Supratentorial Gliomas Research Articles

Efficacy of Ketamine as an Adjuvant to Scalp Block for Hemodynamic Stability in Patients Undergoing Elective Craniotomy for Supratentorial Glioma: A Prospective Randomized Controlled Trial

Abstract Introduction Scalp nerve block (SNB) attenuates the hemodynamic response to pin insertion and delivers excellent postoperative analgesia. This study aimed to evaluate the efficacy of SNB using ketamine as an adjuvant to bupivacaine on perioperative hemodynamic responses and postoperative pain in patients undergoing craniotomy for supratentorial glioma. Materials and Methods Sixty patients were randomized into two groups. They were given scalp nerve block either with bupivacaine and saline (group S) or bupivacaine and ketamine (group K). Primary outcome was to compare the change in mean arterial pressure (MAP) and heart rate (HR) at defined time points from baseline. Secondary outcomes included time to request for first analgesia, total analgesic consumption in intraoperative and postoperative periods till 24 hours, and numeric rating scale pain score at various time points in postoperative period till 24 hours. Results Fifty-seven patients were included in analysis. HR and MAP were comparable intraoperatively till closure. As soon as closure began, a significant increase in HR (group K vs. group S, 69.76 ± 9.03 vs. 93.96 ± 9.98, p-value = < 0.0001) and MAP (group K vs. group S, 79.4 ± 4.12 vs. 87.17 ± 12.67, p-value = 0.002) was noted in group S patients. This increase persisted in the postoperative period as well. The median total opioid consumed during intraoperative period in group K was 200 mcg versus 300 mcg in group S, p-value < 0.0001. Conclusion Adding ketamine as an adjuvant to bupivacaine for SNB not only provides significant hemodynamic stability but also reduces both intra- and postoperative analgesic consumption.

Bone health in childhood low-grade glioma: an understudied problem.

Children with a supratentorial midline low-grade glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG. A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1 January 2003 and 1 January 2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as the presence of vertebral fractures and/or very low bone mineral density (BMD). In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range: 0.1-17.9) and a median follow-up of 6.1 years (range: 0.1-19.9). Five patients (3.1%) had vertebral fractures. In 99 patients, BMD was assessed either by Dual Energy X-ray Absorptiometry (n = 12) or Bone Health Index (n = 95); 34 patients (34.3%) had a low BMD (≤ -2.0). Impaired visual capacity was associated with bone problems in multivariable analysis (OR: 6.63, 95% CI: 1.83-24.00, P = 0.004). In this retrospective evaluation, decreased BMD was prevalent in 34.3% of children with supratentorial midline LGG. For the risk of developing bone problems, visual capacity seems highly relevant. Surveillance of bone health must be an aspect of awareness in the care and follow-up of children with a supratentorial midline LGG. Patients with supratentorial midline LGG may encounter various risk factors for impaired bone health. Bone problems in survivors of childhood supratentorial midline LGG are, however, understudied. This is the first paper to address the prevalence of bone problems in this specific patient population, revealing visual problems as an important risk factor. Diencephalic syndrome historyand/or weight problems associated with hypothalamic dysfunction were related to bone problems in univariate analyses. The results of this study can be used in the development of guidelines to adequately screen and treat these patients to subsequently minimizing bone problems as one of the endocrine complications.

Intraoperative goal-directed fluid management and postoperative brain edema in patients having high-grade gliomas resections: a randomized trial.

