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PURPOSE: The Electronic Medical Record Search Engine (EMERSE) is a software tool built to aid research spanning cohort discovery, population health, and data abstraction for clinical trials. EMERSE is now live at three academic medical centers, with additional sites currently working on implementation. In this report, we describe how EMERSE has been used to support cancer research based on a variety of metrics. METHODS: We identified peer-reviewed publications that used EMERSE through online searches as well as through direct e-mails to users based on audit logs. These logs were also used to summarize use at each of the three sites. Search terms for two of the sites were characterized using the natural language processing tool MetaMap to determine to which semantic types the terms could be mapped. RESULTS: We identified a total of 326 peer-reviewed publications that used EMERSE through August 2019, although this is likely an underestimation of the true total based on the use log analysis. Oncology-related research comprised nearly one third (n = 105; 32.2%) of all research output. The use logs showed that EMERSE had been used by multiple people at each site (nearly 3,500 across all three) who had collectively logged into the system > 100,000 times. Many user-entered search queries could not be mapped to a semantic type, but the most common semantic type for terms that did match was "disease or syndrome," followed by "pharmacologic substance." CONCLUSION: EMERSE has been shown to be a valuable tool for supporting cancer research. It has been successfully deployed at other sites, despite some implementation challenges unique to each deployment environment. [ABSTRACT FROM AUTHOR]

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute–funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings. These meetings are a place to review our priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues we, as informatics leaders, individually face at our respective institutions and cancer centers. Here we provide a brief history of the CI4CC organization and meeting highlights from the latest CI4CC meeting that took place in Napa, California from October 14-16, 2019. The focus of this meeting was "intersections between informatics, data science, and population science." We conclude with a discussion on "hot topics" on the horizon for cancer informatics. [ABSTRACT FROM AUTHOR]

Simple Summary: Trans-disciplinary team science is critical for advancing our understanding and treatment of cancer. A successful scientific team requires working with a diverse group of individuals from basic researchers to clinicians, bioinformaticians, and many others. Each team member has a different expertise and access and is brought together to work toward a shared goal. While the importance of team science has become evident, these teams do not come together easily or randomly. Here, we aim to provide a concise, high-level view by providing some practical tips to help cancer researchers be successful in a trans-disciplinary team. Trans-disciplinary science will continue to be critical for the next wave of scientific advancement to fully understand cancer development, progression, and treatment. The shift from the independent investigator to either leading or being a productive member of a scientific team can be successful by focusing on some key elements that can build and strengthen interactions with a diverse group of people. These include the selection of the team, communication, leadership and mentorship, shared goals, responsibility to the team, authorship, and proactively dealing with conflict. While there are extensive books written on developing teams in the business world, and larger pieces in the medical arena, we attempt to provide here a concise, high-level view as a starting point for those that may be moving from being an independent researcher and are developing their own, larger, trans-disciplinary teams. [ABSTRACT FROM AUTHOR]

Twenty-nine single-nucleotide polymorphisms (SNPs) from previously published genome-wide association studies (GWAS) and multiple ancestry informative markers were genotyped in the Carolina Breast Cancer Study (CBCS) (742 African-American (AA) cases, 1230 White cases; 658 AA controls, 1118 White controls). In the entire study population, 9/10 SNPs in fibroblast growth factor receptor 2 (FGFR2) were significantly associated with breast cancer after adjusting for age, race and European ancestry [odds ratios (OR) range 1.17–1.81]. Associations were observed for SNPs in FGFR2, LSP1, H19, TLR1/TLR6 and RELN for AA; FGFR2, TNRC9, H19 and MAP3K1 for Whites; FGFR2, TNRC9, Msc5A1 and chromosome 8q for women ≥50 years old and FGFR2 and TNRC9 for women <50 years old. FGFR2 haplotypes based upon rs11200014, rs2981579, rs1219648 and rs2420946 were associated with increased risk of breast cancer, including the GTGT haplotype in AAs [OR = 1.27, 95% confidence interval (CI) 1.04–1.56] and younger women of either race [OR = 1.35, 95% CI 1.02–1.78) and the ATGT haplotype in Whites (OR = 1.30, 95% CI 1.15–1.46). Recent GWAS hits for breast cancer in Europeans and Whites (i.e. women of European descent) thus showed evidence of replication among AAs and Whites in the CBCS. Several new haplotypes were associated with breast cancer in AA and younger women, particularly the FGFR2 GTGT haplotype. These results highlight the need to conduct GWAS among younger women and in a variety of racial–ethnic populations. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: To examine trends in the incidence of primary, malignant penile cancer in the United States. Methods and materials: A total of 1,817 men with primary, malignant penile cancer diagnosed between 1973 and 2002 from the Surveillance, Epidemiology and End Results Program Public-use data were used for analysis. Incidence rates were calculated by clinical and demographic variables of interest and decade of diagnosis (1973–1982, 1983–1992, and 1993–2002) using Surveillance, Epidemiology and End Results-Stat 6.1, and trends were examined using the annual percent change statistic. Additional incidence calculations were performed to examine further racial/ethnic differences. Results: The overall incidence of primary, malignant penile cancer from 1973 to 2002 was 0.69 per 100,000. Incidence decreased significantly over time: 0.84 per 100,000 in 1973–1982 to 0.69 per 100,000 in 1982–1992 to 0.58 per 100,000 in 1993–2002. Incidence increased with increasing age at diagnosis. The majority of cases had squamous cell carcinomas, graded as I or II, and originated at the glans penis. Incidence of unknown grade primary, malignant penile cancer decreased significantly over the last 30 years, as did incidence of primary site penis, not otherwise specified primary, malignant penile cancer. The incidence of regional stage disease also increased over time. From 1993 to 2002, White Hispanics had the highest incidence rates (1.01 per 100,000) followed by Alaska Native/American Indians (0.77 per 100,000) and Blacks (0.62 per 100,000). Conclusions: The overall incidence of primary, malignant penile cancer in the United States has decreased, and these rates varied by race/ethnicity. Incidence rates increased with increasing age at diagnosis, and the incidence of regional stage disease increased over time, while incidence of unknown grade primary, malignant penile cancer decreased over the last 30 years. [Copyright &y& Elsevier]

Presents a study on the analysis of different readily available sets of genetic markers for estimating admixture or ancestry in individual and its possible uses for forensic identification of skeletal remains. Comparison on the informative genetic markers in individual; Several marker sets for efficacy used in estimating admixture; Evaluation on the efficiency of markers relative to CODS SR loci.

