Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.

Academic accomplishments of Black neurosurgeons in the United States.

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding. METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites. RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts. CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

Diversity within the neurosurgical oncology workforce in the United States: A cross-sectional study with proposed strategies to pave the path forward.

BACKGROUND: Improving and fostering diversity within the neurosurgical workforce has become a high priority. This cross-sectional study aims to provide data on the diversity of neurosurgical oncology faculty (NSOF) in the US. METHODS: All 115 neurosurgery (NS) Accreditation Council for Graduate Medical Education (ACGME) accredited programs were included in this study. The academic rank, academic and clinical title(s), gender, race, and hiring date of neurosurgical faculty with a primary focus on neurosurgical oncology (NSOF) were recorded. Geographical distribution and "top 10" programs were tabulated according to published data. Underrepresented minorities in medicine (URiM) faculty were identified according to the AAMC definition. RESULTS: The NSOF workforce constitutes 21% of the total NS faculty. Of these, 10.1% are women and 9.9% are URiM (P < .001). Currently, 58% of neurosurgery programs (NSP) do not have URiM and/or women NSOF. The top 10 ranked NSP, according to Blue Ridge Institute for Medical Research, had a significantly less URiM NSOF (P = .019) than nontop 10 ranked programs. There was a decreasing trend in the proportion of URiM at higher academic ranks (P = .019). All of the URiM department chairs (3/113)-all men-and 1/3 women department chairs nationwide subspecialized in neurosurgical oncology. CONCLUSIONS: Neurosurgical oncology is a sought-after subspecialty attracting a fifth of neurosurgeons practicing in ACGME-accredited training programs. Changing demographics and the benefits of workforce diversity represent a great opportunity for our field to continue leading inclusion efforts and attracting the best and brightest.

Stereotactic radiosurgery and resection for treatment of multiple brain metastases: a systematic review and analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has recently emerged as a minimally invasive alternative to resection for treating multiple brain metastases. Given the lack of consensus regarding the application of SRS versus resection for multiple brain metastases, the authors aimed to conduct a systematic literature review of all published work on the topic. METHODS: The PubMed, OVID, Cochrane, Web of Science, and Scopus databases were used to identify studies that examined clinical outcomes after resection or SRS was performed in patients with multiple brain metastases. Radiological studies, case series with fewer than 3 patients, pediatric studies, or national database studies were excluded. Data extracted included patient demographics and mean overall survival (OS). Weighted t-tests and ANOVA were performed. RESULTS: A total of 1300 abstracts were screened, 450 articles underwent full-text review, and 129 studies met inclusion criteria, encompassing 20,177 patients (18,852 treated with SRS and 1325 who underwent resection). The OS for the SRS group was 10.2 ± 6 months, and for the resection group it was 6.5 ± 3.8 months. A weighted ANOVA test comparing OS with covariates of age, sex, and publication year revealed that the treatment group (p = 0.045), age (p = 0.034), and publication year (0.0078) were all independently associated with OS (with SRS, younger age, and later publication year being associated with longer survival), whereas sex (p = 0.95) was not. CONCLUSIONS: For patients with multiple brain metastases, SRS and resection are effective treatments to prolong OS, with published data suggesting that SRS may have a trend toward lengthened survival outcomes. The authors encourage additional work examining outcomes of treatments for multiple brain metastases.

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas.

OBJECTIVE: Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors' institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS: The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher's exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS: Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1-2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS: The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

Using qualitative data to inform the adaptation of a stroke preparedness health intervention.

Qualitative research methods are often used to develop health interventions, but few researchers report how their qualitative data informed intervention development. Improved completeness of reporting may facilitate the development of effective behavior change interventions. Our objective was to describe how we used qualitative data to develop our stroke education intervention consisting of a pamphlet and video. First, we created a questionnaire grounded in the theory of planned behavior to determine reasons people delay in activating emergency medical services and presenting to the hospital after stroke symptom onset. From our questionnaire data, we identified theoretical constructs that affect behavior which informed the active components of our intervention. We then conducted cognitive interviews to determine emergency department patients' understanding of the intervention pamphlet and video. Our cognitive interview data provided insight into how our intervention might produce behavior change. Our hope is that other researchers will similarly reflect upon and report on how they used their qualitative data to develop health interventions.

