Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature.

PURPOSE: The rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas. METHODS: From 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors' institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. Progression-free survival (PFS) and overall survival (OS) rates were compared. Additionally, we performed a systematic literature review to compile further survival data on cerebellar glioblastoma patients. RESULTS: The median OS for cerebellar glioblastoma patients was 18 months (95% CI 11-25). The balanced matched-pair analysis showed no significant difference in survival when compared to patients with supratentorial glioblastoma, exhibiting a median OS of 23 months (95% CI 0-62) (p = 0.63). Respective values for PFS were 8 months (95% CI 4-12) for cerebellar and 7 months (95% CI 0-16) for supratentorial glioblastoma (p = 0.2). The systematic review revealed that median OS for cerebellar glioblastoma in current literature ranges from 7 to 21 months. CONCLUSIONS: The present findings indicate that patients with supra- and infratentorial glioblastoma do not significantly differ in regard to survival outcome parameters. This similarity in prognosis might encourage clinicians to consider surgical interventions for both supra- and infratentorial glioblastoma in a similar manner.

Impact of frailty on survival glioblastoma, IDH-wildtype patients.

PURPOSE: Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. METHODS: We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. RESULTS: A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). CONCLUSION: In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

Factors associated with longer survival among older medicare patients after diagnosis of supratentorial primary brain malignancies: a retrospective cohort study.

OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.

Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

The majority of supratentorial ependymomas in children contain oncogenic fusions, such as ZFTA-RELA or YAP1-MAMLD1. In contrast, posterior fossa (PF) ependymomas lack recurrent somatic mutations and are classified based on gene expression or methylation profiling into group A (PFA) and group B (PFB). We have applied a novel method, NanoString nCounter Technology, to identify four molecular groups among 16 supratentorial and 50 PF paediatric ependymomas, using 4-5 group-specific signature genes. Clustering analysis of 16 supratentorial ependymomas revealed 9 tumours with a RELA fusion-positive signature (RELA+), 1 tumour with a YAP1 fusion-positive signature (YAP1+), and 6 not-classified tumours. Additionally, we identified one RELA+ tumour among historically diagnosed CNS primitive neuroectodermal tumour samples. Overall, 9 of 10 tumours with the RELA+ signature possessed the ZFTA-RELA fusion as detected by next-generation sequencing (p = 0.005). Similarly, the only tumour with a YAP1+ signature exhibited the YAP1-MAMLD1 fusion. Among the remaining unclassified ependymomas, which did not exhibit the ZFTA-RELA fusion, the ZFTA-MAML2 fusion was detected in one case. Notably, among nine ependymoma patients with the RELA+ signature, eight survived at least 5 years after diagnosis. Clustering analysis of PF tumours revealed 42 samples with PFA signatures and 7 samples with PFB signatures. Clinical characteristics of patients with PFA and PFB ependymomas corroborated the previous findings. In conclusion, we confirm here that the NanoString method is a useful single tool for the diagnosis of all four main molecular groups of ependymoma. The differences in reported survival rates warrant further clinical investigation of patients with the ZFTA-RELA fusion.

Supratentorial Extraventricular Ependymomas: Imaging Features and the Added Value of Apparent Diffusion Coefficient.

OBJECTIVE: To improve the understanding and the diagnosis of intracranial ependymal tumors. METHODS: The clinical, radiological and prognostic features of 48 supratentorial extraventricular ependymomas and 74 intraventricular ependymomas were summarized and compared. RESULTS: Supratentorial extraventricular ependymomas, most often located in the frontal lobe (33.3%) and classified as grade III (75.0%), had relatively large eccentric cysts (3.07 ± 2.03 cm), significant enhancement (84.8%), low apparent diffusion coefficient (ADC) values, and associated with higher mortality (41.3%). The majority of intraventricular lesions occurred in the fourth ventricle (86.5%) and classified as grade II (78.4%), had relatively small and multiple cystic changes (1.04 ± 0.87 cm), slight or moderate enhancement (76.9%), high ADC values and associated with lower mortality (20.7%). There were few significant differences between grade II and grade III tumors in these 2 groups, respectively. Young age, high grade and low ADC values are worse prognostic indicators for patients with supratentorial extraventricular ependymomas, but not for those with intraventricular ependymomas. CONCLUSIONS: Conventional radiological features, combined with clinical manifestations and quantitative information provided by diffusion-weighted imaging, may not only enhance the diagnosis and assist in determining prognosis but also provide a better pathophysiological understanding of intracranial ependymal tumors.

