Central Nervous System Cancer Research Articles

Institution of a two-week wait brain/CNS ‘cancer exclusion’ imaging pathway

Background: NICE guidelines (NG12) recommend that clinicians should ‘consider an urgent, direct access, MRI scan of the brain (or CT scan if MRI is contraindicated; to be done within 2 weeks) to assess for brain or central nervous system cancer in adults with progressive, sub-acute loss of central neurological function’. It was found at our institution that, due to delays encountered when referring patients to the existing neurology two-week wait (2WW) pathway, only 54% of patients with suspected cancer from primary care were scanned within two weeks.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019

ObjectiveTo describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. MethodsWe conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. ResultsAcross the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. ConclusionPrevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

The comparative burden of brain and central nervous system cancers from 1990 to 2019 between China and the United States and predicting the future burden.

Brain and central nervous system (CNS) cancers represent a major source of cancer burden in China and the United States. Comparing the two countries' epidemiological features for brain and CNS cancers can help plan interventions and draw lessons. Data were extracted from the Global Burden of Disease repository. The average annual percentage change (AAPC) and relative risks of cancer burdens were calculated using joinpoint regression analysis and age-period-cohort (APC) models, respectively. Moreover, a Bayesian APC model was employed to predict the disease burden over the next decade. From 1990 to 2019, the number of incidences, deaths, and disability-adjusted life-years (DALYs) increased in China and the US, with a larger increase in China. Age-standardized incidence rates in China and the United States have shown an increasing trend over the past three decades, with AAPCs of 0.84 and 0.16%, respectively. However, the rates of age-standardized mortality and age-standardized DALYs decreased in both countries, with a greater decrease in China. Overall, age trends in cancer burden were similar for males and females, with two peaks in the childhood and elderly groups, respectively. The period and cohort effects on incidence showed an overall increasing trend in China and limited change in the US. However, the period effects for mortality and DALY were decreasing in both countries, while the cohort effects tended to increase and then decrease. Moreover, we predicted that the cancer burdens would continue to rise in China over the next decade. The burden of brain and CNS cancers is substantial and will continue to increase in China. Comprehensive policy and control measures need to be implemented to reduce the burden.

Burden of brain and central nervous system cancers in China from 1990 to 2019.

Primary central nervous system (CNS) cancer is a predominant source of mortality and morbidity globally. This study aims to analyze the burden and variation trends of CNS cancer in China from 1990 to 2019. In this cross-sectional study, we analyzed people of all ages with CNS cancer in China from January 1, 1990, to December 31, 2019. We collected the data including incidence, deaths, and disability-adjusted life-years (DALYs) from the Global Burden of Disease (GBD) study 2019. The age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and DALYs rate were compared by age and sex. In 2019, there were more than 94 (95% uncertainty intervals [CI]: 73-114) thousand incident cases, 63 (47-76) thousand deaths and 2.0 (1.5-2.5) million DALYs due to CNS cancer in China in 2019. From 1990 to 2019, the absolute number of incident cases, deaths, and DALYs increased by 107.0% (39.0 to 169.0), 67.0% (12.0 to 117.0), and 16.0% (-23.0 to 63.0). The ASIR increased by 28.0% (-16.0 to 64.0). ASDR and age-standardized DALYs rate decreased by -10.0% (-40.0 to 15.0) and -22.0% (-50.0 to 10.0), respectively. The overall burden due to CNS cancer in China remains high, as evidenced by the sharp increase in the incident cases, deaths, and DALYs from 1990 to 2019. Elderly patients and neonates show relatively high burden. Sex-specific differences in the incidence of CNS cancer in China are observed.

A national stratification of the global macroeconomic burden of central nervous system cancer.

Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.

Potassium Ion Channels in Malignant Central Nervous System Cancers.

Simple SummaryMalignant central nervous system (CNS) cancers are notoriously difficult to treat, with just one-third of patients surviving five years post-diagnosis. Their location within the brain and brainstem presents several challenges to successful treatment, including surgical inaccessibility and designing effective therapies that pass the brain’s protective barrier. Furthermore, high-grade CNS cancer is also prone to recurrence, and the secondary tumours that arise are highly resistant to treatment. Potassium ion channels are a class of transmembrane proteins involved in maintaining the electrical microenvironment of cells. In cancers, these proteins are known to play a significant role in the development of cancer hallmarks like proliferation, invasion, and adaptive drug resistance. Our review explores the relationship between potassium ion channel function and the progression of malignant CNS cancers. Targeting these proteins presents a promising, novel treatment strategy, with several FDA-approved potassium ion channel-targeting drugs already in clinical use for various CNS disorders.Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance. Potassium ion channels have long been implicated in the progression of many cancers due to their integral role in several hallmarks of the disease. Here, we will explore this relationship further, with a focus on malignant CNS cancers, including high-grade glioma (HGG). HGG is the most lethal form of primary brain tumour in adults, with the majority of patient mortality attributed to drug-resistant secondary tumours. Hence, targeting proteins that are integral to cellular plasticity could reduce tumour recurrence, improving survival. This review summarises the role of potassium ion channels in malignant CNS cancers, specifically how they contribute to proliferation, invasion, metastasis, angiogenesis, and plasticity. We will also explore how specific modulation of these proteins may provide a novel way to overcome drug resistance and improve patient outcomes.

