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Very little research has been conducted on brain tumor epidemiology in Pakistan and a few studies that do exist provide regional data only. Conducting population based epidemiological studies in low-and-middle income countries (LMICs) like Pakistan can be particularly challenging due to limited resources, poor clinical and research infrastructure, unreliable or incomplete hospital records and a lack of standardization across the health care system. Population-wide studies and registries play an important role in cancer epidemiology and can help identify the current magnitude of cancer burden and its likely future evolution, allowing for better planning of prevention, diagnosis, management, and rehabilitation. This paper describes our experience in designing and conducting Pakistan Brain Tumor Epidemiology Study (PBTES), a first-ever nationwide study carried out to assess the distribution of brain tumors in Pakistan. In addition to the aforementioned obstacles, we were also faced with the global health crisis caused by the COVID-19 pandemic and had to promptly adjust our study accordingly. Other investigators conducting epidemiological studies in LMICs with similarly challenging and constricting settings could benefit from our experiences.

BACKGROUND The female predominance of meningiomas may reflect a hormonal influence on tumorigenesis. Obesity alters steroid synthesis and chronically exposes men to hyperestrogenemia. OBJECTIVE Identify differences in males undergoing craniotomy for meningioma compared to other tumors or aneurysms. METHODS The National Surgical Quality Improvement Program was retrospectively queried from 2013–2018 for cases of craniotomy for resection of meningioma, other tumor, and aneurysm by CPT code in male patients and confirmed with postoperative ICD-10 code. Height and weight data were used to create body mass index (BMI): underweight (< 18.5), normal (18.5 to< 25), overweight (25 to< 30), class I obesity (30 to< 35), class II obesity (35 to< 40), and class III obesity (40+). RESULTS We identified 2,458 males who underwent craniotomy for meningioma, 9,889 for other tumor, and 386 for aneurysm. Using multivariable logistic regression, age (OR 1.01 per year, 95% CI 1.01-1.01, p< 0.001), diabetes mellitus (OR 1.32, 95% CI 1.17–1.48, p< 0.001), and increasing BMI (overweight: OR 1.55, 95% CI 1.36–1.76, p< 0.001; class I: OR 2.00, 95% CI 1.75–2.30, p< 0.0001; class II: OR 2.05, 95% CI 1.24–1.76, p< 0.001; class III: OR 1.47, 95% CI 1.24–1.76, p< 0.0001) were significantly and independently associated with craniotomy for meningioma compared to other tumor or aneurysm. For other tumor, higher BMI was associated with lower likelihood (overweight: OR 0.70, 95% CI 0.62–0.79, p< 0.001; class I: OR 0.55, 95% CI 0.49–0.63, p< 0.001; class II: OR 0.52, 95% CI 0.44–0.62, p< 0.001; class III: OR 0.74, 95% CI 0.63–0.87, p< 0.001). For aneurysm, there was no significant difference (overweight p=0.70; class I p=0.65; class II p=0.76; class III p=0.57). CONCLUSIONS BMI independently predicts having craniotomy for meningioma when compared to other tumor or aneurysm amongst US male patients.

PURPOSE Central Nervous System (CNS) tumors pose a substantial health problem. Although data on specific time periods and regions of Africa has been previously reported, no study has yet to provide a systemic review on the frequency of CNS tumors for the entire continent of Africa. This study aims to analyze the frequency of CNS tumors in Africa from 1960 to 2017. METHODS A comprehensive literature search on CNS tumors in Africa was performed using multiple online scientific databases. The following keywords were queried in combination with the phrase “CNS tumors in Africa”: incidence, frequency, epidemiology, prevalence, brain, and cancer. A total of 26 articles met the inclusion criteria. Each selected article reported incidence and mortality rates from different regions of Africa between 1960 to 2017. SPSS21 statistical software was used to analyze the data. RESULTS Nigeria, Egypt, and Uganda were found to have the highest incidence of CNS tumors in Africa. Total incidence was 5902, the majority were males, 3190 with mean rate 122.67 (95% CI: 29.27, 216.07) compared to females, 2501 with a mean rate of 96.19 (95% CI: 26.24, 166.15). The most common CNS tumors found were astrocytoma (24.70%), meningioma (22.22%), pituitary adenoma (8.4%), medulloblastoma (4.26%), craniopharyngioma (4.07%), and other not specified (25.17%). CONCLUSION Given the large population of Africa, the reported total incidence may be underestimated when compared to other continents due to the lack of a central brain tumor registry in Africa. Comprehensive knowledge of CNS tumors in Africa is critical to research and the entire healthcare system.

Changes in glioma patients’ immune profiles over the course of disease may predict outcomes. DNA based immunomethylomics quantifies blood immune cells based on cell specific DNA methylation signatures. To assess changes in immune profiles, we are longitudinally collecting blood samples from glioma patients pre-surgery and at other clinically relevant time points. Here we report patients’ pre-surgery immune profiles. All patients underwent biopsy or resection of a presumed new glioma or recurrent lower grade glioma. Blood DNA methylation was assessed with Illumina EPIC methylation arrays. Relative cell fractions of CD4, CD8, B-cells, natural killer cells, monocytes, and neutrophils, were estimated via our validated deconvolution algorithm. Total nucleated cell counts from Nexcelom cytometry were used to compute absolute cell counts. Other measures include total lymphocytes, CD4/CD8 ratio, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR)). The first 125 participants includes 56 newly diagnosed glioblastomas (GBM), 28 newly diagnosed grade II-III gliomas, and 41 recurrent grade II-III gliomas. Median patient age is 49 years. 53 (43%) had recent dexamethasone exposure. In overall non-parametric analyses, most cell subsets, especially CD4, differed across grade, diagnosis group, WHO classification and dexamethasone exposure. In post-hoc pairwise analyses, immune profiles of IDH wildtype GBM patients who had taken dexamethasone differed from patients with GBM or grade II-III glioma who had not taken dexamethasone; they had clinically relevant and statistically significantly lower absolute CD4 counts, total white cell counts, and percent of total lymphocytes, and higher absolute neutrophil counts, NLR and LMR. However, some dexamethasone naïve GBM patients also had altered immune profiles. Comparisons of relative immune cell fractions with those from 454 non-glioma controls from the UCSF Adult Glioma Study showed that across grade and WHO classification, for the most part, immune profiles of glioma patients not exposed to dexamethasone did not differ from controls.

