Personalized prognosis stratification of newly diagnosed glioblastoma applying a statistical decision tree model.

PURPOSE: Glioblastoma (GBM) is the most frequent glioma in adults with a high treatment resistance resulting into limited survival. The individual prognosis varies depending on individual prognostic factors, that must be considered while counseling patients with newly diagnosed GBM. The aim of this study was to elaborate a risk stratification algorithm based on reliable prognostic factors to facilitate a personalized prognosis estimation early on after diagnosis. METHODS: A consecutive patient cohort with confirmed GBM treated between 2010 and 2021 was retrospectively analyzed. Clinical, radiological, and molecular parameters were assessed and included in the analysis. Overall survival (OS) was the primary outcome parameter. After identifying the strongest prognostic factors, a risk stratification algorithm was elaborated with estimated odds of survival. RESULTS: A total of 462 GBM patients were analyzed. The strongest prognostic factors were Charlson Comorbidity Index (CCI), extent of tumor resection, and adjuvant treatment. Patients with CCI ≤ 1 receiving tumor resection had the highest survival odds (88% for 10 months). On the contrary, patients with CCI > 3 receiving no adjuvant treatment had the lowest survival odds (0% for 10 months). The 10-months survival rate in patients with CCI > 3 receiving adjuvant treatment was 56% for patients younger than 70 years and 22% for patients older than 70 years. CONCLUSION: A risk stratification algorithm based on significant prognostic factors allowed a personalized early prognosis estimation at the time of GBM diagnosis, that can contribute to a more personalized patient counseling.

Refinement of response assessment in neuro-oncology (RANO) using non-enhancing lesion type and contrast enhancement evolution pattern in IDH wild-type glioblastomas.

BACKGROUND: Updated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma. METHODS: This retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan-Meier method. RESULTS: Pseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P < 0.001 and HR = 3.71, P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL. CONCLUSIONS: NEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET.

Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.

Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.

BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O6-methylguanine-DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan-Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multiple-method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'-cytosine-phosphate-guanine-3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta-analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies making such comparisons.

Association between socioeconomic status and survival in glioblastoma: An Italian single-centre prospective observational study.

BACKGROUND: To date, no prospective study has been conducted to investigate the role of socioeconomic status (SES) on clinical outcome of glioblastoma (GBM) in Italy, where there is a National Health Service that provides universal coverage regardless of the patient's economic status. METHODS: We performed a prospective observational study investigating the association between SES and survival in GBM patients at our institution, a hub centre for brain cancer research and treatment. We included GBM patients who underwent medical treatment or chemo-radiation between April 2017 and December 2017. The SES was measured using the income-brackets, attributed by the Italian Ministry of Finance on the basis of the income of the fiscal family unit, referring to the previous year. RESULTS: One hundred and six patients were included in the study. In multivariate analysis, overall survival (OS) correlated significantly with higher-income (HR = 0.623.95% CI 0.467-0.832; p = 0.001) and MGMT methylation status (HR = 0.158.95% CI 0.082-0.304; P < 0.001). When adjusted for age, performance status and extension of surgery, survival benefit remained superior for higher-income HR = 0.641 (95% CI 0.478-0.858; p = 0.003) and MGMT methylated tumours HR = 0.167 (95% CI 0.084-0.331; p < 0.001). CONCLUSIONS: SES is an important determinant of prognosis in GBM even in the Italian National Health Service, which provides universal, largely free and relatively comprehensive healthcare. Despite aspirations to achieve equality in healthcare, socioeconomic differences exist and may impact the clinical outcome.