Abstract: Objective. : The incidence of cervical cancer is higher in Hispanic than in non-Hispanic or African American women in the United States, but few studies have examined differences in survival between these groups. The objective of this study was to examine racial/ethnic differences in survival after diagnosis with invasive cervical cancer in a population-based sample of patients while adjusting for patient and tumor characteristics and treatment types. Methods. : We identified 7267 women (4431 non-Hispanic Caucasians, 1830 Hispanic Caucasians, and 1006 non-Hispanic African Americans) diagnosed with primary invasive cervical cancer from 1992 to 1996 (with follow-up through 2000) from the Surveillance, Epidemiology and End Results (SEER) Program. Kaplan–Meier and Cox proportional hazards survival methods were used to assess differences in survival by race/ethnicity. Results. : After adjusting for age at diagnosis, histology, stage, first course of cancer-directed treatment (surgery and radiation therapy), and SEER registry, Hispanic Caucasian women were at 26% decreased risk of death from any cause (hazard ratio (HR) = 0.74, 95% confidence interval (CI): 0.66–0.83) and non-Hispanic African American women were at 19% increased risk of death (HR = 1.19, 95% CI: 1.06–1.33) compared to non-Hispanic Caucasian women over the follow-up period. Conclusion. : Analysis of population-based SEER data indicates significant survival differences by race/ethnicity for women with invasive cervical cancer. Hispanic Caucasian women in SEER had improved survival compared to non-Hispanic Caucasian or non-Hispanic African American women. [Copyright &y& Elsevier]

Objective. To analyze the survival of women with malignant, mixed mullerian tumors of the ovary (OMMMT) compared to women with epithelial ovarian cancer (EOC).Methods. Data from the Surveillance, Epidemiology and End Results (SEER) Program on 14 025 women diagnosed with primary invasive ovarian cancer between 1988 and 1997 were used for this analysis (382 had OMMMT). Differences in distribution of prognostic variables by histological type were compared using a chi-square test. Multivariable survival models were fit using Cox proportional hazards regression analysis to compare risk of death for OMMMT compared to EOC. Analyses were also performed using cases with OMMMT compared to high-grade EOC only.Results. Women with OMMMT were older at diagnosis and were more likely to have primary surgery compared to women with EOC. The majority of women in either histological group had advanced-stage disease at diagnosis. Women with OMMMT had a significant increased risk of death from any cause whether being compared to all women with EOC (HR = 1.69, 95% CI = 1.50,1.90) or to women with high-grade EOC only (HR = 1.58, 95% CI = 1.40,1.79). Women with advanced-stage OMMMT were at a 60% increased risk of death compared to women with advanced-stage, high-grade EOC, after adjustment for other variables of interest (adjusted HR = 1.60, 95% CI = 1.40,1.84). There was no difference in risk of death for these two groups of women with early-stage disease.Conclusion. OMMMT is a rare malignancy compared to EOC and had a significantly worse prognosis compared to EOC. [Copyright &y& Elsevier]

Background: Gene × environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to assess gene ×environment interactions with respect to systolic blood pressure on sibships adjusting for repeated measures and hierarchical nesting structures. A data set containing 410 sibships from the Framingham Heart Study offspring cohort (part of the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed gene × environment models, all adjusting for repeated measurement and varying levels of nesting, were compared for precision of estimates: 1) all sibships with adjustment for two levels of nesting (sibs within sibships and sibs within pedigrees), 2) all sibships with adjustment for one level of nesting (sibs within sibships), and 3) 100 data sets containing random draws of one sibship per extended pedigree adjusting for one level of nesting. Results: The main effects were: gender, baseline age, body mass index (BMI), hypertensive treatment, cigarettes per day, grams of alcohol per day, and marker GATA48G07A. The interaction fixed effects were: baseline age by gender, baseline age by cigarettes per day, baseline age by hypertensive treatment, baseline age by BMI, hypertensive treatment by BMI, and baseline age by marker GATA48G07A. The estimates for all three nesting techniques were not widely discrepant, but precision of estimates and determination of significant effects did change with the change in adjustment for nesting. Conclusion: Our results show the importance of the adjustment for all levels of hierarchical nesting of sibs in the presence of repeated measures. [ABSTRACT FROM AUTHOR]

Simple Summary: It is known that there are sex differences in adverse events experienced following cancer treatment. However, little is known about sex differences in adverse events experienced in individuals with metastatic cancer. Here, using SEER-Medicare data, we investigate sex differences in adverse events in lung cancer individuals with brain metastasis who are 66 years old and older. Sex differences in adverse events were observed and were dependent on lung cancer histology, age at diagnosis, year of diagnosis and treatment as well as potential interplay between these variables. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary hepatic angiosarcoma is a rare tumor of the liver. The prognosis and treatment of this rare tumor remains an enigma. Despite being the most common liver tumor of mesenchymal origin, the prognosis of patients diagnosed with primary hepatic angiosarcoma has never been compared with that of the most common liver tumor which is hepatocellular carcinoma. In this manuscript, we have analyzed all the recorded cases in the National Cancer Center Database and determine the best approach to treat this rare tumor. We have also conducted a brief review of the literature to guide the reader toward the finer nuances of managing patients diagnosed with primary hepatic angiosarcoma, especially in the context of a liver transplant. Background: To determine the risk of mortality and factors associated with survival amongst patients diagnosed with primary hepatic angiosarcoma (PHA). Methods: All patients diagnosed with hepatocellular carcinoma (HCC) or PHA from 2004 to 2014 were identified from the National Cancer Database (NCDB). Further analysis was performed within the cohort of patients with PHA to assess the impact of surgery, chemotherapy, radiation, and facility type on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan–Meier method were used. Results: A total of 117,633 patients with HCC were identified, out of whom 346 patients had PHA. Patients with PHA had a mean age of 62.9 years (SD 13.7), the majority were men (64.7%), white (85.8%), and had a Charlson comorbidity index (CCI) of zero (66.2%). A third of the patients with PHA (35.7%) received chemotherapy, and 14.6% underwent a surgical resection. The median survival was 1.9 months (1.8–2.4 months) compared to patients with HCC (10.4 months, 10.2–10.5) (aHR-2.41, 95% CI: 2.10–2.77, p < 0.0001). Surgical resection was associated with a higher median survival (7.7 versus 1.8 months, aHR-0.23, 95% CI: 0.15–0.37, p < 0.0001). A receipt of chemotherapy was associated with a higher median survival than no chemotherapy (5.1 versus 1.2 months, aHR-0.44, 95% CI: 0.32–0.60, p < 0.0001), although the survival benefit did not persist long term. Conclusion: PHA is associated with poor outcomes. A surgical resection and chemotherapy are associated with improved survival outcomes; however, the long-term benefits of chemotherapy are limited. [ABSTRACT FROM AUTHOR]

Background: Racial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed.Methods: Data came from 270 AA women diagnosed with ovarian cancer and participating in a population-based, case-control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake.Results: One-third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000-$74,999, 2.04; 95% confidence interval [CI], 1.06-3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92-5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14-0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses.Conclusions: Consistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability. [ABSTRACT FROM AUTHOR]