BACKGROUND Glioblastoma (GBM) is the most aggressive primary central nervous system malignancy. The median overall survival is 15 to 18 months with treatment and decreases to nine months after first progression. METHODS This is a retrospective study. Data was collected from all patients with first progression of GBM treated at CCF between Jan 2012 to Jan 2020. Eight cohorts of patients were evaluated: Group 1 received cytotoxic chemotherapy, Group 2 received bevacizumab alone, Group 3 received surgical or reirradiation alone, Group 4 were enrolled in clinical trials. Each group was divided into methylated and unmethylated cohorts. RESULTS Median overall survival was 12.4 months for patients with first progression of GBM (n= 248). Among the methlylated patients, the median overall survival was 16.5 months for group 1, 13.4 for group 2, 23.7 for group 3, and 17.3 for group 4. Among the unmethylated patients, the Median overall survival was 8.6 months for group 1, 7.7 months for group 2, 11.7 months for group 3 and 10.7 months for group 4. (p= 0.00016). Progression free survival (PFS) was 4.3 months for all patients with first progression of GBM. Among the unmethlylated patients, the PFS was 3.6 months for group 1, 15.3 months for group 2, 4.8 months for group 3, and 6.1 months for group 4. Among the unmethylated patients, the PFS was 2.3 months for group 1, 3.9 months for group 2, 3.8 months for group 3, and 4.4 months for group 4. (p < 0.0001). CONCLUSION Patients with first progression of GBM had the best overall survival in the cohort that underwent a surgical or reirradiation. The best progression free survival was for patients who were treated with Bevacizumab if they were methylated and those enrolled in clinical trials if they were unmethylated. The study was statistically significant.

Brain metastases (BM) are typically treated with systemic chemotherapy and stereotactic radiosurgery (SRS). Population-level studies exploring SRS use in different patient populations and its impact on chemotherapy treatment patterns are needed. This study examines data from Surveillance, Epidemiology, and End-Results (SEER) from 2010–2012 and Medicare claims from 2008–2014 to identify the utility of SRS and associated chemotherapy treatment patterns in the breast cancer BM patient population. 25,954 breast cancer patients were identified, of which 6,657 (26%) received SRS. Chi-square and Fisher’s exact tests were used for initial univariate analyses. Univariable logistic regression models were fit for each predictor and multivariable models were selected using LASSO. Compared to patients without SRS, patients who received SRS were older, diagnosed at later disease stages, and less likely to have the Her2-/HR+ subtype. Patients with SRS most commonly received aromatase inhibitors (53.5%), followed by selective estrogen receptor modulators (SERM; 31.7%), taxanes (27.2%), alkylating agents (21.2%), monoclonal antibodies (22.2%), antimetabolite drugs (18.3%), anthracyclines (11.4%), and platinating agents (6.8%). Increased odds of SRS were associated with drug classes including taxanes (aOR: 1.29), monoclonal antibodies (aOR: 1.67), antimetabolites (aOR: 1.77), anthracyclines (aOR: 1.32), and topoisomerase-II inhibitors (aOR: 3.16). Aromatase inhibitors were associated with decreased odds of SRS use (aOR: 0.84). Alkylating agents, platinating agents, and SERM had no such associations. Our findings suggest that use of many chemotherapeutic agents increases with SRS regardless of ability to penetrate the blood-brain-barrier and parallels standard systemic breast cancer treatments. Because large-scale studies on the impact of SRS on breast cancer BM patients are lacking, it is important to identify differences in treatment usage and patterns. Important clinical implications regarding drug usage frequency, adherence to treatment guidelines, and use of different agents across SRS patients may arise by analyzing differences amongst and between populations of patients with and without SRS.

OBJECTIVES To investigate the long-term survival rates and the related predictors in patients with glioblastoma (GBM) using NCDB. METHODS A total of 51570 GBM patients were derived from the NCDB from 2004 to 2011. Three long-term survival measures were defined as patients who lived for at least 3-year, 5-year, or 10-year after diagnosis, respectively. Multivariable binary logistic regressions were performed to identify predictors in relation to 3-year, 5-year, and 10-year survival rates. The relative importance of each survival predictors was calculated, and random forest method was performed to validate the variable importance and decision tree as well. RESULTS A total of 4782 (9.3%), 1481 (3.9%), and 51 (0.9%) GBM patients survived at least 3-year, 5-year, and 10-years, respectively. Significant predictors related to both 3-year and 5-year survival rates from multivariable logistic regression included tumor resection, recent year of diagnosis, age < 65 years, private insurance, adjuvant therapy, non-whites, female, treatment at facility located in South regions or academic facilities, higher income, and non-comorbidity. Moreover, patients who traveled >50 miles for treatment and received care transition were significantly more likely to survival at least 3 years. However, only five predictors were associated with 10-year survivorship: residence-hospital distance >20 miles, non-whites, age < 65 years, resection, and higher income. Based on the calculations of relative importance and random forest method, the most important five factors to predict long-term survival were age, tumor resection, year of diagnosis, comorbidity, and adjuvant therapy (3-year survival); age, tumor resection, comorbidity, gender, and insurance (5-year survival); and age, race, residence-hospital distance, income, and comorbidity (10-year survival), respectively. CONCLUSIONS This study identifies non-molecular factors predicting long-term survivorship among GBM patients using NCDB dataset. Our findings suggested that 3-year and 5-year survivors share similar determinants, while 10-year survivors could be more different in socio-demographics and clinical features.

BACKGROUND Grade II/III glioma are a significant source of morbidity and mortality, with disease behaviour ranging from relatively mild to aggressive. Phase 3 clinical trial data informed contemporary treatment paradigms, but the perceived differences in tolerability between temozolomide-based regimens and procarbazine, CCNU, and vincristine (PCV)-based regimens has resulted in different treatment approaches across centres. We compared the frequency of progression and adverse drug events (ADE) among patients given these two regimens. METHODS Grade II/III glioma patients were identified through cancer registries in Alberta and Manitoba. Clinical data was obtained through electronic medical records. We estimated the distribution of patient age and sex, molecular data, treatment details, ADE, and patient outcomes across groups treated by temozolomide or PCV. RESULTS From 2012–2016, 344 patients were identified. Of these, 51% received chemotherapy: 26 received PCV (5/6 cycles completed by 85%), 142 received temozolomide (5/6 cycles completed by 78%). PCV resulted in grade 3/4 ADE in 38% of cycles, most commonly bone marrow toxicity. Temozolomide resulted in grade 3/4 ADE in 6% of cycles, most commonly nausea and rash. Clinical progression events occurred in 23% and 30% of PCV and temozolomide patients, respectively. Radiological progression events occurred in 50% and 52% of PCV and temozolomide patients, respectively. CONCLUSION Systemic therapy is commonly given to patients with grade II/III glioma, with more temozolomide use compared to PCV. All patients had high completion rates of treatment despite more frequent grade 3/4 adverse events in patients treated with PCV. The frequency of progression was similar across groups.

