Sex Difference in Disease-Related Adverse Events Post-Diagnosis of Lung Cancer Brain Metastases in Medicare Individuals ≥ 66 Years of Age.

Sex differences are evident in adverse events (AEs) related to brain tumors, yet sex differences in AEs specific to brain metastases (BrMs) are underexplored. Lung cancer BrMs dominate among BrM, comprising over half of cases. This study examined sex differences in AEs associated with lung cancer BrMs in individuals aged 66 or older using the SEER-Medicare dataset. Multivariable logistic regression, adjusted for demographic factors and comorbidities, stratified by histological subtype, treatment, age, and year of diagnosis were used to analyze AEs among those with BrMs from primary lung tumors. Year of diagnosis was grouped into prior/post-2013, to account for shifts in treatment paradigms. The results showed nuanced sex-specific AEs. Females diagnosed post-2013 with small-cell, squamous-cell, or other non-small-cell carcinoma BrMs had a higher headache likelihood than males. Males with adenocarcinoma post-2013 were more likely to experience brain herniation. Females aged 76 and older with small-cell BrM exhibited increased vision difficulty risk compared to males of the same age, with no significant difference in other age groups. Males treated for adenocarcinoma faced heightened hemorrhagic stroke risk. This study reveals sex-specific disparities in AEs among older individuals with lung cancer BrMs, varying by histological subtype, age, diagnosis year, and treatment.

Predicting peritumoral glioblastoma infiltration and subsequent recurrence using deep-learning-based analysis of multi-parametric magnetic resonance imaging.

Purpose: Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor. The standard treatment approach is surgical resection to target the enhancing tumor mass, followed by adjuvant chemoradiotherapy. However, malignant cells often extend beyond the enhancing tumor boundaries and infiltrate the peritumoral edema. Traditional supervised machine learning techniques hold potential in predicting tumor infiltration extent but are hindered by the extensive resources needed to generate expertly delineated regions of interest (ROIs) for training models on tissue most and least likely to be infiltrated. Approach: We developed a method combining expert knowledge and training-based data augmentation to automatically generate numerous training examples, enhancing the accuracy of our model for predicting tumor infiltration through predictive maps. Such maps can be used for targeted supra-total surgical resection and other therapies that might benefit from intensive yet well-targeted treatment of infiltrated tissue. We apply our method to preoperative multi-parametric magnetic resonance imaging (mpMRI) scans from a subset of 229 patients of a multi-institutional consortium (Radiomics Signatures for Precision Diagnostics) and test the model on subsequent scans with pathology-proven recurrence. Results: Leave-one-site-out cross-validation was used to train and evaluate the tumor infiltration prediction model using initial pre-surgical scans, comparing the generated prediction maps with follow-up mpMRI scans confirming recurrence through post-resection tissue analysis. Performance was measured by voxel-wised odds ratios (ORs) across six institutions: University of Pennsylvania (OR: 9.97), Ohio State University (OR: 14.03), Case Western Reserve University (OR: 8.13), New York University (OR: 16.43), Thomas Jefferson University (OR: 8.22), and Rio Hortega (OR: 19.48). Conclusions: The proposed model demonstrates that mpMRI analysis using deep learning can predict infiltration in the peri-tumoral brain region for GBM patients without needing to train a model using expert ROI drawings. Results for each institution demonstrate the model's generalizability and reproducibility.

The intersection of race, ethnicity, and urbanicity on treatment paradigms and clinical outcomes for non-malignant primary tumors of the spine.