Simple Summary: Sex differences in cancer are well-established. However, less is known about sex differences in the diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using the nationwide Flatiron Health electronic health record-derived de-identified database, this study showed that males had greater odds of brain metastasis, and poorer real-world overall survival compared to females among those with brain metastasis, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Historical controls continue to be used in early-phase brain tumor trials. We aim to show that historical changes in survival trends for glioblastoma (GBM) call into question the use of noncontemporary controls. Methods We analyzed data from 46 106 primary GBM cases from the SEER database (1998-2016). We performed trend analysis on survival outcomes (2-year survival probability, median survival, and hazard ratios) and patient characteristics (age, sex, resection extent, and treatment type). Results In 2005-2016 (ie, the post–Stupp protocol era), fitting a parameter independently to each year, there was a demonstrable increase in median survival (R2 = 0.81, P <.001) and 2-year survival probability (R2 = 0.55, P =.006) for GBM. Trend analysis of the hazard ratio showed a significant time-dependent downward trend (R2 = 0.62, P =.002). When controlling, via multivariable Cox regression modeling, for age, sex, resection extent, and treatment type, there was a persistent downward trend in hazard ratios with increases in calendar time, especially in the most recent data. Conclusion Contemporary GBM patients face a different overall hazard profile from their historical counterparts, which is evident in changes in measures of patient survival and parametric hazard modeling. Though there was a plateau in these measures before 2005 (pre–Stupp protocol), there is no evidence of a new plateau in recent years even when controlling for known prognostic factors (age, sex, resection extent, and treatment type), suggesting that it may be insufficient to match contemporary patients and noncontemporary controls on the basis of these factors. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have reported higher rates of glioma in areas with higher socioeconomic status (SES) but to the authors' knowledge have not stratified by other factors, including race/ethnicity or urban versus rural location.Methods: The authors identified the average annual age-adjusted incidence rates and calculated hazard ratios for death for gliomas of various subtypes, stratified by a county-level index for SES, race/ethnicity, US region, and rural versus urban status.Results: Rates of glioma were highest in counties with higher SES (rate ratio, 1.18; 95% CI, 1.15-1.22 comparing the highest with the lowest quintiles [P < .001]). Stratified by race/ethnicity, higher rates in high SES counties persisted for white non-Hispanic individuals. Stratified by rural versus urban status, differences in incidence by SES were more pronounced among urban counties. Survival was higher for residents of high SES counties after adjustment for age and extent of surgical resection (hazard ratio, 0.82; 95% CI, 0.76-0.87 comparing the highest with the lowest quintile of SES [P < .001]). Survival was higher among white Hispanic, black, and Asian/Pacific Islander individuals compared with white non-Hispanic individuals, after adjustment for age, SES, and extent of surgical resection, and when restricted to those individuals with glioblastoma who received radiation and chemotherapy.Conclusions: The incidence of glioma was higher in US counties of high compared with low SES. These differences were most pronounced among white non-Hispanic individuals and white Hispanic individuals residing in urban areas. Better survival was observed in high SES counties, even when adjusting for extent of surgical resection, and when restricted to those who received radiation and chemotherapy for glioblastoma. Differences in incidence and survival were associated with SES and race, rather than rural versus urban status. [ABSTRACT FROM AUTHOR]

Primary malignant and non-malignant brain and other central nervous system (CNS) tumors, while relatively rare, are a disproportionate source of morbidity and mortality. Here we provide a brief overview of approaches to modeling important clinical outcomes, such as overall survival, that are critical for clinical care. Because there are a large number of histologically distinct types of primary malignant and non-malignant brain and other CNS tumors, this chapter will provide an overview of prognostication considerations on the most common primary non-malignant brain tumor, meningioma, and the most common primary malignant brain tumor, glioblastoma. In addition, information on nomograms and how they can be used as individualized prognostication tools by clinicians to counsel patients and their families regarding treatment, follow-up, and prognosis is described. The current state of nomograms for meningiomas and glioblastomas are also provided. [ABSTRACT FROM AUTHOR]

Purpose: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas. Methods: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed. Diagnostic performance of the partial T2-FLAIR mismatch sign was evaluated. Subset analyses were performed to assess associations of imaging markers with overall survival (OS). Results: One hundred twenty-one (5.6%) of 2165 grade 4 gliomas were IDH-mutant. Partial T2-FLAIR mismatch was present in 40 (1.8%) cases, 32 of which were IDH-mutant, yielding 26.4% sensitivity, 99.6% specificity, 80.0% positive predictive value, and 95.8% negative predictive value. Multivariate logistic regression demonstrated IDH mutation was significantly associated with partial T2-FLAIR mismatch (odds ratio [OR] 5.715, 95% CI [1.896, 17.221], p = 0.002), younger age (OR 0.911 [0.895, 0.927], p < 0.001), tumor centered in frontal lobe (OR 3.842, [2.361, 6.251], p < 0.001), absence of multicentricity (OR 0.173, [0.049, 0.612], p = 0.007), and presence of cystic (OR 6.596, [3.023, 14.391], p < 0.001) or non-enhancing solid components (OR 6.069, [3.371, 10.928], p < 0.001). Multivariate Cox analysis demonstrated cystic components (p = 0.024) and non-enhancing solid components (p = 0.003) were associated with longer OS, while older age (p < 0.001), frontal lobe center (p = 0.008), multifocality (p < 0.001), and multicentricity (p < 0.001) were associated with shorter OS. Conclusion: Partial T2-FLAIR mismatch sign is highly specific for IDH mutation in WHO grade 4 gliomas. [ABSTRACT FROM AUTHOR]

Background: Primary brain tumors (BTs) are rare, but cause morbidity and mortality disproportionately to their incidence. Prevalence estimates population‐level cancer burdens at a specified time. This study estimates the prevalence of malignant and non‐malignant BTs in comparison to other cancers. Methods: Incidence data were obtained from the Central Brain Tumor Registry of the United States (2000–2019, varying), a combined data set including the Center for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Incidence of non‐BT cancers were obtained from the United States Cancer Statistics (2001–2019). Incidence and survival estimates for all cancers were obtained from SEER (1975–2018). Complete prevalence as of December 31, 2019, was estimated using prevEst. Estimates were generated overall for non‐BT cancers, by BT histopathology, age groups at prevalence (0–14, 15–39, 40–64, 65+ years), and sex. Results: We estimated 1,323,121 individuals with a diagnosis of BTs at the date of prevalence. The majority of BT cases had non‐malignant tumors (85.3%). Among all cancers, BTs were the most prevalent cancer type among those ages 15 to 39 years, second among those ages 0 to 14 years, and in the top five among those ages 40 to 64 years. The plurality of prevalent cases (43.5%) occurred among those ages 65+ years. Overall, females had a higher prevalence of BTs than males, with an overall female:male prevalence ratio of 1.68. Conclusions: BTs contribute significantly to the cancer burden in the United States, particularly among those younger than age 65 years. Understanding complete prevalence is crucial for monitoring cancer burden to inform clinical research and public policy. We include a comparison of prevalence estimates for all primary brain tumors to other common cancers by age group in the United States. We also provide a description of the complete prevalence of primary malignant and nonmalignant brain and other central nervous system tumors in the United States for 2019, an update to a previous study. [ABSTRACT FROM AUTHOR]

