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Carmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect. An observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005-2018). Twenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 surgical bed cysts and six bacterial abscesses. All patients with a surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p

Tumor-treating fields (TTFields) are alternating electric fields applied continuously to the brain by attaching two-pair arrays on the scalp. Although TTFields therapy has demonstrated efficacy against supratentorial glioblastoma (GBM) in adults, its safety and efficacy in children have not been confirmed. Despite differences in the genetic etiology of the adult and pediatric forms of GBM, both have certain clinical behaviors in common, allowing us to test TTFields therapy in pediatric GBM. Recently, several, pediatric case-series using TTFields therapy have been published, and a few, prospective, pediatric studies are ongoing. Because GBMs are extremely rare in pediatric patients, where they comprise a wide variety of genetic subtypes, these pediatric studies are feasibility studies targeting various types of malignant brain tumor. Although they are important for confirming the safety and feasibility of TTFields therapy in the pediatric population, confirming its efficacy against each type of pediatric brain tumor, including the GBM, is difficult. Our clinical research team, therefore, planned an investigator-initiated clinical trial targeting pediatric supratentorial GBMs (as in adults) with the aim of expanding regulatory approval of TTFields therapy for pediatric GBM treatment based on safety and exploratory efficacy data in combination with the accumulated evidence on adult GBMs.

OBJECTIVEIntraoperative MRI (iMRI) is used in the surgical treatment of glioblastoma, with uncertain effects on outcomes. The authors evaluated the impact of iMRI on extent of resection (EOR) and overall survival (OS) while controlling for other known and suspected predictors.METHODSA multicenter retrospective cohort of 640 adult patients with newly diagnosed supratentorial glioblastoma who underwent resection was evaluated. iMRI was performed in 332/640 cases (51.9%). Reviews of MRI features and tumor volumetric analysis were performed on a subsample of cases (n = 286; 110 non-iMRI, 176 iMRI) from a single institution.RESULTSThe median age was 60.0 years (mean 58.5 years, range 20.5–86.3 years). The median OS was 17.0 months (95% CI 15.6–18.4 months). Gross-total resection (GTR) was achieved in 403/640 cases (63.0%). Kaplan-Meier analysis of 286 cases with volumetric analysis for EOR (grouped into 100%, 95%–99%, 80%–94%, and 50%–79%) showed longer OS for 100% EOR compared to all other groups (p < 0.01). Additional resection after iMRI was performed in 104/122 cases (85.2%) with initial subtotal resection (STR), leading to a 6.3% mean increase in EOR and a 2.2-cm3 mean decrease in tumor volume. For iMRI cases with volumetric analysis, the GTR rate increased from 54/176 (30.7%) on iMRI to 126/176 (71.5%) postoperatively. The EOR was significantly higher in the iMRI group for intended GTR and STR groups (p = 0.02 and p < 0.01, respectively). Predictors of GTR on multivariate logistic regression included iMRI use and intended GTR. Predictors of shorter OS on multivariate Cox regression included older age, STR, isocitrate dehydrogenase 1 (IDH1) wild type, no O6-methylguanine DNA methyltransferase (MGMT) methylation, and no Stupp therapy. iMRI was a significant predictor of OS on univariate (HR 0.82, 95% CI 0.69–0.98; p = 0.03) but not multivariate analyses. Use of iMRI was not associated with an increased rate of new permanent neurological deficits.CONCLUSIONSGTR increased OS for patients with newly diagnosed glioblastoma after adjusting for other prognostic factors. iMRI increased EOR and GTR rate and was a significant predictor of GTR on multivariate analysis; however, iMRI was not an independent predictor of OS. Additional supporting evidence is needed to determine the clinical benefit of iMRI in the management of glioblastoma.

Glioblastoma (GBM) is an aggressive cancerous neoplasm of the brain that has numerous morphological subtypes. Primitive neuroectodermal differentiation (hereafter, referred to as embryonal tumor [ET] differentiation) in GBM is one of them and is known to occur in adults. Their presentation in pediatric population is rare and can be a source of diagnostic confusion. The dual pathology leads to doubts where one could ask whether it is ET differentiation in GBM specimen or glial differentiation in ET specimen. This histological discrimination has a bearing on the treatment regimens and prognosis. We report a case of a 10-year-old boy presenting with a supratentorial GBM, isocitrate dehydrogenase wild type with ET differentiation, and multiple benign bony lesions of both extremities. He underwent surgical excision for the brain neoplasm followed by radiotherapy and has shown prolonged survival with no recurrence. In this article, we discuss prognostic factors associated with long-term survival of these tumors.

