Primary CNS Tumors Research Articles

Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression.

BACKGROUNDImmune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.METHODSEn bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.RESULTSWithin gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163+ macrophages were evident throughout the TME of metastatic tumors, whereas in gliomas, CD68+, CD11c+CD68+, and CD11c+CD68+CD163+ cell subtypes were commonly observed. In lung metastases, T cells interacted with CD163+ macrophages as dyads and clusters at the brain-tumor interface and within the tumor itself and as clusters within the necrotic core. In contrast, gliomas typically lacked dyad and cluster interactions, except for T cell CD68+ cell dyads within the tumor. Analysis of transcriptomic data in glioblastomas revealed that innate immune cells expressed both proinflammatory and immunosuppressive gene signatures.CONCLUSIONOur results show that immunosuppressive macrophages are abundant within the TME and that the immune cell interactome between cancer lineages is distinct. Further, these data provide information for evaluating the role of different immune cell populations in brain tumor growth and therapeutic responses.FUNDINGThis study was supported by the NIH (NS120547), a Developmental research project award (P50CA221747), ReMission Alliance, institutional funding from Northwestern University and the Lurie Comprehensive Cancer Center, and gifts from the Mosky family and Perry McKay. Performed in the Flow Cytometry & Cellular Imaging Core Facility at MD Anderson Cancer Center, this study received support in part from the NIH (CA016672) and the National Cancer Institute (NCI) Research Specialist award 1 (R50 CA243707). Additional support was provided by CCSG Bioinformatics Shared Resource 5 (P30 CA046592), a gift from Agilent Technologies, a Research Scholar Grant from the American Cancer Society (RSG-16-005-01), a Precision Health Investigator Award from University of Michigan (U-M) Precision Health, the NCI (R37-CA214955), startup institutional research funds from U-M, and a Biomedical Informatics & Data Science Training Grant (T32GM141746).

The Concomitant Incidence of Multiple Sclerosis and Primary CNS Tumors Leading to Treatment Dilemma. (P16-9.005)

The Concomitant Incidence of Multiple Sclerosis and Primary CNS Tumors Leading to Treatment Dilemma. (P16-9.005)

A Spotlight on the Role of Radiomics and Machine-Learning Applications in the Management of Intracranial Meningiomas: A New Perspective in Neuro-Oncology: A Review.

Background: In recent decades, the application of machine learning technologies to medical imaging has opened up new perspectives in neuro-oncology, in the so-called radiomics field. Radiomics offer new insight into glioma, aiding in clinical decision-making and patients’ prognosis evaluation. Although meningiomas represent the most common primary CNS tumor and the majority of them are benign and slow-growing tumors, a minor part of them show a more aggressive behavior with an increased proliferation rate and a tendency to recur. Therefore, their treatment may represent a challenge. Methods: According to PRISMA guidelines, a systematic literature review was performed. We included selected articles (meta-analysis, review, retrospective study, and case–control study) concerning the application of radiomics method in the preoperative diagnostic and prognostic algorithm, and planning for intracranial meningiomas. We also analyzed the contribution of radiomics in differentiating meningiomas from other CNS tumors with similar radiological features. Results: In the first research stage, 273 papers were identified. After a careful screening according to inclusion/exclusion criteria, 39 articles were included in this systematic review. Conclusions: Several preoperative features have been identified to increase preoperative intracranial meningioma assessment for guiding decision-making processes. The development of valid and reliable non-invasive diagnostic and prognostic modalities could have a significant clinical impact on meningioma treatment.

