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Background: Extensive surgical resection has been found to be associated with longer survival in patients with gliomas, but the interactive prognostic value of molecular pathology of the surgical resection is unclear. This study evaluated the impact of molecular pathology and clinical characteristics on the surgical benefit in WHO grade 3 IDH-mutant gliomas. Methods: Clinical and pathological information of 246 patients with WHO grade 3 IDH-mutant gliomas were collected from the Chinese Glioma Genome Atlas database (2006–2020). The role of the extent of resection on overall survival, stratified by molecular pathology and clinical characteristics, was investigated. We then assessed prognostic factors using a univariate log-rank test and multivariate Cox proportional hazards model in the subgroups. Results: The extent of resection was an independent prognostic factor in the entire cohort, even when adjusted for molecular pathology. Gross total resection was found to be associated with longer survival in all patients and in the astrocytoma group but not in the oligodendroglioma group. Compared with subtotal resections, gross total resections resulted in a longer survival time for astrocytoma patients aged ≤ 45 years. However, there was no survival benefit from total resection in patients with astrocytoma aged > 45 years. Conclusions: Extensive resection benefits only a proportion of patients with WHO grade 3 IDH-mutant gliomas. Younger patients with astrocytomas had survival benefits from extensive resection. In addition to clinical characteristics (especially age), molecular pathology impacted prognosis in patients with gliomas. Our findings provide guiding information to neurosurgeons while planning surgeries. [ABSTRACT FROM AUTHOR]

Purpose: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. Methods: Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. Results: Median age at diagnosis was 1.81 years [IQR, 0.98–3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74–23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8–86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. Conclusion: Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children. [ABSTRACT FROM AUTHOR]

Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients. Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan–Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS). Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143–1.829) whereas ACVR1 (HR 0.712; 95% CI 0.518–0.976) and FGFR1 mutations (HR 0.408; 95% CI 0.208–0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR 0.620; 95% CI 0.386–0.996). Adjusted for age, gender, and tumor location, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors. Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas. Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death. Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1–7). Median age was 10.2 years (range: 0.8–53.8 years), and median tumor volume was 1.5 mL (range: 0.01–22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9–22.0 Gy) at a median isodose line of 57% (range: 50–90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55–422.1), p = 0.02). Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates. [ABSTRACT FROM AUTHOR]

Background: There is no clear consensus regarding the optimal treatment for glioblastoma (GBM) in the elderly. Hypofractionated radiation therapy (hRT) has emerged as a viable and comparable radiation regime compared to standard radiation therapy (sRT), however the survival effect of temozolomide (TMZ) with hRT is uncertain. The aim of this meta-analysis was to evaluate survival outcomes of hRT + TMZ vs sRT + TMZ in this specific demographic. Methods: Searches of 7 electronic databases from inception to January 2019 were conducted following the appropriate guidelines. Articles were screened against pre-specified criteria. The progression free survival (PFS) and overall survival (OS) metrics were then extracted and pooled by meta-analysis evaluating mean difference (MD). Results: A total of 7 individual comparative studies describing hRT + TMZ vs sRT + TMZ (n = 917) respectively satisfied inclusion criteria. Meta-analysis by random-effects modelling indicated that compared to sRT + TMZ, hRT + TMZ resulted in comparable PFS (MD 0.3 months; 95% CI − 2.4 to 2.9; I2 = 91.7%; P-effect = 0.85) and significantly shorter OS (MD − 3.5 months; 95% CI − 6.3 to − 0.6; I2 = 98.9%; P-effect = 0.02). Subgroup analysis between age definitions of elderly of > 65 vs > 70 years old both demonstrated the same significant trend with no statistical difference between the groups. Conclusion: The combination of hRT + TMZ is feasible in well-selected elderly GBM cases, and appears to confer a statistically comparable PFS compared to sRT + TMZ. However, expectations that the OS with hRT + TMZ is comparable to that of sRT + TMZ in all elderly GBM presentations should be tempered. It is likely a specific subgroup of elderly GBM patients will benefit greatly from the addition of TMZ to hRT, and greater investigation is needed to identify their characteristics. [ABSTRACT FROM AUTHOR]