BACKGROUND The diagnosis of a brain metastases is generally made during the follow up examinations of patients with primary known cancer. However, there are some patients presenting brain metastases as the first manifestation of a previously undiagnosed primary tumor (UDP) pathological confirmation of the diagnosis. The timing of a subsequent neurosurgical intervention is influenced by the distribution of primary tumors in UDP patients. The purpose of this study was to investigate the optimal diagnostic approach and the role of surgery for UDP patients. METHODS In a retrospective study, 35 patients admitted to our institution and underwent brain tumor removal from 2017 to 2019 with the diagnosis of cerebral metastases and diagnosed lung cancer as primary tumor subsequently, or previously diagnosed lung cancer. RESULTS UDP patients represented 46% of the whole group. Primary tumor subtype was the adenocarcinoma (n=13, 81%), small cell carcinoma (n=2, 13%), and neuroendocrine carcinoma (n=1, 6%). They did not have bronchoscopy nor excision of lung cancer. On the other hand, the patients previously diagnosed lung cancer represented 54% and subtype was adenocarcinoma (n=14, 74%) and small cell carcinoma (n=5, 26%). EGFR mutation was detected from 7 patients (44%) in UDP group and treated by EGFR tyrosine kinase inhibitor. CONCLUSION The significance of surgical intervention in metastatic brain tumors has been limited. However, active surgical intervention in UDP patients could identify not only histological diagnosis but also molecular biological characteristics. Our study suggests the possibility to avoid whole brain radiation in UDP patient by the active surgery.

BACKGROUND Population-based data on the various causes of death among Primary Brain and CNS tumor patients are lacking. We evaluated the causes of death for all eligible patients using the National Program of Cancer Registries (NPCR) data. METHODS The population-based cancer survival data collected by the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) were used to analyze the causes of death for patients of all ages with primary brain and CNS tumors diagnosed between 2001 and 2016. Patients for whom the cause of death was not listed on the death certificate or whose state death certificate was not available were excluded. Additional analyses to identify factors associated with brain tumor-specific mortality for the most common malignant (Glioblastoma) and non-malignant (Meningioma) were performed using univariable and multivariable logistic regression analysis. RESULTS Major cause of death for patients with malignant tumors was death due to brain and other CNS tumors (49.29%), and for non-malignant tumors were other benign and malignant tumors (31.5%) and heart disease (17.9%). Overall mortality was 36.4% (n=331,953) in patients with Primary Brain and CNS Tumors during the study period. Specifically, 163,621 (49.29%) patients died due to brain and other CNS tumors. A significant proportion of patients with malignant tumors had brain tumor-specific mortality compared to non-malignant tumors (75.4% in malignant vs 4.2% in non-malignant). The factors associated with brain specific mortality in Glioblastoma patients were Age (p< 0.001), Race (p< 0.001) and Primary Site (p< 0.001). Further, the factors associated with brain specific mortality in Non-malignant Meningioma patients were Age (p< 0.001), Sex (p< 0.001), Race (p< 0.001) and Primary Site (P< 0.001). CONCLUSION Cause of death attributed to the brain tumor was significantly higher in malignant brain tumors compared to non-malignant brain tumors.

OBJECTIVES To investigate the impact of biopsy preceding resection compared to upfront resection in glioblastoma overall survival (OS) and post-operative outcomes using the National Cancer Database (NCDB). METHODS A total of 17,334 GBM patients diagnosed between 2010 and 2014 were derived from the NCDB. Patients were categorized into two groups: “upfront resection” versus “biopsy followed by resection”. Primary outcome was OS. Post-operative outcomes including 30-day readmission/mortality, 90-day mortality, and prolonged length of inpatient hospital stay (LOS) were secondary endpoints. Kaplan-Meier methods and accelerated failure time (AFT) models with gamma distribution were applied for survival analysis. Multivariable binary logistic regression models were performed to compare differences in the post-operative outcomes between these groups. RESULTS Patients undergoing “upfront resection” experienced superior survival compared to those undergoing “biopsy followed by resection” (median OS: 12.4 versus 11.1 months, log-rank test: P=0.001). In multivariable AFT models, significant survival benefits were observed among patients undergoing “upfront resection” (time ratio [TR]: 0.83, 95% CI: 0.75–0.93, P=0.001). Patients undergoing upfront GTR had the longest survival compared to upfront STR, GTR following STR, or GTR and STR following an initial biopsy (14.4 vs. 10.3, 13.5, 13.3, and 9.1, months), respectively (TR: 1.00 [Ref.], 0.75, 0.82, 0.88, and 0.67). Recent years of diagnosis, higher income and treatment at academic facilities were significantly associated with the likelihood of undergoing upfront resection after adjusting the covariates. Multivariable logistic regression revealed that 30-day mortality and 90-day mortality were decreased by 73% and 44% for patients undergoing “upfront resection” over “biopsy followed by resection”, respectively (both p < 0.001). CONCLUSIONS Pre-operative biopsies for surgically accessible tumors with characteristic imaging features of Glioblastoma lead to worse survival despite subsequent resection compared to patients undergoing upfront resection.

BACKGROUND The female predominance of meningiomas may reflect hormonal influences on meningioma development, with known presence of estrogen and progesterone receptors. Progestin-associated meningiomas demonstrate a shift in the mutational landscape and are more frequently located at the skull base. Obesity and increased adipocytes increase aromatase and affect male hormone synthesis, thus increases circulating estrogen. OBJECTIVE Report prevalence of obesity in a consecutive series of male patients presenting with meningioma and the interaction with obesity. METHODS A retrospective review (20012019) was performed of male patients diagnosed with meningioma. Body mass index (BMI) >30 kg/m2 was considered obese. Obese male meningioma patients were characterized and compared to nonobese male meningioma patients. RESULTS Of 239 male patients with meningioma, 97 (40.6%) were obese at the time of surgery with overall mean BMI (30.0 kg/m2). This is above the age-adjusted baseline prevalence of obesity for males in Oregon, which was 34.8% between 2015–2016. Mean age at diagnosis for obese males was 55.3 years and 57.0 years for nonobese males. Within the obese group, most lesions were located on the skull base (48.5% n=47) compared to 34.0% convexity (n=33), 15.4% falx (n=16) and 1.0% multiple (n=1). Tumors were WHO grade I (73.6%), grade II (25.6%) or grade III (1.2%). Of the men in our series, patients with skull base meningiomas were more likely to be obese (OR: 1.7, 95% CI: 1.01–2.9, p=0.0309). CONCLUSIONS There is likely a hormonal influence on the pathogenesis of meningioma, and many men diagnosed with this disease are obese. Of 239 male patients with meningioma in our series, 97 (40.6%) were obese which exceeds the 34% age-adjusted baseline prevalence of obesity for males in Oregon. Patients with skull base meningiomas were more likely to be obese, consistent with prior series and suggestive of a hormone-driven association with skull base meningioma.