Quantitative volumetric assessment of baseline enhancing tumor volume as an imaging biomarker predicts overall survival in patients with glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is the commonest malignant primary brain tumor and still has one of the worst prognoses among cancers in general. There is a need for non-invasive methods to predict individual prognosis in patients with GBM. PURPOSE: To evaluate quantitative volumetric tissue assessment of enhancing tumor volume on cranial magnetic resonance imaging (MRI) as an imaging biomarker for predicting overall survival (OS) in patients with GBM. MATERIAL AND METHODS: MRI scans of 49 patients with histopathologically confirmed GBM were analyzed retrospectively. Baseline contrast-enhanced (CE) MRI sequences were transferred to a segmentation-based three-dimensional quantification tool, and the enhancing tumor component was analyzed. Based on a cut-off percentage of the enhancing tumor volume (PoETV) of >84.78%, samples were dichotomized, and the OS and intracranial progression-free survival (PFS) were evaluated. Univariable and multivariable analyses, including variables such as sex, Karnofsky Performance Status score, O6-methylguanine-DNA-methyltransferase status, age, and resection status, were performed using the Cox regression model. RESULTS: The median OS and PFS were 16.9 and 7 months in the entire cohort, respectively. Patients with a CE tumor volume of >84.78% showed a significantly shortened OS (12.9 months) compared to those with a CE tumor volume of ≤84.78% (17.7 months) (hazard ratio [HR] 2.72; 95% confidence interval [CI] 1.22-6.03; P = 0.01). Multivariable analysis confirmed that PoETV had a significant prognostic role (HR 2.47; 95% CI 1.08-5.65; P = 0.03). CONCLUSION: We observed a correlation between PoETV and OS. This imaging biomarker may help predict the OS of patients with GBM.

Anti-PD-1 Immunotherapy in Preclinical GL261 Glioblastoma: Influence of Therapeutic Parameters and Non-Invasive Response Biomarker Assessment with MRSI-Based Approaches.

Glioblastomas (GBs) are malignant brain tumours with poor prognosis even after aggressive therapy. Programmed cell death-1 (PD-1) immune checkpoint blockade is a promising strategy in many types of cancer, but its therapeutic effects in GB remain low and associated with immune infiltration. Previous work suggests that oscillations of magnetic resonance spectroscopic imaging (MRSI)-based response pattern with chemotherapy could act as a biomarker of efficient immune system attack onto GBs. The presence of such oscillations with other monotherapies such as anti-PD-1 would reinforce its monitoring potential. Here, we confirm that the oscillatory behaviour of the response biomarker is also detected in mice treated with anti PD-1 immunotherapy both in combination with temozolomide and as monotherapy. This indicates that the spectral pattern changes observed during therapy response are shared by different therapeutic strategies, provided the host immune system is elicited and able to productively attack tumour cells. Moreover, the participation of the immune system in response is also supported by the rate of cured animals observed with different therapeutic strategies (in the range of 50-100% depending on the treatment), which also held long-term immune memory against tumour cells re-challenge. Taken together, our findings open the way for a translational use of the MRSI-based biomarker in patient-tailored GB therapy, including immunotherapy, for which reliable non-invasive biomarkers are still missing.

Racial and socioeconomic disparities differentially affect overall and cause-specific survival in glioblastoma.

INTRODUCTION: The prognostic role of racial and socioeconomic factors in patients with glioblastoma is controversially debated. We aimed to evaluate how these factors may affect survival outcomes in an overall and cause-specific manner using large, national cancer registry cohort data in the temozolomide chemoradiation era. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was queried for patients diagnosed with glioblastoma between 2005 and 2016. Overall survival was assessed using Cox proportional hazard models using disease intrinsic and extrinsic factors. Cause-specific mortality was assessed using cumulative incidence curves and modeled using multivariate cumulative risk regression. RESULTS: A total of 28,952 patients met the prespecified inclusion criteria and were included in this analysis. The following factors were associated with all-cause mortality: age, calendar year of diagnosis, sex, treatment receipt, tumor size, tumor location, extent of resection, median household income, and race. Asian/Pacific Islanders and Hispanic Whites had lower mortality compared to Non-Hispanic Whites. Cause-specific mortality was associated with both racial and socioeconomic groups. After adjusting for treatment and tumor-related factors, Asian/Pacific and black patients had lower glioblastoma-specific mortality. However, lower median household income and black race were associated with significantly higher non-glioblastoma mortality. CONCLUSIONS: Despite the aggressive nature of glioblastoma, racial and socioeconomic factors influence glioblastoma-specific and non-glioblastoma associated mortality. Our study shows that patient race has an impact on glioblastoma-associated mortality independently of tumor and treatment related factors. Importantly, socioeconomic and racial differences largely contribute to non-glioblastoma mortality, including death from other cancers, cardio- and cerebrovascular events.