OBJECTIVE: Pediatric supratentorial glioblastoma (psGBM) is rare tumor of the central nervous system, the prognosis of it remains controversial due to their rarity. The aim of this study was to evaluate characteristics of pediatric supratentorial glioblastoma, effectiveness of modern treatment modalities, and detect factors related to prognosisMETHODS: Twenty-eight children under 18 years old were pathologically diagnosed with supratentorial glioblastoma at The First Affiliated Hospital of Zhengzhou University between 2014 and 2020.Epidemiological characteristics, clinical features, imaging features, functional outcomes, overall survival, progression-free survival according to multimodal treatments were reviewed retrospectively.RESULTS: Median survival time of children with supratentorial glioblastoma was 11 months and median progression-free survival was 7 months. Half-, one-year and two-year overall survival probabilities were 64.3%,42.9% and 14.3%, respectively. Half-, one-year and two-year progression-free survival probabilities were 53.6%,21.4% and 9.5%, respectively. Extent of resection(p=0.011) and postoperative concurrent chemoradiotherapy (p=0.032) are independent factors of prognosis while gender, age, initial symptom, tumor side, enhancement character, preoperative KPS and with or without cystoid variation and necrosis are not. Three patients lived longer than 2 years, one patient was alive at 46 months after diagnosis and no evidence of recurrence was found.CONCLUSION: Prognosis of pediatric supratentorial glioblastoma remains poor, and its prognosis may not be better than adult’s. Preoperative KPS score is a risk factor, but isn’t an independent risk factor. Concurrent chemoradiotherapy and gross total resection are the main methods to prolong life span.

Background Toll-like receptor 9 (TLR9) is a key immunotherapy target for glioblastoma (GBM). This study explored the correlation of TLR9 expression with tumor location and survival outcomes in patients with supratentorial GBM. Methods We retrospectively identified 46 patients with supratentorial GBMs and divided them into those with high TLR9 (TRL9 High ) and low TLR9 (TRL9 Low ) levels. The 2 groups were compared by patients' ages, sex, preoperative Karnofsky Performance Scale (KPS) score, resection extent, tumor location, progression-free survival (PFS), and overall survival (OS). Results The TLR9 expression percentages for the GBM specimens were TRL9 High : 72% (33/46) and TRL9 Low : 28% (13/46). The 2 groups showed no differences in patient age ( P = 0.147) and sex (χ 2 = 0.002, P = 0.966), preoperative KPS score (χ 2 = 0.033, P = 0.855), or resection extent (χ 2 = 2.405, P = 0.121). Location differed significantly, with 85% (11/13) of TRL9 Low tumors in the left hemisphere and 45% (15/33) of TRL9 High tumors on the same side (χ 2 = 5.82, P = 0.016). The TRL9 Low group had a median PFS of 612 days (range, 77–926 days), significantly longer than the TRL9 High group (355 days; range, 105–861 days; P = 0.042). Median OS of the TRL9 Low group (733 days; range, 163–969 days) was also significantly longer than in the TRL9 High group (396 days; range, 135–1024 days; P = 0.020). Conclusions Patients with TRL9 Low supratentorial GBM tend to have longer survival than those with higher TLR9 expression. Such tumors show a location preference for the left hemisphere.

Supratentorial glioblastoma is the most frequent primary intracranial tumor in adults. Its localization in the cerebellum is extremely rare and such tumor presenting as cerebellopontine angle (CPA) mass in an adult is even rarer. We report the case of primary cerebellar glioblastoma in a 52-year-old woman who presented clinically and radiologically as CPA mass. Its clinical presentation, radiological findings, and treatment instituted are discussed in view of pertinent literature.