PURPOSE Antidepressant drugs have shown anti-tumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level. METHODS Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time-frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival data and the log-rank test was performed for comparisons. RESULTS Four hundred four patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N=46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in overall survival between those patients who had taken antidepressants at some point in their disease course and those who had not (p=0.356). These data were confirmed in a multivariate analysis including age, Karnofsky performance status, gender, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (p=0.315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (p=0.639). CONCLUSIONS This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.

BACKGROUND Brain metastases (BMs) from metastatic prostate cancer (mPCa) are rare so little is known about clinical, genetic, and anatomic risk factors (RFs) for developing BMs. This single-center review of mPCa patients evaluates RFs for BM development. METHODS We reviewed records of mPCa patients at Tulane from 1991 – 2020 to evaluate disease, treatment, cell free DNA, and germline mutations between men with mPCa without confirmed BMs (smPCa) and men with mPCa and confirmed BMs (mPCaBMs). RESULTS We reviewed 580 patients with mPCa, of whom 11 had BMs (1.9%). Median age of stage 4 disease was 60.9 and 67.6 for men with mPCaBMs and smPCa respectively. Most mPCaBMs patients had Gleason 8 disease (81.8%) and higher median initial PSA (32 ng/mL) compared to 52.5% and 22.5 ng/mL for patients with smPCa. The development of castrate resistant disease (p=0.30) and overall survival (p=0.53) did not differ between the two populations. There were no differences in frequency of pathogenic mutations for the 68.9% (mPCaBMs) and 72.7% (smPCa) of patients with available genetic testing. Among the 11 mPCaBMs patients, 81.8% had supratentorial and 45.5% had infratentorial involvement (36.4% both). Forty-five percent had adjacent bony metastasis. Median time from SMs to BMs was 65 months (5.28 – 163.63 months), and median survival after diagnosis of BMs was 6.23 (0.49 – 70.82) months after treatment with WBRT, SRS, or GK. CONCLUSIONS The higher incidence of BMs likely reflects Tulane’s aggressive mPCa population. Interestingly 45% of BMs occurred from direct bony extension. Although 45% had infratentorial disease reflecting posterior fossa predilection, 82% of patients with BMs had supratentorial metastases. Our data suggest that men with mPCaBMs have aggressive disease and younger age at diagnosis. Due to sample size, no clinical or genetic statistically significant RFs for BMs were identified.

BACKGROUND Women have a lower incidence of high grade gliomas (HGGs), which is thought to be related to sex differences and hormone exposure. The association between hormone dependent tumors in women and HGGs remains poorly investigated. METHODS The Surveillance, Epidemiology, and End Results (SEER) database of 18 Registries (2000–2017) was used to assess age-adjusted incidence rates and temporal trends of breast cancer (BC) and HGG. Female BC patients 18 years of age or older and with ductal or lobular BC were then assessed for the risk of subsequent HGG, calculated as the standardized incidence ratio (SIR). RESULTS A total of 976,134 patients diagnosed with BC between 2000–2017 were identified. The temporal trend of BC and HGG incidence rates remained comparable throughout the study, with a higher incidence of BC and lower incidence of HGGs in females. Female BC patients had a 22% lower risk of developing a HGG (SIR 0.78 [0.69–0.87], p< 0.05) compared to general population. HGG risk by age groups in BC females was significant, with a lower risk found in pre-menopausal women (Ages 18–50, SIR 0.66 [0.45–0.94] vs Ages 50+ SIR 0.79 [0.70–0.89], p< 0.05 for both). Among HGG tumors, a decreased risk of developing glioblastoma (SIR 0.83 [0.75–0.93], p< 0.05) and anaplastic astrocytoma (SIR 0.58 [0.35–90, p< 0.05), was found, but not for anaplastic oligodendrogliomas. CONCLUSIONS The findings of our study allude to the protective effect of hormone exposure in the development of HGGs, as shown by the lower risk in female patients with BC compared to the general population.

BACKGROUND PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2–5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory RESULTS: A small meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this updated meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab combination chemotherapy on the clinical outcomes of patients with PCNSL incorporating all available comparative studies. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted. RESULTS Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HROS 0.75, 95%CI: 0.59–0.96, p=0.02; HRPFS 0.67, 95%CI: 0.53–0.85, p=0.001) with a heterogeneity estimate, I2=0%. CONCLUSIONS This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL.

PURPOSE Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs). METHODS 1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics. RESULTS Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment. CONCLUSION RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.

BACKGROUND H3 K27M glioblastoma is an aggressive grade IV tumor located in midline structures, added in 2016 by the WHO. Current outcomes are poor. The rarity of these tumors presents a challenge for definitive research on developing optimal treatments. METHODS We conducted a case series of 12 patients at the Barrow Neurological Institute who were diagnosed with biopsy-proven H3 K27M glioblastoma. The clinical status of these patients was followed from dates of first and last contact. Factors included first line treatment, best response to first line treatment, recurrences, second line treatments, response assessment criteria for all treatment rounds, any discovered metastases, and vital status by date of last contact. RESULTS Of the initial 12 patients, 5 were lost to follow-up before meaningful clinical outcomes could be recorded. Of the remaining 7, all underwent temozolomide and radiation as components of first-line treatment. After first-line treatment, 1/7 (14.2%) had partial response, 3/7 (42.8%) had stable disease, and 3/7 (42.8%) had progressive disease. 4 patients elected to undergo second line treatment: 2 underwent bevacizumab with lomustine, 1 underwent bevacizumab and irinotecan, and 1 underwent surgery with carmustine. Of the 2 who underwent bevacizumab and lomustine, 1 (50%) improved from progressive to stable disease and 1 (50%) stayed at stable disease. Of the 1 patient who underwent bevacizumab and lomustine, outcome worsened from stable to progressive disease. Of the 1 patient who underwent surgery and carmustine, outcome improved from progressive to stable disease. CONCLUSIONS H3 K27M is a highly aggressive tumor with poor outcomes. This case series demonstrates that multiple treatment rounds with chemotherapy and radiation therapy may benefit patients, with bevacizumab/lomustine and surgery/carmustine appearing to lead to promising outcomes. Further research is needed to establish evidence-based protocols so quality of life and survival time in these patients may improve.