Comparative Analysis of Survival Outcomes and Prognostic Factors of Supratentorial versus Cerebellar Glioblastoma in the Elderly: Does Location Really Matter?

BACKGROUND: Cerebellar glioblastomas (cGBMs) are rare tumors that are uncommon in the elderly. In this study, we compare survival outcomes and identify prognostic factors of cGBM compared with the supratentorial (stGBM) counterpart in the elderly. METHODS: Data from the SEER 18 registries were used to identify patients with a glioblastoma (GBM) diagnosis between 2000 and 2016. The log-rank method and a multivariable Cox proportional hazards regression model were used for analysis. RESULTS: Among 110 elderly patients with cGBM, the median age was 74 years (interquartile range [IQR], 69-79 years), 39% were female and 83% were white. Of these patients, 32% underwent gross total resection, 73% radiotherapy, and 39% chemotherapy. Multivariable analysis of the unmatched and matched cohort showed that tumor location was not associated with survival; in the unmatched cohort, insurance status (hazard ratio [HR], 0.11; IQR, 0.02-0.49; P = 0.004), gross total resection (HR, 0.53; IQR, 0.30-0.91; P = 0.022), and radiotherapy (HR, 0.33; IQR, 0.18-0.61; P < 0.0001) were associated with better survival. Patients with cGBM and stGBM undergoing radiotherapy (7 months vs. 2 months; P < 0.001) and chemotherapy (10 months vs. 3 months; P < 0.0001) had improved survival. Long-term mortality was lower for cGBM in the elderly at 24 months compared with the stGBM cohort (P = 0.007). CONCLUSIONS: In our study, elderly patients with cGBM and stGBM have similar outcomes in overall survival, and those undergoing maximal resection with adjuvant therapies, independent of tumor location, have improved outcomes. Thus, aggressive treatment should be encouraged for cGBM in geriatric patients to confer the same survival benefits seen in stGBM. Single-institutional and multi-institutional studies to identify patient-level prognostic factors are warranted to triage the best surgical candidates.

The Merits of Awake Craniotomy for Glioblastoma in the Left Hemispheric Eloquent Area: One Institution Experience.

OBJECTIVE: Awake craniotomy (AC) with intraoperative stimulation mapping is the standard treatment for gliomas, especially those on the eloquent cortex. Many studies have reported survival benefits with the use of AC in patients with glioma, however most of these studies have focused on low-grade glioma. The aim of this study was to evaluate the experience of one treatment center over 10 years for resection of left hemispheric eloquent glioblastoma. METHODS: This retrospective analysis included 48 patients with left hemispheric eloquent glioblastoma who underwent AC and 61 patients who underwent surgery under general anesthesia (GA) between 2008 and 2018. Perioperative risk factors, extent of resection (EOR), preoperative and postoperative Karnofsky Performance Score (KPS), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: The postoperative KPS was significantly lower in the GA patients compared to the AC patients (p = 0.002). The EOR in the GA group was 90.2% compared to 94.9% in the AC group (p = 0.003). The mean PFS was 18.9 months in the GA group and 23.2 months in the AC group (p = 0.001). The mean OS was 25.5 months in all patients, 23.4 months in the GA group, and 28.1 months in the AC group (p < 0.001). In multivariate analysis, the EOR and preoperative KPS independently predicted better OS. CONCLUSION: The patients with left hemispheric eloquent glioblastoma in this study had better neurological outcomes, maximal tumor removal, and better PFS and OS after AC than surgery under GA. Awake craniotomy should be performed in these patients if the resources are available.

Absence of Gender Disparity in Thirty-Day Morbidity and Mortality After Supratentorial Brain Tumor Resection.

BACKGROUND: Gender is a complex social determinant of health affected by both social and biological factors. There is a need to investigate the effect of gender on outcomes, in the absence of confounding characteristics, to mitigate disparities in care. METHODS: A total of 1970 consecutive patients at a university health system undergoing nonmeningioma supratentorial brain tumor resection over a 6-year period (June 9, 2013-April 26, 2019) were analyzed retrospectively. Coarsened exact matching was used to match patients on demographic factors including history of previous surgery, median household income, and race. Outcomes assessed included readmission, emergency department visit, unplanned reoperation, and mortality within 30 days of surgery. Regression analysis was performed among a prematched population and between the matched cohorts with significance set at a P value <0.05. RESULTS: Within the matched population, no significant difference was observed between male and female patients in any of the recorded outcomes after nonmeningioma supratentorial brain tumor resection, including readmission, emergency department evaluation, unplanned reoperation, and mortality within 30 days of resection (P = 0.28-0.85). Similarly, no significant difference was found in any of the morbidity and mortality outcomes in the prematched regression analysis (P = 0.10-0.70). CONCLUSIONS: When gender is isolated from race, household economics, and other key factors, it does not seem to independently predict morbidity or mortality in the short-term postoperative window after supratentorial brain tumor resection. Future studies should investigate the impact of gender in longer follow-up and its interrelation with other social determinants of health contributing to outcome disparity.