We investigated the association between genetic polymorphisms in cytochrome P450 (CYP2R1, CYP24A1, and the CYP3A family) with nonsummer plasma concentrations of vitamin D metabolites (25-hydroxyvitamin D3 (25(OH) D3) and proportion 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) among healthy individuals of sub-Saharan African and European ancestry, matched on age (within 5 years; n = 188 in each ancestral group), in central suburban Pennsylvania (2006-2009). Vitamin D metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Paired multiple regression and adjusted least-squares mean analyses were used to test for associations between genotype and log-transformed metabolite concentrations, adjusted for age, sex, proportion of West-African genetic ancestry, body mass index, oral contraceptive (OC) use, tanning bed use, vitamin D intake, days from summer solstice, time of day of blood draw, and isoforms of the vitamin D receptor (VDR) and vitamin D binding protein. Polymorphisms in CYP2R1, CYP3A43, vitamin D binding protein, and genetic ancestry proportion remained associated with plasma 25(OH)D3 after adjustment. Only CYP3A43 and VDR polymorphisms were associated with proportion 24,25(OH)2D3. Magnitudes of association with 25(OH)D3 were similar for CYP3A43, tanning bed use, and OC use. Significant least-squares mean interactions (CYP2R1/OC use (P = 0.030) and CYP3A43/VDR (P = 0.013)) were identified. A CYP3A43 genotype, previously implicated in cancer, is strongly associated with biomarkers of vitamin D metabolism. Interactive associations should be further investigated. [ABSTRACT FROM AUTHOR]

PURPOSE: Develop a cancer-specific machine learning (ML) model that accurately predicts 30-day unplanned readmissions in patients with solid tumors. METHODS: The initial cohort included patients 18 years or older diagnosed with a solid tumor. Two distinct cohorts were generated: one with and one without detailed social determinants of health (SDOHs) data. For each cohort, data were temporally partitioned in 70% (training), 20% (validation), and 10% (testing). Tree-based ML models were developed and validated on each cohort. The metrics used to evaluate the model's performance were receiver operating characteristic curve (ROC), area under the ROC curve, precision, recall (R), accuracy, and area under the precision-recall curve. RESULTS: We included 13,717 patients in this study in two cohorts (5,059 without SDOH data and 8,658 with SDOH data). Unplanned 30-day readmission occurred in 21.3% of the cases overall. The five main non-SDOH factors most highly associated with an unplanned 30-day readmission (R, 0.74; IQR, 0.58-0.76) were: number of previous unplanned readmissions; higher Charlson comorbidity score; nonelective index admission; discharge to anywhere other than home, hospice, or nursing facility; and higher anion gap during the admission. Neighborhood crime index, neighborhood median home values, annual income, neighborhood median household income, and wealth index were the main five SDOH factors important for predicting a high risk for an unplanned hospital readmission (R, 0.66; IQR, 0.56-0.72). The models were not directly comparable. CONCLUSION: Key drivers of unplanned readmissions in patients with cancer are complex and involve both clinical factors and SDOH. We developed a cancer-specific ML model that with reasonable accuracy identified patients with cancer at high risk for an unplanned hospital readmission. New cancer-specific ML models accurately predict 30-day unplanned readmissions in patients with solid tumors. [ABSTRACT FROM AUTHOR]

Medicaid eligibility expansion, though not directly applicable to children, has been associated with improved access to care in children with cancer, but associations with overall survival are unknown. Data for children ages 0 to 14 years diagnosed with cancer from 2011 to 2018 were queried from central cancer registries data covering cancer diagnoses from 40 states as part of the Centers for Disease Control and Prevention's National Program of Cancer Registries. Difference-in-differences analyses were used to compare changes in 2-year survival from 2011-2013 to 2015-2018 in Medicaid expansion relative to nonexpansion states. In adjusted analyses, there was a 1.50 percentage point (95% confidence interval = 0.37 to 2.64) increase in 2-year overall survival after 2014 in expansion relative to nonexpansion states, particularly for those living in the lowest county income quartile (difference-in-differences  = 5.12 percentage point, 95% confidence interval = 2.59 to 7.65). Medicaid expansion may improve cancer outcomes for children with cancer. [ABSTRACT FROM AUTHOR]

Background: There is a male predominance of acute myeloid leukemia (AML) incidence, but survival data are conflicting. The objective of this study is to carry out a comprehensive analysis of sex differences in AML, and to investigate the impact of sex disparities in survival. Methods: The cohort included patients ≥18 years diagnosed with AML (2010–2022). Demographics, treatment patterns, treatment adverse events, and survival were analyzed. The population was described and compared by sex, and sex‐based risks and associations were obtained via Cox proportional‐hazards regression. Results: In total, 1020 AML patients were analyzed (57.4% males), with lower risk of death for females (aHR = 0.41, 95% CI 0.26–0.66). Among females, BMT (aHR = 0.51, 95% CI 0.27–0.97), hospitalization record (aHR = 0.65, 95%CI 0.45–0.93), and higher appointment completion rates (aHR = 0.98, 95% CI 0.98–0.98) were associated with lower risk of death. Overall, and similarly in males, higher age at diagnosis (aHR = 1.03, 95% CI 1.02–1.04) and a TP53 mutation (aHR = 2.24, 95% CI 1.69–2.97) were associated with higher risk of death. Conclusion: Sex differences exist in both AML incidence and overall survival. Treatment and health care factors should be addressed by caregivers and public policies developed to reduce mortality rates and mitigate existing sex differences. [ABSTRACT FROM AUTHOR]

Background A newly developed brain molecular marker (BMM) data item was implemented by US cancer registries for individuals diagnosed with brain tumors in 2018—including IDH and 1p/19q-co-deletion statuses for adult-type diffuse gliomas. We thus investigated the testing/reporting completeness of BMM in the United States. Methods Cases of histopathologically confirmed glioblastoma, astrocytoma, and oligodendroglioma diagnosed in 2018 were identified in the National Cancer Database. Adjusted odds ratios (ORadj) and 95% confidence intervals (CI) of BMM testing/reporting were evaluated for association with the selected patient, treatment, and facility-level characteristics using multivariable logistic regression. As a secondary analysis, predictors of MGMT promoter methylation testing/reporting among IDH-wildtype glioblastoma individuals were assessed. Key limitations of the BMM data item were that it did not include any details regarding testing technique or assay type and could not distinguish between a lack of testing and a lack of cancer registry reporting of testing results. Results Among 8306 histopathologically diagnosed adult-type diffuse gliomas nationally, overall BMM testing/reporting completeness was 81.1%. Compared to biopsy-only cases, odds of testing/reporting increased for subtotal (ORadj= 1.38 [95% CI: 1.20–1.59], P <.001) and gross total resection (ORadj=1.50 [95% CI: 1.31–1.72], P <.001). Furthermore, the odds were lowest at community centers (hospitals (67.3%; ORadj=0.35 [95% CI: 0.26–0.46], P <.001) and highest at academic/NCI-designated comprehensive cancer centers (85.4%; referent). By geographical location, BMM testing/reporting completeness ranged from a high of 86.8% at New England (referent) to a low of 76.0 % in the West South Central region (ORadj=0.57 [95% CI: 0.42–0.78]; P <.001). Extent of resection, Commission-on-Cancer facility type, and facility location were additionally significant predictors of MGMT testing/reporting among IDH-wildtype glioblastoma cases. Conclusions Initial BMM testing/reporting completeness for individuals with adult-type diffuse gliomas in the United States was promising, although patterns varied by hospital attributes and extent of resection. [ABSTRACT FROM AUTHOR]