Best practices for the pregnant neurosurgical resident: balancing safety and education.

Establishment of a diverse neurosurgical workforce includes increasing the recruitment of women in neurosurgery. The impact of pregnancy on the training and career trajectory of female neurosurgeons poses a barrier to recruitment and retention of women in neurosurgery. A recent Women in Neurosurgery survey evaluated female neurosurgeons' perception and experience regarding childbearing of female neurosurgeons and identified several recommendations regarding family leave policies. Additionally, pregnancy may carry higher risk in surgical fields, yet little guidance exists to aid both the pregnant resident and her training program in optimizing the safety of the training environment with specific considerations to risks inherent in neurosurgical training. This review of current literature aims to address best practices that can be adopted by pregnant neurosurgery residents and their training programs to improve the well-being of these residents while considering the impact on their education and the educational environment for their colleagues.

Impact of race on care, readmissions, and survival for patients with glioblastoma: an analysis of the National Cancer Database.

BACKGROUND: The objective of this study was to explore racial/ethnic factors that may be associated with survival in patients with glioblastoma by querying the National Cancer Database (NCDB). METHODS: The NCDB was queried for patients diagnosed with glioblastoma between 2004 and 2014. Patient demographic variables included age at diagnosis, sex, race, ethnicity, Charlson-Deyo score, insurance status, and rural/urban/metropolitan location of zip code. Treatment variables included surgical treatment, extent of resection, chemotherapy, radiation therapy, type of radiation, and treatment facility type. Outcomes included 30-day readmission, 30- and 90-day mortality, and overall survival. Multivariable Cox regression analyses were performed to evaluate variables associated with race and overall survival. RESULTS: A total of 103 652 glioblastoma patients were identified. There was a difference in the proportion of patients for whom surgery was performed, as well as the proportion receiving radiation, when stratified by race (P < .001). Black non-Hispanics had the highest rates of unplanned readmission (7.6%) within 30 days (odds ratio [OR]: 1.39 compared to White non-Hispanics, P < .001). Asian non-Hispanics had the lowest 30- (3.2%) and 90-day mortality (9.8%) when compared to other races (OR: 0.52 compared to White non-Hispanics, P = .031). Compared to White non-Hispanics, we found Black non-Hispanics (hazard ratio [HR]: 0.88, P < .001), Asian non-Hispanics (HR: 0.72, P < .001), and Hispanics (HR: 0.69, P < .001) had longer overall survival. CONCLUSIONS: Differences in treatment and outcomes exist between races. Further studies are needed to elucidate the etiology of these race-related disparities and to improve outcomes for all patients.

A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. METHODS: A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. RESULTS: Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden (P = .0055) and PTEN mutations (P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival (P < .0001). Clinical factors significantly associated with GBM survival included age (P < .0001), preoperative Karnofsky Performance Scale score (P = .0001), sex (P = .0164), and clinical trial participation (P < .0001). Higher preoperative T1-enhancing volume (P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival (P = .0022). CONCLUSIONS: Our newly devised long-term survival-predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

Comparative epidemiology of gliosarcoma and glioblastoma and the impact of Race on overall survival: A systematic literature review.

