Search

Background: Survival of patients with glioblastoma (GBM) increased in the 2000s, most prominently after the addition of temozolomide to the standard-of-care treatment protocol. The reason for subsequent improvements in survival in the late 2000s and early 2010s was less clear, with explanations including the introduction of bevacizumab, better surgical methods, and advances in supportive care. It is uncertain whether the trend of improving population-level survival has continued., Materials and Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed comparing survival of adult GBM patients diagnosed in consecutive 3-year periods from 2000 to 2017. Kaplan-Meier survival analysis and Cox proportional hazards models were used., Results: A total of 38,352 patients diagnosed with GBM between 2000 and 2017 met inclusion criteria. Median survival and percent survival to 12 and 24 months all progressively increased between 2000 and 2011. There were no significant differences in survival comparing 2009-2011 with 2012-2014 or 2015-2017. During the 2015-2017 period, median survival was 11 months, with 12 and 24-month survival proportions of 45.7% (95% confidence interval, 44.5-47.0) and 19.0% (95% confidence interval, 18.6-21.2), respectively., Conclusions: After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued. Subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the role of olfactory function in patients with glioblastoma multiforme (GBM) as a prognostic clinical measure., Methods: In a prospective case-control study, olfactory testing was performed in 73 patients with primary GBM at baseline during first-line treatment and at later follow-ups. An age-matched control cohort consisted of 49 patients with neurologic diseases, excluding those known to affect olfactory function per se. Depending on the olfactory testing score, patients were allotted to a hyposmia group (HG) or normosmia group (NG). MRI analysis was performed to assess whether tumor location affects olfactory pathways., Results: Patients with GBM had olfactory dysfunction significantly more often compared to the control cohort ( p = 0.003). Tumor location could not explain this finding since no relevant difference in MRI-based olfactory pathway involvement was found between HG and NG ( p = 0.131). Patients with olfactory dysfunction had significantly worse overall survival (OS) and progression-free survival (PFS) compared to those without dysfunction (median OS 20.9 vs 40.6 months, p = 0.035; median PFS, 9 vs 19 months, p = 0.022). Multivariate analysis in patients without MRI-based involvement of olfactory pathways confirmed olfaction is an independent prognostic factor for OS (hazard ratio [HR] 0.43; p = 0.042) and PFS (HR 0.51; p = 0.049)., Conclusion: This pilot study provides the first indication that olfactory dysfunction is frequently observed in GBM and may be associated with worse survival outcome in GBM. However, validation of these results in an independent cohort is needed., (© 2019 American Academy of Neurology.)

Objective: To perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics., Methods: We conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes., Results: One hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8-67.7) months, astrocytoma 6.5 (0.1-28.5) months, and glioblastoma 3.8 (0.1-32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival., Conclusion: Patients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment., (© 2019 American Academy of Neurology.)

Background: Glioblastoma multiforme (GBM) is a rare and deadly disease, with a reported average incidence rate of 3.19 cases per 100,000 inhabitants. Fotemustine, a third-generation nitrosourea with an alanine phosphor carrier that facilitates cellular penetration, has been extensively investigated in the setting of recurrent/progressive disease after initial treatment. Fotemustine is usually administered following a schedule consisting of 3 doses every week, followed by maintenance doses administered every 3 weeks., Methods: In this phase I/II trial, we aimed to assess whether the use of a biweekly regimen allowed administration of higher dose than the standard 100 mg/m dose approved per label indication in a population of patients with recurrent GBM. In this phase I/II trial, fotemustine was administered intravenously over 1 hour every 2 weeks at either 120 or 140 mg/m doses for up to 1 year, until disease progression, unacceptable toxicity, or patient's request to withdraw from the study. The phase I part of the trial was conducted following the classic 3+3 study design. The phase II part of the trial was a single-arm study. The primary efficacy endpoint was the percentage of patients who had not progressed after 24 weeks (PFS-24)., Results: Thirty-seven patients were enrolled in this phase I/II trial from August 2006 to November 2011. Treatment was well tolerated in the overall population. Main severe toxicity was grades 3 and 4 thrombocytopenia, which occurred in 4 of 6 patients treated at the 140 mg/m dose level and in 3 of 31 patients treated at 120 mg/m. Median PFS and overall survival were 12.1 (1-40.2) weeks and 19.7 (1-102) weeks, respectively., Conclusion: We conclude that fotemustine can be safely administered at 120 mg/m biweekly. The efficacy of such modified schedule and doses should be compared to the biweekly schedule at 80 mg and the standard weekly schedule at 80 to 100 mg/m.

Background: Several studies have examined the association between hyperglycemia in the first 10 to 12 weeks following surgery and postoperative survival in glioblastoma multiforme (GBM) patients. We hypothesize that episodes of hyperglycemia before, during and/or following surgery for primary GBM are independent predictors of disease progression and mortality., Materials and Methods: A total of 162 adult patients were included in the analysis. All patients received adjuvant temozolamide. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5 years were analyzed using different glycemic cutoff values. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS., Results: Kaplan-Meier curves revealed a trend toward increased PFS and OS with lower glucose concentrations with the exception of glucose concentrations >180 mg/dL in the intraoperative/postoperative day 0 time period. Univariate analysis of blood glucose levels did not demonstrate a statistically significant effect on PFS in any time period, however hyperglycemia was statistically significant for OS in the preoperative time period. Although, multivariate analysis showed no statistically significant association with hyperglycemia on PFS, a statistically significant decrease in OS was seen for plasma glucose concentrations >112 mg/dL (P=0.01) and >180 mg/dL (P=0.01) in the preoperative period. There was a decreasing effect on OS with blood glucose concentrations greater than the median in multiple time periods (P=0.02)., Conclusions: Preoperative hyperglycemia is associated with poor OS after GBM surgery.