Patients with high-grade gliomas often have severe brain edema. Goal-directed fluid management protects neurological function, but whether reduces postoperative brain edema remains unknown. Patients having elective resection of supratentorial malignant gliomas were randomly assigned to goal-directed versus routine fluid management. Patients assigned to goal-directed management group were given 3mL kg-1 hydroxyethyl starch solution when stroke volume variation exceeded 15% for 5 minutes. Fluid was managed per routine by attending anesthesiologists in reference patients. The primary outcome was cerebral edema volume after surgery as assessed by computerized tomography. A total of 480 eligible patients were randomly assigned to the goal-directed (n = 240) or the routine fluid management group (n = 240). The amounts of crystalloid (5.4 vs. 7.0ml kg-1 hour-1, P < 0.001), colloid (1.1 vs. 1.7ml kg-1 hour-1, P < 0.001), and overall fluid balance (0.3 vs. 1.9ml kg-1 hour-1, P < 0.001) were significantly lower in goal-directed fluid management. There was no significant difference in postoperative brain edema volume between groups (36.0cm3 vs. 38.9cm3, mean difference: 0.18cm3, 95% CI: -5.7 to 5.9). Goal-directed patients had lower intraoperative dural tension (risk ratio: 0.63, 95% CI: 0.50 to 0.80, P < 0.001). There was no significant difference in Karnofsky Performance Status between the two groups at 30 days after surgery. Goal-directed fluid therapy substantially reduced intravenous fluid volumes, but did not reduce postoperative brain edema in patients having brain tumor resections.

Histopathological study of cases of supratentorial glioma in tertiary care hospital

Histopathological study of cases of supratentorial glioma in tertiary care hospital

QOL-03. BONE HEALTH IN CHILDREN WITH SUPRASELLAR AND THALAMIC LOW GRADE GLIOMA; AN UNDERSTUDIED PROBLEM

Abstract BACKGROUND Children with a supratentorial midline Low Grade Glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG. METHODS A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1-1-2003 and 1-1-2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as presence of vertebral fractures or collapse, any fractures not related to (the intensity of) trauma, treatment with bisphosphonates, and/or very low bone mineral density (BMD). RESULTS In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range 0.1 – 17.9) and a median follow-up of 6.1 years (range 0.1 – 19.9). ‘Any’ bone problem occurred in 22.4% (36/161) and nontraumatic fractures in 3.7%. Impaired visual capacity was associated with bone problems in multivariate analysis (OR 3.56 95% CI 1.30 – 9.76, p = 0.014). CONCLUSIONS In this retrospective evaluation, bone problems and decreased BMD were prevalent in 36.1% of children with supratentorial midline LGG. Risk to develop bone problems appears to be multifactorial, but visual capacity seems highly relevant. Surveillance of bone health must be an aspect for awareness in the care and follow-up of children with a supratentorial midline LGG.

Incidence and risk factors of post-operative delirium in glioma patients: A prospective cohort study in general wards.

Glioma patients are at high risk for postoperative delirium (POD), yet studies focusing on this population in general neurosurgical ward settings are limited. This paper investigates the incidence of POD and related risk factors in glioma patients hospitalized in general wards. Prospective observational study. This prospective study included 133 adult glioma patients hospitalized in the general neurosurgery ward. In addition to collecting routine perioperative general clinical data, patients' psychological status was assessed preoperatively using the Hospital Anxiety and Depression Scale (HADS). POD was assessed within 3 days postoperatively using the Confusion of Consciousness Assessment method, twice daily. The incidence of POD was calculated, and risk factors were identified using logistic regression analysis. The incidence of POD in glioma patients admitted to the general ward was 31.6% (40/133). Multivariate regression revealed advanced age (age > 50 years), frontal lobe tumour, presence of preoperative anxiety or depression, retention of a luminal drain, postoperative pain, indwelling catheter these six factors were independent risk factors for the development of delirium in patients after surgery. In general ward settings, supratentorial glioma patients exhibit a high risk of POD. Critical risk factors include preoperative psychological conditions, as well as postoperative pain, drainage and catheterization. Rigorous preoperative evaluations, effective pain management strategies and the integration of humanistic care principles are essential in mitigating the risk of POD for glioma patients. In general ward settings, this study reveals the high occurrence of POD in glioma patients and identifies preoperative psychological states, age, tumour location and several postoperative factors as significant risk factors for POD, which provides a framework for targeted interventions. By integrating these insights into clinical practice, healthcare teams can better identify glioma patients at risk for POD and implement preventive measures, thereby enhancing recovery and overall care quality for glioma patients in general neurosurgical wards. This study adheres to the STROBE guidelines, ensuring a transparent and comprehensive reporting of the observational research methodology and results. Patients involvement was limited to the provision of data through their participation in the study's assessments and the collection of clinical information. The study did not involve a direct patient or public contribution in the design, conduct, analysis, or interpretation of the data, nor in the preparation of the manuscript.

