Raised cardiovascular disease mortality after central nervous system tumor diagnosis: analysis of 171,926 patients from UK and USA

Abstract Background Patients with central nervous system (CNS) tumors may be at risk of dying from cardiovascular disease (CVD). We examined CVD mortality risk in patients with different histological subtypes of CNS tumors. Methods We analyzed UK(Wales)-based Secure Anonymized Information Linkage (SAIL) for 8743 CNS tumors patients diagnosed in 2000–2015, and US-based National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) for 163,183 patients in 2005–2015. We calculated age-, sex-, and calendar-year-adjusted standardized mortality ratios (SMRs) for CVD comparing CNS tumor patients to Wales and US residents. We used Cox regression models to examine factors associated with CVD mortality among CNS tumor patients. Results CVD was the second leading cause of death for CNS tumor patients in SAIL (UK) and SEER (US). Patients with CNS tumors had higher CVD mortality than the general population (SAIL SMR = 2.64, 95% CI = 2.39–2.90, SEER SMR = 1.38, 95% CI = 1.35–1.42). Malignant CNS tumor patients had over 2-fold higher mortality risk in US and UK cohorts. SMRs for nonmalignant tumors were almost 2-fold higher in SAIL than in SEER. CVD mortality risk particularly cerebrovascular disease was substantially greater in patients diagnosed at age younger than 50 years, and within the first year after their cancer diagnosis (SAIL SMR = 2.98, 95% CI = 2.39–3.66, SEER SMR = 2.14, 95% CI = 2.03–2.25). Age, sex, race/ethnicity in USA, deprivation in UK and no surgery were associated with CVD mortality. Conclusions Patients with CNS tumors had higher risk for CVD mortality, particularly from cerebrovascular disease compared to the general population, supporting further research to improve mortality outcomes.

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Raised cardiovascular disease mortality after central nervous system tumour diagnosis: analysis of 171 926 patients from UK and USA

10.1101/2021.03.29.21254512 ◽

2021 ◽

Author(s):

KAI JIN ◽

Michael TC Poon ◽

Paul M Brennan ◽

Catherine LM Sudlow ◽

Jonine D Figueroa

Keyword(s):

Cardiovascular Disease ◽

Central Nervous System ◽

Nervous System ◽

General Population ◽

Mortality Risk ◽

Cox Regression ◽

Malignant Tumours ◽

Targeted Interventions ◽

Cns Tumours ◽

Cvd Mortality

Background Patients with central nervous system (CNS) tumours have significant morbidity and mortality. Some studies showed CNS tumours patients may be at risk for cardiovascular disease (CVD) mortality. The magnitude of CVD risk among CNS tumours patients has not been comprehensively assessed. If CVD mortality is elevated in this population, there may be a potential for risk reduction to improve outcomes. We examined CVD mortality risk in patients with malignant and non-malignant CNS tumours. Methods We conducted analyses using UK (Wales)-based Secure Anonymised Information Linkage (SAIL) for 8743 CNS tumour patients diagnosed in 2000-2015 (54.9% of whom died) and US-based National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) for 163183 patients in 2005-2015 (39.6% of whom died). We calculated age-, sex-, and calendar-year- adjusted standardised mortality ratios (SMRs) for CVD death in CNS tumour patients compared to Welsh and US residents. We used multivariable cause-specific Cox regression models to examine factors associated with CVD mortality among CNS tumour patients. We stratified all analyses by malignancy and main histological types. Results CVD was the second commonest cause of death for CNS tumour patients in SAIL (UK) and SEER (US) (9.5% & 11.7%, respectively). Patients with CNS tumours had higher CVD mortality than the general population (SAIL SMR=2.64, 95% CI=2.39-2.90; SEER SMR=1.38, 95% CI=1.35-1.42). Malignant CNS tumour patients had over 2-fold higher CVD mortality risk in both US and UK cohorts. SMRs for non-malignant tumours were almost 2-fold higher in SAIL than in SEER (SAIL SMR=2.73, 95% CI=2.46-3.02; SEER SMR=1.30, 95% CI=1.26-1.33). The greatest magnitude of excess CVD mortality risk, particularly from cerebrovascular disease, was substantially greater in patients diagnosed at age younger than 50 years and within the first year after their cancer diagnosis (SAIL SMR=2.98, 95% CI=2.39-3.66; SEER SMR=2.14, 95% CI=2.03-2.25). Age, sex, race/ethnicity in USA, deprivation in UK and no surgery were associated with CVD mortality. Discussion CVD mortality is high among patients diagnosed with both malignant and non-malignant CNS tumours compared to the general population. Targeted interventions and risk stratification tools might improve survival.

