Brain Tumor Mortality Research Articles

Abstract 5467: Identification of possible new treatment options for rare pediatric CNS tumors using a panel of validated and characterized PDX models

Abstract Central nervous system (CNS) malignancies are the most frequent group of childhood solid tumors. While pediatric mortality due to CNS tumors has decreased over the past 40 years, however, there has been no significant change in brain and other CNS tumor mortality in children and adolescents since 2007*. Advances in research and innovative therapies are crucial to improving outcomes and reducing mortality. Collaborative efforts between researchers, healthcare professionals, and the pharmaceutical industry play a pivotal role in developing more effective treatments for these indications. One important piece in this endeavor is the availability of well characterized preclinical models for rigorous preclinical testing. In the framework of the ITCCP4 consortium (www.ITCCP4.eu) our group determined the pharmacological profile of ten orthotopically implanted pediatric brain tumor PDX models. The panel comprises amongst others four CNS-BCOR models, one ZFTA::RELA ependymoma model and two models of PFA ependymoma. We tested the models in a single mouse trial format with 16 arms covering standard of care therapy including radiation as well as targeted agents. All tumors were intracranially implanted into immune-compromised NSG mice. Tumor load was determined using a fluorescence based in vivo imaging technology based on the lentiviral transient transduction of PDX cells with iRFP713 prior to implantation into the brain. In addition, body weight and neurological scoring were monitored to determine the overall condition of the animals. At the end of the study brain tissue was harvested and tumor load confirmed by immunohistochemistry. Vismodegib, a first in class inhibitor of the hedgehog signaling pathway, was the most efficacious treatment with a significantly extended overall survival (Log Rank, p< 0.001) and a reduced tumor load compared to untreated control arms. The effect was most prominent in the subclass of CNS-BCOR models leading to growth delay or stable disease. Several targeted agents such as Ipatasertib (AKT inhibitor), Idasanutlin (MDM2-antagonist) and standard of care such as Carboplatin and Radiotherapy induced stable disease as well but had no significant effect on overall survival. The positive results for Vismodegib, Ipatasertib as well as Idasanutlin will be validated in a smaller subset of models in a conventional set-up to confirm the current dataset. In summary, the single mouse trial format using intracranially implanted PDX models proved to be a feasible tool to identify most promising drug candidates for pediatric ependymoma. *Ostrom QT, Price M, Ryan K, Edelson J, Neff C, Cioffi G, et al.. CBTRUS statistical report: pediatric brain tumor foundation childhood and adolescent primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018. Neuro-Oncology (2022) 24(Supplement_3):iii1-38. Citation Format: Eva Oswald, Dorothee Lenhard, Kanstantsin Lashuk, Olivier Delattre, Didier Surdez, Johannes Gojo, Daniela Lötsch-Gojo, Walter Berger, Stefan Pfister, Julia B. Schueler. Identification of possible new treatment options for rare pediatric CNS tumors using a panel of validated and characterized PDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5467.

Gender, Racial, and Geographical Disparities in Malignant Brain Tumor Mortality in the USA

Introduction: Malignant brain tumors are malignancies which are known for their low survival rates. Despite advancements in treatments in the last decade, the disparities in malignant brain cancer mortality among the US population remain unclear. Methods: We analyzed death certificate data from the US CDC WONDER from 1999 to 2020 to determine the longitudinal trends of malignant brain tumor mortality. Malignant brain tumor (ICD-10 C71.0–71.9) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated by standardizing the AAMR to the year 2000 US population. Results: From 1999 to 2020, there were 306,375 deaths due to malignant brain tumors. The AAMR decreased from 5.57 (95% CI, 5.47–5.67) per 100,000 individuals in 1999 to 5.40 (95% CI, 5.31–5.48) per 100,000 individuals in 2020, with an annual percent decrease of −0.05 (95% CI, −0.22, 0.12). Whites had the highest AAMR (6.05 [95% CI, 6.02–6.07] per 100,000 individuals), followed by Hispanics (3.70 [95% CI, 3.64–3.76]) per 100,000 individuals, blacks (3.09 [95% CI, 3.04–3.14] per 100,000 individuals), American Indians (2.82 [95% CI, 2.64–3.00] per 100,000 individuals), and Asians (2.44 [95% CI, 2.38–2.50] per 100,000 individuals). The highest AAMRs were reported in the Midwest region (5.58 [95% CI, 5.54–5.62] per 100,000 individuals) and the rural regions (5.66 [95% CI, 5.61–5.71] per 100,000 individuals). Conclusions: Our study highlights the mortality disparity among different races, geographic regions, and urbanization levels. The findings underscore the importance of addressing the disparities in malignant brain tumors that existed among males, white individuals, and rural populations.