Glioblastoma survival is better analyzed on preradiotherapy MRI than on postoperative MRI residual volumes: A retrospective observational study.

OBJECTIVES: Establishing an overall survival prognosis for resected glioblastoma during routine postoperative management remains a challenge. The aim of our single-center study was to assess the usefulness of basing survival analyses on preradiotherapy MRI (PRMR) rather than on postoperative MRI (POMR). PATIENTS AND METHODS: A retrospective review was undertaken of 75 patients with glioblastoma treated at our institute. We collected overall survival and MRI volumetric data. We analyzed two types of volumetric data: residual tumor volume and extent of resection. Overall survival rates were compared according to these two types of volumetric data, calculated on either POMR or PRMR and according to the presence or absence of residual enhancement. RESULTS: Analysis of volumetric data revealed progression of some residual tumors between POMR and PRMR. Kaplan-Meier analysis of the correlations between extent of resection, residual tumor volume, and overall survival revealed significant differences between POMR and PRMR data. Both MRI scans indicated a difference between the complete resection subgroup and the incomplete resection subgroup, as median overall survival was longer in patients with complete resection. However, differences were significant for PRMR (25.3 vs. 15.5, p =  0.012), but not for POMR (21.3 vs. 15.8 months, p =  0.145). With a residual tumor volume cut-off value of 3 cm3, Kaplan-Meier survival analysis revealed non-significant differences on POMR (p =  0.323) compared with PRMR (p =  0.007). CONCLUSION: Survival in patients with resected glioblastoma was more accurately predicted by volumetric data acquired with PRMR. Differences in predicted survival between the POMR and PRMR groups can be attributed to changes in tumor behavior before adjuvant therapy.

Assessing the Role of Patient Race in Disparity of 90-Day Brain Tumor Resection Outcomes.

BACKGROUND: This study assesses the influence of race on patient outcomes in a brain tumor surgery population. METHODS: Coarsened exact matching was used to retrospectively analyze 1700 supratentorial brain tumor procedures over a 6-year period (June 7, 2013 to April 29, 2019) at a single, multihospital academic medical center. Outcome measures included readmission, mortality, emergency room visits, and reoperation. RESULTS: McNemar test (mid-P) showed no significant difference in 90-day mortality between the 2 races (P = 0.3018). However, there was a significant difference in 90-day readmissions between the 2 races (P = 0.0237). There was no significant difference in 90-day emergency room visits (P = 0.0579), 90-day return to surgery after index admission (P = 0.6015), or return to surgery within 90 days (P = 0.6776) between the 2 races. There was also no significant difference in return to surgery for the duration of the follow-up period (P = 0.8728). CONCLUSIONS: This study suggests that race alone does not result in disparate outcomes; however, there was an associated difference in 90-day postsurgical readmissions. Despite coarsened exact matching, persistent differences in median household income may play a role in the disparate outcome noted.

Utility of copy number variants in the classification of intracranial ependymoma.

Ependymomas are neuroepithelial tumors that differentiate along the ependymal cell lineage, a lining of the ventricles of the brain and the central canal of the spinal cord. They are rare in adults, but account for around 9% of brain tumors in children, where they usually have an aggressive course. Efficient stratification could lead to improved care but remains a challenge even in the genomic era. Recent studies proposed a multivariate classification system based on tumor location, age, and broad genomic findings like global patterns of methylation and copy number variants (CNVs). This system shows improved prognostic utility, but is relatively impractical in the routine clinical setting because it necessitates multiple diagnostic tests. We analyzed 13 intracranial grade II and III ependymoma specimens on a DNA microarray to identify discrete CNVs that could support the existing classification. The loss of chr22 and the gain of 5p15.31 were common throughout our cohort (6 and 11 cases, respectively). Other CNVs correlated well with the previously proposed classification system. For example, gains of chr20 were unique to PF-EPN-B tumors of the posterior fossa and may differentiate them from PF-EPN-A. Given the ease of detecting CNVs using multiple, clinically validated methods, these CNVs should be further studied to confirm their diagnostic and prognostic utility, for incorporation into clinical testing algorithms.