Background There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States. Methods Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDC's National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016. Results CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033–0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008–0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005–0.006). Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged. Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR: 5.23, 95% CI: 4.05–7.54, P  < .001). Conclusions This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To test the feasibility of using 3D MRF maps with radiomics analysis and machine learning in the characterization of adult brain intra-axial neoplasms. Methods: 3D MRF acquisition was performed on 78 patients with newly diagnosed brain tumors including 33 glioblastomas (grade IV), 6 grade III gliomas, 12 grade II gliomas, and 27 patients with brain metastases. Regions of enhancing tumor, non-enhancing tumor, and peritumoral edema were segmented and radiomics analysis with gray-level co-occurrence matrices and gray-level run-length matrices was performed. Statistical analysis was performed to identify features capable of differentiating tumors based on type, grade, and isocitrate dehydrogenase (IDH1) status. Receiver operating curve analysis was performed and the area under the curve (AUC) was calculated for tumor classification and grading. For gliomas, Kaplan-Meier analysis for overall survival was performed using MRF T1 features from enhancing tumor region. Results: Multiple MRF T1 and T2 features from enhancing tumor region were capable of differentiating glioblastomas from brain metastases. Although no differences were identified between grade 2 and grade 3 gliomas, differentiation between grade 2 and grade 4 gliomas as well as between grade 3 and grade 4 gliomas was achieved. MRF radiomics features were also able to differentiate IDH1 mutant from the wild-type gliomas. Radiomics T1 features for enhancing tumor region in gliomas correlated to overall survival (p < 0.05). Conclusion: Radiomics analysis of 3D MRF maps allows differentiating glioblastomas from metastases and is capable of differentiating glioblastomas from metastases and characterizing gliomas based on grade, IDH1 status, and survival. Key Points: • 3D MRF data analysis using radiomics offers novel tissue characterization of brain tumors. • 3D MRF with radiomics offers glioma characterization based on grade, IDH1 status, and overall patient survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study investigates the well-known observation/quandary that cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. This has motivated us to explore whether these sex biases may have a common basis. To study that, we assembled and analyzed a large collection of cancer and AID incidence datasets, including matched data from 29 countries. We first, quite strikingly, find that the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. To our knowledge, this is the first time this across-tissue relationship has been quantitatively demonstrated. Second, we find by analyzing healthy human tissue gene expression data that the sex bias in the expression of mitochondrial-encoded genes stands out as the common key factor whose levels across human tissues are most strongly and positively associated with both cancer and AID incidence rate sex biases, pointing to the key potential role of these genes in determining sex bias in both disorders. These findings may further prompt researchers to explore how pertaining findings in cancer studies could cross fertilize AID studies and vice versa, potentially enhancing our ability to prevent and treat these diseases. Cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. To explore whether these sex biases have a common basis, we collected 167 AID incidence studies from many countries for tissues that have both a cancer type and an AID that arise from that tissue. Analyzing a total of 182 country-specific, tissue-matched cancer-AID incidence rate sex bias data pairs, we find that, indeed, the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. The common key factor whose levels across human tissues are most strongly associated with these incidence rate sex biases is the sex bias in the expression of the 37 genes encoded in the mitochondrial genome. [ABSTRACT FROM AUTHOR]

BACKGROUND Hispanic individuals who suffer from melanoma are diagnosed later and have a worse prognosis. Because the Hispanic population is one of the fastest growing in the United States, it is important to spread awareness of melanoma. OBJECTIVE The study aimed to evaluate whether an online educational video about skin cancer could improve knowledge about melanoma and encourage self-skin examinations (SSE). METHODS The authors directed Hispanic patients to an online survey, which assessed for knowledge about melanoma risk factors and prevention. This was followed by a 5-minute online video about melanoma. A second survey was sent immediately after the video, and a third survey was sent 1 month later. All project materials were in Spanish and available online. RESULTS Eighty-six participants completed the full experiment. After watching the online video, a significantly higher proportion of participants provided correct answers for melanoma risk factors and prevention techniques. A similar increase was seen in the number of individuals who reported performing SSEs. CONCLUSION This study provides evidence that an online educational video targeted at the Hispanic population has potential to improve melanoma awareness. This type of intervention may lead to earlier diagnosis and better prognosis for Hispanic individuals. [ABSTRACT FROM AUTHOR]

Background The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification. Methods CBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update. "Obsolete" (terms not currently in use) histology nomenclature along with their International Classification of Disease, Oncology 3rd edition (ICD-O-3) codes were identified, some histologies were reclassified to 2016 WHO, and new codes found in 2016 WHO were incorporated. An evaluation of the frequency of histology codes affected in the realignment process, and incidence and survival pre- and post-realignment was conducted. Results After review, 67 codes were noted as obsolete, 51 codes were reclassified, and 12 new codes were incorporated. Histology groups most affected were mesenchymal tumors and neuronal/mixed neuronal-glial tumors. Reorganization resulted in 2588 (0.65%) cases with grouping reassignment or reporting change, indicating that the 2016 WHO Classification revision has impacted the collection and reporting of primary brain and other CNS tumors. Conclusion This work demonstrates the need to be responsive to changes in classification and coding in order to ensure the most up-to-date and accurate statistics for brain and CNS tumors. This will require collaboration from all stakeholders within the brain tumor community, so to have the ability to reconcile clinical practices and surveillance requirements. [ABSTRACT FROM AUTHOR]

Background Context: Primary malignant non-osseous spinal tumors are relatively rare and this has led to a paucity of studies specifically examining the epidemiology of malignant spinal tumors.Purpose: To provide an updated and more comprehensive study examining the epidemiology and relative survival of these rare tumors.Study Design/setting: Data was retrospectively acquired from the Central Brain Tumor Registry of the United States (CBTRUS).Patient Sample: Primary malignant non-osseous spinal tumor cases diagnosed between 2000 and 2017 in the United States.Outcome Measures: Incidence rates (IRs), relative survival rates, and hazard ratios (HR) were measured.Methods: IRs were calculated only for histologically-confirmed cases between 2000 and 2017. Relative survival estimates were calculated from survival information on malignant spinal tumors between 2001 and 2016 for death from any cause. Multivariable Cox proportional hazards regression models were constructed to control for age, sex, race, and ethnicity.Results: From 2000 to 2017, approximately 587 new cases of malignant non-osseous spinal tumors were diagnosed every year in the United States. The overall IR was 0.178 per 100,000 persons. Ependymomas were the most commonly diagnosed tumor in all age groups. The 10-year relative survival rates were 94.1%, 62.1%, 62.0%, and 13.3% for ependymomas, lymphomas, diffuse astrocytomas, and high-grade astrocytomas, respectively. Females have a significantly lower risk of death as compared with males for ependymomas (HR: 0.74, p<.001) and diffuse astrocytomas (HR: 0.70, p=.005). African-Americans have a significantly higher risk of death compared with Caucasians when diagnosed with ependymomas (HR: 1.52, p=.009) or lymphomas (HR: 1.55, p=.009).Conclusion: Primary malignant non-osseous spinal tumors are primarily diagnosed in adulthood or late adulthood. Ependymal tumors are the most commonly diagnosed primary malignant non-osseous spinal tumors and have the highest 10-year relative survival rates. High-grade astrocytomas are rare and portend the worst prognosis. [ABSTRACT FROM AUTHOR]