OBJECTIVE: Gliosarcoma (GSM) is a rare subtype of glioblastoma (GBM) that accounts for approximately four percent of high-grade gliomas. There is scarce epidemiological data on patients with GSM as a distinct subgroup of GBM. METHODS: A systematic literature review was performed of peer-reviewed databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the impact of race and ethnicity on survival in patients with GSM compared to patients with GBM. RESULTS: Following initial abstract screening, a total of 138 articles pertaining to GSM and 275 pertaining to GBM met criteria for full-text review, with 5 and 27 articles included in the final analysis for GSM and GBM, respectively. The majority of patients in both cohorts were non-Hispanic Whites, representing 85.6 % of total GSM patients and 87.7 % of GBM patients analyzed. Two GSM studies stratified survival by race, with one reporting the longest median survival for the Hispanic population of 10.6 months and the shortest median survival for the Asian population of 9 months. Among the GBM studies analyzed, the majority of studies reported shorter survival and higher risk of mortality among White Non-Hispanics compared to non-White patients; and of the 15 studies which reported data for the Asian population, 12 studies reported this race category to have the longest survival compared to all other races studied. Younger age, female sex, MGMT promoter methylation status, and adjuvant chemoradiation therapy were associated with improved survival in both GSM and GBM cohorts, although these were not further stratified by race. CONCLUSION: GSM portends a similarly poor prognosis to other GBM subtypes; however, few studies exist which have examined factors associated with differences in survival between these histologic variants. This review of the literature suggests there is a possible association between race and survival for patients with GBM, however data supporting this conclusion for patients with GSM is lacking. These findings suggest that GSM is a distinct disease from other GBM subtypes, with epidemiologic differences that should be further explored.

Association of Race with Survival in Intracranial World Health Organization Grade II and III Meningioma in the United States: Systematic Literature Review.

BACKGROUND: Recent literature has shown significant differences in meningioma incidence among different races, but minimal conclusive data exist on the role of race and ethnicity in overall survival for patients with high-grade intracranial meningioma. We conducted a systematic review to investigate the impact of race and ethnicity on survival in patients with high-grade intracranial meningioma. METHODS: A systematic literature review was conducted for studies using Ovid, PubMed, Cochrane, Embase, and Scopus databases. Databases were queried for the following: Meningioma AND [Ethnic OR Demography, OR African American OR Arab OR Hispanic OR Asian, OR White OR race OR racial] AND [survival OR survival analysis OR survival rate OR treatment outcome OR Survivor OR Outcome]. RESULTS: A literature search yielded a total of 412 abstracts, which were screened according to criteria that were determined a priori, and a total of 129 full-text articles were reviewed. Four articles were included in the final analysis, reporting on a total of 13,424 patients. Three studies saw an overall survival benefit in White non-Hispanics compared with Black non-Hispanics, and 1 reported a survival benefit in White non-Hispanics and Black non-Hispanics among patients who received gross total resection. One study additionally reported an increased likelihood of White patients receiving gross total resection when compared with non-White patients. CONCLUSIONS: The limited data available suggest that White patients have improved measures of survival compared with nonw-White patients, for reasons that are likely complex and multifactorial. Further studies are needed to explore these survival differences seen.

Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes.

BACKGROUND: Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data. OBJECTIVE: To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection. METHODS: We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression. RESULTS: Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio = 2.5, 95% confidence interval: 1.8-3.4, P < .001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P < .001) and a lower rate of neurological complications (11% vs 20%, respectively, P = .018) than those who underwent intralesional resection. CONCLUSION: Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option.

Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival. METHODS: Data were obtained from the National Cancer Database (NCDB) for years 2010 to 2014. GBM (WHO Grade IV; N = 2073) and non-GBM (WHO Grades II and III; N = 2963) were defined using the histology grouping of the Central Brain Tumor Registry of the United States. Non-GBM was divided into oligodendrogliomas/mixed gliomas and astrocytomas. Sex differences in survival were analyzed using Kaplan-Meier and multivariable Cox proportional hazards models adjusted for known prognostic variables. RESULTS: There was a female survival advantage in patients with GBM both in the unadjusted (P = .048) and adjusted (P = .003) models. Unadjusted, median survival was 20.1 months (95% CI: 18.7-21.3 months) for women and 17.8 months (95% CI: 16.9-18.7 months) for men. Adjusted, median survival was 20.4 months (95% CI: 18.9-21.6 months) for women and 17.5 months (95% CI: 16.7-18.3 months) for men. When stratifying by age group (18-55 vs 56+ years at diagnosis), this female survival advantage appeared only in the older group, adjusting for covariates (P = .017). Women (44.1%) had a higher proportion of methylated MGMT (O6-methylguanine-DNA methyltransferase) than men (38.4%). No sex differences were found for non-GBM. CONCLUSIONS: Using the NCDB data, there was a statistically significant female survival advantage in GBM, but not in non-GBM.