The SHORT Score for Preoperative Assessment of the Risk for Short-Term Survival in Glioblastoma.

BACKGROUND: Despite recent improvements in treatment of glioblastoma (GBM), some patients still have a short survival. We sought to develop a new risk score for preoperative assessment of short-term survival (STS) (<6 months) in patients with GBM. METHODS: All adult patients who underwent surgical resection of GBM between 2004 and 2014 were included (N = 379). Demographic and clinical parameters, which were available at admission, were assessed. Variables were evaluated in univariate and multivariate analyses. The score was validated in a separate cohort of patients with GBM who underwent surgical resection between 2015 and 2018. RESULTS: The following independent predictors of STS were integrated into a new score: body height (<169 cm, 1 point), arterial hypertension (1 point), age (≤54 years, 0 points; 55-74 years, 1 points; ≥75 years, 2 points), and poor clinical status (Karnofsky performance scale [KPS] score: ≤60%, 2 points; 70%-80%, 1 point; ≥90%, 0 points). The new risk score, SHORT (Small body height, Hypertension, Older age, Reduced KPS score, short-Term survival), ranged from 0 to 6 points and showed good accuracy of risk estimation for STS in GBM (area under the curve: 0.715). STS rates were 9.7%, 23.1%, and 70% in patients with GBM scoring <2 points, 2-4 points, and >4 points (P < 0.0001). The score was successfully validated (area under the curve: 0.770). CONCLUSIONS: This study presents the SHORT score for preoperative assessment of STS risk in patients with GBM. This risk score needs external validation in larger patient cohorts from other institutions. Our score might be a tool to facilitate treatment decisions in patients with GBM before surgery.

Biweekly fotemustine schedule for recurrent glioblastoma in the elderly: activity and toxicity assessment of a multicenter study.

Aim: To assess the efficacy and safety of alternative fotemustine administration schedule in elderly patients with recurrent glioblastoma. Patients & methods: Patients aged >65 years with recurrent glioblastoma received fotemustine (80 mg/m2; days 1, 15, 30, 45 and 60, and subsequently every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months. Main secondary end point was safety. Results: 58 patients were enrolled at two centers. PFS at 6 months was 47% (27 patients) and overall response rate was 29%. Median PFS and survival were 6 and 7 months, respectively, and longer in responders versus nonresponders. No grade 3-4 hematological toxicities occurred. Conclusion: The alternative fotemustine administration schedule was an effective and safe treatment for recurrent glioblastoma in elderly patients.

The Neurologic Assessment in Neuro-Oncology (NANO) Scale as an Assessment Tool for Survival in Patients With Primary Glioblastoma.

BACKGROUND: The Neurologic Assessment in Neuro-Oncology (NANO) scale is a standardized objective metric designed to measure neurological function in neuro-oncology. Current neuroradiological evaluation guidelines fail to use specific clinical criteria for progression. OBJECTIVE: To determine if the NANO scale was a reliable assessment tool in glioblastoma (GBM) patients and whether it correlated to survival. METHODS: Our group performed a retrospective review of all patients with newly diagnosed GBM from January 1, 2010, through December 31, 2012, at our institution. We applied the NANO scale, Karnofsky performance score (KPS), Eastern Cooperative Oncology Group (ECOG) scale, Macdonald criteria, and the Response Assessment in Neuro-Oncology (RANO) criteria to patients at the time of diagnosis as well as at 3, 6, and 12 mo. RESULTS: Initial NANO score was correlated with overall survival at time of presentation. NANO progression was correlated with decreased survival in patients at 6 and 12 mo. A decrease in KPS was associated with survival at 3 and 6 mo, an increase in ECOG score was associated only at 3 mo, and radiological evaluation (RANO and Macdonald) was correlated at 3 and 6 mo. Only the NANO scale was associated with patient survival at 1 yr. NANO progression was the only metric that was linked to decreased overall survival when compared to RANO and Macdonald at 6 and 12 mo. CONCLUSION: The NANO scale is specific to neuro-oncology and can be used to assess patients with glioma. This retrospective analysis demonstrates the usefulness of the NANO scale in glioblastoma.