Background The Central Brain Tumor Registry of the United States (CBTRUS) contains information on all primary brain and other central nervous system (CNS) tumors diagnosed in the United States (US). Here we summarize the 2021 CBTRUS annual statistical report for clinicians. Methods Incidence survival data are obtained from the Centers for Disease Control's National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Survival data are obtained from NPCR. Mortality data are obtained from the National Vital Statistics System. Incidence and mortality rates are age-adjusted using the 2000 US population and presented per 100,000 population. Results An annual average of 86,355 cases of primary malignant and nonmalignant CNS tumors were diagnosed over the period 2014–2018, corresponding to an average annual age-adjusted incidence rate of 24.25. The most commonly occurring malignant tumor was glioblastoma (14.3%), and the most common predominately nonmalignant tumor was meningioma (39%). Over the 2014–2018 period, there were 16,606 annual average deaths due to malignant primary CNS tumors, corresponding to an average annual age-adjusted mortality rate of 4.43. In this report we detail key incidence, survival, and mortality statistics for major primary CNS tumor histologies, highlighting relevant differences by age, sex, and race. Conclusions This summary describes the most up to date population-based incidence of primary malignant and nonmalignant brain and other CNS tumors in the US, and mortality and survival for primary malignant tumors and aims to serve as a useful resource for clinicians. [ABSTRACT FROM AUTHOR]

Background Pineoblastoma (PB) is a rare malignant brain tumor originating in the pineal gland. Here, we provide a comprehensive epidemiological analysis of PB in the United States from 2000 to 2017. Methods Data on 1133 patients with PB were acquired from the Central Brain Tumor Registry of the United States, in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, from 2000 to 2017. Age-adjusted incidence rates (AAIRs) per 100 000 and incidence rate ratios (IRRs) were reported for age, sex, race, and ethnicity. Using the National Program of Cancer Registries survival database, median survival and hazard ratios (HRs) were evaluated for overall survival from 2001 to 2016. Results Incidence was highest in ages 0–4 years (AAIR: 0.049, 95% CI: 0.042–0.056), decreasing as age increased. Incidence was higher among patients who are Black compared to patients who are White (IRR: 1.71, 95% CI: 1.48–1.98, P <.001), and was impacted by age at diagnosis, with Black-to-White incidence highest in children ages 5–9 years (IRR: 3.43, 95% CI: 2.36–4.94, P <.001). Overall survival was lower for males (HR: 1.39, 95% CI: 1.07–1.79, P =.013). All age groups, excluding those over 40, had improved survival compared to ages 0–4 years. Those who received surgical intervention had better survival compared to those who did not receive surgical treatment. Conclusion PB incidence is highest among children and patients who are Black, and there may be a potential interaction between these factors. Survival is worse among males, young children, and elderly adults, and those who received no surgery. Comprehensive, population-based statistics provide critical information on PB characteristics that could be useful in impacting patient care and prognosis. [ABSTRACT FROM AUTHOR]

Esophageal cancer is the seventh most common type of cancer in the world, the sixth leading cause of cancer-related death and its incidence is expected to rise 140% in the world in a period of 10 years until 2025. The overall incidence is higher in males, while data about prognosis and survival are not well established yet. The goal of this study was to carry out a comprehensive analysis of differences between sexes and other covariates in patients diagnosed with primary esophageal cancer. Data from 2005 to 2020 were obtained from the University Hospitals (UH) Seidman Cancer Center and from 2005 to 2018 from SEER. Patients were categorized according to histological subtype and divided according to sex. Pearson Chi-square test was used to compare variables of interest by sex and the influence of sex on survival was assessed by Kaplan Meier, log rank tests and Cox proportional hazards regression models. A total of 1205 patients were used for analysis. Sex differences in all types were found for age at diagnosis, histology, smoking status and prescriptions of NSAIDs and in SCC for age at diagnosis and alcoholism. Survival analysis didn't showed differences between males and females on univariable and multivariable models. Males have a higher incidence of Esophageal Cancer and its two main subtypes but none of the comprehensive set of variables analyzed showed to be strongly or unique correlated with this sex difference in incidence nor are they associated with a sex difference in survival. [ABSTRACT FROM AUTHOR]