Effects of the Use of Neuronavigation in Patients with Supratentorial Brain Gliomas: A Cohort Study

AbstractDespite the growing acceptance of neuronavigation in the field of neurosurgery, there is limited comparative research with contradictory results. This study aimed to compare the effectiveness (tumor resection rate and survival) and safety (frequency of neurological complications) of surgery for brain gliomas with or without neuronavigation. MethodsThis retrospective cohort study evaluated data obtained from electronic records of patients who underwent surgery for gliomas at Dr. Alejandro Dávila Bolaños Military Hospital and the Clinic Hospital of Barcelona between July 2016 and September 2022. The preoperative and postoperative clinical and radiologic characteristics were analyzed and compared according to the use of neuronavigation. ResultsThis study included 110 patients, of whom 79 underwent surgery with neuronavigation. Neuronavigation increased gross total resection by 57% in patients in whom it was used; gross total resection was performed in 56% of patients who underwent surgery with neuronavigation as compared with 35.5% in those who underwent surgery without neuronavigation (risk ratio [RR], 1.57; P=0.056). The incidence of postoperative neurologic deficits (transient and permanent) decreased by 79% with the use of neuronavigation, (12% vs. 33.3%; RR, 0.21; P=0.0003). Neuronavigation improved survival in patients with grade IV gliomas (15 months vs. 13.8 months), but it was not statistically significant (odds ratio (OR), 0.19; P=0.13). ConclusionsNeuronavigation improved the effectiveness (greater gross total resection of tumors) and safety (fewer neurological deficits) of brain glioma surgery. However, neuronavigation does not significantly influence the survival of patients with grade IV gliomas.

Clinical and imaging characteristics of supratentorial glioma with IDH2 mutation.

The rarity of IDH2 mutations in supratentorial gliomas has led to gaps in understanding their radiological characteristics, potentially resulting in misdiagnosis based solely on negative IDH1 immunohistochemical staining. We aimed to investigate the clinical and imaging characteristics of IDH2-mutant gliomas. We analyzed imaging data from adult patients with pathologically confirmed diffuse lower-grade gliomas and known IDH1/2 alteration and 1p/19q codeletion statuses obtained from the records of our institute (January 2011 to August 2022, Cohort 1) and The Cancer Imaging Archive (TCIA, Cohort 2). Two radiologists evaluated clinical information and radiological findings using standardized methods. Furthermore, we compared the data for IDH2-mutant and IDH-wildtype gliomas. Multivariate logistic regression was used to identify the predictors of IDH2 mutation status, and receiver operating characteristic curve analysis was employed to assess the predictive performance of the model. Of the 20 IDH2-mutant supratentorial gliomas, 95% were in the frontal lobes, with 75% classified as oligodendrogliomas. Age and the T2-FLAIR discordance were independent predictors of IDH2 mutations. Receiver operating characteristic curve analysis for the model using age and T2-FLAIR discordance demonstrated a strong potential for discriminating between IDH2-mutant and IDH-wildtype gliomas, with an area under the curve of 0.96 (95% CI, 0.91-0.98, P = .02). A high frequency of oligodendrogliomas with 1p/19q codeletion was observed in IDH2-mutated gliomas. Younger age and the presence of the T2-FLAIR discordance were associated with IDH2 mutations and these findings may help with precise diagnoses and treatment decisions in clinical practice.

Functional and oncological outcomes after right hemisphere glioma resection in awake versus asleep patients: a systematic review and meta-analysis.