High APLN Expression Predicts Poor Prognosis for Glioma Patients.

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN/APLNR system was involved in a variety of pathological and physiological functions, such as tumorigenesis and development. However, its prognostic roles in patients with central nervous system (CNS) cancers remain unknown. The present study was designed to explore the expression profile, prognostic significance, and interaction network of APLN/APLNR by integrating data from Oncomine, GEPIA, LOGpc, STRING, GeneMANIA, and immunohistochemical staining. The results demonstrated that APLN and APLNR mRNA expression were significantly increased in CNS cancers, including both low-grade glioma (LGG) and glioblastoma (GBM), when compared with normal CNS tissues. The high APLN, but not APLNR, expression was significantly correlated with overall survival (OS), recurrence free survival (RFS), and progression free survival (PFS) of LGG patients. However, neither APLN nor APLNR expression was significantly related to prognostic value in terms of OS, disease free interval (DFI), disease specific survival (DSS), or progression free interval (PFI) for GBM patients. Additionally, immunohistochemistry staining confirmed the increased APLN expression in tissues of LGG patients with grade II than grade I. These results showed that an elevated APLN level could predict poor OS, RFS, and PFS for LGG patients, and it could be a promising prognostic biomarker for LGG.

Impact of obstructive sleep apnea on cancer risk: a systematic review and meta-analysis.

We aimed to study the effect of obstructive sleep apnea (OSA) on cancer risk. We searched PubMed, Embase, and Cochrane databases for relevant studies. The qualities of included studies were assessed using Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted analyses were performed. We also conducted subgroup analyses stratified by gender, severity of OSA, study design, and cancer type. After literatures search, 18 studies were included in thepresent study. In the unadjusted analysis, we discovered an increased cancer risk in patients with OSA with a pooled relative risk (RR) in theOSA group of 1.49 (95% confidence interval (CI): 1.32-1.69, I2 = 32%, P = 0.15). In adjusted analysis, OSA correlated with cancer risk (RR: 1.36, 95% CI: 1.18-1.56, I2 = 54%, P < 0.01). In subgroup stratified by gender and OSA severity, OSA statistically with cancer risk in females (RR: 1.27, 95% CI: 1.06-1.51) and moderatetosevere OSAgroups (RR: 2.62, 95% CI: 1.64; 4.19). In subgroup stratified by study design, a trend toward statistically significant differences was observed in prospective studies (RR: 1.21, 95% CI: 0.99-1.48) and cross-sectional studies (RR: 1.81, 95% CI: 0.96-3.41). Patients with OSA in theretrospective study group had a statistically higher chance of developing cancer (RR: 1.41, 95% CI: 1.11-1.79). When stratified by cancer group, statistically significant differences was observed in many types of cancer (breast cancer: RR: 1.32, 95% CI: 1.03-1.70; central nervous system cancer: RR: 1.71, 95% CI: 1.06-2.75; kidney cancer: RR: 1.81, 95% CI: 1.20-2.74; liver cancer: RR: 1.19, 95% CI: 1.10-1.29; andpancreatic cancer: RR: 1.23, 95% CI: 1.14-1.33). This systematic review and meta-analysis suggests that obstructive sleep apnea may increase risk of cancer.

