures and perioperative complications in 13 cases, for control of intraventricular catheter or Rickham port placement in 8 cases, for evaluation of extent of tumour resection in 4 cases, for verification of electrode placement during percutaneous trigeminal rhizotomy in 3 cases, for evaluation of decompression after cervical corpectomy and thoracic discopathy in 3 cases, in complex fractures in 2 cases and as angio-CT after aneurysm clipping in 1 case. There was no significant prolongation of procedure duration. Intraoperative CT proved to be safe for a patient and for personnel. During the three-year evaluation period, the increasing use and indications for intraoperative CT were noted. Integration of CT with navigation is planned in the near future. CONCLUSIONS: Intraoperative CT is a very useful tool in spine surgery as well as in functional neurosurgery and neurooncology.

Comparison of the Functional State and Motor Skills of Patients after Cerebral Hemisphere, Ventricular System, and Cerebellopontine Angle Tumor Surgery.

Brain tumor location is an important factor determining the functional state after brain tumor surgery. We assessed the functional state and course of rehabilitation of patients undergoing surgery for brain tumors and assessed the location-dependent risk of loss of basic motor skills and the time needed for improvement after surgery. There were 835 patients who underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. Karnofsky Performance Scale, Barthel Index, and the modified Rankin scale were used to assess functional status, whereas Gait Index was used to assess gait efficiency. Motor skills, overall length of stay (LOS) in hospital, and LOS after surgery were recorded. Patients were classified into four groups: cerebral hemisphere (CH), ventricular system (VS), and cerebellopontine angle (CPA) tumors; and a control group not requiring rehabilitation. VS tumor patients had the lowest scores in all domains compared with the other groups before surgery (p < 0.001). Their performance further deteriorated after surgery and by the day of discharge. They most often required long-lasting postoperative rehabilitation and had the longest LOS (35 days). Operation was most often required for CH tumors (77.7%), and all metrics and LOS parameters were better in these patients (p < 0.001). Patients with CPA tumors had the best outcomes (p < 0.001). Most patients (83.4%) with brain tumors did not require specialized rehabilitation, and LOS after surgery in the control group was on average 5.1 days after surgery. VS tumor patients represent a rehabilitation challenge. Postoperative rehabilitation planning must take the tumor site and preoperative condition into account.

Meningovertebral ligaments could be a barrier for migration of a herniated intervertebral disc: An anatomical study.

Purpose: Intervertebral disc degeneration can manifest as sequestration. In most cases, the material could be found ipsilateral to the annular tear; however, a contralateral migration is also possible. We present an anatomical description of anterior meningovertebral ligaments (MVLs) as a possible barrier for disc migration. Methods: Anatomical dissection of 20 fresh human cadavers was carried out. Complete lumbar laminectomies with facetectomies were performed. All lumbar segments were exposed. Morphologic and morphometric descriptions of anterior MVLs were presented, with special attention to possible routes of herniated disc migration. Results: Anterior MVLs were present in all cases. They were divided in three separate groups: medial, lateral, and attached to the nerve roots. The medial group was the thickest, its mean length was 26.2 ± 1.2 mm, and it had no attachment to the disc in 51% of cases. The lateral group was less firm than the medial group, its mean length was 26.9 ± 1.0 mm, and it had no relation with the disc in 47% of cases. Ligaments related to the nerve root were the most delicate and always attached to the intervertebral disc. Their mean length was 14.9 ± 1.8 mm. Conclusions: The medial group of anterior MVLs are strong connective tissue bands dividing the anterior epidural space. The lateral group is more delicate, and in most cases, lateral MVLs lack annular attachment. MVLs could be an anatomical barrier for disc migration in particular cases.

Rehabilitation Outcomes for Patients with Motor Deficits after Initial and Repeat Brain Tumor Surgery.

Repeat surgery is often required to treat brain tumor recurrences. Here, we compared the functional state and rehabilitation of patients undergoing initial and repeat surgery for brain tumors to establish their individual risks that might impact management. In total, 835 patients underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. The Karnofsky performance status, Barthel index, and the modified Rankin scale were used to assess functional status, and the gait index was used to assess gait efficiency. Motor skills, postoperative complications, and length of hospital stay were recorded. Patients were classified into two groups: first surgery (n = 103) and repeat surgery (n = 30). Eighteen percent of patients required reoperations, and these patients required prolonged postoperative rehabilitation as often as those operated on for the first time. Rehabilitation was more often complicated in the repeat surgery group (p = 0.047), and the complications were more severe and persistent. Reoperated patients had significantly worse motor function and independence in activities of daily living before surgery and at discharge, but the deterioration after surgery affected patients in the first surgery group to a greater extent according to all metrics (p < 0.001). The length of hospital stay was similar in both groups. These results will be useful for tailoring postoperative rehabilitation during a hospital stay on the neurosurgical ward as well as planning discharge requirements after leaving the hospital.

Survival after reoperation for recurrent glioblastoma multiforme: A prospective study.

PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant brain tumor. Moreover, GBM recurs in nearly all patients. Although a standard STUPP protocol has been widely used for newly diagnosed GBM, no standard regimen has been established for recurrent patients. Here we evaluated the clinical value of recurrent GBM reoperation by comparing overall survival and quality of life (QoL) in patients with recurrent GBM undergoing repeat surgery or conservative treatment. METHODS: This was a prospective study of 165 patients with GBM receiving first operations for their disease between 2011 and 2013 at two tertiary neurosurgery centers in Poland. Thirty-five eligible patients were re-operated for recurrence (the study group), and 35 patients were selected as the control group using propensity score matching. A model was created to determine advantageous prognostic factors for longer survival of patients qualifying for reoperation using stepwise linear regression. RESULTS: The mean overall survival of patients undergoing repeat surgery was 528 days compared to 297 days in patients who did not undergo repeat surgery. Reoperation did not result in a significant deterioration in performance status as measured by the Karnofsky Performance Scale. Older age, the presence of symptoms of increased intracranial pressure, and a shorter period between initial operation and reoperation were independent predictors of a worse outcome. CONCLUSION: In selected patients, reoperation for recurrent GBM prolongs survival with no significant deteriorations in performance status.