The right hemisphere has been underestimated by being considered as the non-dominant hemisphere. However, it is involved in many functions, including movement, language, cognition, and emotion. Therefore, because lesions on this side are usually not resected under awake mapping, there is a risk of unfavorable neurological outcomes. The goal of this study is to compare the functional and oncological outcomes of awake surgery (AwS) versus surgery under general anesthesia (GA) in supratentorial right-sided gliomas. A systematic review of the literature according to PRISMA guidelines was performed up to March 2023. Four databases were screened. Primary outcome to assess was return to work (RTW). Secondary outcomes included the rate of postoperative neurological deficit, postoperative Karnofsky Performance Status (KPS) score and the extent of resection (EOR). A total of 32 articles were included with 543 patients who underwent right hemisphere tumor resection under awake surgery and 294 under general anesthesia. There were no significant differences between groups regarding age, gender, handedness, perioperative KPS, tumor location or preoperative seizures. Preoperative and long-term postoperative neurological deficits were statistically lower after AwS (p = 0.03 and p < 0.01, respectively), even though no difference was found regarding early postoperative course (p = 0.32). A subsequent analysis regarding type of postoperative impairment was performed. Severe postoperative language deficits were not different (p = 0.74), but there were fewer long-term mild motor and high-order cognitive deficits (p < 0.05) in AwS group. A higher rate of RTW (p < 0.05) was documented after AwS. The EOR was similar in both groups. Glioma resection of the right hemisphere under awake mapping is a safer procedure with a better preservation of high-order cognitive functions and a higher rate of RTW than resection under general anesthesia, despite similar EOR.

Dynamic Cortical Connectivity During Propofol Sedation in Glioma Patients.

The behavioral manifestations and neurophysiological responses to sedation can assist in understanding brain function after neurological damage, and can be described by cortical functional connectivity. Glioma patients may experience neurological deficits that are not clinically detectable before sedation. We hypothesized that patients with gliomas exhibit distinct cortical connectivity patterns compared to non-neurosurgical patients during sedation. This is a secondary analysis of a previously published prospective observational study. Patients scheduled for resection of supratentorial glioma (n=21) or a non-neurosurgical procedure (n=21) under general anesthesia were included in this study. Frontal electroencephalography (EEG) signals were recorded at different sedation levels as assessed by the Observer Assessment of Alertness/Sedation (OAA/S) score. Kernel principal component analysis and k-means clustering were used to determine possible temporal dynamics from the weighted phase lag index characteristics. Ten EEG connectivity states were identified by clustering (76% consistency), each with unique properties. At OAA/S 3, the median (Q1, Q3) occurrence rates of state 6 (glioma group, 0.110 [0.083, 0.155] vs. control group, 0.070 [0.030, 0.110]; P=0.008) and state 7 (glioma group, 0.105 [0.083, 0.148] vs. control group: 0.065 [0.038, 0.090]; P=0.001), which are dominated by beta connectivity, were significantly different between the 2 groups, reflecting differential conversion of the beta band between the left and right brain regions. In addition, the temporal dynamics of the brain's functional connectivity was also reflected in the transition relationships between metastable states. There were differences in EEG functional connectivity, which is dynamic, between the glioma and nonglioma groups during sedation.

1244 Immunotherapy With Autological Dendritic Cells in the Structure of Complex Treatment of Gliomas

INTRODUCTION: Malignant gliomas are the most common primary brain tumor. Despite the variety of modern treatments, it is still a fatal disease with an extremely poor prognosis. The use of immunotherapy as a technique for the treatment of malignant tumors has great promise, retraining and exploiting the patient's immune response against tumors. METHODS: Long-term results of treatment of 220 patients with malignant supratentorial gliomas (anaplastic astrocytomas, glioblastomas) were analyzed. Of these patients, 110 patients, in addition to standard methods of treatment (surgery, radiation therapy and chemotherapy), underwent specific antitumor immunotherapy with autologous dendritic cells. In 110 patients, only standard methods were used in the structure of complex treatment. The relapse-free period and median life expectancy were assessed. RESULTS: Conducting specific antitumor immunotherapy in patients with malignant gliomas was safe and did not lead to an increase in the number of complications compared with the control group. It was revealed that the use of immunotherapy based on autologous dendritic cells, in addition to standard methods of treating patients, increases the average life expectancy (in patients with anaplastic astrocytomas up to 40.5 months (p = 0.001), in patients with glioblastomas up to 21.8 months (p = 0.002)) and increases the relapse-free period (in patients with anaplastic astrocytomas up to 17.4 months (p = 0.002), in patients with glioblastomas up to 14.3 months (p = 0.003)) provided that three or more courses are taken. Conducting 1 or 2 courses of immunotherapy does not significantly affect the average life expectancy and median survival of patients. CONCLUSIONS: The development and use in clinical practice of specific antitumor immunotherapy based on autologous dendritic cells seems to be a very promising direction for further research, the development of which will improve the long-term results of patient treatment.