Follow up of Medulloblastoma’s Treatment Retrospective Study of 144 Cases

Introduction: Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Patients and Methods: A retrospective study including 144 patients with medulloblastoma were performed at the Neurosurgery Department in Ait IDDIR Health Hospital Establishment between The period of January 2004 and December 2014. In each case, diagnosis was made clinically and confirmed radiologically and histo-pathologically. All patients were operated and received the adjuvant treatment Results and discussion: Out of 144 patients, 63 (44%) patients were females and 81 (56%) were males. We have 59 cases who had age ranged from 05 months to 5 years, however, we had 85 cases who had more than 5 years; we identified 29 (58%) children and 21 (42%) adults. Clinical manifestations of meduloblastoma vary widely according to the location. The vermis is the main location of the child with 95%. The most frequent clinical manifestations found were Intracranial hypertension syndrome and static and kinetic cerebellar syndrome, 98% patients had intracranial hypertension at diagnosis: 1,4% with engagement (2 cases) and 0,7% with coma(01 case). A ventriculo-peritoneal shunt was performed in all patients, 01 case after surgical removal. The most common complications were as follows: Meningitis ( 0,2%),ventriculitis (0,2%), CSF leakage (0,4%), post-surgical hematoma (0,2%), Shunt dysfunction ( 0,6%), aggravation of the cerebellar syndrom (0,4%), affection of mixed nerves ( 0,2%) and cerebellar mutism (0,4%). Tumor architecture was classified as classic (Grade II) and desmoplasic. We had T2M0 in 41(28,47%) cases, T2M2 in 2 (1,38%)cases ,T3aM0 in 98(68%)cases,T3bM3 in 2(1,38%) cases and T3bM4 in 1 (0,7%)case. During follow-up period, recurrence occurred in 15 (10%) cases, sustentorial metastasis in 04 (2,7%) cases, leptomeningeal dissemination in 03 (2%) cases and medullary metastasis in 03 (2%) cases. The five years survival rate was 84%. Conclusion: the surgical treatment of medulloblastoma remains a difficult therapeutic challenge because they have the most virulent form of the disease and are at highest risk for treatment-related sequelae.

Pseudoprogression prediction in high grade primary CNS tumors by use of radiomics

Our aim is to define the capabilities of radiomics and machine learning in predicting pseudoprogression development from pre-treatment MR images in a patient cohort diagnosed with high grade gliomas. In this retrospective analysis, we analysed 131 patients with high grade gliomas. Segmentation of the contrast enhancing parts of the tumor before administration of radio-chemotherapy was semi-automatically performed using the 3D Slicer open-source software platform (version 4.10) on T1 post contrast MR images. Imaging data was split into training data, test data and an independent validation sample at random. We extracted a total of 107 radiomic features by hand-delineated regions of interest (ROI). Feature selection and model construction were performed using Generalized Boosted Regression Models (GBM). 131 patients were included, of which 64 patients had a histopathologically proven progressive disease and 67 were diagnosed with mixed or pure pseudoprogression after initial treatment. Our Radiomics approach is able to predict the occurrence of pseudoprogression with an AUC, mean sensitivity, mean specificity and mean accuracy of 91.49% [86.27%, 95.89%], 79.92% [73.08%, 87.55%], 88.61% [85.19%, 94.44%] and 84.35% [80.19%, 90.57%] in the full development group, 78.51% [75.27%, 82.46%], 66.26% [57.95%, 73.02%], 78.31% [70.48%, 84.19%] and 72.40% [68.06%, 76.85%] in the testing group and finally 72.87% [70.18%, 76.28%], 71.75% [62.29%, 75.00%], 80.00% [69.23%, 84.62%] and 76.04% [69.90%, 80.00%] in the independent validation sample, respectively. Our results indicate that radiomics is a promising tool to predict pseudo-progression, thus potentially allowing to reduce the use of biopsies and invasive histopathology.

DICER1 mutations in primary central nervous system tumors: new insights into histologies, mutations, and prognosis.