Diagonal likelihood ratio test for equality of mean vectors in high-dimensional data.

We propose a likelihood ratio test framework for testing normal mean vectors in high-dimensional data under two common scenarios: the one-sample test and the two-sample test with equal covariance matrices. We derive the test statistics under the assumption that the covariance matrices follow a diagonal matrix structure. In comparison with the diagonal Hotelling's tests, our proposed test statistics display some interesting characteristics. In particular, they are a summation of the log-transformed squared t-statistics rather than a direct summation of those components. More importantly, to derive the asymptotic normality of our test statistics under the null and local alternative hypotheses, we do not need the requirement that the covariance matrices follow a diagonal matrix structure. As a consequence, our proposed test methods are very flexible and readily applicable in practice. Simulation studies and a real data analysis are also carried out to demonstrate the advantages of our likelihood ratio test methods.

Voxel-Wise Analysis of Fluoroethyltyrosine PET and MRI in the Assessment of Recurrent Glioblastoma During Antiangiogenic Therapy.

OBJECTIVE: In MRI of patients with recurrent glioblastoma, bevacizumab-induced normalization of tumor vascularity can be difficult to differentiate from antitumor effects. The aim of this study was to assess the utility of 18F-fluoroethyl-L-tyrosine (FET) PET in the evaluation of recurrent glioblastoma treated with bevacizumab. SUBJECTS AND METHODS: MRI and FET PET were performed before and after administration of two doses of bevacizumab to 11 patients with recurrent glioblastoma. The ratio between normalized FET uptake at follow-up and baseline of the entire (volume of T2 FLAIR abnormality) and enhancing tumor were assessed for prediction of progression-free survival (PFS) and overall survival (OS). Voxel-wise Spearman correlation between normalized FET uptake and contrast-enhanced T1 signal intensity was assessed and tested as a predictor of PFS and OS. RESULTS: Mean Spearman correlation between FET uptake and contrast-enhanced T1 signal intensity before therapy was 0.65 and after therapy was 0.61 (p = 0.256). The median PFS after initiation of bevacizumab therapy was 111 days, and the OS was 223 days. A post-treatment to pretreatment PET uptake ratio (mean and 90th percentile) greater than 0.7 for both entire and enhancing tumor was associated with lower PFS and OS (p < 0.001-0.049). The increase in correlation between PET uptake and contrast-enhanced T1 intensity after treatment was associated with lower PFS (p < 0.001) and OS (p = 0.049). CONCLUSION: There is only a moderate correlation between FET PET uptake and contrast-enhanced T1 signal intensity. High posttreatment-to-pretreatment FET PET uptake ratio and increase in correlation between PET uptake and contrast-enhanced T1 signal intensity after bevacizumab treatment are associated with poor PFS and OS.

MGMT Gene Promoter Methylation Status - Assessment of Two Pyrosequencing Kits and Three Methylation-specific PCR Methods for their Predictive Capacity in Glioblastomas.

BACKGROUND: Although methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection. MATERIALS AND METHODS: Methylation of MGMT promoter was examined by methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP, methylation-sensitive high-resolution melting analysis, and two commercial pyrosequencing (PSQ) kits. Survival was compared among 48 patients with glioblastoma according to assay results. RESULTS: Only PSQ and MSP significantly separated patients who benefited from temozolomide, with PSQ being the superior method. For PSQ analysis, the cut-off value that best correlated with prognostic outcome was 7% methylation of MGMT. Median survival in patients with MGMT promoter methylation above this cut-off value was 7.8 months longer compared to those with less than 7% methylation. Two-year overall survival for the two groups was 42% and 7.4%, respectively. CONCLUSION: PSQ is the method of choice for MGMT promoter methylation analysis in routine clinical practice.