Abstract 1437: Generating primary mouse models of diffuse midline glioma through a combination of the RCAS/tv-a retrovirus system and CRISPR/Cas9 gene editing

Abstract Diffuse midline gliomas (DMGs) are deadly brain tumors that arise in the brainstem of children and young adults, resulting in a median survival of less than two years. Genetically engineered mouse models (GEMMs) are critical to studying tumorigenesis and tumor-immune interactions in DMG, which may inform the design of new urgently-needed treatment approaches. One approach to generate DMG GEMMs uses RCAS/tv-a, an avian retrovirus gene delivery system to express transgenes in specific brain cell lineages in the mouse brain. However, this approach often requires resource-intensive breeding to generate mice with the desired genetic alterations in their germline. As a result, we aimed to establish a new approach that combines this system with CRISPR/Cas9 gene editing technology. This methodology has been described for model adult supratentorial gliomas in mice but has not been described for pediatric or brainstem gliomas. To express Cas9 and the avian retrovirus receptor TVA in mouse neural stem cells, we bred mice of genotype Nestin-TVA; Nestin-Cre; LoxP-STOP-LoxP-Cas9-EGFP. RCAS retrovirus plasmids were generated containing various guide RNAs (gRNAs) targeting DMG-relevant genes for disruption by Cas9, including Trp53, Cdkn2a, Atm, Ppm1d, Pten, and a non-targeting control (Cntl). For each gRNA, two plasmids were generated, one with a platelet-derived growth factor beta ligand (PDGFB) oncogene driver and one with a blue fluorescent protein (BFP) marker. In a pilot experiment, avian fibroblast cells transduced with RCAS-Trp53_gRNA_BFP and RCAS-Cntl_gRNA-PDGFB were injected into postnatal day 4 mouse brainstems of the aforementioned genotype and observed for tumor formation. High grade tumor formation was observed. We also observed high grade tumors in mice of genotype Nestin-TVA; LoxP-STOP-LoxP-Cas9-EGFP when injected with an additional RCAS-Cre construct, indicating that Cre can be expressed from the mouse germline or delivered via a retrovirus payload to drive tumorigenesis. Immunohistochemistry confirmed tumor features that model human DMG, expression of Cas9 and PDGFB, and loss of p53. Thus, RCAS/tv-a and CRISPR/Cas9 can be combined to model pediatric glioma tumorigenesis in the mouse brainstem. This approach to mouse modeling will streamline future GEMM DMG research by allowing new genes of interest to be rapidly perturbed by simply generating RCAS retrovirus constructs. The workflow may also enable sophisticated experiments such as pooled in vivo genetic experiments that screen gRNAs targeting various tumor suppressor genes or therapeutic targets. Citation Format: Sophie R. Wu, Harrison Q. Liu, Joshua Tolliver, Spencer M. Maingi, Vennesa Valentine, Nerissa T. Williams, Zachary J. Reitman. Generating primary mouse models of diffuse midline glioma through a combination of the RCAS/tv-a retrovirus system and CRISPR/Cas9 gene editing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1437.