Deep Learning Techniques for Brain Lesion Classification Using Various M.R.I. (from 2010 to 2022): Review and Challenges

Brain tumors are conditions brought on by the development of aberrant brain cells. They are classified into non-cancerous (benign) and cancerous (malignant). The morbidity and mortality of brain tumors are challenging to determine. A study in the United Kingdom disclosed that around 15 out of every 100 individuals with brain cancer could survive for ten or more years after being diagnosed. The remedial maneuvers of the brain tumors depend upon the kind of brain tumor, degree of cellular abnormality, location of Cancer in the brain, and other variables. The treatment decision needs assistance from the Deep learning algorithms using magnetic resonance imaging (M.R.I.) data to diagnose brain tumors due to the high dimensionalities of the remedial maneuvers. MRI is a scanning technique that uses strong radio waves and strong magnetic fields to generate detailed images of the body's interior. The study employed deep learning models to detect the tumor region in brain M.R.I. scans, including a Convolutional Neural Network model. The proposed processes involved dataset modification and preprocessing, detection, identification, and classification via CNN. Data mining techniques were utilized to uncover significant relationships and patterns from the data, resulting in successful early brain lesion identification and classification using deep learning approaches.

Incidence and Mortality of Malignant Brain Tumors after 20 Years of Mobile Use

(1) Objective: This population-based study was performed to examine the trends of incidence and deaths due to malignant neoplasm of the brain (MNB) in association with mobile phone usage for a period of 20 years (January 2000–December 2019) in Taiwan. (2) Methods: Pearson correlation, regression analysis, and joinpoint regression analysis were used to examine the trends of incidence of MNB and deaths due to MNB in association with mobile phone usage. (3) Results: The findings indicate a trend of increase in the number of mobile phone users over the study period, accompanied by a slight rise in the incidence and death rates of MNB. The compound annual growth rates further support these observations, highlighting consistent growth in mobile phone users and a corresponding increase in MNB incidences and deaths. (4) Conclusions: The results suggest a weaker association between the growing number of mobile phone users and the rising rates of MNB, and no significant correlation was observed between MNB incidences and deaths and mobile phone usage. Ultimately, it is important to acknowledge that conclusive results cannot be drawn at this stage and further investigation is required by considering various other confounding factors and potential risks to obtain more definitive findings and a clearer picture.

IMG-02. VISUALIZATION OF TIGIT IN THE GLIOMA MICROENVIRONMENT: THE CREATION OF A PET IMAGING TRACER

Abstract Pediatric high-grade gliomas (HGGs) are aggressive tumors and are one of the drivers of pediatric brain tumor mortality. Few effective treatment options exist for pediatric HGGs beyond surgery and chemoradiation. Additionally, some HGGs, such as diffuse midline glioma, are often surgically inaccessible and respond poorly to chemotherapy leaving radiotherapy as the only treatment for this disease. While immune checkpoint inhibitors (ICIs) have seen success in treating cancers outside the CNS, ICIs for gliomas have shown limited efficacy. TIGIT is an IC receptor that is expressed on activated T-cells and has a critical role in suppressing T-cell and NK cell function. Prior work by our group has shown TIGIT to be a promising target for adult gliomas. These studies included analysis of transcriptomic data, and preclinical studies in glioma-bearing mice. We therefore assessed pediatric glioma transcriptomic datasets and identified via optimal cutoff analysis that at a specific mRNA threshold, TIGIT expression is associated with worsened survival. As TIGIT expression may be both prognostic and a biomarker for anti-TIGIT ICI therapy, we created a radiolabeled immunoPET tracer capable of binding TIGIT antigen that could be visualized via PET imaging. Referred to as “89Zr-DFO-TIGIT”, we found this tracer bound TIGIT with moderate immunoreactivity (57.7% ± 3.5%) as determined by bead-based immunoreactivity assays. As proof of feasibility, we injected glioma-bearing mice (GL261 cell line) with 89Zr-DFO-TIGIT which enabled the visualization of TIGIT in the tumor microenvironment via PET imaging. Thereafter, we performed biodistribution studies which found there to be significantly increased 89Zr-DFO-TIGIT in mouse tumor-bearing hemispheres as compared to non-tumor-bearing hemispheres. PET imaging also showed tracer-to-tumor uptake increased from day one to day eight. Our findings demonstrate the capability of 89Zr-DFO-TIGIT to visualize and quantify TIGIT in the glioma microenvironment, highlighting how this tracer may be of value in pediatric brain tumor immunotherapy studies.