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

[Clinical prognostic factors of adult supratentorial glioblastoma].

Objective: To analyze the treatment effect of patients with glioblastoma (GBM) and explore prognostic factors. Methods: The clinical data of 635 patients diagnosed as GBM at Neurosurgical Oncology Department Ⅳ of Beijing Tiantan Hospital, Capital Medical University from January 2007 to March 2018 were retrospectively reviewed. There were 386 males and 249 females with an age of (48.7±11.8) years (range: 18-75 years). Patients were divided into three groups according to the time of admission: 2007-2010 group(n=174), 2011-2014 group (n=237) and 2015-2018 group (n=224). Kaplan-Meier plot was used to analyze the effects of different treatment periods, treatment schemes and clinical factors on the survival of patients with GBM. Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: The median progression-free survival (PFS) and overall survival (OS) of patients in 2007-2010 group, 2011-2014 group, 2015-2018 group was 9.0 months (95% CI: 7.5-10.5), 10.0 months (95% CI: 8.8-11.2), 12.0 months (95% CI: 10.7-13.3) and 17.0 months (95% CI: 13.2-20.8), 20.0 months (95% CI: 16.9-23.1), 23.0 months(95% CI: 17.5-28.5), respectively. The PFS and OS of patients improved significantly over the years (χ(2)=9.693, P=0.008 and χ(2)=8.616, P=0.013). Multivariate survival analysis showed that age, extent of resection, radiotherapy and tumor distant dissemination were independent prognostic factors (all P<0.05). Conclusions: With the continuous development of clinical treatment regimen, the therapeutic effect of Chinese GBM patients has improved remarkably. Age, extent of resection, radiotherapy and tumor distant dissemination are independent prognostic factors associated with survival time.

Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival.

BACKGROUND AND PURPOSE: Glioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management. MATERIALS AND METHODS: A total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBVL) with the lowest ADC quartile (ADCL) and highest ADC quartile (ADCH) in each tumor, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier's and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival. RESULTS: Two compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADCL-rCBVL compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADCL-rCBVL compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). CONCLUSIONS: Our results suggest that the ADCL-rCBVL compartment may potentially indicate a clinically measurable resistant compartment.

Surgical outcome in cortical ependymoma: A single centre experience of 18 cases.

Cortical ependymomas (CE) are rare subset of supratentorial ependymoma which are located in the peripheral cortical rim without any connection to the ventricular lining. With limited cases previously reported, current knowledge on diagnosis and management of tumors is lacking. We present the largest single center experience on CE reported so far and highlight their clinico-radiological aspects, histopathological features as well the results of their surgical excision. We studied 18 CE patients undergoing surgical excision at our center between September 2009 to November 2017. Clinical, radiological, histopathological and operative data was obtained from hospital records. Functional assessment of our patients were done using the Karnofsky's performance score (KPS). Survival analysis was done using Kaplan-Meier method and log rank test. Mean age of patients in our study group was 19 ±â€¯11.1 years. Frontal lobe was the most frequently involved region. Features of raised intracranial pressure like holocranial headache (n = 15, 83.33%) and vomiting (n = 9, 50%) were most common presenting complaints in our study. Gross total resection of tumor was achieved in eleven patients (61.11%). Histopathology showed equal number (n = 9) of WHO grade 2 and 3 ependymoma. During 111 months follow-up, four patients (22.22%) developed recurrence and three patients (16.66%) died. Five years overall survival (OS), progression-free survival (PFS) rate were 74.3% and 70.7%. In view of higher risk of progression to higher histo-pathological grade and local recurrence years after surgical excision, a long clinical and radiological follow-up is advised.

Posterior fossa recurrence of WHO grade II and III supratentorial gliomas.

