Central Nervous System Cancer Research Articles

The burden of childhood and adolescent cancers in North Africa and the Middle East (NAME) region: findings from the Global Burden of Disease study 2019

IntroductionDespite the significant burden of childhood and adolescent cancers, no specific studies recently discussed the burden of cancer in this group in the North Africa and the Middle East (NAME) region. Therefore, we aimed to study the burden of cancers in this group in this region.Materials and methodsWe retrieved the Global Burden of Disease (GBD) data for children and adolescent cancers (0–19 years old) in the NAME region from 1990 to 2019. 21 types of neoplasms were grouped as “neoplasms”, comprising 19 specific cancer groups as well as “other malignant neoplasms” and “other neoplasms”. Three significant parameters of incidence, deaths, and Disability-Adjusted Life Years (DALYs) were studied. The data are presented with 95% uncertainty intervals (UI), and reported rates per 100,000.ResultsIn 2019, almost 6 million (95% UI: 4.166 M–8.405 M) new cases and 11,560(9770-13,578) deaths due to neoplasms occurred in the NAME region. Incidence was higher in females (3.4 M), while deaths (6226 of overall 11,560) and DALYs (501,118 of overall 933,885) were estimated as higher in males. Incidence rates did not significantly change since 1990, while deaths and DALYs rates declined significantly. After excluding “other malignant neoplasms” and “other neoplasms”, leukemia was responsible for the highest number of incidence and deaths (incidence: 10,629(8237-13,081), deaths: 4053(3135-5013), followed by brain and central nervous system cancers (incidence: 5897(4192-7134), deaths: 2446(1761-2960)), and non-Hodgkin lymphoma (incidence: 2741 (2237-3392), deaths: 790(645–962)). Incidence rates of neoplasms were similar for most countries, but countries varied more in terms of death rates. Afghanistan 8.9(6.5–11.9), Sudan 6.4(4.5–8.6), and the Syrian Arab Republic 5.6(4.3–8.3) had the highest overall death rates.ConclusionThe NAME region is observing relatively constant incidence rates and a decreasing pattern in the deaths and DALYs. Despite this success, several countries are lagging behind in development. Different issues such as economic problems, armed conflicts and political instabilities, lack of equipment or experienced staff or poor distribution, stigmatization and disbelief in the healthcare systems account for unfavorable numbers in some countries. Such problems require urgent solutions as new sophisticated and personalized cares raise the alarm for even more inequalities between high and low-income countries.

Xanthone Derivatives in the Fight against Glioblastoma and Other Cancers

Xanthone derivatives constitute an interesting and widely studied group of compounds, both in terms of the activity of naturally occurring plant ingredients and as a scaffold with high biological activity potential for medicinal chemists. This group of compounds has already been the subject of reviews. However, our purpose was to prepare a publication for medicinal chemists to have a clear overview of anticancer activity, particularly in central nervous system cancer glioblastoma, and to be able to compare their new achievements to the anticancer activity that has already been found in this group. An integral part of the work is a tabular summary of the literature results of antineoplastic activity (e.g., IC50 values) for xanthone derivatives in various types of in vitro viability assays.

Mortality and Years of Life Lost Due to Brain and Other Central Nervous System Cancer in Wuhan, China, from 2010 to 2019

Brain cancer is one of the worst types of cancer worldwide. Understanding the epidemiology of CNS cancer is critical for properly allocating healthcare resources. We collected data on CNS cancer deaths in Wuhan, China, during 2010-2019. We constructed the cause-eliminated life tables to calculate life expectancy (LE), mortality, and years of life lost (YLLs) by age and sex. The BAPC model was used to forecast the future trends of age-standardized mortality rate (ASMR). Decomposition analysis was adopted to explore the contribution of population growth, population aging, and age-specific mortality to the change in total CNS cancer deaths. In 2019, the ASMR of CNS cancer was 3.75, and the ASYR was 135.70 in Wuhan, China. ASMR was expected to decrease to 3.43 in 2024. The age distribution of deaths due to CNS cancer was concentrated in the middle-aged and older population, with a peak in the 65-69 age group. Caidian, Jianghan, and Qingshan had the greatest ASMRs in 2019 in Wuhan, with ASMRs of 6.32, 4.78, and 4.75, respectively. Population aging is critical to the change in total CNS cancer deaths. We analyzed the current status, temporal trends, and gender and age distributions of the burden of CNS cancer in Wuhan, during 2010-2019, providing a valuable reference for better lessening the CNS cancer burden.