INTRODUCTION Primary central nervous system (CNS) sarcomas are rare mesenchymal non-meningothelial tumors accounting for less than 0.2% of intracranial lesions. Diagnosis and management are challenging due to the current lack of substantive clinical, histological and molecular data. METHODS We retrospectively identified all patients with diagnosis of primary CNS sarcoma at the Hospital Fundación Pediatrico la Misericordia (HOMI) in Bogota, Colombia. We collected patient demographics, disease characteristics, and outcomes for analysis. RESULTS Between 2008 and 2020, twenty-four consecutive patients were diagnosed at the HOMI representing 6% of all CNS tumors diagnosed over the same time period. The median age at presentation was 9.48 years (range:1.6–13.4). The median time of symptoms prior to diagnosis was 2 weeks (0.1–24). The most common presentation was headache (21/24- 89%) and vomiting (19/24- 79%). The frontal lobe was involved in 63% of patients (15/24) and only one patient presented with a cerebellar lesion. Histologically, these tumors were characterized by a pleomorphic spindle cell architecture and high mitotic activity. All samples lacked immunoreactivity to GFAP, CD34, EMA, and S100 and all samples had strong nuclear immunopositivity for TLE-1; BCL-2 was reactive in eighteen cases. Gross total resection was attained in fifteen patients, most patients received focal radiation therapy and ICE chemotherapy. Progression-free survival at 12 and 24 months was 57% and 31% respectively. Overall survival was 77% at 12 months and 39% at 24 months. Thirteen patients relapsed, 11 presented with local failures, and 2 with intracranial recurrences outside of the radiation field. CONCLUSION Our study identifies TLE-1 as a diagnostic marker of primary CNS sarcoma, a highly malignant supratentorial tumor of childhood. Further molecular studies are urgently needed to elucidate the biology of this disease and the unusually high incidence observed in the Colombian pediatric population.

BACKGROUND Prognostic significance of IDH-mutation in glioma is incompletely understood in children and adolescents/young adults (YAs). We compared the clinico-genomic features, outcomes and prognostic factors observed in IDH-mutant gliomas across age groups. METHODS Clinical, histologic and molecular data of patients with IDH-mutant gliomas from 8 pediatric institutions (spanning twenty years) and adult patients from two institutions (from 2013–2019) were identified. Patients were grouped as pediatric (< 19y), YA (19y to < 40y) or older adult (≥ 40y). Genomic alterations, including somatic mutations and copy number variants, were captured with institutional next generation sequencing. Factors were compared across age categories using Fisher’s exact test or analysis-of-variance. Cox proportional-hazards regression tested factors for association with overall (OS) and progression-free survival (PFS). RESULTS Of 379 patients, 48(13%) were pediatric, 204(54%) YA and 127(33%) older adult. Histological subtype differed significantly by age group (p< 0.0001). YAs had higher rates of malignant transformation (p=0.01) and shorter time-from-diagnosis-to-malignant transformation (p=0.01) compared to other age groups. Analysis of genomic alterations revealed an age-related difference in distribution in ATRX mutations only (p=0.0018). Median PFS and OS for the entire cohort were 4.62 and 17.19 years. In univariate models, PFS differed by age group (p=0.0012), with YAs having the worst outcomes. Lack of MGMT methylation (p=0.024) predicted poorer OS. Upfront observant management was predictive of poorer PFS. Gene mutations were not associated with PFS. In multi-variable models, YAs had shorter PFS compared to pediatric (hazard ratio [HR]=2.03, p=0.01) and older adults (HR=1.59, p=0.003) after adjusting for histology, extent of resection, and initial therapy. Age at diagnosis was not associated with OS in multi-variable analysis. CONCLUSIONS Within our cohort, YA with IDH-mutant tumors progressed more quickly compared to their pediatric counterparts. Further study of YA patients with IDH-mutant glioma is critical to better define best practices for this group.

BACKGROUND Varicella zoster virus (VZV) is a neurotropic a-herpesvirus that causes chickenpox and establishes latency in the dorsal root ganglion. Live attenuated VZV vaccine was approved for use in 1995, with the CDC estimating 95% of teens had been vaccinated in 2014. Prior epidemiological literature suggests an association between VZV infection and glioma risk. METHODS We conducted a systematic review and meta-analysis of prior studies on the association between VZV infection and glioma risk. We also identified genetic instruments for VZV infection from prior GWAS and tested these for association with glioma risk in TCGA and GliomaScan (2244 cases, 4914 controls). RESULTS In six previous studies, individuals with positive chickenpox history or anti-VZV IgG seropositivity had 1.8-fold lower odds of glioma (ORmeta=0.55, 95%Cl=0.39–0.77), with similar effects by grade. GWAS hits for personal history of chickenpox (HLA-A Gly107 and rs9266089) and shingles (HLA-AArg97, HLA-DRB1 PheSerHis13, rs2523591, rs41316748 and rs7047299) were not associated with glioma risk, nor were polygenic scores (P >0.05). DISCUSSION Prior VZV infection is associated with reduced glioma risk and, based on analysis of genetic instruments, this appears to be an acquired protection caused by VZV infection rather than innate immunologic differences. VZV infection in known to elicit a broader antibody response than vaccination, but it is unknown whether VZV vaccination provides comparable protection against glioma. Because 89% of U.S. adults have had chickenpox, the “prevented fraction” of glioma due to chickenpox is ~29% of annual incidence. If VZV vaccination confers an equivalent 1.8-fold reduction in glioma risk, this prevented fraction could increase to 32%. However, if VZV vaccination is less protective, it could decrease to just 2%. This potentially drastic increase in glioma incidence in coming decades merits mechanistic studies comparing the neuro-immunologic consequences of VZV vaccination versus chickenpox infection and warrants early public health attention.

Histopathologic evaluation has been an integral part of clinical diagnosis for central nervous system tumors, providing information essential for classification, management, and treatment of the disease. Hematoxylin and eosin (H&E) staining is routinely used in histology, providing detail of tissue morphology, structure, and cellular composition. MOTIVATION: Slide staining is rife with color intensity variations, mainly due to differences in materials and staining protocols among others. These variations introduce inaccuracies in downstream computational analysis and quantification of disease, disabling the generalization of computational models. To overcome these variations, current approaches arbitrarily select a slide within the cohort to normalize all slides of the cohort, leading to non-reproducible results in other cohorts. We develop a population-based whole slide image (WSI) normalization method based on overall region driven stain vectors and color histogram, weighted by corresponding percent contribution to overall slide (PCOS). METHODS: We identified a cohort of 509 H&E stained WSIs with corresponding anatomical annotations from the Ivy Glioblastoma Atlas Project. These WSIs and annotations were reviewed by two neuropathologists for correctly annotated regions. Each region was weighted according to PCOS, WSIs with PCOS < 0.05% were discarded. Then, the optical densities and histograms calculated. Resulting color histogram and optical density was applied to the WSI cohort. Finally, stain intensity variability pre- and post- normalization was compared. RESULTS: Normalizing WSIs based on our approach, results in a significant (p < 0.01, Wilcoxon) improvement in color intensity variation for eight of nine regions tested, with the exception of “Pseudopalisading Cells with no visible Necrosis” (p = 0.8). DISCUSSION: This novel transformative technique is insensitive to artificially staining background density and straightforward to apply. Furthermore, the approach shows promise towards a viable and robust tool for stain normalization in large WSIs cohorts, with the potential towards a stain normalization standard generalizable to other diseases.

BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumor in adults with a slightly higher incidence and shortened survival in males as compared to females in the United States. Recently, there has been a focus on specific health disparities between rural versus urban populations. There is growing interest in these disparities as it pertains to CNS tumors. Here, we characterize a rural population of females diagnosed with GBM as part of an ongoing investigation to drive research and further discussion around this important topic. METHODS We performed a single institutional retrospective review of patients with GBM in rural Pennsylvania between 2006 and 2019. We collected clinical, demographic, and tumor specific data including chronic comorbid disease, marital status, age at diagnosis, obstetric history, BMI, and tumor location. RESULTS Of the 611 patients diagnosed with GBM from 2006–2019, 41% (n= 249) were female with a median overall survival of 9.5 months compared to 10.7 months in males. At diagnoses, 69% (n=173) of females had chronic comorbid allergy/immunology disorders, 41% (n=101) had endocrine disorders, 53% (n=132) had hypertension, and 43% (n=106) had mood disorders. Tumor laterality was predominantly right-sided (58%, n=145) and frequently involved the frontal lobe (38%, n=94). The temporal lobe was the second most commonly involved (32%, n=80). The median age at diagnosis was 65-years-old [range, 21–92]. Fifty-six percent (n=140) of women were married with an average of 2.27 childbirths. The median body mass index (BMI) was 27.5 [range, 16.3–64.9] with 66% of females classified as overweight/obese at diagnosis. Greater than 95% of females were insured. CONCLUSION There is a high incidence of chronic comorbid disease and obesity amongst females in this rural population, and females demonstrated a poorer overall survival as compared to males. Further comparisons are needed to characterize rural female GBM populations versus those in urban areas.

Patients with Glioblastoma Multiforme (GBM) have a poor prognosis with few long-term survivors (>2 years from diagnosis). This review analyses key characteristics of this cohort. METHODS: Retrospective single-centre review of GBM patients treated with the STUPP protocol at a Regional Neuro-oncology centre, Nov-09–Sept-19. Demographics, histology and treatment details were reviewed, with progression (PFS) and overall survival (OS) analysed. RESULTS: In 282 patients (mean age 55 years;M:F ratio 2:1), 77% of patients underwent de-bulking surgery and 35% were MGMT-methylated. Median OS was 72.1 weeks with a statistically significant survival benefit in patients who underwent debulking surgery (p=0.0001), were methylated for MGMT (P=0.0026) or those less than 50yrs (p=< 0.0001). 14% patients were treated within clinical trials. 66 patients (23%) were alive at 24 months. Baseline characteristics - mean age 52yrs; 53% MGMT-methylated; 88% debulking surgery; 16 (24%) patients with histological low grade components and 1 (1%) was of small cell. 55 (83%) relapsed of which (19) 35% received 2 lines of further treatment,14 (25%) had re do surgery, 32 (80%) received CCNU/PCV with or without surgery (24% vs 56%), 7 (13%) received TMZ-alone and 3 (5%) were not suitable for treatment. 8 (3%) were alive at 5 years. Baseline characteristics - mean age 46 years; MGMT (4 methylated, 2 unmethylated, 2 unknown); 3 (38%) had lower-grade histological components. 6 (75%) relapsed - 1 patient received TMZ (within a clinical trial) and 5 PCV/CCNU (2 within a clinical trial). 3 patients had further progression of which 2 received a further 1 line of treatment and 1 a further 3 lines. 6 (75%) remain alive, 2 (33%) in remission following STUPP. CONCLUSIONS: This real world data demonstrates that despite poor prognosis, features including methylation, younger age and surgical resection assist to predict long-term survivors. This highlights the importance of clinical trials.

There are relatively few studies on brain metastases in the military population, despite increased risk factors for the development of some cancers. This data was compared to the results from previously published epidemiological data Surveillance, Epidemiology, and End Results (SEER; Cagney et al, 2017) from the general population. PURPOSE: The purpose of our research was to compare the frequency and etiology of metastatic brain cancer in the military and veteran population in our database relative to the general population. METHODS: Retrospective chart review of diagnoses retrieved from the Electronic Medical Record dated January 1, 2016 to July 1, 2019 capturing visits to the Baylor Scott & White Medical Center with specific ICD 10 brain cancer codes for nonhematologic malignancies originating outside of the CNS. RESULTS: Data from 63 individuals that met criteria for the study was analyzed. The military group was predominantly male (92.1%), white (66.7%) and non-Hispanic (90.5%). In our current sample (N=63) 74.6% had metastatic lung cancer with a histology subset of 24.5% having adenocarcinoma. Compared to the SEER general population our sample was more likely to have metastatic lung cancer with a similar frequency in the histologic subset adenocarcinoma. CONCLUSION: In this exploratory study using retrospective data, trends were found for lung cancer diagnosis with brain metastatic disease, appearing more common in the military sample from a single-center relative to previously published estimates in the general population. Rates were similar for adenocarcinoma. More research into the higher frequency of lung cancer in the military population compared to the general population should be further explored.

BACKGROUND Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises close to 5% of cases. Several ALK inhibitors (ALKI) have been approved with activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This meta-analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of ALKI-naïve ALK+ lung cancer trials with brain metastases; treatment with Crizotinib (CRZ), Alectinib (ALC), Brigatinib (BRG), and Ceritinib (CER); and comparative studies reporting brain metastases specific responses/events. A Bayesian and a frequentists network meta-analysis were conducted using netmeta package and the random-effects model. RESULTS Eight studies comprising a total of 665 participants with ALKI-naive ALK+ lung cancer brain metastases were included. When compared pair-wise to CRZ, ALC (RR=0.49;95%CI:0.36–0.66), BRG (RR=0.39;95%CI:0.24–0.64), and CER (RR=0.36;95%CI:0.19–0.68) demonstrated significantly superior response rates in patients with untreated or previously treated lung cancer brain metastases. When the efficacy of each ALKI was compared to each other, BRG and CER were ranked the highest, followed by ALC and CRZ in decreasing order. CONCLUSIONS This network meta-analysis is the first to compare and rank approved ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ.