Significance and Background: Tumor Treating Fields (TTFields) are non-invasive, low-intensity electric fields with anti-mitotic activity delivered using the Optune® System, which is approved for the treatment of adult patients with newly diagnosed and recurrent supratentorial glioblastoma (GBM). TTFields are delivered via 4 transducer arrays that are applied directly to the scalp to target the tumor. The first generation Optune® system consisting of a field generator, portable lithium batteries, carrying bag, and transducer arrays weighed approximately ~ 2.7 Kg (6 pounds). The system has been redesigned to improve the convenience and manageability of TTFields therapy for GBM patients. The second generation Optune® System uses new digital signal generation technology to reduce the size and weight to ~ 1.2 Kg (2.7 pounds) including the battery, which may positively affect patient convenience and compliance with treatment. Purpose: To understand the effect of size and weight advantages of the second generation Optune® System on patient satisfaction, compliance (time on therapy), and usability. Interventions: Ten GBM patients (N=10, male = 8, female = 2, median age: 52.9 years [31-79]) were monitored at multiple time points over the first month of transitioning to the second generation Optune® System using a questionnaire assessing the convenience and ease of daily usage as well as duration of daily use and frequency of complications associated with usage (alarms). Evaluation: A 10 point numerical analog scale was utilized to assess feedback at baseline (on the original system) and at 5 specific time points over the first month of second generation Optune System usage. Patient feedback highlighted the benefits of enhanced features such as quieter operation and portability. Discussion: Overall, patients were very satisfied with the new system in terms of convenience and usability and experienced less number of alarms. Patient compliance using the second generation Optune® System was maintained and in most cases improved compared with the original Optune® System. Innovation: TTFields treatment that target compliance rates of 75% (18 hours per day) improve survival outcomes as observed in GBM clinical trials. The results of this patient survey indicate that the improved size, weight and convenience of the second generation Optune® System help patients comply with daily treatment duration goals.

BACKGROUND The prognosis for glioblastoma (GBM) varies among patients. Ventricular opening during surgery has been reported as a prognostic factor for GBM patients, but the influence of ventricular opening itself on patient prognosis remains controversial. OBJECTIVE Accumulating evidence has suggested that the subventricular zone (SVZ) harbors a neural stem cell niche and is associated with gliomagenesis. Several reports have hypothesized that aggressive characteristics of GBM in contact with the SVZ may be associated with the recruitment of neural stem cells from the SVZ that have abilities associated with invasive proliferation, leading to poor prognosis. We presumed that the degree of ventricular opening would correlate with the degree of SVZresection and with prognosis in GBM patients. This study therefore investigated whether the degree of ventricular opening correlates with prognosis in GBM patients treated with the standard protocol of chemo-radiotherapy. METHODS Participants comprised 111 patients with newly diagnosed GBM who underwent surgery and postoperative radiotherapy and TMZ-based chemotherapy from 2005 to 2018. We classified 111 patients into “No ventricular opening” (NVO), “Ventricular opening, small” (VOS; distance < 21 mm) and “Ventricular opening, wide” (VOW; distance > 21 mm) groups. We evaluated the relationship between degree of ventricular opening and prognosis using survival analyses that included other clinicopathological factors. RESULTS Log-rank testing revealed age, KPS, extent of resection, MGMT status, IDH1 mutation, and degree of ventricular opening correlated significantly with overall survival. Multivariate analysis identified the degree of ventricular opening (small vs. wide) as the most significant prognostic factor (hazard ratio = 3.674; p < 0.0001). CONCLUSIONS We demonstrated that wide opening of the lateral ventricle (LV) contributes to longer survival compared with small opening among GBM patients. Our results indicate that wide opening of the LV may correlate with the removal of a larger proportion of tumor stem cells from the SVZ.