Maximal Resection of Gliomas Adjacent to the Corticospinal Tract Using 3-T Intraoperative Magnetic Resonance Imaging

BackgroundGliomas adjacent to the corticospinal tract (CST) should be carefully resected to preserve motor function while achieving maximal surgical resection. Modern high-field intraoperative magnetic resonance imaging (iMRI) enables precise visualization of the residual tumor and intraoperative tractography. We prospectively evaluated the extent of resection and distance between the tumor resection cavity and CST using 3-T iMRI combined with motor evoked potentials (MEP) in glioma surgery. MethodParticipants comprised patients who underwent surgery for solitary supratentorial glioma located within 10 mm of the CST. All cases underwent surgery using neuronavigation with overlaid CST under MEP monitoring. The correlation between distance from CST and transcortical MEP amplitude was calculated using Spearman rank correlation. ResultsAmong the 63 patients who underwent surgery, 27 patients were enrolled in the study. Gross total resections were achieved in 26 of the 27 cases. Volumetric analysis showed the extent of resection was 98.6%. Motor function was stable or improved in 24 patients (Stable/Improved group) and deteriorated in 3 patients (Deteriorated group). All patients in the Deteriorated group showed motor deficit before surgery. Mean intraoperative minimal distance was significantly longer in the Stable/Improved group (7.3 mm) than in the Deteriorated group (1.1 mm; p < 0.05). MEP amplitude correlated with minimal distance between the resection cavity and CST (R=0.64). ConclusionsResection of gliomas adjacent to CST with a navigation system using 3-T iMRI could result in an ultimate EOR >98%. The combination of intraoperative tractography and MEP contributes to maximal removal of motor-eloquent gliomas.

Primary central nervous system tumors survival in children in ten Colombian cities: a VIGICANCER report.

Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities. We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis. During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively. We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases

BackgroundDistant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway.MethodsA total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed.ResultsOf the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway.ConclusionDistant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

Comparison of two region-of-interest placement methods for histogram analysis of apparent diffusion coefficient maps for glioma grading.

We assessed the value of histogram analysis (HA) of apparent diffusion coefficient (ADC) maps for grading low-grade (LGG) and high-grade (HGG) gliomas. We compared the diagnostic performance of two region-of-interest (ROI) placement methods (ROI 1: the entire tumor; ROI 2: the tumor excluding cystic and necrotic portions). We retrospectively evaluated 54 patients with supratentorial gliomas (18 LGG and 36 HGG). All subjects underwent standard 3T contrast-enhanced magnetic resonance imaging. Histogram parameters of ADC maps calculated with the two segmentation methods comprised mean, median, maxi-mum, minimum, kurtosis, skewness, entropy, standard deviation (sd), mean of positive pixels (mpp), uniformity of positive pixels, and their ratios (r) between lesion and normal white matter. They were compared using the independent t-test, chi-square test, or Mann-Whitney U test. For statistically significant results, receiver operating characteristic curves were constructed, and the optimal cutoff value, sensitivity, and specificity were determined by maximizing Youden's index. The ROI 1 method resulted in significantly higher rADC mean, rADC median, and rADC mpp for LGG than for HGG; these parameters had value for predicting the histological glioma grade with a cutoff (sensitivity, specificity) of 1.88 (77.8%, 61.1%), 2.25 (44.4%, 97.2%), and 1.88 (77.8%, 63.9%), respectively. The ROI 2 method resulted in significantly higher ADC mean, ADC median, ADC mpp, ADC sd, ADC max, rADC median, rADC mpp, rADC mean, rADC sd, and rADC max for LGG than for HGG, while skewness was lower for LGG than for HGG (0.27 [0.98] vs 0.91 [0.81], p = 0.014). In ROI 2, ADC median, ADC mpp, ADC mean, rADC median, rADC mpp, and rADC mean performed well in differentiating glioma grade with cutoffs (sensitivity, specificity) of 1.28 (77.8%, 88.9%), 1.28 (77.8%, 88.9%), 1.25 (77.8%, 91.7%), 1.81 (83.3%, 91.7%), 1.74 (83.3%, 91.7%), and 1.81 (83.3%, 91.7%), respectively. HA parameters had value for grading gliomas. Ex-cluding cystic and necrotic portions of the tumor for measuring HA parameters was preferable to using the entire tumor as the ROI. In this segmentation, rADC median showed the highest performance in predicting histological glioma grade, followed by rADC mpp, rADC mean, ADC median, ADC mpp, and ADC mean.