Longitudinal and behavioral preclinical animal studies generate complex data, which may not be well matched to statistical approaches common in this literature. Analyses that do not adequately account for complexity may result in overly optimistic study conclusions, with consequences for reproducibility and translational decision-making. Recent work interrogating methodological shortcomings in animal research has not yet comprehensively investigated statistical shortcomings in the analysis of complex longitudinal and behavioral data. To this end, the current cross-sectional meta-research study rigorously reviewed published mouse or rat controlled experiments for motor rehabilitation in three neurologic conditions to evaluate statistical choices and reporting. Medline via PubMed was queried in February 2020 for English-language articles published January 1, 2017- December 31, 2019. Included were articles that used rat or mouse models of stroke, Parkinson's disease, or traumatic brain injury, employed a therapeutic controlled experimental design to determine efficacy, and assessed at least one functional behavioral assessment or global evaluation of function. 241 articles from 99 journals were evaluated independently by a team of nine raters. Articles were assessed for statistical handling of non-independence, animal attrition, outliers, ordinal data, and multiplicity. Exploratory analyses evaluated whether transparency or statistical choices differed as a function of journal factors. A majority of articles failed to account for sources of non-independence in the data (74–93%) and/or did not analytically account for mid-treatment animal attrition (78%). Ordinal variables were often treated as continuous (37%), outliers were predominantly not mentioned (83%), and plots often concealed the distribution of the data (51%) Statistical choices and transparency did not differ with regards to journal rank or reporting requirements. Statistical misapplication can result in invalid experimental findings and inadequate reporting obscures errors. Clinician-scientists evaluating preclinical work for translational promise should be mindful of commonplace errors. Interventions are needed to improve statistical decision-making in preclinical behavioral neurosciences research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Professional society guidelines recommend follow-up colonoscopy for patients with resected colonic adenomas. However, adherence to guideline recommendations in routine clinical practice has not been well characterized. METHODS: The authors used a population-based sample of Medicare beneficiaries to identify all patients aged ≥70 years who had a claim for colonoscopy with polypectomy or hot biopsy during the period from 2001 to 2004. Medicare claims through 2009 identified colonoscopy within the following 5 years as well as fecal occult blood testing, sigmoidoscopy, and barium enema. RESULTS: In total, 12,771 patients were included. At 5 years, 45.7% of patients underwent another colonoscopy, and 32.3% of procedures included a polypectomy. The rates of fecal occult blood testing, flexible sigmoidoscopy, and barium enema at 5 years were 54%, 3.8%, and 2.9%, respectively. There was a marked decrease in repeat colonoscopy at 1 year, 3 years, and 5 years with more recent years of index procedures. Other predictors of undergoing repeat colonoscopy were younger age, African American race, and a colonoscopy before the index examination. There was no association with physician specialty. The decreasing use of colonoscopy with time was maintained in a multivariable analysis. CONCLUSIONS: In a sample of elderly Medicare beneficiaries, there was under use of follow-up colonoscopy at 5 years after polypectomy, and <50% of patients received a repeat examination. In particular, the use of this procedure decreased over the 4-year study period. Coupled with other data indicating the overuse of follow-up colonoscopy in patients without polyps, there appeared to be significant discordance between guidelines and actual practice. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: After a colonoscopy that is negative for cancer, a subset of patients may be diagnosed with colorectal cancer, also termed interval cancer. The frequency and predictors have not been well studied in a population-based US cohort. METHODS: The authors used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 57,839 patients aged ≥69 years who were diagnosed with colorectal cancer between 1994 and 2005 and who underwent colonoscopy within 6 months of cancer diagnosis. Colonoscopy performed between 6 and 36 months before cancer diagnosis was a proxy for interval cancer. RESULTS: By using the case definition, 7.2% of patients developed interval cancers. Factors that were associated with interval cancers included proximal tumor location (distal colon: multivariable odds ratio [OR], 0.42; 95% confidence interval [CI], 0.390-0.46; rectum: OR, 0.47; 95% CI, 0.42-0.53), increased comorbidity (OR, 1.89; 95% CI, 1.68 2.14 for ≥3 comorbidities), a previous diagnosis of diverticulosis (OR, 6.00; 95% CI, 5.57-6.46), and prior polypectomy (OR, 1.74; 95% CI, 1.62-1.87). Risk factors at the endoscopist level included a lower polypectomy rate (OR, 0.70; 95% CI, 0.63-0.78 for the highest quartile), higher colonoscopy volume (OR, 1.27; 95% CI, 1.13-1.43), and specialty other than gastroenterology (colorectal surgery: OR, 1.45; 95% CI, 1.16-1.83; general surgery: OR, 1.42; 95% CI, 1.24-1.62; internal medicine: OR, 1.38; 95% CI, 1.17-1.63; family practice: OR, 1.16; 95% CI, 1.00-1.35). CONCLUSIONS: A significant proportion of patients developed interval colorectal cancer, particularly in the proximal colon. Contributing factors likely included both procedural and biologic factors, emphasizing the importance of meticulous examination of the mucosa. Cancer 2012;118: 3044-52. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The management of colon polyps containing invasive carcinoma includes surgical resection or colonoscopic polypectomy. To date, there are very limited population-based data comparing outcomes with the 2 management approaches. METHODS: Using the linked Surveillance Epidemiology and End Results-Medicare database, we identified 2077 patients aged ≥66 years with an initial diagnosis of stage T1N0M0 malignant polyp from 1992-2005. Patients were categorized as surgical or polypectomy depending on the most invasive treatment. To adjust for potential selection bias in treatment assignment, using multivariate analysis, patients were divided into quintiles of likelihood of polypectomy (propensity scores), and outcomes were compared in each quintile. RESULTS: Surgical resection was performed in 1340 (64.5%) patients and polypectomy was performed in 737 (35.5%) patients. Predictors for undergoing polypectomy ( P<.001) included older age, greater comorbidity, no history of polyps, diagnosis in 2002 or later, left colon site of cancer, well-differentiated tumors, and colonoscopy performed in an outpatient setting. Both 1-year and 5-year survival were higher in the surgical group (92% and 75%, respectively) than in the polypectomy group (88% and 62%, respectively). The unadjusted hazard ratio was 1.51 (95% confidence interval [CI], 1.31-1.74). After adjusting for propensity quintile, the hazard ratio was 1.15 (95% CI, 0.98-1.33). Within each propensity quintile, the risk of death was similar between the 2 groups (interaction test P = .96). CONCLUSIONS: In this large, population-based sample, more than one-third of patients with malignant polyps were treated with colonoscopic polypectomy. Outcomes were similar to surgical patients with comparable clinical characteristics and could be offered to patients who meet appropriate clinical criteria. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The molecular behavior of biological systems can be described in terms of three fundamental components: (i) the physical entities, (ii) the interactions among these entities, and (iii) the dynamics of these entities and interactions. The mechanisms that drive complex disease can be productively viewed in the context of the perturbations of these components. One challenge in this regard is to identify the pathways altered in specific diseases. To address this challenge, Gene Set Enrichment Analysis (GSEA) and others have been developed, which focus on alterations of individual properties of the entities (such as gene expression). However, the dynamics of the interactions with respect to disease have been less well studied (i.e., properties of components ii and iii). Results: Here, we present a novel method called Gene Interaction Enrichment and Network Analysis (GIENA) to identify dysregulated gene interactions, i.e., pairs of genes whose relationships differ between disease and control. Four functions are defined to model the biologically relevant gene interactions of cooperation (sum of mRNA expression), competition (difference between mRNA expression), redundancy (maximum of expression), or dependency (minimum of expression) among the expression levels. The proposed framework identifies dysregulated interactions and pathways enriched in dysregulated interactions; points out interactions that are perturbed across pathways; and moreover, based on the biological annotation of each type of dysregulated interaction gives clues about the regulatory logic governing the systems level perturbation. We demonstrated the potential of GIENA using published datasets related to cancer. Conclusions: We showed that GIENA identifies dysregulated pathways that are missed by traditional enrichment methods based on the individual gene properties and that use of traditional methods combined with GIENA provides coverage of the largest number of relevant pathways. In addition, using the interactions detected by GIENA, specific gene networks both within and across pathways associated with the relevant phenotypes are constructed and analyzed. [ABSTRACT FROM AUTHOR]

Background: The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa - the continent with the highest genetic variation. Here, we dissect the within- Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA. Methods and Principal Findings: We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today's African-descended Americans of North and South America and the Caribbean. Conclusions: Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled or that were available for them at the time. This historical connection is reflected in different relative contributions from populations of W/WC/SW/SE Africa to geographically distinct Africa-derived populations of the Americas, adding to the complexity of genomic ancestry in groups ostensibly united by the same demographic label. [ABSTRACT FROM AUTHOR]

Background The development of brain metastases (BM) is one of the most feared complications of cancer due to the substantial neurocognitive morbidity and a grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have demonstrated promising intracranial response rates for tumors of multiple histologies. As overall survival for these patients improves, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been an adequate study to specifically explore these questions of survivorship and practice standardization for patients with advanced cancer and BM. Methods Here, we present results from a cross-sectional survey in which we analyze responses from 237 patients, 209 caregivers, and 239 physicians to identify areas of improvement in the clinical care of BM. Results In comparing physician and patient/caregiver responses, we found a disparity in the perceived discussion of topics pertaining to important aspects of BM clinical care. We identified variability in practice patterns for this patient population between private practice and academic physicians. Many physicians continue to have patients with BM excluded from clinical trials. Finally, we obtained patient/physician recommendations on high-yield areas for federal funding to improve patient quality of life. Conclusion By identifying potential areas of unmet need, we anticipate this wealth of actionable information will translate into tangible benefits for both patients and caregivers. Future studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