A Systematic Review on the Potential Acceleration of Neurocognitive Aging in Older Cancer Survivors.

As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer's disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies.

Paternity through use of assisted reproduction technology in male adult and childhood cancer survivors: a nationwide register study.

How does a history of cancer affect the likelihood of using assisted reproduction in order to achieve paternity? As compared to men with no history of cancer, use of assisted reproduction to achieve paternity was more frequent in fathers with a history of cancer, mainly those with testicular, prostate, and hematological and lymphatic malignancies. Although it is well known that different types of cancer and their treatment may have a negative impact on fertility, there is a lack of data regarding the use of IVF and ICSI among male cancer survivors. In this population-based nation-wide study using the Swedish Medical Birth Register, we identified all men who fathered their first-born child in Sweden between 1994 and 2014. Using personal identification numbers, anonymized data from the Swedish National Quality of Assisted Reproduction Register, Swedish Cancer Register, Swedish Multi-generation Register, and Swedish Education Register were linked with the Swedish Medical Birth Register. During the study period, a total of 1 181 488 men fathering their first-born child were identified. Of these, 26 901 fathers had a cancer diagnosis. Fathers diagnosed with cancer with <12 months from offspring conception, or with a cancer diagnosis after offspring conception, were excluded (n = 21 529). The remaining fathers who had a history of cancer (n = 5372) were divided into three groups based on age at cancer diagnosis (<15, ≥15 and <24, or ≥24 years). For subgroup analyses, they were also grouped according to the cancer location using ICD-7 codes. The fathers with no cancer diagnosis (n = 1 154 587), were included as controls. In total, 1 159 959 men were included. Associations between IVF/ICSI use and history of cancer were evaluated using logistic regression models, unadjusted and adjusted for paternal education, fathers age at childbirth, and year of conception, yielding crude and adjusted odds ratio (aOR), respectively, with a 95% CI. As compared to controls, childhood cancer survivors were only more likely to achieve paternity through ICSI (aOR 3.52, 95% CI 2.52-4.93; P < 0.001) but not through IVF treatment (aOR 1.02, 95% CI 0.61-1.70; P = 0.955). Similarly, teenage and young adult cancer survivors were more likely to father through ICSI treatment (aOR 6.84, 95% CI 5.64-8.30; P < 0.001) but not using IVF (aOR 1.27, 95% CI 0.90-1.80; P = 0.17). However, adult cancer survivors were more likely to conceive through either ICSI (aOR 5.52, 95% CI 4.86-6.27; P < 0.001) or IVF treatment (aOR 1.32, 95% CI 1.09-1.60; P = 0.004). In subgroup analyses, childhood survivors of testicular cancer (aOR 5.15, 95% CI 1.20-22.0; P = 0.027), soft tissue and bone cancers (aOR 4.70, 2.13-10.4; P < 0.001), hematological and lymphatic cancers (aOR 4.49, 95% CI 2.72-7.40; P < 0.001), or central nervous system (CNS) and eye cancers (aOR 2.64, 95% CI 1.23-5.67; P = 0.012), were at an increased likelihood of fathering through ICSI. Teenage and young adult survivors of testicular cancer (aOR 15.4, 95% CI 11.5-20.7; P < 0.001), hematological and lymphatic cancers (aOR 9.84, 95% CI 6.93-14.0; P < 0.001), or soft tissue and bone cancers (aOR 6.83, 95% CI 3.53-13.2; P < 0.001) were more likely to father through ICSI treatment. Adult survivors of prostate cancer (aOR 15.7, 95% CI 6.70-36.9; P < 0.001), testicular cancer (aOR 9.54, 95% CI 7.81-11.7; P < 0.001), hematological and lymphatic cancers (aOR 11.3, 95% CI 8.63-14.9; P < 0.001), digestive, respiratory, and urogenital tract cancers (aOR 2.62, 95% CI 1.75-3.92; P < 0.001), CNS and eye cancers (aOR 2.74, 95% CI 1.48-5.08; P = 0.001), or skin cancer (aOR 1.68, 95% CI 1.08-2.62; P = 0.022) were more likely to father through ICSI treatment. Only teenage and young adult survivors of hematological and lymphatic cancers (aOR 1.98, 95% CI 1.10-3.56; P = 0.022) and adult survivors of testicular cancer (aOR 1.88, 95% CI 1.37-2.58; P < 0.001) were significantly more likely to achieve fatherhood using IVF treatment. Information on men failing to father children was not available, and thus our results cannot estimate the risk of infertility in men with a history of cancer. Use of ART, in particular ICSI, was significantly more frequent in fathers with malignancies of the male reproductive tract or hematological and lymphatic systems. Our findings highlight which groups of male cancer survivors would benefit from access to fertility care, thereby improving future fertility treatment policies. The study received funding from the Swedish Cancer Society, Swedish Childhood Cancer Society, and the Swedish Government Fund for Clinical Research. There are no competing interest. N/A.