We sought to characterize clinical outcomes for adult and pediatric patients with primary CNS tumors harboring DICER1 mutations or loss of DICER1. We conducted a retrospective cohort study of 98 patients who were treated between 1995 and 2020 for primary CNS tumors containing DICER1 mutations or loss of DICER1 on chromosome 14q, identified by targeted next generation sequencing. Kaplan-Meier plots and log rank tests were used to analyze survival. Cox proportional-hazards model was used for univariate and multivariable analyses for all-cause mortality (ACM). Within our cohort, the most common malignancies were grade 3/4 glioma (61%), grade 1/2 glioma (17%), and CNS sarcoma (6%). Sarcoma and non-glioma histologies, and tumors with biallelic DICER1 mutations or deletions were common in the pediatric population. Mutations occurred throughout DICER1, including missense mutations in the DexD/H-box helicase, DUF283, RNaseIIIa, and RNaseIIIb domains. For patients with grade 3/4 glioma, MGMT methylation (Hazard ratio [HR] 0.35, 95% Confidence Interval [CI] 0.16-0.73, p = 0.005), IDH1 R132 mutation (HR 0.11, 95% CI 0.03-0.41, p = 0.001), and missense mutation in the DexD/H-box helicase domain (HR 0.06, 95% CI 0.01-0.38, p = 0.003) were independently associated with longer time to ACM on multivariable analyses. DICER1 mutations or loss of DICER1 occur in diverse primary CNS tumors, including previously unrecognized grade 3/4 gliomas as the most common histology. While prior studies have described RNaseIIIb hotspot mutations, we document novel mutations in additional DICER1 functional domains. Within the grade 3/4 glioma cohort, missense mutation in the DexD/H-box helicase domain was associated with prolonged survival.

Spectrum of Central Nervous System Tumours at Tertiary Care Centre in Nepal

IntroductionMost of the Central Nervous System tumors are benign. There is increase in the incidence in recent days which might be due to improved diagnosis with advancement in the ancillary studies. This study aims to provide a single centre histopathological spectrum of tumor of CNS. MethodsThis is a retrospective cross-sectional study of 138 cases of CNS tumors managed surgically in the department of neurosurgery from 2017 to 2020.All the histological subtypes and grading were reviewed. Data of the study population were analysed using SPSS version 25 and Microsoft excel. All the patients were classified as per the 2007 World Health Organization classification of central nervous system tumors. ResultsA total of 138 cases were analysed.One hundred and thirteen constitutes brain tumors and remaining 25 constitute the spinal tumors. Of the total cases, 132 were primary CNS tumor and remaining six were secondary CNS tumor. In cranial, 61 (44.2%) were extra axial tumors. There were 122 low grade tumor and remaining 16 were high grade tumors. Tumors of neuroepithelial origin were the most common 54 (38.9%) CNS tumors followed by meningiothelial tumors 36 (26.0%).Tumor were equally distributed in both the sex.Mean age of study population was 37.38 years ranging from 0.5 years to 75 years. ConclusionsThe present study concludes that the most common CNS tumour at our centre were neuroepithelial tumor mainly pilocytic astrocytoma followed by meningothelial.

164 Racial Disparities in Surgical Recommendations for Primary Central Nervous System Tumors

INTRODUCTION: Racial disparities in treatment and outcomes disproportionately affect patients of color in many surgical fields. There is limited research on these disparities within the field of neurosurgery and most studies report solely on outcomes, not management, of populations at a single institution. METHODS: The National Cancer Institute Surveillance, Epidemiology, and End Results database (1971-2015) was used to collect demographic and clinical variables on patients with meningioma (n = 63674), glioblastoma (n = 35258), pituitary adenoma (n = 27506), vestibular schwannoma (n = 11525), astrocytoma (n = 5402), or oligodendroglioma (n = 3977). Univariate and multivariate logistic regression were performed to identify factors independently associated with recommendation against surgical resection. RESULTS: Independent of age at diagnosis, sex, tumor histology, grade, and size, Black patients with meningioma (OR 1.20, 95% CI 1.12-1.27, p < 0.001), glioblastoma (OR 1.15, 95% CI 1.02-1.30, p = 0.023), pituitary adenoma (OR 1.19, 95% CI 1.11-1.28, p < 0.001), and vestibular schwannoma (OR 1.56, 95% CI 1.26-1.93, p < 0.001) were more likely to be recommended against surgical resection compared to White patients. Results were consistent after accounting for patient insurance status and rural-urban continuum code for the county of treatment. CONCLUSION: On review of the NCI SEER database, Black patients were more likely to be recommended against surgery compared to White patients for a number of primary CNS neoplasms, independent of clinical and demographic factors. Further research is needed to identify specific contributions to this inequity.

WHAT ELEMENTS CONTRIBUTE TO IMPROVING BRAIN CANCER TREATMENTS?