Estimated lifetime survival benefit of tumor treating fields and temozolomide for newly diagnosed glioblastoma patients.

AIM: To estimate the mean lifetime survival benefit, an essential component of health economic evaluations in oncology, of adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) for newly diagnosed glioblastoma patients. METHODS: We integrated EF-14 trial data with glioblastoma epidemiology data. The model provided for an evidence-based approach to estimate lifetime survival for the material number of EF-14 trial patients still alive at 5 years. RESULTS & CONCLUSION: Patients treated with TTFields and TMZ had an incremental mean lifetime survival of 1.8 years (TTFields/TMZ: 4.2 vs TMZ alone: 2.4). Patients alive at year 2 after starting TTFields had a 20.7% probability of surviving to year 10. The results presented here provide the required incremental survival benefit necessary for a future assessment of the incremental cost-effectiveness of TTFields.

Effect of marital status on survival in glioblastoma multiforme by demographics, education, economic factors, and insurance status.

The relationship between marital status and glioblastoma multiforme (GBM) has not been addressed in depth. Here, we aimed to investigate the association between marital status and survival in GBM. We searched the Surveillance, Epidemiology, and End Results (SEER) database and extracted the data of eligible patients diagnosed with GBM after 2004. Marital status was classified as married, divorced/separated, widowed, and single. A Kaplan-Meier test was conducted to compare the survival curves of different groups. Multivariate Cox regression was performed to evaluate overall survival (OS) and cause-specific survival (CSS) in different groups. Subgroup analysis was applied according to demographics, typical education and income levels in the locale, and insurance status. A total of 30 767 eligible patients were included. The median OS values were 9, 7, 3, 9 months in married, divorced/separated, widowed, and single patients, respectively. After adjustment for other covariates, married patients had better OS and CSS than other patients had. In addition to marital status, demographic factors, disease progression factors, local educational level, and insurance status were also associated with survival in GBM. Furthermore, subgroup analyses revealed the protective effect of marriage in most of the comparisons. Notably, the protective effect of marriage becomes more and more apparent as time goes on. The advantageous effect of marriage on GBM survival is especially prominent in patients who are male, older than 60 years of age, White, or living in middle-income counties. In conclusion, marital status is an independent prognostic factor for GBM.

Insurance correlates with improved access to care and outcome among glioblastoma patients.

Background: The current standard of care for glioblastoma (GBM) constitutes maximal safe surgical resection, followed by fractionated radiation and temozolomide. This treatment regimen is logistically burdensome, and in a health care system in which access to care is variable, there may be patients with worsened outcomes due to inadequate access to optimal treatment. Methods: The National Cancer Database was queried for patients with diagnoses of GBM in 2006-2014. Patients were grouped according to insurance status: private insurance, Medicare, Medicaid, or uninsured. Treatments provided (surgery, radiation, and chemotherapy) were compared between groups in univariate and multivariable logistic regression analysis. Results: A total of 61614 patients were analyzed. Compared with private insurance, the odds of surgery for Medicaid and uninsured patients were 0.72 (95% CI: 0.66-0.79) and 0.77 (95% CI: 0.69-0.87), respectively (P < 0.001). The multivariable odds of receiving radiotherapy were 0.91 (95% CI: 0.86-0.96), 0.62 (95% CI: 0.57-0.68), and 0.47 (95% CI: 0.43-0.52) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). In addition, the odds of receiving chemotherapy were 0.94 (95% CI: 0.89-0.99), 0.53 (95% CI: 0.49-0.57), and 0.41 (95% CI: 0.38-0.46) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). Conclusion: Insurance status and type of insurance coverage appear to impact treatments rendered for GBM, independently of other variables. Furthermore, we find that such differential access to care significantly impacts survival. Ensuring adequate access to care for all patients with diagnoses of glioblastoma is critical to optimize survival, especially as therapies continue to advance.