The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics.

The blood-brain barrier is critically important for the treatment of both primary and metastatic cancers of the central nervous system (CNS). Clinical outcomes for patients with primary CNS tumors are poor and have not significantly improved in decades. As treatments for patients with extracranial solid tumors improve, the incidence of CNS metastases is on the rise due to suboptimal CNS exposure of otherwise systemically active agents. Despite state-of-the art surgical care and increasingly precise radiation therapy, clinical progress is limited by the ability to deliver an effective dose of a therapeutic agent to all cancerous cells. Given the tremendous heterogeneity of CNS cancers, both across cancer subtypes and within a single tumor, and the range of diverse therapies under investigation, a nuanced examination of CNS drug exposure is needed. With a shared goal, common vocabulary, and interdisciplinary collaboration, the field is poised for renewed progress in the treatment of CNS cancers.

Tebentafusp (Kimmtrak)

&#x0D; CADTH recommends that Kimmtrak be reimbursed by public drug plans for the treatment of unresectable or metastatic uveal melanoma (mUM) if certain conditions are met.&#x0D; Kimmtrak should only be covered to treat adults with uveal melanoma whose cancer cannot be removed by surgery or has spread and who have tested positive for the HLA-A*02:01 gene. Patients receiving Kimmtrak should be in relatively good health (i.e., have a good performance status, as determined by a specialist). Cancer in central nervous system should either be controlled or that there be no spread of cancer to the brain at all.&#x0D; Kimmtrak should only be reimbursed if prescribed by a specialist with expertise in managing uveal melanoma and cytokine release syndrome, and the cost of Kimmtrak is reduced.&#x0D;

Trend of incidence and mortality of brain and central nervous system cancer in Iran from 1990 to 2017: A global burden of disease-based study.