Universal multi-factor feature selection method for radiomics-based brain tumor classification

Brain tumor mortality is high, and accurate classification before treatment can improve patient prognosis. Radiomics, which extracts numerous features from medical images, has been widely applied in brain tumor classification studies. Feature selection (FS) is a critical step in radiomics because it reduces redundant information and enhances classification performance. However, the lack of universal FS methods limits the development of radiomics-based brain tumor classification studies. To address this issue, we summarize the characteristics of the FS methods used in related studies and propose a universal method based on three selection factors called triple-factor cascaded selection (TFCS). Particularly, these factors correspond to the correlation between features and task labels, interdependence among features, and role of features in the model. The TFCS method divides FS into two steps. First, it utilizes mutual information to select features that are strongly correlated with the task and contain less redundant information. Recursive feature elimination is then employed to obtain the subset with the best classification performance. To validate the universality of the TFCS, we conducted experiments on seven datasets containing 13 brain tumor classification tasks and evaluated the overall performance using five types of indicators. Results: TFCS exhibited excellent overall performance for all tasks. Compared to the 13 related methods, it takes less time, has moderate parsimony, the best classification performance, adaptability, and stability, and shows better universality. Our study demonstrates that the reasonable utilization of multiple factors can enhance FS performance and provide new insights for future method design.

Brain Tumor Mortality Assessment in Pregnant Women in Iraqi Patient

Brain Tumor Mortality Assessment in Pregnant Women in Iraqi Patient

Absorbed dose in the operator’s brain in interventional radiology practices: evaluation through KAP value conversion factors

In order to address the recent concerns over a possible increasing in brain tumour mortality among interventional radiologists and cardiologist, this work evaluated the exposure conditions of the operator’s brain during interventional procedures using Monte Carlo simulations with anthropomorphic phantoms. The absorbed doses in several predefined segments of the operator’s brain were estimated in a typical interventional radiology irradiation scenario. The doses were normalized to the KAP values simulated for ten X-ray beam qualities and four projections (PA, RAO 25°, LAO 25° and CRA 25°). For the interventional radiology scenario, because of the position of the operator, no difference was found in the exposure between the left and right regions of the brain for the first operator. However, for the second operator standing at a farer distance from the tube, the exposure of the left part of the brain is up to two times higher than that of the right part. The results are in agreement with dose measurements reported in the literature. The conversion factors, obtained as the absorbed dose per KAP, can be used to obtain a first estimate of the exposure of the brain of the operators during interventional procedures.

A Spearman Algorithm Based Brain Tumor Detection Using CNN Classifier for MRI Images

Medical imaging and its processing is an area of interest which is helps for easier and analysis of the medical issues. These modalities can provide visual representations of the interior of a body for clinical analysis and medical interventions. Medical imaging also establishes a database of normal anatomy and physiology to make it possible to identify abnormalities. So it helping easier diagnosis and planning treatment. These detailed and informative mapping can be processed to exact the information instead of dealing with the whole data. The medical imaging technique plays a central role for diagnosis of brain tumors. During the recent years, the mortality rate of individuals due to brain tumor is rising rapidly. Brain tumor is a serious life-threatening issue. Near the beginning and exact detection of brain tumor helps to reduces the brain tumor mortality rate, but it is a complicated and challenging task. To solve these difficulties use different brain tumor detection algorithms. Nowadays a number of brain tumor detection and classification algorithms are existing, but several classification processes have need of large time for classify the result. In order to improve the efficiency of brain tumor detection process, propose a spearman based brain tumor segmentation and Convolution Neural Network (CNN) based classification technique. This classifier provides best and accurate result. The proposed technique is estimated on the basis of their performance parameters on MRI brain images.

Glioma and Alzheimer's Disease.