Purpose of Review: Glioblastoma is the most common malignant brain tumor in adults and carries a particularly poor prognosis. Since 2005, state-of-the-art therapy consists of maximal well tolerated surgical resection followed by combined radiotherapy and chemotherapy with temozolomide. Over the past decade, further advances have been achieved in various disciplines, most prominently including antiangiogenic treatment with bevacizumab. Still, whether these therapeutic innovations have translated to the general population remains unclear., Recent Findings: Population-based outcome and pattern of care (POC) studies have recently documented the rapid dissemination of the treatment standard to community practice across countries. This has resulted in a modest but significant increase in survival at the population level. However, the increase was significantly less marked in elderly patients in whom undertreatment is a concern. Other serious concerns address diverging POC between academic versus nonacademic centers, patients with high-income versus low-income, and racial and marital status disparities. With regard to bevacizumab treatment, there is still insufficient evidence of a beneficial impact on population-based survival, so far., Summary: Despite the rapid incorporation of the current standard treatment in clinical practice and the thereby achieved modest survival gain at the population-level, prevailing POC needs to be reconsidered and standardized, especially for elderly glioblastoma patients who bear a large disease burden and carry the worst prognosis. Future POC studies are urgently needed and would benefit from the systematic inclusion of quality-of-life data and molecular tumor markers, so that this information could be captured in population-based cancer registries.

Purpose of Review: First described in 2002, the presence and role of human cytomegalovirus (HCMV) infection in glioblastoma (GBM) has remained a controversial topic. New research indicates HCMV gene products likely promote GBM pathogenesis and that therapies aimed at HCMV might influence disease progression., Recent Findings: Recently, investigators have begun to analyze HCMV genome and proteins present in GBM cells in vivo. Furthermore, the research has demonstrated that several HCMV gene products that have oncomodulatory properties are expressed in GBM and may be impacting tumor pathogenesis in vivo. These HCMV gene products modulate GBM proliferation, apoptosis, angiogenesis, invasion and immune evasion. A recent mouse model provides mechanistic information as to how CMV may promote gliomagenesis in the setting of tumor suppressor dysfunction and STAT3 signaling. In addition, clinical outcomes of GBM patients are associated with the degree of HCMV infection. Novel therapies aimed at direct antiviral and immunotherapy approaches to HCMV suggest that these modalities may impact the future treatment of this disease., Summary: A more precise understanding of the role of HCMV infection in gliomagenesis and GBM pathogenesis could reveal novel therapeutic and preventive strategies.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures., Methods: Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents., Results: In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven., Conclusions: If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed., Methods: Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases., Results: In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk., Conclusions: If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Background: Functional single nucleotide polymorphisms (SNP) in codon 72 of TP53 have been shown to be a risk factor, a prognostic marker, and related factor to age at onset in various cancers., Methods: We investigated blood samples from 254 patients with glioblastoma and 238 healthy controls., Results: TP53 codon 72 status was not correlated with prognosis and did not differ between glioblastoma and control populations. However, the Pro/Pro genotype was overrepresented in patients <45 years (20.6% vs 6.4% in patients with glioblastoma >45 years, p = 0.002, vs 5.9% in control group, p = 0.001). We then confirmed this result on an independent series of young patients with glioblastoma. Finally, the analysis of tumor DNA found the Pro allele associated with occurrence of TP53 somatic mutation., Conclusion: Our data suggest that TP53 functional variation is particularly critical for oncogenesis of glioblastoma in young patients.

Background: The relationship between socioeconomic status and health care disparities in the incidence of brain tumors is unclear., Objective: To identify the associations between age, sex, and Medicaid enrollment and the incidence of primary malignant brain tumors in Michigan in 1996 and 1997., Methods: Records were obtained from the Michigan Cancer Surveillance Program on the 1,006 incident cases during this period and cross-checked with Medicaid enrollment files., Results: Persons enrolled in Medicaid were more likely than non-enrolled persons to develop a malignant brain tumor of any type, a glioblastoma multiforme, and an astrocytoma for certain subgroups. In addition, incidence rates for malignant brain tumors in persons enrolled in Medicaid peaked at a younger age., Conclusion: Sociodemographic status may be associated with cerebral malignancy and should be considered when targeting treatment and educational interventions at persons at risk.

Glioblastoma (GBM) is the most important primary brain tumor, both in terms of its incidence and its devastating impact on the unfortunate patients who have it. Although several well-defined hereditary syndromes predispose to malignant gliomas, most cases occur in the absence of a such a syndrome. The role of environmental factors, based on the known associations to date, also appears limited when compared with the total number of patients affected. It is clear that much remains to be discovered to better elucidate the causes of GBM, but the increasing recognition of molecular subtypes may help advance this field. This review highlights current insights into the molecular epidemiology of GBM.

With traditional epidemiologic research designs, few environmental risk factors for malignant brain tumors have been revealed, and although syndromes exist where brain tumors occur frequently, these explain a small proportion of the overall incidence. In a similar way, the search for genetic causes has been thwarted by the rarity of families with multiple affected relatives, inhibiting genetic linkage, sib-pair, or even population-based association studies. Molecular genetic studies generally involve searching for candidate proto-oncogenes and tumor suppressor genes by comparing DNA from tumor material with constitutional (germline) DNA. However, it remains difficult to distinguish causative genetic aberrations from chaotic neoplastic processes, and studies so far have not yielded consistent information on the location of such causative genetic lesions. The current literature covering the molecular genetics of glioma is discussed herein and alternative approaches that can be used to identify genetic causes of glioma described.