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Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽

10.3390/cancers13123028 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3028

Author(s):

George I. Lambrou ◽

Apostolos Zaravinos ◽

Maria Braoudaki

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cns Tumors ◽

Normal Brain ◽

Cns Tumor ◽

Different Types ◽

Receiver Operator Curve Analysis ◽

The Central Nervous System ◽

Tumor Types ◽

Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

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Long-term medical imaging use in children with central nervous system tumors

PLoS ONE ◽

10.1371/journal.pone.0248643 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248643

Author(s):

Erin J. A. Bowles ◽

Diana L. Miglioretti ◽

Marilyn L. Kwan ◽

Ute Bartels ◽

Adam Furst ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Medical Imaging ◽

Tumor Grade ◽

Tumor Diagnosis ◽

Cns Tumors ◽

Cns Tumor ◽

Longitudinal Imaging ◽

The U.S

Background Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. Procedure We conducted a retrospective cohort study of children aged 0–20 years diagnosed with CNS tumors between 1996–2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. Results We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09–1.13) and 2.14 MRIs (95%CI 2.12–2.16) in the U.S., and 1.67 CTs (95%CI 1.65–1.68) and 1.86 MRIs (95%CI 1.85–1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. Conclusions MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

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A population-based study of cardiovascular disease mortality risk in US cancer patients

European Heart Journal ◽

10.1093/eurheartj/ehz766 ◽

2019 ◽

Vol 40 (48) ◽

pp. 3889-3897 ◽

Cited By ~ 59

Author(s):

Kathleen M Sturgeon ◽

Lei Deng ◽

Shirley M Bluethmann ◽

Shouhao Zhou ◽

Daniel M Trifiletti ◽

...

Keyword(s):

Cardiovascular Disease ◽

Heart Disease ◽

General Population ◽

Cancer Diagnosis ◽

Mortality Risk ◽

First Year ◽

Cardiovascular Disease Mortality ◽

Disease Mortality ◽

Cvd Mortality

Abstract Aims This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. Methods and results The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973–2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89–3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population. Conclusion The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

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An Integrated Analysis of Tumor Purity of Common Central Nervous System Tumors in Children Based on Machine Learning Methods

Frontiers in Genetics ◽

10.3389/fgene.2021.707802 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian Yang ◽

Jiajia Wang ◽

Shuaiwei Tian ◽

Qinhua Wang ◽

Yang Zhao ◽

...

Keyword(s):

Machine Learning ◽

Central Nervous System ◽

Nervous System ◽

Random Forest ◽

Cns Tumors ◽

Integrated Analysis ◽

Immune Microenvironment ◽

Cns Tumor ◽

Tumor Sample ◽

Tumor Purity

Background: Tumor purity is defined as the proportion of cancer cells in the tumor tissue, and its effects on molecular genetics, the immune microenvironment, and the prognosis of children’s central nervous system (CNS) tumors are under-researched.Methods: We applied random forest machine learning, the InfiniumPurify algorithm, and the ESTIMATE algorithm to estimate the tumor purity of every child’s CNS tumor sample in several published pediatric CNS tumor sample datasets from Gene Expression Omnibus (GEO), aiming to perform an integrated analysis on the tumor purity of children’s CNS tumors.Results: Only the purity of CNS tumors in children based on the random forest (RF) machine learning method was normally distributed. In addition, the children’s CNS tumor purity was associated with primary clinical pathological and molecular indicators. Enrichment analysis of biological pathways related to the purity of medulloblastoma (MB) revealed some classical signaling pathways associated with MB biology and development-related pathways. According to the correlation analysis between MB purity and the immune microenvironment, three immune-related genes, namely, CD8A, CXCR2, and TNFRSF14, were negatively related to MB purity. In contrast, no significant correlation was detected between immunotherapy-associated markers, such as PD-1, PD-L1, and CTLA4; most infiltrating immune cells; and MB purity. In the tumor purity–related survival analysis of MB, ependymoma (EPN), and children’s high-grade glioma, we discovered a minor effect of tumor purity on the survival of the aforementioned pediatric patients with CNS tumors.Conclusion: Our purity pediatric pan-CNS tumor analysis provides a deeper understanding and helps with the clinical management of pediatric CNS tumors.