INTRODUCTION Steroids are commonly used for treatment of peritumoral edema and increased intracranial pressure in brain tumor patients. However, despite the widespread use of steroids, relatively little evidence is available about the optimal dosing scheme in brain tumor patients. PURPOSE The aim of this study is to increase insight in the practice variation of steroid dosing and tapering schedules among the neuro-oncology community. METHODS An electronic survey consisting of 27 questions regarding dosing and tapering schedules and adverse events of steroids was conducted among neurosurgeons internationally between 6 December 2019 and 1 June 2020. The survey was distributed by the electronic mailing lists of the Europeans Association of Neurosurgical Societies and via social media platforms. Collected data was assessed for quantitative and qualitative analysis using the Kruskal-Wallis test. RESULTS The survey obtained 175 responses. 87% of respondents answered all questions. Steroids are prescribed routinely perioperatively by 80% of respondents. Prescribed doses range from 2 to 64 mg/day in dosing schedule ranging from one to four times a day. The most prescribed steroid is dexamethasone in a dose of 16 mg/day. No significant association is seen between the prescribed dose and frequency of adverse events, years of experience, country, type of institution or having an institutional guideline. CONCLUSION Steroids are routinely prescribed perioperatively in brain tumor patients. However, there is a great practice variation in steroid dosing and tapering schedules among neurosurgeons. Future investigation is needed to identify an optimal dosing scheme and implement (inter)national guidelines for the dosing of steroids.

INTRODUCTION Intracranial tumor is a debilitating health burden that cause sever disability. The incidence rate for intracranial tumor is 4.63 per 100,000 populations. Through the development of diagnostic and therapeutic modalities, the survival of intracranial tumor improved although modest. There were several factors such as demographic, clinical, and histopathological affect intracranial tumor survival. However, there were no study about intracranial tumors and factors affecting it survival in Indonesia. This study provides insight of intracranial tumor patients and factor affecting 1-year survival in Cipto Mangunkusumo General Hospital from 2014–2016. METHODS The design of this study is retrospective cohort. The subjects were followed-up 1 year after diagnosis. The data retrieved from Dept. of Neurosurgery and Dept. of Neurology Cipto Mangunkusumo General Hospital neuro-oncology registry. Subjects with intracranial tumors underwent surgery/biopsy were included in this study. The factors analyzed in this study were demography, clinical characteristics, histopathology, and treatment types. Analysis of survival were done with Kaplan-Meier curve and cox regression. RESULTS There were 317 subjects in this study. Overall 1-year survival of intracranial tumors were 75.4%. There was increased risk of death (HR 1.88; CI95% 1.2–2.94; p = 0.005) in subjects >46 years old. There was no different of risk of death (HR 0.66; CI95% 0.92–1.03; p = 0.067) between men and women. There was no different of risk of death (HR 1.39; CI95% 0.72–2.70; p = 0.333) between supratentorial and infratentorial tumor. There was difference of survival among histopathology (p < 0.001) and therapeutic approaches (p < 0.001). DISCUSSION This is the first study in Indonesia that analyze survival of intracranial tumor. Several factors such as age, histopathology, and therapeutic approaches were found to affect 1-year survival of intracranial tumor. To get a representative insight of intracranial tumor in Indonesia, a larger cohort study should be conducted.

INTRODUCTION Steroid is commonly initiated for newly recognized brain tumors. For primary CNS lymphoma (PCNSL), however, its lympholytic effect can partially treat the tumor and obfuscate the surgical-pathological diagnosis needed to initiate chemotherapy. Evidence for this remains controversial. In this study we investigated the incidence of the vanishing tumor phenomenon and its association with steroid use. METHODS Patients > age 18 with PCNSL were identified from January 1, 2000 to April 30, 2020 within the University of Michigan Health System. Clinic and operative notes, pathology, imaging, and lumbar puncture results were reviewed. Inclusion required histopathologic diagnosis from brain tissue, cerebrospinal fluid, or autopsy, including diagnosis on repeat biopsy. Patients with prior/concurrent systemic lymphoma, HIV, organ transplant, or diagnosis established from primary ocular disease were excluded. Date(s) of biopsy, steroid initiation, and recurrence (by imaging) were abstracted. We defined vanishing tumor as a lesion whose radiographic improvement or disappearance resulted in deferred or nondiagnostic biopsy, with later confirmation of PCNSL. Steroid use and vanishing tumor were modeled using univariable logistic regression. RESULTS We identified 162 cases of PCNSL, of which 103 patients (63.6%) received steroids prior to biopsy. Twenty-three had vanishing tumor: 11 with deferred biopsies, 12 with non-diagnostic biopsies. Twenty-two of the 23 received steroid. Mean cumulative dose, in dexamethasone equivalents, was 555 + 704 mg prior to nondiagnostic/deferred biopsy (N=17) compared to 186 + 376 mg prior to successful biopsy (N=76) (Wilcoxon p< .001). Median time to recurrence after deferred or non-diagnostic biopsy (N=21) was 53 days (range: 8–648); two cases never recurred. Steroid use increased the risk of vanishing tumor by 14% per 100 mg dexamethasone equivalent (95% CI of odds ratio [1.03–1.29], p=0.02). CONCLUSION Vanishing tumor phenomenon is common in PCNSL, delays diagnosis, and is driven by steroid use.

BACKGROUND Disparities in healthcare delivery in the United States based on race and socioeconomic status are well-documented. Our study examined these disparities along with demographic differences in patients with gliomas. METHODS Data was collected retrospectively from an NCI Comprehensive Cancer Center between 2008–2020; 163 African-American patients and 1207 non-Hispanic white patients were included. Demographic variables were entered as predictors of tumor grade and type in an ANOVA model and multinomial logistic regression, respectively. A MANOVA model was used to assess differences in treatments received. Predictors of outcome were determined using cox regression. RESULTS Significant differences (p< 0.05) were found between African-American and non-Hispanic white patient groups in; age at diagnosis (48.68 vs 56.12 years, respectively), male/female gender ratio (0.75 vs 1.22), annual household income ($29,442 vs $40,028), insurance type (53.1% private and 42% public vs 63.4% private and 33.6% public) and marital status (43% married vs 74.1%). When controlling for these, there were no significant differences in tumor grade, type, MGMT methylation or IDH1 alteration statuses. Race alone did not predict treatment received, however, two-way interactions between race and other variables did. While gender differences in resection were small for non-Hispanic white controls, resection took place more often in African-American females than males (F = 4.779, p = 0.029). The deleterious effect of increased age on overall survival was diminished in African-Americans (B = -0.033, p < 0.001), while the effect of tumor grade was more pronounced (B = 0.595, p < 0.001). DISCUSSION This study suggests that disparities in outcomes are identified when race is considered within the context of other demographic, socioeconomic, and clinical factors. Moreover, these observations demonstrate the need for further studies into intersectional effects on treatment access and clinical outcomes, along with aggressive countermeasures to ensure equity of care.