Radiographic growth rate as a predictor of aggressiveness of diffuse gliomas without 1p19q codeletion.

The 2021 WHO classification of CNS tumors has refined the definition of adult-type diffuse gliomas without 1p19q codeletion. Nevertheless, the aggressiveness of gliomas is based exclusively on histomolecular criteria performed on a limited sample of the tumor. The authors aimed to assess whether the spontaneous radiographic tumor growth rate is associated with tumor aggressiveness and allows preoperative identification of malignancy grade of adult-type diffuse gliomas without 1p19q codeletion. The authors retrospectively reviewed the records of adult patients harboring a newly diagnosed supratentorial diffuse glioma without 1p19q codeletion, with available preoperative MRI follow-up between January 2008 and April 2022. The spontaneous radiographic tumor growth rate was quantified by tumor volume segmentation and regression of the evolution of the mean tumor diameter over time and was compared with clinical, imaging, histomolecular, and survival data. Ninety-six patients were included. The spontaneous radiographic tumor growth rates (mean 17.8 ± 38.8 mm/year, range 0-243.5 mm/year) significantly varied according to IDH1/2 mutation (p < 0.001), grade of malignancy (p < 0.001), and presence of microvascular proliferation (p < 0.001). The spontaneous radiographic tumor growth rate allowed preoperative identification of high-grade cases: 100% of grade 3 and 4 IDH-mutant diffuse astrocytomas had a spontaneous radiographic tumor growth rate ≥ 8.0 mm/year, and 100% of IDH-wild-type glioblastomas had a spontaneous radiographic tumor growth rate ≥ 42.0 mm/year. A spontaneous radiographic growth rate ≥ 8.0 mm/year was an independent predictor of shorter progression-free (p = 0.014) and overall (p = 0.007) survival. A mitotic count threshold ≥ 4 mitoses was the optimal threshold for identifying aggressive IDH-mutant astrocytomas based on spontaneous radiographic tumor growth. The spontaneous radiographic tumor growth rates could be used as an additional tool to preoperatively screen tumor aggressiveness of adult-type diffuse gliomas without 1p19q codeletion.

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review

Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46). Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.

What Happens to Serum Levels of Visinin-Like Protein-1, Caveolin-1 and Neuron-Specific Enolase after Supratentorial Glioma Resection: A Pilot Study.

To observe changes in the serum levels of visinin-like protein-1 (VILIP-1), caveolin-1 (Cav-1) and neuron-specific enolase (NSE) after glioma resection. Consecutive 14 glioma patients with different histologic grade and 14 age and gender-matched healthy subjects were included in this pilot study. From the patients serum samples were taken in preoperative and on day 2 and 10 of postoperative periods. Healthy subjects provided serum sample once. The serum changes of three proteins were evaluated by ELISA. The results were compared between preoperative and postoperative periods and between patients and controls. Preoperative serum levels of VILIP-1 (p=0.008) and Cav-1 (p=0.012) were significantly higher in the patients. Mean serum levels of VILIP-1 (p=0.002) and Cav-1 (p=0.013) again were significantly higher than those of the controls. NSE did not show significant changes compared to controls in none of the periods. There was a steady decline regarding all three molecules from preoperative to postoperative day 10. However, statistical comparisons did not reveal any significant difference with respect the decline in any molecule. Significant positive correlation was detected between preoperative serum levels of VILIP-1 and Cav-1 (p=0.00001) in the patients and the controls (p=0.0000). This pilot study suggested that Cav-1 and particularly VILIP-1 may be used as a valuable serum biomarker for follow-up and for early detection of recurrence in high-grade gliomas. Future studies including larger cohort of patients with homogeneous group of glioma is required.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.