OBJECTIVE/BACKGROUND: Posterior fossa (PF) recurrences of supratentorial (ST) World Health Organization (WHO) grade II and III gliomas are thought to be rare and to have grim prognoses. METHODS: This study entailed searching through our database and reviewing the records of patients with grade II and III ST gliomas who developed PF recurrence with no overt secondary gliomatosis or leptomeningeal spread. RESULTS: Of 2266 grade II and III gliomas, 14 fulfilled the inclusion criteria: 5 oligodendrogliomas (O; 1 OII, 4 OIII); 7 astrocytomas (A; 4 AII, 3 AIII); and 2 oligoastrocytomas (OA; both OAIII). The male/female gender ratio was 10/4, and median age at recurrence was 43 years. Two groups were identified. In one group (n=8; 1 AII, 3 AIII, 2 OAIII, 2 OIII), a rapidly growing contrast-enhancing PF mass (6/8) was associated with ST progression, and median survival time after detection was only 6.5 months despite radiotherapy and/or chemotherapy. In the second group (n=6; 3 AII, 1 OII, and 2 OIII), a non-contrast-enhancing (5/6), asymptomatic (5/6), slow-growing PF mass remained isolated, and treatment with radio- or chemotherapy produced objective responses in three patients and durable stabilization in the remaining three. After a median follow-up of 63months, only one patient died due to delayed recurrence of the ST lesion, while the remaining five patients are still alive. CONCLUSION: Non-contiguous PF relapses of ST grade II and III gliomas are rare. A high-grade ST tumor that is concomitantly progressing appears to be a predictor of poor survival. Conversely, the tumor course may be indolent if the ST lesion is low-grade and non-progressive at the time of PF involvement. The possible mechanism(s) behind this tropism are also discussed.

Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma.

PURPOSE: To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL). METHODS AND MATERIALS: A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/µL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method. RESULTS: Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/µL vs 900 cells/µL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different. CONCLUSIONS: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

Clinical prognostic value of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in glioblastoma.

The presence of the single-nucleotide polymorphism (SNP) rs11554137:C>T in the IDH1 gene is associated with a significantly lower survival in acute myeloid leukemia patients. The impact of its presence in glioblastoma on patient survival is unclear. We retrospectively reviewed 171 adult (> 18 years of age) patients treated at a single, tertiary academic center for supratentorial glioblastoma (WHO grade IV) between 2013 and 2017. We conducted Kaplan-Meier overall and progression free survival analyses based on the IDH1 and IDH2 gene status of patients' glioblastoma (IDH wild type, mutant, and IDH1 rs11554137:C>T SNP). Multivariate Cox survival analyses were conducted accounting for age at diagnosis, preoperative Karnofsky performance status score, treatment (extent of resection, postoperative radiotherapy, and temozolomide), IDH gene variant, and MGMT promoter methylation status. Presence of rs11554137:C>T SNP in glioblastoma samples did not correlate with presence of IDH1 mutation. Patients with rs11554137:C>T SNP did not have histories of prior lower-grade gliomas. Patients with IDH mutant glioblastoma had a distinctly higher survival profile than both rs11554137:C>T SNP and IDH wild type glioblastomas. No survival difference was noted between patients with glioblastoma harboring the SNP and patients with IDH wild type glioblastoma. In this study, clinical prognostication in glioblastoma patients was largely dependent on the classification of IDH mutant and wild type glioblastoma, and not on the presence of IDH1 rs11554137:C>T SNP in the tumor.

Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation.

Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%-60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses -22 (n = 11), -14 (n = 7), -13 (n = 5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.

Clinical, radiological, and histological features and treatment outcomes of supratentorial extraventricular ependymoma: 14 cases from a single center.

OBJECTIVE Reports on supratentorial extraventricular ependymoma (STE) are relatively rare. The object of this study was to analyze the clinical, radiological, and histological features and treatment outcomes of 14 patients with STE. METHODS Overall, 227 patients with ependymoma underwent surgical treatment in the authors' department between January 2010 and June 2015; 14 of these patients had STE. Data on clinical presentation, radiological studies, histopathological findings, surgical strategies, and treatment outcomes in these 14 cases were retrospectively analyzed. RESULTS The patients consisted of 6 women and 8 men (sex ratio 0.75). Mean age at diagnosis was 24.5 ± 13.5 years (range 3-48 years). Tumors were predominantly located in the frontal and temporal lobes (5 and 4 cases, respectively). Typical radiological features were mild to moderate heterogeneous tumor enhancements on contrast-enhanced MRI. Other radiological features included well-circumscribed, "popcorn" enhancement and no distinct adjoining brain edema. Gross-total resection was achieved in 12 patients, while subtotal removal was performed in 2. Radiotherapy was administered in 7 patients after surgery. Seven tumors were classified as WHO Grade II and the other 7 were verified as WHO Grade III. The mean follow-up period was 22.6 months (range 8-39 months). There were 3 patients with recurrence, and 2 of these patients died. CONCLUSIONS Supratentorial extraventricular ependymoma has atypical clinical presentations, various radiological features, and heterogeneous histological forms; therefore, definitive diagnosis can be difficult. Anaplastic STE shows malignant biological behavior, a higher recurrence rate, and a relatively poor prognosis. Gross-total resection with or without postoperative radiotherapy is currently the optimal treatment for STE.