BACKGROUND: Non-malignant primary tumors of the spine (NMPTS) patients in rural areas face unique barriers that may limit their capacity to receive optimal care. With a lower geographical distribution of neurosurgical specialists and limited healthcare infrastructure, rural NMPTS patients may receive certain treatments at a lower frequency than metropolitan patients. NMPTS We sought to examine the association between residential urbanicity, race-ethnicity, treatment patterns, and survival outcomes for cases diagnosed with NMPTS. METHODS: Cases of NMPTS diagnosed between 2004 and 2019 were identified from the Central Brain Tumor Registry of the United States (CBTRUS), a combined dataset of CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) data. Using multivariable logistic regression, we evaluated the association between urbanicity and treatment (including surgery and radiation), adjusted for age at diagnosis, sex, and race-ethnicity. Patient-level all-cause survival data were obtained from the NPCR Survival Analytical Database (2004-2018). RESULTS: A total of 38,414 cases were identified, 33,097 of whom lived in metropolitan and 5317 of whom lived in non-metropolitan regions. Nerve sheath tumors and meningiomas were the most common tumor histopathologies across both regions, with no clinically significant difference in other histopathologies (p<0.001). There were statistically significant differences between the frequency and type of surgery received by urbanicity (p<0.001). Overall all-cause survival was significantly lower for NH Blacks residing in non-metropolitan areas when compared to NH Blacks residing in metropolitan areas (p<0.0001). CONCLUSION: Our data demonstrates significant differences in the incidence of NMPTS across both race-ethnicity and urbanicity. However, a wider analysis of all-cause mortality reveals disparities in health outcomes across both race-ethnicity and urbanicity for Black and Hispanic populations. To address the disparity in health outcomes, policymakers and health providers need to work with local communities in rural areas to improve access to equitable and quality healthcare.

Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma.

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

Contemporary Prognostic Signatures and Refined Risk Stratification of Gliomas: An Analysis of 4,400 Tumors.

BACKGROUND: With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received. METHODS: We assembled a cohort of patients with a histopathologically diagnosed glioma from The Cancer Genome Atlas, Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women's Hospital. This incorporated retrospective clinical, histological, and molecular data alongside prospective assessment of patient survival. RESULTS: 4,400 gliomas were identified: 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (all p<0.01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received. CONCLUSIONS: By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations.

Elevated meningioma risk among individuals who are Non-Hispanic Black is strongest for grade 2-3 tumors and synergistically modified by male sex.

Background: Meningioma risk factors include older age, female sex, and African-American race. There are limited data exploring how meningioma risk in African-Americans varies across the lifespan, interacts with sex, and differs by tumor grade. Methods: The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry covering the entire U.S. population. Meningioma diagnoses from 2004-2019 were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) compared to non-Hispanic white individuals (NHW) across 10-year age intervals, and stratified by sex and by WHO tumor grade. Results: 53,890 NHB individuals and 322,373 NHW individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the NHB-to-NHW IRR was elevated for both grade 1 and grade 2/3 tumors. The IRR peaked in the seventh decade of life regardless of grade, and was higher for grade 2/3 tumors (IRR=1.57; 95% CI: 1.46-1.69) than grade 1 tumors (IRR=1.27; 95% CI: 1.25-1.30) in this age group. The NHB-to-NHW IRR was elevated in females (IRR=1.17; 95% CI: 1.16-1.18) and further elevated in males (IRR=1.28; 95% CI: 1.26-1.30), revealing synergistic interaction between NHB race/ethnicity and male sex (P Interaction =0.001). Conclusions: Relative to NHW individuals, NHB individuals are at elevated risk of meningioma from young adulthood through old age. NHB race/ethnicity conferred higher risk of meningioma among men than women, and higher risk of developing WHO grade 2/3 tumors. Results identify meningioma as a significant source of racial disparities in neuro-oncology and may help to improve preoperative predictions of meningioma grade.

Atopy improves survival and decreases risk of brain metastasis in cutaneous melanoma.