Brian cancer is a serious disease that has recently been discovered in an increasing number of people. It isnt a simple problem to solve, and it involves several procedures to overcome it. Brain cancer is also the 10th biggest cause of mortality for both men and women, according to Cancer.Net. In the coming years, it is also expected that 18,600 persons (10,500 men and 8,100 women) will die from primary malignant brain and CNS tumors. Moreover, people with a malignant brain or CNS tumor have a 36 percent 5-year survival rate. Although there are numerous therapies for brain cancer, such as chemotherapy and radiation, the death rate remains high, and those treatments arent the most comfortable. As a result, complementary therapies and other supplements are utilized to promote the health and well-being of brain cancer patients. Workout, diet, acupuncture, aromatherapy, talking therapy, and music are some of the various treatments discussed in this article. The primary goal of this article is to learn more about the aspects that can help improve and enhance the success of brain cancer treatment. Furthermore, to investigate and research the advantages of each aspect, as well as how it might be used in future medical treatments.

Demographic, Clinical, and Tumor Profile Of Meningioma In Mohammad Hoesin Hospital Palembang, Indonesia

Introduction. Meningioma was the most frequently reported primary intracranial tumor. There had been a few reports about meningioma profile in Indonesia. The objective of this study is to identify the profile of meningioma based on demographic, clinical, and tumor characteristics. Methods. This is a cross-sectional study using secondary data from medical records. There were 67 meningioma patients based on histopathological examination at Mohammad Hoesin Hospital from January to December 2018. Various data were recorded, including demografic profile, history of hormonal contraceptive use, neurologic symptoms, and tumor characteristic. Results. During 2018, the incidence of meningioma was 68,3% of all primary CNS tumors. Meningioma was mostly found in the age group 35-44 years (44.8%). Most of the patients was female (92.5%) and 29 patients (46.8%) had a history of hormonal contraceptive use. Headache showed the highest rate of clinical manifestation in meningioma patient (34.3%). Based on the location, convexity meningioma was the most frequently found (65.7%). Of the 67 meningioma patients, only 26 datas were obtained regarding a history of radiation exposure and all without a history of radiation. There was only one patient (1.5%) with a family history of malignancy (breast tumor). Based on histopathological examination, 60 patients (89.6%) reported as WHO grade I, mostly the meningothelial subtype (40%). The outcome was generally good in most patients (88.1%). Conclusion. In our institution, meningioma is the most commonly found primary brain tumor. Headache was the most common clinical manifestation and these tumors were mostly located in convexity of the brain, with the majority being WHO grade I and meningothelial subtype.

Flow Cytometry Approaches to Obtain Medulloblastoma Stem Cells from Bulk Cultures.

Cancer stem cells are considered the reservoir cancer cells that are resistant to most of the forms of cancer therapies and cause relapse of the tumor. Medulloblastoma (MB), a primary CNS tumor, is a very fast-growing tumor affecting younger population. In order to characterize medulloblastoma cancer stem cells or studying the drug resistance in MB mediated through the cancer stem cells, it becomes essential to isolate and study them. Isolation and characterization of tumor cells is a critical step in understanding the cancer progression and to devise novel approaches against them as drug targets. Typically, characterization of stem cells is done through surface marker analysis and with the advent of flow cytometry based techniques, this has become incredibly straightforward. Flow cytometry employs a uniformly linear flow of cells created by complex hydraulics of the flow cytometer followed by illuminating flow path with a LASER beam. This gives very valuable information about cell composition in forward scatter (FSC) and side scatter (SSC). The surface molecules of the cells can further be stained with various florescent dyes which upon excitation with the LASER beam will give the signal that will be detected by the instrument. Flow cytometer is high-throughput equipment and requires careful operation to get valuable information about the samples. In this chapter, we describe how from a bulk cell sample of medulloblastoma cells, cancer stem cells are isolated.

Population-based analysis of radiation-induced gliomas after cranial radiotherapy for childhood cancers.