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Practical Neuropathology Synoptic Reporting for Central Nervous System Tumors

Archives of Pathology & Laboratory Medicine ◽

10.5858/2010-0193-ra.1 ◽

2011 ◽

Vol 135 (6) ◽

pp. 789-792

Author(s):

Mark W. Becher

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Data Extraction ◽

Tnm Classification ◽

Cns Tumors ◽

Imaging Data ◽

Cns Tumor ◽

Narrative Report ◽

Laboratory Information Systems ◽

Synoptic Reporting

Abstract Context.—Synoptic reporting for central nervous system (CNS) tumors has never been formally addressed, and neuropathologists lack practical templates that they can adapt to their laboratory information system to be compliant with College of American Pathologists (CAP) standards. Objectives.—To provide practical synoptic report templates designed for CNS tumors that allow for easy data extraction and CAP compliance and improve the reporting of CNS tumors. Data Sources.—Review of literature and synoptic report format experience in our practice. Conclusions.—Synoptic reporting of required elements is a recently introduced standard for CNS tumors. It is difficult to use a universal non-CNS tumor synoptic report template for CNS tumors because they are heavily weighted to include items not important or required for CNS tumors, such as margins and the TNM classification system. In addition, the CAP CNS protocol, published in 2008, is an immense comprehensive document that is not conducive to simple inclusion in a narrative report. We describe our experience using a synoptic template for CNS tumors that includes all required elements, is tailored to the practice of neuropathology, and can easily be adapted to other laboratory information systems. Because of the multidisciplinary nature of CNS tumor diagnoses, neuropathologists typically collect clinical, demographic, and imaging data on all CNS tumor cases. These data can readily be entered into a primary synoptic report that could replace our standard narrative report.

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PATH-21. CLINICAL UTILITY OF DNA METHYLATION PROFILING FOR DIAGNOSIS OF CHALLENGING CENTRAL NERVOUS SYSTEM TUMORS: THE TORONTO EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noz175.617 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi147-vi147

Author(s):

Shirin Karimi ◽

Jeffrey Zuccato ◽

Yasin Mamatjan ◽

Sheila Mansouri ◽

Suganth Suppiah ◽

...

Keyword(s):

Dna Methylation ◽

Central Nervous System ◽

Nervous System ◽

Clinical Utility ◽

Cns Tumors ◽

Cns Tumor ◽

Dna Methylation Profiling ◽

Diffuse Gliomas ◽

Methylation Profiling

Abstract The update on the WHO classification of central nervous system (CNS) tumors incorporated molecular signatures for a more accurate diagnosis. Recently, DKFZ has demonstrated the utility of DNA methylation profiling(MP) for molecular classification of CNS tumors. We performed a prospective clinical study over the last three years to evaluate the clinical utility ofDNA MP on FFPE samples of 66 challenging CNS tumor cases using online DKFZ classifier. Eleven samples were excluded due to low tumor DNA content or low calibration(predictive) scores(CS)< 0.3.DNA MP confirmed the original pathology diagnoses in 15(27%)cases. The integrated molecular diagnoses were changed in 38/55(70%) including establishment of a new diagnostic entity, change in molecular signature and subtyping. TheWHO grades were changed in 16(27%) of the tumors; about two-thirds resulted in upgrading. We detected non-canonical IDH mutations in 9 diffuse gliomas and the CNV plots revealed false positive FISH results for 1p/19q co-deletion in two diffuse gliomas. The CNV plots contributed to the final diagnosis in 40(72%) patients. The molecular subtypes of medulloblastoma, ependymoma and glioblastoma subclasses were determined in 36(65%) cases. Seventy-five percent of cases with confirmation of initial diagnosis or change in molecular diagnosis had CS > 0.5, among which 51% had a CS >0.9. The median and range CS of cases with new diagnostic entity and confirmed cases were 0.86(0.37–0.99) and 0.98(0.42–0.99), respectably. Furthermore, we detected higher CS in IDH-mutant gliomas in comparison to glioblastoma IDH-wild type(P=0.04). We also observed lower CS in mesenchymal glioblastoma in comparison to other subclasses. The MGMT promoter methylation was determined in 17/20(85%) glioblastoma cases. While the DKFZ group established CS of 0.9 as a cut-off for matching to methylation classes, our findings suggest lower threshold values in challenging CNS tumor cases. Our experience indicates clinical utility of MP of challenging CNS tumors as a reliable ancillary diagnostic tool in routine neuropathology practice.