Background: Brain and central nervous system (CNS) cancers make up about 3% of all cancers around the world and are more common among men than women. Present study aimed to evaluate the occurrence trend of brain and CNS cancers in Iran from 1990 to 2017. Methods: This study using global burden of disease (GBD) 1990 to 2017 data demonstrated the trend of incidence and mortality of brain and nervous system cancer in Iran. All-age, sex-based, age-standardized, age-specific (from 1990 to 2017), and age distribution of incidence and mortality rates of brain and nervous system cancer were estimated in Iran during 2017. Results: Both incidence and mortality rates of brain and nervous system cancer increased from 1990 to 2005 in Iran, Eastern Mediterranean Region, and global level. During 1990, incidence and mortality rates of brain and nervous system cancer were higher in women than men, but gradually both rates increased in men and exceeded women in Iran. From 1990 to 2017, the value of age-adjusted rate was higher than all-age rate of brain and nervous system cancer. The most incidence and mortality of brain and nervous system cancer from 1990 to 2017 occurred in age group of > 70 and the least values were seen in 15-49-year-old group in Iran. Conclusion: The brain tumor occurrence and mortality in Iran was higher than other Eastern Mediterranean Region countries. Incidence and mortality of this cancer has an increasing trend in Iran and this trend somewhat was independent from population aging.

National and subnational burden of brain and central nervous system cancers in Iran, 1990-2019: Results from the global burden of disease study 2019.

Central nervous system cancers (CNS cancers) impose a significant burden upon healthcare systems worldwide. Currently, the lack of a comprehensive study to assess various epidemiological indexes of CNS cancers on national and subnational scales in Iran can hamper healthcare planning and resource allocation in this regard. This study aims to fill this gap by providing estimates of CNS cancer epidemiological measures on national and subnational levels in Iran from 1990 to 2019. This study is a part of Global Burden of Disease (GBD) 2019 that contains epidemiological measures including prevalence, incidence, mortality, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) of CNS cancers. Age standardization was utilized for comparing different provinces. In 2019, 5811 (95% Uncertainty Interval: 2942-7046) national new cases and 3494 (1751-4173) deaths due to CNS cancers were reported. National age-standardized incidence (ASIR), deaths (ASDR), and DALYs rates were 7.3 (3.7-8.8), 4.6 (2.3-5.5), and 156.4 (82.0-187.0) per 100,000 in 2019, respectively. Subnational results revealed that ASDR and ASIR have increased in the past 30 years in all provinces. Although incidence rates have increased in all age groups and genders since 1990, death rates have remained the same for most age groups and genders except for young patients aged under 15, where a decrease in mortality and YLLs can be observed. The incidence, deaths, and DALYs of CNS cancers increased at national and subnational levels. These findings should be considered for planning and resource allocation.

NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

Epidemiological Study of Different Types of Cancers Among Adults PERSIAN Guilan Cohort Study

Background Cancer is the leading cause of death in the world after cardiovascular disease, and is the third leading cause of death in Iran. Objective This epidemiological study aims to investigate different types of cancers in Sowme’e Sara County, Guilan, Iran. Methods This analytical cross-sectional study is a part of the PERSIAN Guilan cohort study that was conducted on 10520 adult men and women in Sowme’e Sara County. The prevalence rate was determined per 100,000 people. Descriptive statistics (mean, standard deviation, frequency, and percentage) were used for describing data. Statistical analyzes were performed in STATA version 13 software. Results In this study, 94 patients with cancer and 98 types of cancer were recorded. Most of patients were female (n=65, 68.4%). The mean age at diagnosis in men and women was 47.61±11.23 and 44.30±7.87 years, respectively (Total=45.58±10.09 years). The most common cancers were breast cancer, brain &amp; central nervous system cancer, and prostate cancer. The minimum age for diagnosis in men and women were 23 and 19 years, respectively,. Conclusion Screening for breast cancer in women and prostate cancer in men living in Sowme’e Sara County should be done which is currently underway using mammography and prostate specific antigen tests.

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

The Role of Neuro-Inflammation and Innate Immunity in Pathophysiology of Brain and Spinal Cord Tumors.