BACKGROUND Race/ethnicity have been previously shown to significantly affect survival after diagnosis with glioblastoma, but the cause of this survival difference is not known. The aim of this study was to examine variation in treatment pattern and time to treatment by race/ethnicity, and the extent to which this affects survival. METHODS Data were obtained from the National Cancer Database (NCDB) for adults >= 40 with glioblastoma (histologic codes 9440–9442 and topographical codes C71.0–C71.9) from 2004–2016 (N=117,710). Treatment patterns and time to treatment by race/ethnicity were compared using univariable and multivariable logistic and linear regression models, respectively. Models were adjusted for age, sex, insurance status, pre-existing comorbidities, type of treating institution, and distance to institution. RESULTS Black non-Hispanics (BNH) were 17% less likely to receive radiation (p=1.47x10-8) and 32% less likely to receive chemotherapy (p=1.10x10-31) than White non-Hispanics (WNH). Among those that did receive treatment, it took 3.3 additional days on average for BNH to receive radiation (p=2.12x10-11) and 4.6 additional days to receive chemotherapy in comparison to WNH (p=4.14x10-10). Hispanics were 21% less likely to receive radiation (p=4.79x10-12), and 23% less likely to receive chemotherapy (p=7.51x10-14) than WNH. Among those that did receive treatment, it took 3.3 additional days on average for Hispanics to receive radiation (p=4.07x10-9) and 4 additional days to receive chemotherapy in comparison to WNH (p=1.51x10-6). There were no significant differences in time to surgery, or in to treatment for Asian Pacific Islanders or American Indian/Alaska Natives. CONCLUSIONS Both likelihood of receiving treatment and time to radiation and chemotherapy vary significant between BNH and Hispanics as compared to WNH, and this difference is not fully explained by comorbidities or access to health care.

The purpose of the study of the study is to investigate the incidence, prevalence, and survival of malignant glioma (MG) using population-based Korean National Health Insurance Database (NHID) data. We identified patients with MG as C71 codes in KCD 5–7 according to ICD-10 from 2007 to 2017. Epidemiological characteristics of MG, including annual incidence, prevalence, mortality rates, and survival rates, were collected and analyzed according to socioeconomic state (SES) and treatment modalities. 45,066 new patients with MG were identified from 2007 to 2017. An age-adjusted incidence of 7.47 per 100,000 people. The mean age at diagnosis was 54 years. The male to female ratio was 1.11. Mortality and survival probability were analyzed among total subjects and in subgroups. The mortality of female patients was lower than that of male patients (hazard ration, 0.69; 95% CI, 0.67–0.71), and younger age and higher income had significantly lower mortality rate. The 1-, 3-, 5-, and 10-year total relative survival rates were estimated at 63.4%, 46.2%, 39.4%, and 34.8%, respectively. This is the first population-based study to determine the incidence and prevalence of MG according to epidemiological characteristics in Korea using NHID data. Our study found that female sex and high SES were factors that significantly lowered the mortality rate in MG, and younger groups and operated patients showed significantly higher survival rates.

BACKGROUND Social determinants of health (SDH) are modifiable factors that contribute to health outcomes. Despite studies linking SDHs with cervical, ovarian, and prostate cancer outcomes, few studies have explored SDHs in glioma patients. We conducted a cross-sectional survey to characterize and contextualize SDHs in glioma patients by community income, rural/urban residence, and treatment status. METHODS Two validated instruments: PRAPARE (Protocol for responding to and assessing patents’ assets risks and experiences) and AHC (accountable health communities instrument) quantified SDHs; along with study-specific supplemental questions. Risk scores were calculated and combined into an overall and domain-specific (economic, education, neighborhood environment, social context, and healthcare) SDH risk, with a higher score being indicative of higher SDH risk. Scores were compared between low-income (LIC) vs high-income (HIC) communities (defined by median household income), urban vs rural (defined by zip code), and active treatment vs surveillance (determined by patient medical record) using Wilcoxon rank-sum test. RESULTS 100 glioma patients were enrolled: mean age 53 years (range: 22–78); 49% male; 18% oligodendroglioma, 34% diffuse astrocytoma, 38% glioblastoma, 10% other glioma; 68% resided in LICs, 27% in rural zip codes, and 51% were on active treatment. Overall, SDH risk scores were low (mean= 4.43-out-of-38). Scores in the healthcare domain were the highest. Compared to patients from LICs, patients from HICs had higher healthcare risk scores (p< 0.05). Surveillance patients had higher overall SDH risk on the AHC than patients in active treatment (p< 0.05), with age being a confounder. In multivariable analysis, younger age, and astrocytoma histology were associated with higher social health risk. CONCLUSION Glioma patients report relatively few SDH risk factors on standardized instruments designed for general clinic populations. The higher health risk observed in patients in HICs and higher AHC risk for those in surveillance will be further explored in planned qualitative analysis.

BACKGROUND Adolescents and young adults (AYAs; 15–39 yrs.) are a population recognized as facing significant challenges in cancer care and research, characterized by historically poor participation in clinical trials. The clinical trial enrollment rate among AYAs with CNS tumor is unclear. We report the findings from our study evaluating the clinical trial enrollment rate of AYAs with CNS glioma at DFCI, comparing the rates between its affiliated adult and children’s hospitals. METHODS We performed a retrospective cohort study of patients with primary CNS glioma treated at our center between 2008–18. Eligible patients were identified using institutional databases at Boston Children’s Hospital and Brigham and Women’s Hospital. Manual chart review and data abstraction from the electronic medical record were performed to obtain key variables. Clinical trial enrollment rates were reported, followed by univariate and multivariate logistic regression models to identify factors affecting clinical trial enrollment. RESULTS In the adult setting, a total of 608 AYA patients with glioma were identified to meet our inclusion criteria and presented with a median age of 32 years (range:15–39). 92 out of 608 (15%) patients enrolled in a clinical trial during their treatment course. Within this cohort, tumor type was significantly associated with clinical trial enrollment, with higher-grade tumors associated with better enrollment rates (p< 0.001). On the contrary in the pediatric setting, a total of 52 AYA patients were identified from the children’s hospital, with a median age of 17.2 years (range:15–25.4) of whom, 19 out of 52 (36.5%) patients were enrolled on a clinical trial. CONCLUSION Clinical trial enrollment rate remains poor among AYAs with CNS tumors, with tumor type/histology grade associated with enrollment rate. Higher enrollment rates were seen among early AYAs treated at the children’s hospital.

BACKGROUND 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 28,954 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. CONCLUSION 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.