Background: Glioblastoma multiforme with a primitive neuronal component is a rare entity, with few cases reported in the literature. Case Description: A patient who had a supratentorial glioblastoma multiforme with a primitive neuronal component developed spinal metastasis during the disease course. With his history of leukemia during childhood, he was likely exposed to therapeutic ionizing brain radiation, which could have increased the risk of developing brain cancer in adulthood. Conclusions: The range of incidence rates of dissemination in the literature is 2%–4%, typically in cases of cerebellar glioblastoma multiforme, but as high as 25% in autopsy series. Our case highlights several other topics in the literature, such as immunohistochemical patterns that differ between the primary tumor and spinal metastases and dissemination locations, typically leptomeningeal or ventricular invasion. Key words: Component, Glioblastoma, Metastases, Neuronal, Primitive, Spinal

Introduction High-grade gliomas surgery in eloquent areas must achieve two pivotal aims: oncological efficacy and preservation of unimpaired neurological functions or improvement of impaired neurological functions. Here, we evaluated the safety and the usefulness of 5-ALA fluorescence-guided surgery in eloquent areas. Material and methods Single center, retrospective and consecutive series of adult patients operated on for a supratentorial glioblastoma between November 2012 and November 2015. Results Fifty-one patients with a glioblastoma located within an eloquent area were included: 24 patients operated on with 5-ALA (5-ALA group), and 27 patients operated on under white light (control group). Preoperative motor and language deficits were similar in the 5-ALA group (50%, 37.5%) as in the control group (59.3%, 55.6%) ( P = 0.510; P = 0.200). Three-month postoperative motor and language deficits rates were similar in the 5-ALA group (12.5%, 12.5%) as in the control group (29.6%, 14.8%) ( P = 0.180; P = 0.990). The extent of resection did not significantly vary between groups ( P = 0.280). The overall survival did not significantly vary between groups ( P = 0.080) but the progression-free survival was significantly higher in the 5-ALA group than in the control group ( P = 0.020). The 12-month progression-free survival was significantly higher in 5-ALA group (60%) than in control group (21%; P = 0.006). In multivariate analysis, the 5-ALA was an independent prognostic factor associated with progression-free survival ( P = 0.030). Conclusion 5-ALA fluorescence-guided surgery for glioblastoma located in eloquent areas is effective to improve progression-free survival. To preserve functional outcomes, it requires the routine use of intraoperative functional mapping to respect functional boundaries.

Objective Gross total resection (GTR) of glioblastoma may be achieved with the aid of intraoperative magnetic resonance imaging (Io-MRI), which detects residual tumor during surgery, with the aim of maximizing resection, therefore reducing the risk of recurrence. Moreover, intraoperative fiber tracking and neuronavigated electrophysiologic cortical and subcortical mapping may help prevent postoperative deficits. Methods There were 114 patients who underwent surgical removal of newly diagnosed supratentorial glioblastoma between January 2009 and January 2013: 78 (group A) were operated on with the aid of Io-MRI, and 36 were operated on without Io-MRI (group B). The protocol included preoperative magnetic resonance imaging and Io-MRI with diffusion tensor imaging in all the cases that presented eloquent areas of involvement. The extent of resection (EOR) was compared in the 2 groups 24–72 hours after surgery. Results The first Io-MRI detected a GTR in 31 patients (39.7%) and a residual tumor in 47 patients (60.3%) in group A. Twenty-one patients had residual tumor within eloquent areas: Io-MRI with fiber tracking permitted further resection, achieving GTR in 12 patients. GTR was radiologically detected in the remaining 26 patients (33.3% of group A) who had residual tumor in noneloquent areas after 1 or 2 further resection extensions. Io-MRI enhanced both EOR and 6-month progression-free survival (6-PFS): the overall GTR for group A amounted to 88.5% (n = 69), whereas for group B it was 44% (n = 16). 6-PFS accounted for 73% (n = 57) for group A and 38.9% (n = 14) for group B. Conclusions Our experience suggests that Io-MRI may lead to EOR optimization and associated 6-PFS improvement.

Object In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). Methods Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000–August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). Results Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein–positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40–0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53–0.96; p = 0.02). Conclusions Neurofilament protein–positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein–GBM's unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Backgrond: To compare the survival of glioblastoma multiforme (GBM) patients operated on at public hospital with that of patients operated on at the private hospital. Method: We carried out a retrospective analysis of the patients’ medical records, the surgical reports, and the pre and post-operative images of patients with a histopathological confirmed adult supratentorial glioblastoma multiform (GBM). Sixty-three patients were treated at public hospital and 21 at private hospitals. Results: The present study revealed that the survival of patients treated in private hospitals was statistically superior to that of patients treated in public hospitals (11.9 vs 7.7). Conclusions: Our study advances towards the confirmation of the hypothesis that socioeconomic and educational factors influence the KPS and the performance of RT treatment, with negative effects over the GBM patients’ survival.