Diagnosis, treatment, and survival in spinal dissemination of primary intracranial glioblastoma: systematic literature review.

OBJECTIVE: Spinal metastases from primary intracranial glioblastoma (GBM) are infrequently reported, and the disease has yet to be well characterized. A more accurate description of its clinical presentation and patient survival may improve understanding of this pathology, guide patient care, and advocate for increased inclusion in GBM research. The authors sought to describe the clinical presentation, treatment patterns, and survival in patients with drop metastases secondary to primary intracranial GBM. METHODS: A systematic review was performed using the PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases were queried for abstracts that included patients with primary intracranial GBM and metastases to the spinal axis. Descriptive statistics were used to evaluate characteristics of the primary brain lesion, timing of spinal metastases, clinical symptoms, anatomical location of the metastases, and survival and treatment parameters. Kaplan-Meier analysis and log-rank analysis of the survival curves were performed for selected subgroups. RESULTS: Of 1225 abstracts that resulted from the search, 51 articles were selected, yielding 86 subjects. The patients' mean age was 46.78 years and 59.74% were male. The most common symptom was lumbago or cervicalgia (90.24%), and this was followed by paraparesis (86.00%). The actuarial median survival after the detection of spinal metastases was 2.8 months and the mean survival was 2.72 months (95% CI 2.59-4.85), with a 1-year cumulative survival probability of 2.7% (95% CI 0.51%-8.33%). A diagnosis of leptomeningeal disease, present in 53.54% of the patients, was correlated, and significantly worse survival was on log-rank analysis in patients with leptomeningeal disease (p = 0.0046; median survival 2.5 months [95% CI 2-3] vs 4.0 months [95% CI 2-6]). CONCLUSIONS: This study established baseline characteristics of GBMs metastatic to the spinal axis. The prognosis is poor, though these results will provide patients and clinicians with more accurate survival estimates. The quality of studies reporting on this disease pathology is still limited. There is significant need for improved reporting methods for spinal metastases, either through enrollment of these patients in clinical trials or through increased granularity of coding for metastatic central nervous system diseases in cancer databases.

Racial/ethnic differences in survival for patients with gliosarcoma: an analysis of the National cancer database.

PURPOSE: Gliosarcoma is characterized by the World Health Organization as a Grade IV malignant neoplasm and a variant of glioblastoma. The association of race and ethnicity with survival has been established for numerous CNS malignancies, however, no epidemiological studies have reported these findings for patients with gliosarcoma. The aim of this study was to examine differences by race and ethnicity in overall survival, 30-day mortality, 90-day mortality, and 30-day readmission. METHODS: Data were obtained by query of the National Cancer Database (NCDB) for years 2004-2014. Patients with gliosarcoma were identified by International Classification of Diseases for Oncology, Third Edition (ICD-O-3)-Oncology morphologic code 9442/3 and topographical codes C71.0-C71.9. Differences in survival by race/ethnicity were examined using univariable and multivariable Cox proportional hazards models. Readmission and mortality outcomes were examined with univariable and multivariable logistic regression. RESULTS: A total of 1988 patients diagnosed with gliosarcoma were identified (White Non-Hispanic n = 1,682, Black Non-Hispanic n = 165, Asian n = 40, Hispanic n = 101). There were no differences in overall survival, 30- and 90-day mortality, or 30-day readmission between the races and ethnicities examined. Median survival was 10.4 months for White Non-Hispanics (95% CI 9.8, 11.2), 10.2 months for Black Non-Hispanics (95% CI 8.6, 13.1), 9.0 months for Asian Non-Hispanics (95% CI 5.1, 18.2), and 10.6 months for Hispanics (95% CI 8.3,16.2). 7.3% of all patients examined had an unplanned readmission within 30 days. CONCLUSION: Race/ethnicity are not associated with differences in overall survival, 30-day mortality, 90-day mortality, or 30-day readmission following surgical intervention for gliosarcoma.

Rethinking medulloblastoma from a targeted therapeutics perspective.