Importance: Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance. Objective: To determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma. Design: A retrospective cohort study conducted from June 2022 to March 2024. Setting: Population-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries. Participants: Individuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare. Exposures: Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims. Main Outcomes and Measures: Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values. Results: A total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], pFDR<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], pFDR=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], pFDR<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165). Conclusions and Relevance: Atopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

CBTRUS Statistical Report: American Brain Tumor Association & NCI Neuro-Oncology Branch Adolescent and Young Adult Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

Recent analyses have shown that, whereas cancer survival overall has been improving, it has not improved for adolescents and young adults ages 15-39 years (AYA). The clinical care of AYA with primary brain and other central nervous system (CNS) tumors (BT) is complicated by the fact that the histopathologies of such tumors in AYA differ from their histopathologies in either children (ages 0-14 years) or older adults (ages 40+ years). The present report, as an update to a 2016 publication from the Central Brain Tumor Registry of the United States and the American Brain Tumor Association, provides in-depth analyses of the epidemiology of primary BT in AYA in the United States and is the first to provide biomolecular marker-specific statistics and prevalence by histopathology for both primary malignant and non-malignant BT in AYA. Between 2016 and 2020, the annual average age-specific incidence rate (AASIR) of primary malignant and non-malignant BT in AYA was 12.00 per 100,000 population, an average of 12,848 newly diagnosed cases per year. During the same period, an average of 1,018 AYA deaths per year were caused by primary malignant BT, representing an annual average age-specific mortality rate of 0.96 per 100,000 population. When primary BT were categorized by histopathology, pituitary tumors were the most common (36.6%), with an AASIR of 4.34 per 100,000 population. Total incidence increased with age overall; when stratified by sex, the incidence was higher in females than males at all ages. Incidence rates for all primary BT combined and for non-malignant tumors only were highest for non-Hispanic American Indian/Alaska Native individuals, whereas malignant tumors were more frequent in non-Hispanic White individuals, compared with other racial/ethnic groups. On the basis of histopathology, the most common molecularly defined tumor was diffuse glioma (an AASIR of 1.51 per 100,000). Primary malignant BT are the second most common cause of cancer death in the AYA population. Incidence rates of primary BT overall, as well as specific histopathologies, vary significantly by age. Accordingly, an accurate statistical assessment of primary BT in the AYA population is vital for better understanding the impact of these tumors on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies, and for clinicians treating these patients.

Sex-Specific Differences in Patients with IDH1-Wild-Type Grade 4 Glioma in the ReSPOND Consortium.

BACKGROUND AND PURPOSE: Understanding sex-based differences in patients with glioblastoma is necessary for accurate personalized treatment planning to improve patient outcomes. Our purpose was to investigate sex-specific differences in molecular, clinical, and radiologic tumor parameters, as well as survival outcomes in patients with glioblastoma, isocitrate dehydrogenase-1 wild-type (IDH1-WT), grade 4. MATERIALS AND METHODS: Retrospective data of 1832 patients with glioblastoma, IDH1-WT with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as age, molecular parameters, preoperative Karnofsky performance score (KPS), tumor volumes, epicenter, and laterality were assessed through nonparametric tests. Spatial atlases were generated by using preoperative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. RESULTS: Glioblastoma was diagnosed at a median age of 64 years in women compared with 61.9 years in men (false discovery rate [FDR] = 0.003). Men had a higher KPS (above 80) as compared with women (60.4% women versus 69.7% men, FDR = 0.044). Women had lower tumor volumes in enhancing (16.7 cm3 versus 20.6 cm3 in men, FDR = 0.001), necrotic core (6.18 cm3 versus 7.76 cm3 in men, FDR = 0.001), and edema regions (46.9 cm3 versus 59.2 cm3 in men, FDR = 0.0001). The right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in men. There were no sex-specific differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNA-methyltransferase promoter and undergoing subtotal resection increased the mortality risk in both men and women. CONCLUSIONS: Our study demonstrates significant sex-based differences in clinical and radiologic tumor parameters of patients with glioblastoma. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for men and women.

Sex differences in adverse events in Medicare individuals ≥ 66 years of age post glioblastoma treatment.