Burden and trends of brain and central nervous system cancer from 1990 to 2019 at the global, regional, and country levels

BackgroundRegularly updated epidemiological data on the burden of brain and central nervous system (CNS) cancers are important in the prioritization of research and the allocation of resources. This study aimed to investigate incidence, mortality, disability, and trends in brain and CNS cancers between 1990 and 2019.MethodsEpidemiological data, including the cancer incidence, mortality, disability-adjusted life years(DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (per 100,000 population) stratified by region, country, sex, and age group were retrieved and extracted using the Global Health Data Exchange (GHDx) query tool.ResultsIn 2019, there were 347,992(262,084–388,896) global cases of brain and CNS cancers, which showed a significant increase (94.35%) from the period between 1990 to 2019. The global ASIR in 2019 was 4.34 (3.27–4.86) per 100, 000 population, which showed an increasing trend for the years 1990–2019 (13.82% [-27.27–32.83]). In 2019, there were 246,253 (185,642–270,930) global deaths caused by brain and CNS cancers, which showed a significant increase (76.36%) during the study period. The global ASMR in 2019 was 3.05(2.29–3.36) per 100, 000 population, which did not change significantly over the study period (-1.19% [-36.79–13.86]). In 2019, there were 8,659,871 DALYs, which was a 109.04% increase compared with 1990. Similarly, during 1990–2019, the age-standardized DALY rate decreased by 10.39%. Additionally, 76.60% of the incident cases, 72.98% of the deaths, and 65.16% of the DALYs due to brain and CNS cancers occurred in the high-income and upper-middle-income regions.ConclusionsIn conclusion, brain and CNS cancers remain a major public health burden, particularly in high-income regions. The global incidence, deaths, and DALYs of brain and CNS cancers were shown to have increased significantly from 1990 to 2019. The global ASIR kept rising steadily, while the ASMR and age-standardized DALY rate declined over the past three decades.

Clinical and epidemiological profile of the child population diagnosed with central nervous system cancer in Medellin, Colombia

Clinical and epidemiological profile of the child population diagnosed with central nervous system cancer in Medellin, Colombia

Disease burden, risk factors, and trends of primary central nervous system (CNS) cancer: A global study of registries data.

This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of central nervous system (CNS) cancer by sex, age, and country. We extracted incidence and mortality of CNS cancer from the GLOBOCAN (2020), Cancer Incidence in Five Continents series I-X, WHO mortality database, the Nordic Cancer Registries, and the Surveillance, Epidemiology, and End Results Program. We searched the Global Health data exchanges for the prevalence of its associated risk factors. We tested the trends by Average Annual Percentage Change (AAPC) from Joinpoint regression analysis with 95% confidence intervals in different age groups. The age-standardized rates (ASRs) of CNS cancer incidence and mortality were 3.5 and 2.8 per 100,000 globally. Southern Europe (ASR = 6.0) and Western Asia (ASR = 4.2) had the highest incidence and mortality, respectively. The incidence was associated with Human Development Index, Gross Domestics Products per capita, prevalence of traumatic brain injuries, occupational carcinogens exposure, and mobile phone use at the country level. There was an overall stable and mixed trend in the CNS cancer burden. However, increasing incidence was observed in younger male population from five countries, with Slovakia (AAPC = 5.40; 95% CI 1.88, 9.04; P = .007) reporting the largest increase. While the overall global trends of cancer have been largely stable, significant increasing trends were found in the younger male population. The presence of some higher-HDI countries with increasing mortality suggested an ample scope for further research and exploration of the reasons behind these epidemiological trends.

Burden of neurological diseases in Asia from 1990 to 2019: a systematic analysis using the Global Burden of Disease Study data

ObjectivesThe burden of neurological disorders is increasing worldwide, including Asia. The purpose of this study was to determine the burden of neurological disorders between 1990 and 2019 in Asia using...

Synthesis and antiproliferative activity characterization of new imidazothiazolotriazine oxindolylidene derivatives containing various substituents in the oxindole ring.

The online version contains supplementary material available at 10.1007/s10593-022-03125-3.

1436P Genotoxic effect of bullying in children and adolescents with and without central nervous system cancer

Micronuclei analysis is considered in oncology as a potential biomarker, used for risk assessment and prognosis purposes. This pilot study aimed to determine if there is a genotoxic effect caused by bullying in children and adolescents, through the examination of the difference between the frequency of bullying, micronuclei, and other nuclear abnormalities, between Central Nervous System cancer patients and healthy volunteers.

Multi-Arm GlioblastoMa Australasia (MAGMA): protocol for a multiarm randomised clinical trial for people affected by glioblastoma

IntroductionGlioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world...

Palliative care in pediatric patients with central nervous system cancer: Descriptive and comparative study.