Inflammation and innate immune system play a central role in cancers, including those affecting the central nervous system (CNS). Currently, classification of neoplasms, especially regarding gliomas, is established on molecular mutations in isocitrate dehydrogenase (IDH) genes and the presence of co-deletion 1p/19q. Treatment, in most of brain and spinal cord tumors, is centered on surgery, radiotherapy and pharmacological approaches with chemotherapeutic agents. However, the results of the treatments, after several decades, are not completely satisfactory. Cytokines and angiogenic factors are closely linked to the brain cancer behavior. Moreover, recent studies suggest a link between inflammation and tumorigenesis, underlying the complex nature of this topic, especially the anti- and pro-tumoral activities of inflammation and the two-way interactions between immune and tumor cells. The current understanding of the mechanisms by which CNS cancer cells modulate the immune system, especially how bi-directional communications between immune cells and tumor cells create an immunosuppressed microenvironment, gives important information about the promotion of tumor survival and growth. Here, we have briefly reviewed the current literature on this topic, focusing on the possible role of inflammation and innate immunity involved in the origin and in the development of CNS tumors.

Epidemiology of Brain and Other Central Nervous System Cancers in the North Africa and Middle East Region: A Systematic Analysis of the Global Burden of Disease Study 1990–2019

To present estimates of prevalence and incidence of and contributors to central nervous system (CNS) cancers, death, years of life lost, years lived with disability, and disability-adjusted life years from 1990 to 2019 in North Africa and the Middle East. Primary measures were retrieved from Global Burden of Disease 2019. Contribution of various factors to observed incidence and mortality changes was investigated with decomposition and age-period-cohort analyses. In 2019, 27,529 (95% uncertainty interval [UI]: 18,554-32,579; percent change compared with 1990:+152.5%) new CNS cancers and 17,773 (95% UI:12,096-20,936; percent change compared with 1990:+111.5%) deaths occurred. Meanwhile, 71.0% increase led to 71,6271 (95% UI: 493,932-848,226) disability-adjusted life years in 2019 with a halved years of life lost/years lived with disability ratio of 66.3%(proxy of worse care quality). Altogether, 97,195 (95% UI: 64,216-115,621; percent change compared with 1990:+280.5%) patients with prevalent cases were alive in 2019. All decomposed indices, including aging, cause-specific incidence, and population growth, contributed substantially to increased incidence of CNS cancers. Moreover, age brackets, study period (1990-2019), and 5-year cohorts all demonstrated positive effects, while age had a mixed influence in different age groups. Palestine harbored the highest age-standardized disability-adjusted life years rate in 2019 (232.0 [95% UI: 175.6-279.5]), while Tunisia had the lowest (41.8 [95% UI: 27.6-57.1] per 100,000). The greatest burden increase was found in Saudi Arabia (32.3%). The burden of CNS cancers is rising in North Africa and the Middle East, with major heterogeneities among countries. Improved early detection and health care access across countries are required to bridge inequalities and address the rising burden of CNS malignancies.

In This Issue

In This Issue

Pediatric Central Nervous System Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.

Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome.

The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.

Structural Features Affecting the Interactions and Transportability of LAT1-Targeted Phenylalanine Drug Conjugates.

L-type amino acid transporter 1 (LAT1) transfers essential amino acids across cell membranes. Owing to its predominant expression in the blood-brain barrier and tumor cells, LAT1 has been exploited for drug delivery and targeting to the central nervous system (CNS) and various cancers. Although the interactions of amino acids and their mimicking compounds with LAT1 have been extensively investigated, the specific structural features for an optimal drug scaffold have not yet been determined. Here, we evaluated a series of LAT1-targeted drug-phenylalanine conjugates (ligands) by determining their uptake rates by in vitro studies and investigating their interaction with LAT1 via induced-fit docking. Combining the experimental and computational data, we concluded that although LAT1 can accommodate various types of structures, smaller compounds are preferred. As the ligand size increased, its flexibility became more crucial in determining the compound's transportability and interactions. Compounds with linear or planar structures exhibited reduced uptake; those with rigid lipophilic structures lacked interactions and likely utilized other transport mechanisms for cellular entry. Introducing polar groups between aromatic structures enhanced interactions. Interestingly, compounds with a carbamate bond in the aromatic ring's para-position displayed very good transport efficiencies for the larger compounds. Compared to the ester bond, the corresponding amide bond had superior hydrogen bond acceptor properties and increased interactions. A reverse amide bond was less favorable than a direct amide bond for interactions with LAT1. The present information can be applied broadly to design appropriate CNS or antineoplastic drug candidates with a prodrug strategy and to discover novel LAT1 inhibitors used either as direct or adjuvant cancer therapy.