PURPOSE: Glioblastoma (GB) is the most common primary malignant brain tumor with the highest incidence occurring in older adults with a median age at diagnosis of 64 years old. While treatment often improves survival it brings toxicities and adverse events (AE). Here we identify sex differences in treatment patterns and AE in individuals ≥ 66 years at diagnosis with GB. METHODS: Using the SEER-Medicare dataset sex differences in adverse events were assessed using multivariable logistic regression performed to calculate the male/female odds ratio (M/F OR) and 95% confidence intervals [95% CI] of experiencing an AE adjusted for demographic variables and Elixhauser comorbidity score. RESULTS: Males with GB were more likely to receive standard of care (SOC; Surgery with concurrent radio-chemotherapy) [20%] compared to females [17%], whereas females were more likely to receive no treatment [26%] compared to males [21%]. Females with GB receiving SOC were more likely to develop gastrointestinal disorders (M/F OR = 0.76; 95% CI,0.64-0.91, p = 0.002) or blood and lymphatic system disorders (M/F OR = 0.79; 95% CI,0.66-0.95, p = 0.012). Males with GB receiving SOC were more likely to develop cardiac disorders (M/F OR = 1.21; 95% CI,1.02-1.44, p = 0.029) and renal disorders (M/F OR = 1.65; 95% CI,1.37-2.01, p < 0.001). CONCLUSIONS: Sex differences for individuals, 66 years and older, diagnosed with GB exist in treatment received and adverse events developed across different treatment modalities.

NCI Cancer Research Data Commons: Resources to Share Key Cancer Data.

Since 2014, the NCI has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer Data Service, Imaging Data Commons, and Clinical and Translational Data Commons), including their unique and shared features, accomplishments, and challenges. Also discussed is how the CRDC data commons implement Findable, Accessible, Interoperable, Reusable (FAIR) principles and promote data sharing in support of the new NIH Data Management and Sharing Policy. See related articles by Brady et al., p. 1384, Pot et al., p. 1396, and Kim et al., p. 1404.

NCI Cancer Research Data Commons: Cloud-Based Analytic Resources.

The NCI's Cloud Resources (CR) are the analytical components of the Cancer Research Data Commons (CRDC) ecosystem. This review describes how the three CRs (Broad Institute FireCloud, Institute for Systems Biology Cancer Gateway in the Cloud, and Seven Bridges Cancer Genomics Cloud) provide access and availability to large, cloud-hosted, multimodal cancer datasets, as well as offer tools and workspaces for performing data analysis where the data resides, without download or storage. In addition, users can upload their own data and tools into their workspaces, allowing researchers to create custom analysis workflows and integrate CRDC-hosted data with their own. See related articles by Brady et al., p. 1384, Wang et al., p. 1388, and Kim et al., p. 1404.

NCI Cancer Research Data Commons: Lessons Learned and Future State.

More than ever, scientific progress in cancer research hinges on our ability to combine datasets and extract meaningful interpretations to better understand diseases and ultimately inform the development of better treatments and diagnostic tools. To enable the successful sharing and use of big data, the NCI developed the Cancer Research Data Commons (CRDC), providing access to a large, comprehensive, and expanding collection of cancer data. The CRDC is a cloud-based data science infrastructure that eliminates the need for researchers to download and store large-scale datasets by allowing them to perform analysis where data reside. Over the past 10 years, the CRDC has made significant progress in providing access to data and tools along with training and outreach to support the cancer research community. In this review, we provide an overview of the history and the impact of the CRDC to date, lessons learned, and future plans to further promote data sharing, accessibility, interoperability, and reuse. See related articles by Brady et al., p. 1384, Wang et al., p. 1388, and Pot et al., p. 1396.

NCI Cancer Research Data Commons: Core Standards and Services.

The NCI Cancer Research Data Commons (CRDC) is a collection of data commons, analysis platforms, and tools that make existing cancer data more findable and accessible by the cancer research community. In practice, the two biggest hurdles to finding and using data for discovery are the wide variety of models and ontologies used to describe data, and the dispersed storage of that data. Here, we outline core CRDC services to aggregate descriptive information from multiple studies for findability via a single interface and to provide a single access method that spans multiple data commons. See related articles by Wang et al., p. 1388, Pot et al., p. 1396, and Kim et al., p. 1404.

Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015-2019.

Background: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers. Methods: Incidence data were obtained from the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan-Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System. Results: The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology. Conclusions: This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.

The impact of COVID-19 on 2020 monthly incidence trends of primary brain and other CNS tumors.

BACKGROUND: To mitigate disease spread, restrictions implemented in the United States surrounding the COVID-19 pandemic created an environment that led to delays in cancer diagnosis. The data needed to accurately analyze the impact of the pandemic on brain and CNS tumor incidence has not been available until now. Utilizing incidence data from the Central Brain Tumor Registry of the United States (CBTRUS) we analyzed the impact of the COVID-19 pandemic on primary brain and other CNS tumor incidence for the first year of the pandemic. METHODS: Monthly age-adjusted incidence rates and incidence trends for 2019 and 2020 were determined for age at diagnosis, sex, race, ethnicity, diagnostic confirmation, behavior, tumor histopathology, and county-level urbanization. Monthly incidence rate ratios comparing 2020 and 2019 were evaluated for the same factors. RESULTS: Overall, there was a notable decrease in incidence rates in March-May 2020 when compared to 2019. These decreases were driven by nonmalignant tumors, with a 50% incidence decrease between March 2020 and 2019. Individuals who were Black had a larger incidence decrease in early 2020 than individuals who were White. Radiographically confirmed tumors saw larger incidence decreases than histologically confirmed tumors. There were no changes in monthly incidence of glioblastoma in 2020 compared to 2019. CONCLUSIONS: These data provide evidence that disruptions in medical care, such as governmental and health care mandates, in response to the COVID-19 pandemic resulted in an overall decreased incidence of primary brain tumors in early 2020.

Analysis of anemia and iron supplementation among glioblastoma patients reveals sex-biased association between anemia and survival.

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.

Association Between Urbanicity and Outcomes Among Patients with Spinal Cord Ependymomas in the United States.

BACKGROUND: Spinal cord ependymomas (SCEs) represent the most common intramedullary spinal cord tumors among adults. Research shows that access to neurosurgical care and patient outcomes can be greatly influenced by patient location. This study investigates the association between the outcomes of patients with SCE in metropolitan and nonmetropolitan areas. METHODS: Cases of SCE between 2004 and 2019 were identified within the Central Brain Tumor Registry of the United States, a combined dataset including the Centers for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results Program data. Multivariable logistic regression models were constructed to evaluate the association between urbanicity and SCE treatment, adjusted for age at diagnosis, sex, race and ethnicity. Survival data was available from 42 National Program of Cancer Registries (excluding Kansas and Minnesota, for which county data are unavailable), and Cox proportional hazard models were used to understand the effect of surgical treatment, county urbanicity, age at diagnosis, and the interaction effect between age at diagnosis and surgery, on the survival time of patients. RESULTS: Overall, 7577 patients were identified, with 6454 (85%) residing in metropolitan and 1223 (15%) in nonmetropolitan counties. Metropolitan and nonmetropolitan counties had different age, sex, and race/ethnicity compositions; however, demographics were not associated with differences in the type of surgery received when stratified by urbanicity. Irrespective of metropolitan status, individuals who were American Indian/Alaska Native non-Hispanic and Hispanic (all races) were associated with reduced odds of receiving surgery. Individuals who were Black non-Hispanic and Hispanic were associated with increased odds of receiving comprehensive treatment. Diagnosis of SCE at later ages was linked with elevated mortality (hazard ratio = 4.85, P < 0.001). Gross total resection was associated with reduced risk of death (hazard ratio = 0.37, P = 0.004), and age did not interact with gross total resection to influence risk of death. CONCLUSIONS: The relationship between patients' residential location and access to neurosurgical care is critical to ensuring equitable distribution of care. This study represents an important step in delineating areas of existing disparities.