Background: Cancer mortality and Alzheimer’s disease (AD) mortality increase with age, but some studies have shown an inverse relationship of the two diseases, that is, older persons with cancer have a reduced risk of AD and vice versa. However, other analyses suggest that AD and brain tumor might be positively correlated.Objective: In the current study, we wished to determine the relationship of AD mortality to malignant brain tumor mortality in US states and counties.Methods: Data and maps of malignant brain tumor mortality and Alzheimer’s disease mortality (1999–2016) are from the CDC Wonder tool (https://wonder.cdc.gov/cmf-icd10.html). Data on malignant brain tumor types and their frequencies are from the Surveillance, Epidemiology, and End Results Program (SEER, https://seer.cancer.gov). Data on the genetics of lower grade glioma are from the TCGA Lower Grade Glioma (LGG) dataset in TCGA (The Cancer Genome Atlas).Results: SEER data indicate that astrocytomas make up 58.2% of malignant brain tumors in patients 65 and older; glioblastoma and anaplastic astrocytoma make up 41.6%. We found a significant positive correlation between AD mortality rate and malignant brain tumor mortality rate 1999–2016 in persons age 65 and older in A) 1,101 US counties, p < 0.001 and B) 50 US states, p < 0.001.Conclusion: Adult malignant brain tumors may share some environmental risks with AD. Malignant brain tumors and AD also have some genes in common: TREM2, SPI1, CD33, and INPP5D. The interaction of environment and genetics is complex and overlaps in malignant brain tumors and AD.

Identification of a five B cell-associated gene prognostic and predictive signature for advanced glioma patients harboring immunosuppressive subtype preference.

High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.

The Association between Cellular Phone Usage and Brain Neoplasms

Background: The association between cellular phones and brain tumors is a question that is frequently asked of the medical and scientific community. The prevalence of cell phone use and the significant morbidity and mortality of brain tumors contribute to this pairing. Cell phones are known to emit radio frequency energy in the form of both ionizing and non-ionizing radiation. Ionizing radiation is known to be within X-rays, which do have an association with cancer. Objective: To assess if the use of the cell phone has an association with brain tumors. Methods: The searches performed through PubMed were conducted to find studies that sought to provide evidence as to whether or not increased cell phone exposure contributed to the development of brain tumors. Also searched for was increased regional metabolism of the brain with the use of the cell phone switched in the on position. Studies were restricted to being published during or after the year 2000 and presented in the English language. Results: The studies largely support the conclusion that cell phone usage does not lead to the development of brain cancer. Studies employed different strategies, such as the prospective cohort and case-control studies to reach this conclusion. Both studies failed to show statistically significant evidence that cell phones were associated with brain tumors of the central nervous system. Conclusions: Questions raised by crossover studies demonstrating increased regional brain glucose metabolism continue to remain largely unanswered by current research and remain a starting point for future research. The prevalence of the issue strengthens its position among others as a matter that the medical community must continue to address to meet the needs of an increasingly exposed patient population. The overall hypothesis that cell phone usage does not lead to the development of brain tumors was supported.

The incidence rate and mortality of malignant brain tumors after 10 years of intensive cell phone use in Taiwan

The issue of whether cell phone usage can contribute toward the development of brain tumors has recently been reignited with the International Agency for Research on Cancer classifying radiofrequency electromagnetic fields as 'possibly' carcinogenic to humans in a WHO report. To our knowledge, this is the largest study reporting on the incidence and mortality of malignant brain tumors after long-term use of the cell phone by more than 23 million users. A population-based study was carried out the numbers of cell phone users were collected from the official statistics provided by the National Communication Commission. According to National Cancer Registry, there were 4 incidences and 4 deaths due to malignant neoplasms in Taiwan during the period 2000-2009. The 10 years of observational data show that the intensive user rate of cell phones has had no significant effect on the incidence rate or on the mortality of malignant brain tumors in Taiwan. In conclusion, we do not detect any correlation between the morbidity/mortality of malignant brain tumors and cell phone use in Taiwan. We thus urge international agencies to publish only confirmatory reports with more applicable conclusions in public. This will help spare the public from unnecessary worries.

Stat Bite Brain Tumor Mortality By Race And Ethnicity in U.S. in 2007

Stat Bite Brain Tumor Mortality By Race And Ethnicity in U.S. in 2007

Surgical morbidity and mortality of pediatric brain tumors: a single center audit

ObjectivesThe primary aim of this study is to perform an internal quality control of pediatric brain tumor surgery in the neurosurgical department of the VU University Medical Center Amsterdam (The Netherlands). Secondly, this study aims to contribute to the accumulating data concerning outcome in pediatric neurosurgery, in order to establish institutional practice benchmarks.MethodsWe report the surgical mortality and morbidity of 121 patients (0–18 years) surgically treated for a brain tumor from January 1999 to August 2007. Patients, in whom only a brain tumor biopsy was performed, were excluded.ResultsMean age at first surgery was 8.2 years. Of the 121 patients, 14 had a second surgery, and two underwent a third surgery (for a total of 137 operations). Of all 121 primary surgeries, 66% were total resections, 26% subtotal resections, and 8% partial resections. The overall surgical morbidity rate in this study was 69% after first surgery, 50% after second surgery, and one out of two after third surgery.ConclusionThese overall morbidity rates are comparable to other published mixed case series. The surgical mortality rate was 0.8%; this is comparable to the lowest rates reported for high-volume neurosurgical centers. We encourage other neurosurgical centers to collect, analyze, and publish their data. These data can then serve as a basis for comparison with other pediatric neurosurgical centers and will eventually lead to an improvement of pediatric neurosurgical practice and patient care.