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AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children

Discover Oncology ◽

10.1007/s12672-021-00459-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yong-Ping Chen ◽

Li Yuan ◽

Hui-Ran Lin ◽

Xiao-Kai Huang ◽

Ji-Chen Ruan ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chinese Children ◽

Cns Tumors ◽

Childhood And Adolescence ◽

Control Analysis ◽

Central Nervous System Tumor ◽

Nucleotide Polymorphisms ◽

Cns Tumor ◽

Tumor Susceptibility

Abstract Introduction Central nervous system (CNS) tumors comprise 15–20% of all malignancies occurring in childhood and adolescence. Previous researches have shown that overexpression and amplification of the AURKA gene could induce multiple human malignancies, with which the connection of CNS tumor susceptibility has not been extensively studied. Material and methods In this study, we assessed whether and to what extent AURKA gene single nucleotide polymorphisms (SNPs) (rs1047972 C > T, rs2273535 T > A, rs8173 G > C) were associated with CNS tumor susceptibility, based on a case–control analysis in 191 CNS tumor patients and 248 controls. We determined this correlation using odds ratios (ORs) and 95% confidence intervals (CIs). Results AURKA gene rs8173 G > C exhibited a crucial function to CNS tumor susceptibility fall-off (GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46–0.998, P = 0.049). In addition, the combined effect of lowering the risk of developing CNS tumors was more pronounced in carriers with 3 protective genotypes than others (adjusted OR = 0.55, 95% CI = 0.31–0.98, P = 0.044). Further stratification analysis illustrated that the existence of rs8173 GC/CC and three protective genotypes lowered CNS tumor risk in some subgroups. Conclusions Our research suggested that the AURKA gene rs8173 G > C could significantly reduce CNS tumor susceptibility in Chinese children. More functional experiments are needed to explore the role of the AURKA gene rs8173 G > C.

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Trends in the risk of cardiovascular disease in women with breast cancer in a Dutch nationwide cohort study

BMJ Open ◽

10.1136/bmjopen-2018-022664 ◽

2019 ◽

Vol 9 (5) ◽

pp. e022664 ◽

Cited By ~ 2

Author(s):

Josefien Buddeke ◽

Sofie A M Gernaat ◽

Michiel L Bots ◽

Desirée H J G van den Bongard ◽

Diederick E Grobbee ◽

...

Keyword(s):

Breast Cancer ◽

Cardiovascular Disease ◽

Cohort Study ◽

General Population ◽

Mortality Risk ◽

Breast Cancer Mortality ◽

Heart Valve Disease ◽

Relative Reduction ◽

The Absolute ◽

Cvd Mortality

ObjectivesTo investigate trends in cardiovascular disease (CVD) risk following breast cancer using national registry data.MethodsA nationwide cohort study was conducted, comprising 163 881 women with in situ (7.6%) or invasive (92.4%) breast cancer and women of the general population, ranging from 3 661 141 in 1996 to 4 566 573 in 2010. CVD mortality rate in women with and without breast cancer and hospitalisation rate after breast cancer were calculated for the years 1996–2010. Age-adjusted CVD and breast cancer mortality within 5 years after breast cancer admission (1997–2010) were compared with 1996 calculated with a Cox proportional hazard analysis.ResultsThe absolute 10-year CVD mortality risk following breast cancer decreased from 56 per 1000 women in 1996 to 41 in 2005 (relative reduction=27.8%). In the general population, this decreased from 73 per 1000 women in 1996 to 55 in 2005 (–23.9%). The absolute risk of CVD hospitalisation within 1 year following breast cancer increased from 54 per 1000 women in 1996 to 67 in 2009 (+23.6%), which was largely explained by an increase in hospitalisation for hypertension, pulmonary embolism, rheumatoid heart/valve disease and heart failure. The 5-year CVD mortality risk was 42% lower (HR 0.58, 95% CI=0.48 to 0.70) for women admitted for breast cancer in 2010 compared with 1996.ConclusionsCVD mortality risk decreased in women with breast cancer and in women of the general population, with women with breast cancer having a lower risk of CVD mortality. By contrast, there was an increase in hospitalisation for CVD in women with breast cancer.

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