Background: Although the majority of current medulloblastoma adjuvant therapy protocols treat patients with ≥ 1.5 cm2 residual tumor as high risk with increased craniospinal irradiation, the true prognostic significance of extent of resection (EOR) in medulloblastoma is unknown.Objectives: We sought to synthesize the body of literature on EOR and survival to determine if a definitive association exists.Data sources/eligibility criteria: A PubMed search was conducted for the terms “medulloblastoma” combined with “extent of resection,” “overall survival,” “progression free survival,” “gross total resection,” “near total resection,” “partial resection,” or “subtotal resection.” Studies that performed a statistical analysis of EOR and survival were included.Results: Sixteen articles including 1489 patients found a statistically significant association between EOR and survival, 20 articles including 2335 patients did not find a significant association between EOR and survival, and 14 articles including 2950 patients had mixed results. The three articles that accounted for molecular subgroup found varying associations between EOR and progression free survival, while no association was found between EOR and overall survival.Limitations: This review is limited by inconsistent definitions of EOR, the retrospective nature of the articles analyzed, and infrequent use of multivariate statistical analyses.Conclusions: The prognostic importance of EOR for medulloblastoma is unclear and warrants re-evaluation, particularly in the context of molecular subgrouping. [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB.Method: Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis.Results: In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model.Conclusions: In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study is to assess whether postoperative residual non-enhancing volume (PRNV) is correlated and predictive of overall survival (OS) in glioblastoma (GBM) patients.Methods: We retrospectively analyzed a total 134 GBM patients obtained from The University of Texas MD Anderson Cancer Center (training cohort, n = 97) and The Cancer Genome Atlas (validation cohort, n = 37). All patients had undergone postoperative magnetic resonance imaging immediately after surgery. We evaluated the survival outcomes with regard to PRNV. The role of possible prognostic factors that may affect survival after resection, including age, sex, preoperative Karnofsky performance status, postoperative nodular enhancement, surgically induced enhancement, and postoperative necrosis, was investigated using univariate and multivariate Cox proportional hazards regression analyses. Additionally, a recursive partitioning analysis (RPA) was used to identify prognostic groups.Results: Our analyses revealed that a high PRNV (HR 1.051; p-corrected = 0.046) and old age (HR 1.031; p-corrected = 0.006) were independent predictors of overall survival. This trend was also observed in the validation cohort (higher PRNV: HR 1.127, p-corrected  = 0.002; older age: HR 1.034, p-corrected  = 0.022). RPA analysis identified two prognostic risk groups: low-risk group (PRNV < 70.2 cm3; n = 55) and high-risk group (PRNV ≥ 70.2 cm3; n = 42). GBM patients with low PRNV had a significant survival benefit (5.6 months; p = 0.0037).Conclusion: Our results demonstrate that high PRNV is associated with poor OS. Such results could be of great importance in a clinical setting, particularly in the postoperative management and monitoring of therapy. [ABSTRACT FROM AUTHOR]

Glioblastoma stands out as the most frequent central nervous system neoplasia, presenting a poor prognosis. The aim of this study was to verify the frequency and clinical significance of the aneuploidy of chromosomes 7 and 10, EGFR amplification, PTEN and TP53 deletions and 1p/19q deficiency in adult patients diagnosed with glioblastoma. The sample consisted of 40 patients treated from November 2011 to March 2015 at two major neurosurgery services from Southern Brazil. Molecular cytogenetic analyses of the tumor were performed through fluorescent in situ hybridization (FISH). The clinical features evaluated consisted of age, sex, tumor location, clinical symptoms, family history of cancer, type of resection and survival. The mean age of the patients was 59.3 years (ranged from 41 to 83). Most of them were males (70%). The median survival was 145 days. Chromosome 10 monosomy was detected in 52.5% of the patients, chromosome 7 polysomy in 50%, EGFR amplification in 42.5%, PTEN deletion in 35%, TP53 deletion in 22.5%, 1p deletion in 5% and 19q deletion in 7.5%. Age was shown to be a prognostic factor, and patients with lower age presented higher survival ( p = 0.042). TP53 and PTEN deletions had a negative impact on survival ( p = 0.011 and p = 0.037, respectively). Our data suggest that TP53 and PTEN deletions may be associated with a poorer prognosis. These findings may have importance over prognosis determination and choice of the therapy to be administered. [ABSTRACT FROM AUTHOR]

The S100B protein is associated with brain damage and a breached blood-brain barrier. A previous pilot study showed that high serum levels of S100B are associated with shorter survival in glioma patients. The aim of our study was to assess the prognostic value in terms of survival and longitudinal dynamics of serum S100B for patients with newly diagnosed and recurrent glioma. We obtained blood samples from patients with newly diagnosed and recurrent glioma before the start (baseline) and at fixed time-points during temozolomide chemotherapy. S100B-data were dichotomized according to the upper limit of the reference value of 0.1 μg/L. Overall survival (OS) was estimated with Kaplan-Meier curves and groups were compared with the log rank analysis. To correct for potential confounders a Cox regression analysis was used. We included 86 patients with newly-diagnosed and 27 patients with recurrent glioma. Most patients in both groups had baseline serum levels within normal limits. In the newly diagnosed patients we found no significant difference in OS between the group of patients with S100B levels >0.1 μg/L at baseline compared to those with <0.1 μg/L. In the patients with recurrent glioma we found a significantly shorter OS for patients with raised levels. In both groups, S100B values did not change significantly throughout the course of the disease. Serum S100B levels do not seem to have prognostic value in newly diagnosed glioma patients. In recurrent glioma patients S100B might be of value in terms of prognostication of survival. [ABSTRACT FROM AUTHOR]

Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively ( P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival. [ABSTRACT FROM AUTHOR]

The methylation of O-methylguanine DNA methyltransferase ( MGMT) gene promoter is a key biological marker in clinical neuro-oncology. Nevertheless, there is no consensus concerning the best technique for its assessment. In a recent study comparing five methods to analyze MGMT status, we found that the best prediction of survival was obtained with a pyrosequencing (PSQ) test assessing methylation of 5 CpGs (CpGs 74-78). In the present study we extended our PSQ analysis to 16 CpGs (CpGs 74-89) identified as critical for transcriptional control of the gene. The predictive value of the methylation levels at each CpG, as well as the mean methylation levels of selected sets of consecutive CpGs was tested in a cohort of 89 de novo glioblastoma patients who had received standard of care treatment (Stupp protocol). Using an optimal risk cut-off, each CpG or combination of CpGs, was associated with overall survival (OS) and progression free survival. The best predictive models for OS after stratification on performance score and age were obtained with CpG 89, CpG 84 and mean methylation of CpG 84-88 (Hazard ratio (HR), 0.31; p < 0.0001). The improvement compared to the predictive value of the test analyzing average methylation of CpG 74-78 (HR, 0.32; p < 0.0001) was however marginal. We recommend to test CpGs 74-78 when analyzing MGMT methylation status by PSQ because a commercial kit that has successfully been used in several studies is available, allowing reproducible and comparable results from one laboratory to another. [ABSTRACT FROM AUTHOR]

Pediatric infratentorial ependymomas are difficult to cure. Despite the availability of advanced therapeutic modalities for brain tumors, total surgical resection remains the most important prognostic factor. Recently, histological grade emerged as an independent prognostic factor for intracranial ependymoma. We retrospectively reviewed the treatment outcome of 33 pediatric patients with infratentorial ependymoma. Progression-free survival (PFS) and overall survival (OS) rates were calculated and relevant prognostic factors were analyzed. Fourteen patients (42%) were under the age of 3 at diagnosis. Gross total resection was achieved in 16 patients (49%). Anaplastic histology was found in 13 patients (39%). Adjuvant therapies were delayed until progression in 12 patients (36%). Actuarial PFS rates were 64% in the first year and 29% in the fifth year. Actuarial OS rates were 91% in the first year and 71% in the fifth year. On univariate analysis, brainstem invasion ( P = 0.047), anaplastic histology ( P = 0.004), higher mitotic count ( P = 0.001), and higher Ki-67 index ( P = 0.004) were significantly related to a shorter PFS. Gross total resection ( P = 0.029) and a greater age at diagnosis ( P = 0.033) were significantly related to a longer PFS. On multivariate analysis, anaplastic histology alone was significantly related to a shorter PFS ( P = 0.023). Gross total resection ( P = 0.039) was significantly related to a longer overall survival (OS) on multivariate analysis. Anaplastic histology and gross total resection were the most important clinical factors affecting PFS and OS, respectively. Anaplastic histology, mitotic count, and Ki-67 index can be used as universal and easily available prognostic parameters in infratentorial ependymomas. [ABSTRACT FROM AUTHOR]

Oligoastrocytomas form a poorly defined subgroup of glialtumors, and few clinical series have been reported.We performed a retrospective study to elucidate thehistopathological features of these tumors and to relatethe clinical signs and symptoms and proliferative potentialto survival. Oligoastrocytomas were defined as glial tumorswith at least 10% neoplastic astrocytes and 10%neoplastic oligodendrocytes; tumors were graded with the St.Anne-Mayo criteria for astrocytomas and oligodendrogliomas. Proliferative potentialwas estimated with antibodies against proliferating cell nuclearantigen (PCNA). Median survival of 52 patients (medianage, 42 years) was 75 weeks (range 2–703weeks). Actuarial 1-, 2-, 3-, and 5-year survivalrates were 67%, 43%, 40%, and 29%, respectively.For 15 patients with grade 3 and 33with grade 4 lesions (St. Anne-Mayo astrocytoma classification),median survival was 217 and 55 weeks, respectively.For 19 patients with grade 2 and 33with grade 3 lesions (St. Anne-Mayo oligodendroglioma classification),median survival was 305 and 55 weeks, respectively.Interobserver agreement between three experienced neuropathologists on identificationof astrocytes, oligodendrocytes, and unclassifiable cells was low,indicating considerable subjectivity in the histopathological diagnosis. MedianPCNA labeling indices correlated with tumor grade, butindividual values varied so widely within grades thatthey had no predictive value for survival. Ina multivariate analysis, symptoms of increased intracranial pressureand microvascular proliferation were independently associated with poorprognosis. The biological behavior of subgroups appeared tobe distinctly less aggressive than that of ‘pure’astrocytomas of similar grade. Better histopathological definition ofoligoastrocytomas and improved assessment of percentages of constituentcell types may allow more accurate prognosis. [ABSTRACT FROM AUTHOR]