Cranial radiotherapy (RT) used for pediatric CNS cancers and leukemias carries a risk of secondary CNS malignancies, including radiation-induced gliomas (RIG). Our aim was to characterize the epidemiology of RIG. This retrospective study used SEER data (1975-2016). Cohort 1 included patients diagnosed with glioma as a second malignancy ≥2 years after receiving treatment for a first malignancy diagnosed at 0-19 years, either a primary CNS tumor (1a, n = 57) or leukemia (1b, n = 20). Cohort 2 included patients who received RT for a pediatric CNS tumor and died of presumed progressive disease >7 years after diagnosis, since previous studies have documented many missed RIGs in this group (n = 296). Controls (n = 10 687) included all other patients ages 0-19 years who received RT for a first CNS tumor or leukemia. For Cohort 1, 0.77% of patients receiving cranial RT developed RIG. 3.39% of patients receiving cranial RT for primary CNS tumors fell in cohort 2. Median latency to RIG diagnosis was 11.1 years and was significantly shorter for cohort 1b than 1a. Median OS for cohort 1 was 9.0 months. Receiving surgery, radiation, or chemotherapy were all associated with a nonstatistically significant improvement in OS (P .1-.2). A total of 1.8% of all brain tumor deaths fell in cohort 1, with 7.9% in cohort 2. A total of 1%-4% of patients undergoing cranial RT for pediatric cancers later developed RIG, which can occur 3-35 years after RT. Given the substantial and likely underestimated impact on overall CNS tumor mortality, RIG is deserving of increased attention in preclinical and clinical studies.

Our Experience Of Pediatric Brain Tumour In Medan: Demographic Study In Adam Malik General Hospital 2019-2020

Abstract
 Introduction: Primary brain and central nervous system tumors are the most prevalent and frequent neoplasm in children and adolescents aged 0 to 19 years. Brain and CNS tumors are the second leading cause of cancer-related deaths in children and adolescents aged 0 to 19 years old. Previous studies in several countries have reported the incidence rate of primary brain and CNS tumors in children and adolescent, ranged from 1.08 to 5.57 per 100,000 population. The incidence of brain tumor in pediatric patients has increased in the past decades, due to innovations in the imaging studies and the increase of benign form diagnoses. The highest occurrence of pediatric brain tumor is in the United States. Based on the study by Rictherova et al. in 2018, according to the age groups, the highest incidence is in adolescents aging 15-19 years with 6.38 per 100,000 children, followed by children aging under 1 year with 6.2 per 100,000 children.
 Method: A total of 58 patients were reported in this study. Data was collected from medical bank data of Neurosurgical Department of Faculty of Medicine of North Sumatera in Indonesia. The variables that we collected were as follows: gender, tumor diagnosis, Glasgow-Coma Scale (GCS) score on admission, and age group. We classified age group into <1 year, 2-4 years, 5-9 years, 10-14 years, and 15-19 years old. The data was computed using the SPSS 25th edition.
 Result: Out of 58 diagnosis, boys were the predominance frequency with a total of 69% and girls were 31%. most patients had medulloblastoma (27.6%) followed by glioma (24.1%), craniopharyngioma (8.6%), and meningioma (8.6%). Other types of tumor, namely cerebral abscess, cerebromalacia, choroid plexus papilloma, craniopharyngioma, ependymoma, neurofibromatosis 1, soft tissue tumor, were accounted for 1.7%, respectively
 Discussion: Primary brain and central nervous system tumors are the most prevalent and frequent neoplasm in children and adolescents aged 0 to 19 years. Brain and CNS tumors are the second leading cause of cancer-related deaths in children and adolescents aged 0 to 19 years old. In our study, from a total of 58 patients, most of the patients (69%) were boys with a frequency of 40. Girls were only accounted for 18 (31%). A study by Stiller et al. in 2019 regarding incidence of childhood CNS tumors in Britain also reported similar result, with 2275 boys and 1891 girls out of 4166 tumor patients. The most common diagnosis was medulloblastoma (27.6%), in line with the study by Stiller et al. and Suresh et al. The most common age group with brain tumor was 10-14 years old (34.5%).
 Conclusion: Based on our study, from the total of 58 patients, most of the patients were boys (69%). The most common tumor diagnosis in our study was medulloblastoma (27.6%) followed by glioma (24.1%). The results in our study had been in line with other literatures. However, the age group distribution was not in line with other literatures as our study reported the age group of 10-14 years old having the highest percentage of brain tumors. Overall, this study had reported the demographic result of pediatric brain tumor in Adam Malik General Hospital from 2019-2020.