QOL-21. REAL-WORLD QUALITY-OF-LIFE AND HEALTH UTILITIES FOR PATIENTS WITH CNS CANCERS ON THE XCELSIOR PLATFORM

Abstract OBJECTIVE xCures operates a direct-to-patient, real-world evidence platform according to the nationwide observational research protocol XCELSIOR (NCT03793088), which aggregates medical data in an FDA-compliant electronic database. There is a relative scarcity of published results on real-world Quality-of-Life (QoL) outcomes and resulting health state utilities for patients with Central Nervous System (CNS) cancers. We sought to use the xCures platform to help address this issue. METHODS XCELSIOR participants were invited weekly to complete the EuroQol 5-Dimension (EQ-5D-5L) QoL survey. A EuroQol-endorsed model was used to estimate health state utilities from patient surveys. Survey results, utility estimates, and clinical information were analyzed to understand the influence of common mutations in glioma on patient reported outcomes. RESULTS 30 patients (21 glioblastoma, 4 oligodendroglioma, 2 diffuse midline glioma, 2 diffuse astrocytoma, 1 Schwannoma) completed at least one EQ-5D-5L survey over the course of 9 weeks. Health state utilities were positively correlated (p&amp;lt; .03) with Karnofsky Performance Score (KPS). The average utility for EGFR-mutated patients (N=6) was .578 (SD=.334) while for EGFR-wildtype patients (N=7) it was .747 (SD=.227). The average utility for MGMT-methylated patients (N=13) was .816 (SD=.139) while for non-methylated patients (N=10) it was .583 (SD=.379). The average utility for IDH-mutated patients (N=9) was .789 (SD=.153) while for non-mutated patients (N=17) it was .685 (SD=.324). The average utility for patients with a 1p/19q co-deletion (N=4) was .837 (SD=.126) while for those without a co-deletion (N=8) it was .744 (SD=.244). CONCLUSION The xCures platform has enabled the study of real-world QoL outcomes for patients with CNS cancers. This is the first report studying the influence of genetic mutations on QoL collected through patient reported outcomes. Future research aims to perform similar studies with larger number of patients.

The hsa-miR-516a-5p and hsa-miR-516b-5p microRNAs reduce the migration and invasion on T98G glioblastoma cell line

microRNAs (miRNAs) are involved in numerous functions and processes in the brain and other organs through the regulation of gene and protein expression. miRNA dysregulation is associated with the development of several diseases, including the brain and Central Nervous System cancer (CNS). The hsa-miR-516a-5p and hsa-miR-516b-5p are involved in proliferation, migration, and invasion in different tumor models, but their antitumor effect has not been evaluated in cancer of CNS. Therefore, we aimed to assess the effect of the miRNAs hsa-miR-516a-5p and miRNA hsa-miR-516b-5p on the Glioblastoma cell line (T98G). We used synthetic miRNA mimics to induce the overexpression of both miRNAs in the cell line, which was corroborated by RT-qPCR. Next, we evaluated the effect on proliferation, migration, and invasion using the CyQuant direct kit, ThinCert ™ inserts and invasion BioCoat ™ Matrigel® Invasion Chambers. We found upregulation of these miRNAs induced significant changes on the migration and invasion processes of T98G cells, but not affected the proliferation rate. These results suggest that both microRNAs could be playing an important role in the control of tumor progression towards metastasis. The bioinformatics analysis showed that target genes for these miRNAs are involved in different biological processes such as in cell adhesion molecule binding and cell junction disassembly, which are important for cancer progression. Further studies and experimental validation are needed to identify the genes regulated by microRNAs.