INTRODUCTION: Medulloblastoma is an aggressive but potentially curable central nervous system tumor that remains a treatment challenge. Analysis of therapeutic targets can provide opportunities for the selection of agents. METHODS: Using multiplatform analysis, 36 medulloblastomas were extensively profiled from 2009 to 2015. Immunohistochemistry, next generation sequencing, chromogenic in situ hybridization, and fluorescence in situ hybridization were used to identify overexpressed proteins, immune checkpoint expression, mutations, tumor mutational load, and gene amplifications. RESULTS: High expression of MRP1 (89%, 8/9 tumors), TUBB3 (86%, 18/21 tumors), PTEN (85%, 28/33 tumors), TOP2A (84%, 26/31 tumors), thymidylate synthase (TS; 80%, 24/30 tumors), RRM1 (71%, 15/21 tumors), and TOP1 (63%, 19/30 tumors) were found in medulloblastoma. TOP1 was found to be enriched in metastatic tumors (90%; 9/10) relative to posterior fossa cases (50%; 10/20) (p = 0.0485, Fisher exact test), and there was a positive correlation between TOP2A and TOP1 expression (p = 0.0472). PD-1 + T cell tumor infiltration was rare, PD-L1 tumor expression was uncommon, and TML was low, indicating that immune checkpoint inhibitors as a monotherapy should not necessarily be prioritized for therapeutic consideration based on biomarker expression. Gene amplifications such as those of Her2 or EGFR were not found. Several unique mutations were identified, but their rarity indicates large-scale screening efforts would be necessary to identify sufficient patients for clinical trial inclusion. CONCLUSIONS: Therapeutics are available for several of the frequently expressed targets, providing a justification for their consideration in the setting of medulloblastoma.

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design.

INTRODUCTION: Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents. METHODS: Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8-110), and fluorescent and chromogenic in situ hybridization (n = 5-70) to determine mutational and expression status. RESULTS: The median age of patients in the cohort was 60 years, with a range spanning 6-90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%). CONCLUSION: If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.

Identification of metabolites in plasma for predicting survival in glioblastoma.

Circulating metabolomics profiling holds prognostic potential. However, such efforts have not been extensively carried out in glioblastoma. In this study, two-step (training and testing) metabolomics profiling was conducted from the plasma samples of 159 glioblastoma patients. Metabolomics profiling was tested for correlation with 2-year overall and disease-free survivals. Arginine, methionine, and kynurenate levels were significantly associated with 2-year overall survival in both the training and testing sets. In the combined sets, elevated levels of arginine and methionine were associated with a 34% and 37% increased probability whereas kynurenate was associated with a 55% decreased probability of 2-year overall survival. These three metabolites were also significantly associated with 2-year disease-free survival. Risk scores were generated using the linear combination of levels of these significant metabolites. Glioblastoma patients with a high-risk score exhibited a 2.41-fold decreased probability of 2-year overall survival (hazard ratio (HR) = 2.41; 95% Confidence Interval (CI) = 1.20-4.93) and a 3.17-fold decreased probability of 2-year disease free survival (HR = 3.17, 95%CI = 1.42-7.54) relative to those with a low-risk score. In conclusion, we identified a unique plasma metabolite profile that is predictive of glioblastoma prognosis.

Serum HOTAIR and GAS5 levels as predictors of survival in patients with glioblastoma.

Circulating long non-coding RNAs (lncRNAs) are a new class of cancer biomarkers. However, their significance in predicting outcomes in glioblastoma patients is unclear. We measured the levels of six known oncogenic lncRNAs-CRNDE, GAS5, H19, HOTAIR, MALAT1, and TUG1 in serum samples from 106 patients with primary glioblastoma and analyzed their association with outcomes. High levels of HOTAIR were associated with decreased probability of 2-year overall survival (adjusted hazard ratio [HR] = 2.04; 95% confidence interval [CI] = 1.08-9.76), and disease-free survival (adjusted HR = 1.82; 95% CI = 1.04-6.17). High levels of GAS5 were associated with increased probability of 2-year overall survival (adjusted HR = 0.44; 95% CI = 0.18-0.99), and disease-free survival (adjusted HR = 0.46; 95% CI = 0.16-0.98). HOTAIR and GAS5 levels could serve as reciprocal prognostic predictors of survival and disease progression in patients with glioblastoma.