From 65 to 70 years old: what is the best approach in the treatment of glioblastoma?

Background: Glioblastoma (GBM) is the most common primary CNS tumor in adults. Between 65-70 years of age, treatment involves the best possible surgical removal followed by radiotherapy (RT), with or without temozolomide (TMZ). After assessing whether patients can tolerate TMZ, doubts regarding RT regimens persist in this age group. This study aimed to compare the overall survival (OS) in GBM patients aged 65-70 years, in two RT regimens with TMZ: Stupp (RT 60 Gy/30 fractions (fx)+TMZ) versus mini-Stupp (RT 40.05 Gy/15 fx+TMZ) and 2 regimens of RT without TMZ: 40 Gy/15 fx versus 25 Gy/5 fx.Methods: All GBM patients, 65-70 years, undergoing RT from 1 January 2014 to 31 December 2020 were retrieved and retrospectively evaluated. Patients were divided into 4 groups: group 1 was Stupp; group 2 was mini-Stupp; group 3 was 40,05 Gy/15 fx without TMZ; and group4 was 25 Gy/5 fx without TMZ.Results: Sixty patients were retrieved with median follow up of 12 months. In the analysis of groups 1 and 2, all variables were comparable (0.21<p<0.6). Median OS was 18 and 15 months, respectively, with no statistically significant difference (p=0.13). The OS at 2 years was 26% and 21% respectively, decreasing to 13% and 0% at 3 years.Analyzing groups 3 and 4, all variables were comparable (0.06<p<0.88). OS had no difference (p=0.5) with 7 months of median OS for both groups.Conclusions: From 65-70 years, if CHT is not viable, the 25 Gy/5 fx should be the standard. When CHT is possible, mini-Stupp appears to be equivalent to Stupp.

EPID-21. EPIDEMIOLOGY AND RISK FACTORS OF PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN AND ADULTS IN THE MIAMI CANCER INSTITUTE (MCI) COHORT

Abstract BACKGROUND Many epidemiological studies assess risk factors and incidence of primary CNS tumors in the United States; few describe the incidence in specific geographic locations. Environmental or ethnic/racial factors may affect the incidence of primary CNS tumors. Miami-Dade County (MDC) is an ethnically-diverse US county, with 69.4% Hispanic, 12.9% White Non-Hispanic, 15.5% Black Non-Hispanic, Asian 1.6%, 0.3% Native, and 0.3% other. We characterized primary CNS tumors at Miami Cancer Institute (MCI) relative to national reports. METHODS We reviewed electronic medical records for all patients (n=1221) diagnosed with CNS tumors at MCI from 2017 to 2021. Descriptive and statistical analyses assessed environmental and clinical variables. RESULTS Malignant CNS tumors account for 74% of MCI primary CNS tumors. Diffuse gliomas (41%), meningiomas (26%), and embryonal tumors (5%) were the most common histologies; embryonal tumors most common at younger ages (median: 18 years). The most abundant histological subtypes were glioblastoma (54%), benign meningioma (92%), and medulloblastoma (73%), respectively. Ethnic/racial composition of glioma patients at MCI was 55.9% Hispanic, 24.6% White Non-Hispanic, 6.4% Black Non-Hispanic, 1.8% Other Non-Hispanic, 1.3% Asian, 10% unreported, comparable to MDC. Compared to national averages, the age distribution at MCI was higher among lower grade gliomas (range: 15-96, Median: 61 years), yet lower for malignant gliomas (range: 1-93, median: 47 years). The incidence of malignant CNS tumors did not differ by gender; benign primary CNS tumors were significantly more frequent in females (245/324, 76%; p< 0.001). Smoking history did not associate with incidence of primary CNS tumors; 793/1221 (65%) self-reported as non-smoker. CONCLUSION The ethnic/racial composition and incidence of primary CNS tumors by histology at MCI significantly differs from national CBTRUS database (Ostrom et al). This cohort will be further characterized by genetic profiles, race, diet, allergies, family history, substance use, clinical trial enrollment, therapeutic modalities, and overall survival rate.