Data regarding the palliative needs of pediatric patients with central nervous system (CNS) cancer are scarce. We aimed to describe the attention provided by a pediatric palliative care (PPC) team to patients with CNS cancer and the differences in care compared to patients who did not receive PPC. This retrospective study was based on the clinical records of deceased patients with CNS cancer attended by a PPC team over 10 years, analyzing their trajectory and provision of PPC, including medical, psychological, social, and nursing interventions. Furthermore, we compared the last month of life care of deceased patients with CNS cancer in the same institution, based on whether they were attended by the PPC team. Of 71 patients, 59 received PPC, with a median of 1.6 months (Interquartile range: 0.6-5.2) from referral to death. Home hospitalization was provided to 84.8%, nursing interventions were registered in 89.8%, psychological characteristics in 84.7%, and social interventions in 88.1%. The most common symptoms were pain, dyspnea, and constipation. When comparing patients from the same hospital who received PPC (n = 36) with those who did not (n = 12), the former spent fewer days in the hospital in their last month and last week (p < 0.01) and were more likely to die at home (50% vs. 0%; p < 0.01). Patients with CNS cancer show various medical, social, and psychological needs during end-of-life care. Providing specific PPC interventions decreased the number of days spent at the hospital and increased the rate of death at home.

Polymeric Nanoparticles in Brain Cancer Therapy: A Review of Current Approaches.

Translation of novel therapies for brain cancer into clinical practice is of the utmost importance as primary brain tumors are responsible for more than 200,000 deaths worldwide each year. While many research efforts have been aimed at improving survival rates over the years, prognosis for patients with glioblastoma and other primary brain tumors remains poor. Safely delivering chemotherapeutic drugs and other anti-cancer compounds across the blood–brain barrier and directly to tumor cells is perhaps the greatest challenge in treating brain cancer. Polymeric nanoparticles (NPs) are powerful, highly tunable carrier systems that may be able to overcome those obstacles. Several studies have shown appropriately-constructed polymeric NPs cross the blood–brain barrier, increase drug bioavailability, reduce systemic toxicity, and selectively target central nervous system cancer cells. While no studies relating to their use in treating brain cancer are in clinical trials, there is mounting preclinical evidence that polymeric NPs could be beneficial for brain tumor therapy. This review includes a variety of polymeric NPs and how their associated composition, surface modifications, and method of delivery impact their capacity to improve brain tumor therapy.

Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers.

The evaluation of nanomechanical properties of tissues in health and disease is of increasing interest to scientists. It has been confirmed that these properties, determined in part by the composition of the extracellular matrix, significantly affect tissue physiology and the biological behavior of cells, mainly in terms of their adhesion, mobility, or ability to mutate. Importantly, pathophysiological changes that determine disease development within the tissue usually result in significant changes in tissue mechanics that might potentially affect the drug efficacy, which is important from the perspective of development of new therapeutics, since most of the currently used in vitro experimental models for drug testing do not account for these properties. Here, we provide a summary of the current understanding of how the mechanical properties of brain tissue change in pathological conditions, and how the activity of the therapeutic agents is linked to this mechanical state.

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates.

Advances in pharmacotherapy have brought extraordinary benefits to humanity. However, unmet medical needs in patients remain, particularly in the treatment of central nervous system (CNS) diseases and cancers. CNS drug delivery into the brain across the endothelium is difficult due to the blood-brain barrier (BBB), which is composed mainly of tight junctions and efflux transporters, such as multiple drug resistance 1 (MDR1) (P-glycoprotein). On the other hand, the development of anti-cancer drugs is a challenging task due to their frequent off-target side effects and the complicated mechanisms of cancer pathogenesis and progression. Brain cancer treatment options are surgery, radiation therapy, and chemotherapy. It is difficult to remove all tumor cells, even by surgical removal after a craniotomy. Accordingly, innovative brain cancer drugs are needed. Currently, antibody (Ab) drugs that show high therapeutic effects are often used clinically. Furthermore, antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan, an anti-HER2 (human epidermal receptor 2) ADC with low-molecular cancer drugs through the suitable linker, have been developed. In the case of trastuzumab deruxtecan, it is internalized into cancer cells across the membrane via receptor-mediated endocytosis. Moreover, it is reported that drug delivery into the brain across the BBB was carried out via receptor-mediated transcytosis (RMT), using anti-receptor Abs as a vector against the transferrin receptor (TfR) or insulin receptor (InsR). Thus, anti-TfR ADCs with cancer drugs are promising brain cancer agents due to their precise distribution and low side effects. In this review, I introduce the implementations and potential of brain cancer drug delivery into the brain across the BBB, based on RMT using ADCs.

Burden of brain and other central nervous system cancer in China, 1990–2019: a systematic analysis of observational data from the global burden of disease study 2019

ObjectiveTo evaluate the trends in disease burden and the epidemiological features of central nervous system (CNS) cancer in China from 1990 to 2019.DesignA population-based observational study.SettingThe incidence, prevalence, death and...