Mortality among chemical workers at Texas City plant: 1940–2001

To evaluate the mortality experience of workers at a major chemical manufacturing site and to examine brain and liver cancers excesses reported at this site in previous studies. This study included 9,730 employees at the Texas City location who worked between 1940 and 2001. Standardized mortality ratios and confidence intervals were calculated. There was less than expected deaths due to all cause mortality and no increase in all cancer mortality. Brain tumor mortality, which did exceed expected rates in past years, was at expected levels in recent years. Liver cancer mortality was greater than expected. Brain tumor mortality was either due to chance in the early years or the cause of the brain tumors has been eliminated. Mortality due to liver cancer is higher than expected but only among men hired before 1950.

Leukaemia, brain tumours and exposure to extremely low frequency magnetic fields: cohort study of Swiss railway employees

Aims: To investigate the relationship between extremely low frequency magnetic field (ELF-MF) exposure and mortality from leukaemia and brain tumour in a cohort of Swiss railway workers. Methods: 20 141...

Cellular telephone use and time trends in brain tumour mortality in Switzerland from 1969 to 2002

A rising concern exists that with the widespread use of mobile communication technologies, the incidence of brain tumours may increase. On the basis of data from the Swiss national mortality registry from 1969 to 2002, annual age-standardized brain tumour mortality rates per 100,000 person-years were calculated using the European standard population. Time trend analyses were performed by the Poisson regression for six different age groups in men and women separately. The study period was divided into two intervals: before and after 1987, when the analogue mobile technology was introduced in Switzerland. Age-standardized brain tumour mortality rates ranged between 3.7 and 6.7 for men and 2.5 and 4.4 for women per 100,000 person-years. For the whole study period, a significant increase in brain tumour mortality was observed for men and women in the older age groups (60-74 and 75+ years) but not in the younger ones in whom mobile phone use was more prevalent. Time trend analyses restricted to data from 1987 onwards revealed relatively stable brain tumour mortality rates in all age groups. For instance, the annual change in brain tumour mortality rate for the 45-59-year age group was -0.3% (95% confidence interval: -1.7; 1.1) for men and -0.4% (95% confidence interval:-2.2; 1.3) for women. We conclude that after the introduction of mobile phone technology in Switzerland, brain tumour mortality rates remained stable in all age groups. Our results suggest that mobile phone use is not a strong risk factor in the short term for mortality from brain tumours. Ecological analyses like this, however, are limited in their ability to reveal potentially small increases in risk for diseases with a long latency period.

Brain Tumor Mortality and Radiation Exposure: A Case Control Study of Nuclear Workers

Brain Tumor Mortality and Radiation Exposure: A Case Control Study of Nuclear Workers

Occludin Expression in Brain Tumors and its Relevance to Peritumoral Edema and Survival

Peritumoral brain edema (PTBE) is a serious causative factor that contributes the morbidity or mortality of brain tumors. The development of PTBE is influenced by many factors, including such tight junction proteins as occludin. We evaluated the PTBE volume and survival time with respect to the occludin expression in various pathological types of brain tumors. Fresh-frozen specimens from sixty patients who had brain tumors were obtained during surgery and the tumors were confirmed pathologically. The occludin expression was investigated by Western blot analysis. The PTBE volume was measured by using preoperative magnetic resonance (MR) imaging, and the survival time in each patient was estimated retrospectively. Occludin was detected in 41 (68.3%) of the cases with brain tumors and it was not expressed in the other 19 (31.7%) cases. Although the lowest expression was revealed in high-grade gliomas, its expression was variable according to the pathology of the brain tumors (p>0.05). The difference of PTBE volume between occludin-positive and negative brain tumors was statistically significant (2072.46+/-328.73 mm(3) vs. 7452.42+/-1504.19 mm(3), respectively, p=0.002). The mean survival time was longer in the occludin-positive tumor group than in the occludin-negative group (38.63+/-1.57 months vs. 26.16+/-3.83 months, respectively; p=0.016). This study suggests that the occludin expression is highly correlated to the development of PTBE in brain tumors and it might be a prognostic indicator for patient survival.