EPID-20. THE RISING INCIDENCE AND PREVALENCE OF BRAIN TUMOURS: A CANADIAN EPIDEMIOLOGICAL STUDY

Abstract BACKGROUND Primary malignant brain tumours account for over one third of all brain tumours and are associated with high morbidity and mortality. The purpose of this paper is to estimate the rate and trends of incidence and prevalence for primary malignant CNS tumours in Canada from 1992 to 2017. METHODS An epidemiological study using publicly available data from Statistics Canada: Canadian Cancer Registry (CCR) from 1992 to 2017 for all of Canada was conducted. Incidence and prevalence per 100,000, age-standardized incidence, and age-standardized prevalence per 100,000 person-years of primary malignant CNS tumours were calculated and stratified by sex and age: pediatric (0-19), adult (20-64), and elderly ( >64) populations. RESULTS During the study period, incidence and prevalence increased by 27.3% and 28.8%, respectively. Males accounted for 56% of all diagnoses and experienced decreased survival compared to females one year after diagnosis (p-value = 0.04). Age-standardized rates of incidence and prevalence were highest in elderly populations. CONCLUSIONS Overall, the incidence of primary malignant CNS tumours has increased from 1992 to 2017 with males and the elderly disproportionately affected. Increased healthcare resources and awareness are needed to better identify and deliver evidence-based care for these patients.

EPID-08. IMPORTANCE OF THE INTERSECTION OF AGE AND SEX TO UNDERSTAND VARIATION IN INCIDENCE AND SURVIVAL FOR PRIMARY MALIGNANT GLIOMAS

Abstract BACKGROUND Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States. METHODS Incidence data from 2000-2017 were obtained from the Central Crain Tumor Registry of the United States, which obtains data from the CDC’s National Program of Cancer Registries and NCI’s Surveillance Epidemiology and End Results Program (SEER), and survival data from the CDC’s NPCR Registries. Age-adjusted incidence rates and rate ratios per 100,000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models were performed by age group, generating hazard ratios to assess male-to-female survival differences. RESULTS Overall, glioma incidence was higher in males. Male-to-female incidence was lowest in ages 0-9 years (IRR: 1.04, 95% CI:1.01 - 1.07, p=0.003), increasing with age, peaking at 50-59 years (IRR:1.56, 95% CI: 1.53 - 1.59, p< 0.001). Females had worse survival for ages 0-9 (HR:0.93, 95% CI:0.87-0.99), though male survival was worse for all other age groups, with the difference highest in those 20-29 years (HR:1.36, 95% CI:1.28-1.44). Incidence and survival differences by age and sex also varied by histological subtype of glioma. CONCLUSION To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. The current work shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival.

EXTH-69. FUNCTIONAL GENOMICS UNCOVER GENETIC DEPENDENCIES IN ATRTS

Abstract Brain tumors are the leading cause of cancer-related deaths in children. Embryonal brain tumors including medulloblastoma and atypical teratoid rhabdoid tumors (ATRTs) account for 15% of all primary brain and CNS tumors under the age of 14 years, with ATRTs being most prevalent in infants. Despite intensive research efforts, survival estimates for ATRT patients stay relatively low as compared to other tumor entities with a median survival of around 17 months. We here describe genome-wide CRISPR/Cas9 knockout screens in combination with small-molecule drug assays to identify targetable vulnerabilities in ATRTs. Based on functional genomic screening revealing ATRT context-specific genetic vulnerabilities (n = 671 genes), we successfully generated a small-molecule library that shows preferential activity in ATRT cells as compared to a broad selection of other human cancer cell lines. Of note, none of these drugs differentially affect ATRT cells from distinct molecular subgroups, suggesting that top candidate inhibitors might serve as pan-ATRT therapeutic avenues. CDK4/6 inhibitors, among the most potent drugs in our library, are capable of inhibiting tumor growth due to mutual exclusive dependency of ATRTs on either CDK4 or CDK6. Our approach might serve as a blueprint for fostering the identification of functionally-instructed therapeutic strategies in other incurable diseases beyond ATRT, whose genomic profiles also lack actionable alterations so far.