PURPOSE: State and national cancer registries do not systematically include Veteran data, which hinders analysis of the diagnosis patterns, treatment trajectories, and clinical outcomes of Veterans compared with non-Veteran populations. This study used data matching approaches to compare cases included in the Oncology Domain of the Veterans Affairs (VA) Corporate Data Warehouse and the Ohio Cancer Incidence Surveillance System, using brain tumors as an exemplar. METHODS: We used direct data matching, on the basis of protected health information (PHI) common to both databases, to compare primary brain tumors from Veterans and non-Veterans diagnosed from 2000 to 2016. Working with this matched data set, we used six data elements that did not contain PHI, to assess the feasibility of using deterministic data matching to compare Veterans and non-Veterans. RESULTS: Between 2000 and 2016, 223 Veterans from Ohio had a primary brain tumor; of those, 55 (25%) were not included in Ohio Cancer Incidence Surveillance System. Direct data matching showed that Veterans experienced a greater proportion of glioblastomas (41%) compared with non-Veterans (21%). Sex did not account for this difference. Deterministic data matching within the matched data set found that 75% (126 of 168) of Veterans had exact matches for at least five of six non-PHI variables common to both databases. CONCLUSION: This study indicated that direct and deterministic data matching approaches to compare brain tumors in Veterans and in non-Veterans is feasible. This approach has the potential to promote comparisons of the distribution of tumors, the impact of chemical and environmental exposures, treatment trajectories, and clinical outcomes among Veteran and non-Veteran populations with brain tumors as well as other cancers and rare diseases. [ABSTRACT FROM AUTHOR]

Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood.This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross‐sectional FDA’s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques.In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49–69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14–2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12–2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12–2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46–60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%–36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%–20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01–2.42); p = 0.045).In two independent real‐world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension. [ABSTRACT FROM AUTHOR]

Purpose: This is a radiomics study investigating the ability of texture analysis of MRF maps to improve differentiation between intra-axial adult brain tumors and to predict survival in the glioblastoma cohort. Methods: Magnetic resonance fingerprinting (MRF) acquisition was performed on 31 patients across 3 groups: 17 glioblastomas, 6 low-grade gliomas, and 8 metastases. Using regions of interest for the solid tumor and peritumoral white matter on T1 and T2 maps, second-order texture features were calculated from gray-level co-occurrence matrices and gray-level run length matrices. Selected features were compared across the three tumor groups using Wilcoxon rank-sum test. Receiver operating characteristic curve analysis was performed for each feature. Kaplan-Meier method was used for survival analysis with log rank tests. Results: Low-grade gliomas and glioblastomas had significantly higher run percentage, run entropy, and information measure of correlation 1 on T1 than metastases (p < 0.017). The best separation of all three tumor types was seen utilizing inverse difference normalized and homogeneity values for peritumoral white matter in both T1 and T2 maps (p < 0.017). In solid tumor T2 maps, lower values in entropy and higher values of maximum probability and high-gray run emphasis were associated with longer survival in glioblastoma patients (p < 0.05). Several texture features were associated with longer survival in glioblastoma patients on peritumoral white matter T1 maps (p < 0.05). Conclusion: Texture analysis of MRF-derived maps can improve our ability to differentiate common adult brain tumors by characterizing tumor heterogeneity, and may have a role in predicting outcomes in patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Background: The aetiology of glioma is poorly understood. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to search for glioma risk factors.Methods: We performed an MR-PheWAS analysing 316 phenotypes, proxied by 8387 genetic variants, and summary genetic data from a GWAS of 12,488 glioma cases and 18,169 controls. Causal effects were estimated under a random-effects inverse-variance-weighted (IVW-RE) model, with robust adjusted profile score (MR-RAPS), weighted median and mode-based estimates computed to assess the robustness of findings. Odds ratios per one standard deviation increase in each phenotype were calculated for all glioma, glioblastoma (GBM) and non-GBM tumours.Results: No significant associations (P < 1.58 × 10-4) were observed between phenotypes and glioma under the IVW-RE model. Suggestive associations (1.58 × 10-4 < P < 0.05) were observed between leukocyte telomere length (LTL) with all glioma (ORSD = 3.91, P = 9.24 × 10-3) and GBM (ORSD = 4.86, P = 3.23 × 10-2), but the association was primarily driven by the TERT variant rs2736100. Serum low-density lipoprotein cholesterol and plasma HbA1C showed suggestive associations with glioma (ORSD = 1.11, P = 1.39 × 10-2 and ORSD = 1.28, P = 1.73 × 10-2, respectively), both associations being reliant on single genetic variants.Conclusions: Our study provides further insight into the aetiological basis of glioma for which published data have been mixed. [ABSTRACT FROM AUTHOR]

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naïve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations. [ABSTRACT FROM AUTHOR]

Background Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not examined on a comprehensive scale for all ages and by histology. Despite the rarity of ependymomas, morbidity/mortality associated with an ependymoma diagnosis justifies closer examination. Methods Incidence data were obtained from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, and survival data from Surveillance Epidemiology and End Results, from 2000 to 2016 for anaplastic ependymoma and ependymoma, not otherwise specified (NOS). Age-adjusted incidence rates (IRs) per 100 000 person-years were analyzed by age, sex, race, and location. Survival analysis was performed with Kaplan-Meier curves and multivariable Cox proportional hazards models. Results Incidence of anaplastic ependymoma was highest in ages 0 to 4 years. African American populations had lower incidence but had a 78% increased risk of death compared to white populations (hazard ratio [HR]: 1.78 [95% CI, 1.30-2.44]). Incidence was highest for anaplastic ependymoma in the supratentorial region. Adults (age 40+ years) had almost twice the risk of death compared to children (ages 0-14 years) (HR: 1.97 [95% CI, 1.45-2.66]). For ependymoma, NOS, subtotal resection had a risk of mortality 1.86 times greater than gross total resection ([HR: 1.86 [95% CI, 1.32-2.63]). Conclusions African American populations experienced higher mortality rates despite lower incidence compared to white populations. Extent of resection is an important prognostic factor for survival. This highlights need for further evaluation of treatment patterns and racial disparities in the care of patients with ependymoma subtypes. [ABSTRACT FROM AUTHOR]

Background Metabolic syndrome is identified as a risk factor for the development of several systemic cancers, but its frequency among patients with glioblastoma and its association with clinical outcomes have yet to be determined. The aim of this study was to investigate metabolic syndrome as a risk factor for and affecting survival in glioblastoma patients. Methods A retrospective cohort study, consisting of patients with diagnoses at a single institution between 2007 and 2013, was conducted. Clinical records were reviewed, and clinical and laboratory data pertaining to 5 metabolic criteria were extrapolated. Overall survival was determined by time from initial surgical diagnosis to date of death or last follow-up. Results The frequency of metabolic syndrome among patients diagnosed with glioblastoma was slightly greater than the frequency of metabolic syndrome among the general population. Within a subset of patients (n = 91) receiving the full schedule of concurrent radiation and temozolomide and adjuvant temozolomide, median overall survival was significantly shorter for patients with metabolic syndrome compared with those without. In addition, the presence of all 5 elements of the metabolic syndrome resulted in significantly decreased median survival in these patients. Conclusions We identified the metabolic syndrome at a slightly higher frequency in patients with diagnosed glioblastoma compared with the general population. In addition, metabolic syndrome with each of its individual components is associated with an overall worse prognosis in patients receiving the standard schedule of radiation and temozolomide after adjustment for age. [ABSTRACT FROM AUTHOR]