Summary The authors report 11 patients with cerebral glioblastoma who lived at least 5 years after their initial diagnosis. There were 6 female and 5 male; the mean age was 39 years (range 24‐55 years). All patients were treated surgically and postoperatively received whole-brain radiotherapy and chemotherapy. Five patients (45%) presented local recurrences after an average interval of 3.9 years from treatment. At average follow-up of 9 years (range 5‐14 years), 7 patients (64%) were alive after an average interval of 8.1 years; 4 patients (36%) died from local relapse. Survival was influenced by patient age and, to a lesser degree, by treatment. A review of the literature, together with our own series, suggest that death from recurrence disease is unusual in glioblastoma patients who survive more than 5 years.

Purpose To assess the efficacy of high-dose contrast enhanced magnetic resonance imaging (MRI) in detection and delineation of infiltrating tumour in glioblastoma. Material and methods In a phase II clinical trial 14 patients with suspected supratentorial glioblastoma underwent MRI with Gd-DO3A-butriol (Gadovist, Schering AG, Berlin) with doses of 0.1 up to 0.3 mmol/kg. Results Increasing the dose of Gd-DO3A-butriol resulted in improved enhancement (14/14) and better delineation of infiltrating tumour (9/14) up to 2 cm beyond enhancement after standard dose. In two of the 9 patients additional enhancement in the peritumoural oedema was only seen after the third injection. Conclusions Successful surgery requires precise preoperative delineation of tumour borders. After high-dose MRI it might be possible to select those patients who would benefit from more radical attempts at eradicating the macroscopic as well as most of the microscopic compartment of glioblastoma.

The concept of different genetic pathways leading to glioblastoma multiforme (GBM) has gained considerable acceptance, and two major groups are now described, primary or de novo GBM and secondary GBM. The present study was undertaken to elucidate whether additional pathways exist and to determine whether there is any correlation between these different variants and clinical parameters, such as age, duration of symptoms, and outcome. For this purpose, immunophenotyping was performed to study the simultaneous expression of p53 protein and epidermal growth factor receptor (EGFR) in 58 cases of adult supratentorial GBM. By this method, four variants of GBM could be distinguished: 34% were p53 positive only, 38% were EGFR positive only, 14% were double negative (p53 negative/EGFR negative), and 14% were double positive (p53 positive/EGFR positive). Interestingly, all nine cases of secondary GBM in which there was clinical and histological evidence of progression from a preexisting low-grade lesion were p53 positive. Differences were observed with regard to the age distribution of the four variants, in that the p53 negative/EGFR negative tumors occurred most frequently in the younger age group (21-40 years). In the elderly group (61-80 years), two-thirds of the tumors were p53 negative/EGFR positive primary GBMs, and no case of the double positive or double negative variant was encountered. The differences in duration of symptoms and symptom-free survival according to age group and genetic subset were not statistically significant. There were no differences in outcome within each age category for any GBM variant, although the longest mean symptom-free survival was noted among patients aged 41-60 years with the p53 positive/EGFR negative variant. This study therefore indicates that at least four subsets of GBM exist, but despite different genotypes, the biologic behavior remains similar. Other genetic alterations therefore need to be investigated to identify prognostic makers.

Reporting a series of 27 supratentorial glioblastomas in pediatric patients treated surgically in the Department of Neurosurgical Sciences-Neurosurgery Section—of “La Sapienza” University of Rome, we discuss the principal clinical features, treatment and prognosis of the tumour with reference to the salient published series.

Although medulloblastoma is said to be capable of astrocytic differentiation, the development of an astrocytic neoplasm in association with a medulloblastoma is extremely rare. We report the light and electron microscopic features of a supratentorial glioblastoma that occurred 13 years after radiation therapy for a cerebellar medulloblastoma. The diverse ultrastructural features of the glioblastoma may reflect the multipotentiality of the cells in medulloblastoma. An alternate interpretation is that the glioblastoma represents a radiation-induced neoplasm after therapy for a medulloblastoma.