CTNI-58. EFFICACY AND SAFETY OF LAROTRECTINIB IN ADULT AND PEDIATRIC PATIENTS WITH TROPOMYOSIN RECEPTOR KINASE (TRK) FUSION-POSITIVE PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS

Abstract BACKGROUND NTRK gene fusions are oncogenic drivers in various CNS and non-CNS tumors. Larotrectinib is a first-in-class, highly selective TRK inhibitor approved for patients with TRK fusion cancer, with a 75% objective response rate (ORR) in 206 evaluable patients with various non-CNS cancers (Hong et al, ASCO 2021). We report data on patients with TRK fusion-positive primary CNS tumors. METHODS Patients with TRK fusion-positive primary CNS tumors in 2 clinical trials (NCT02637687, NCT02576431) were identified. Objective responses were investigator-assessed. RESULTS As of July 2020, 33 patients with TRK fusion-positive primary CNS tumors were identified (19 high-grade gliomas [HGG], 8 low-grade gliomas [LGG], 2 glioneuronal tumors, 2 neuroepithelial tumors, 1 CNS neuroblastoma, 1 small round blue cell tumor). Median age was 8.9 years (range 1.3-79.0). Patients were heavily pre-treated, with 45% having ≥ 2 prior systemic therapies. ORR was 30% (95% CI 16-49): 3 complete responses (all pediatric), 7 partial responses, 20 stable disease, and 3 progressive disease. ORR in patients with HGG and LGG were 26% (95% CI 9-51) and 38% (95% CI 9-76), respectively. Median time to response was 1.9 months. Responses were seen regardless of the number of prior systemic therapies. The 24-week disease control rate was 73% (95% CI 54-87). Median PFS was 18.3 months (95% CI 6.7-not estimable [NE]) and median overall survival (OS) was not reached (95% CI 16.9-NE) at a median follow-up of 16.5 months; 12-month OS rate was 85% (95% CI 71-99). Treatment duration ranged from 1.2 to 31.3+ months. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 3 patients (9%). There were no treatment discontinuations due to TRAEs. CONCLUSIONS In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and favorable safety regardless of age or number of prior systemic therapies.

INNV-27. AN INNOVATIVE VIRTUAL MULTI-INSTITUTIONAL, MULTIDISCIPLINARY NEURO-ONCOLOGY TUMOR BOARD: THE NIH-NOB EXPERIENCE DURING THE COVID-19 PANDEMIC

BACKGROUNDThe American Academy of Neurology Institute and Society for Neuro-Oncology recommend multidisciplinary tumor board (MTB) meetings as a quality metric in neuro-oncology. With the COVID-19 pandemic resulting in travel restrictions, we expanded our existing MTB by transitioning to a virtual format that maintained our commitment to providing consultation for primary CNS tumor cases. This transition permitted participation by neuro-oncology teams from over 30 Brain Tumor Trials Collaborative (BTTC)/National Cancer Institute-Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) centers across the United States. Here, we describe results from opening our MTB remotely to these teams.METHODSWe retrospectively reviewed records from remote MTB meetings held between April 2020 and March 2021. To gauge the impact of our MTB on clinical management, we administered a brief survey querying BTTC members.RESULTSTwenty-eight providers presented 41 cases during 24 virtual MTB meetings (range: 1-4 cases per meeting). Two cases (5%) were presented only for educational value. Approximately half (54%) of the cases discussed dealt with diagnosis/management of an NCI-CONNECT rare CNS tumor. During MTB discussions of the 39 cases seeking diagnosis/management recommendations, 32% received clinical trial recommendations, 10% were suggested to enroll in the NCI Neuro-Oncology Branch (NOB) Natural History Study (NCT02851706), 17% received a recommendation to obtain central neuropathology review, and 100% received recommendations for further disease management. Most BTTC survey respondents (83%) found these recommendations impactful in the management/treatment of their presented case or generally useful/informative for their clinical practice.CONCLUSIONWe describe the feasibility and utility of an innovative virtual multi-institutional MTB. These novel remote meetings allowed for discussion of complex neuro-oncology cases and recommendations from experts, particularly important for those with rare CNS tumors. Our study’s findings during the COVID-19 pandemic of the value of providing remote access to MTBs should apply post-pandemic.