Quality of Life and its associated factors amongst Patients with Brain Tumors at a Tertiary Care Hospital in Pakistan: An Analytical Cross-Sectional Study

IntroductionDespite quality of life (QoL) being recognized as an important outcome in neuro-oncology, there is a lack of research from Pakistan where sociocultural differences may influence QoL. This study aimed to measure the QoL in patients with primary brain tumors (PBTs), and assess its association with mental health outcomes, resilience, and social support.MethodsA cross-sectional survey was conducted among primary brain tumor patients. QoL was measured using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Resilience was assessed by Wagnild and Young's Resilience Scale, mental health outcomes using Hospital Anxiety and Depression Scale, and social support using the Enriched Social Support Instrument.ResultsOur study included a total of 250 patients, with median age of 42 years (range 33-54 years). The mean global QoL of the sample was 75.73 ± 14.9. On multivariable linear regression, global QoL was inversely associated with no or low income, having hypertension (-5.77), currently using a urine catheter (-15.33), having low social support (-28.16) suffering from mild (-9.88) or symptomatic (-17.59) depression, or mild anxiety (-7.11), while resilience (0.28) demonstrated a significant positive association. Conclusion The quality of life of patients with primary brain tumors in Pakistan is a function of clinical factors such as comorbid disease and use of a urinary catheter, social factors such a family income and social support, and psychological factors such as mental illness and resilience. Our findings may be of use in the development of QoL-improving interventions within the sociocultural setting of Pakistan.

Quality of Life and its associated factors amongst Patients with Brain Tumors at a Tertiary Care Hospital in Pakistan: An Analytical Cross-Sectional Study

Introduction Despite quality of life (QoL) being recognized as an important outcome in neuro-oncology, there is a lack of research from Pakistan where sociocultural differences may influence QoL. This study aimed to measure the QoL in patients with primary brain tumors (PBTs), and assess its association with mental health outcomes, resilience, and social support. Methods A cross-sectional survey was conducted among primary brain tumor patients. QoL was measured using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Resilience was assessed by Wagnild and Young's Resilience Scale, mental health outcomes using Hospital Anxiety and Depression Scale, and social support using the Enriched Social Support Instrument. Results Our study included a total of 250 patients, with median age of 42 years (range 33-54 years). The mean global QoL of the sample was 75.73 ± 14.9. On multivariable linear regression, global QoL was inversely associated with no or low income, having hypertension (-5.77), currently using a urine catheter (-15.33), having low social support (-28.16) suffering from mild (-9.88) or symptomatic (-17.59) depression, or mild anxiety (-7.11), while resilience (0.28) demonstrated a significant positive association. Conclusion The quality of life of patients with primary brain tumors in Pakistan is a function of clinical factors such as comorbid disease and use of a urinary catheter, social factors such a family income and social support, and psychological factors such as mental illness and resilience. Our findings may be of use in the development of QoL-improving interventions within the sociocultural setting of Pakistan.

COT-18 Trends in Primary Brain Tumors in Kumamoto Prefecture with Declining Birthrate and Aging Population - Kumamoto Prefecture Brain Tumor Epidemiological Survey

Backgrounds: The demographic characteristics of Kumamoto Prefecture are that there is little population movement and the total population remains constant at about 1.8 million, but in recent years the birthrate is declining and the population is aging. We have been conducting the Kumamoto Prefecture Brain Tumor Epidemiological Survey since 1989 in cooperation with neurosurgical institutions in the prefecture. In this study, we examined whether recent demographic changes have affected the incidence of primary brain tumors (BT). Methods: Patients with primary BT were collected annually from 44 institutions in Kumamoto Prefecture (as of 2020), and the number of incidences per 100,000 population was calculated for each BT for each year, excluding patients living outside the prefecture and duplicate cases. Results: The total number of primary BT was 11441 (top 3: meningioma 40%, pituitary adenoma 17%, glioma 17%). Of 4261 men with primary BT, the top 3 were meningioma (27%), glioma (23.7%), and pituitary adenoma (18.4%)), and 7180 women (top 3: meningioma (47.7%), pituitary adenoma (16.2%), and glioma (12.9%)). The number of primary BT increased every year, and the incidence increased significantly when comparing 1989–2004 and 2005–2020 (13.6 vs. 25.0/100,000, p<0.000001). Typical brain tumors (meningioma, pituitary adenoma, glioma, schwannoma, malignant lymphoma) also increased year by year, especially asymptomatic meningioma. The median age of asymptomatic meningiomas was significantly higher than that of symptomatic meningiomas (69 vs. 65 years, p<0.0001). Gliomas increased significantly in the later stages compared with the early stages in children (0–14 years) and the elderly (65 years and older). Conclusion: Our results suggest that an increase in the number of BT such as glioblastoma, which are more common in the elderly, as well as an increase in the number of opportunities for intracranial examinations in the aging of the population may be responsible for the increased incidence of primary BT.

Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors

Mismatch repair-deficient (MMRD) brain tumors are rare among primary brain tumors and can be induced by germline or sporadic mutations. Here, we report 13 MMRD-associated (9 sporadic and 4 Lynch syndrome) primary brain tumors to determine clinicopathological and molecular characteristics and biological behavior. Our 13 MMRD brain tumors included glioblastoma (GBM) IDH-wildtype (n = 9) including 1 gliosarcoma, astrocytoma IDH-mutant WHO grade 4 (n = 2), diffuse midline glioma (DMG) H3 K27M-mutant (n = 1), and pleomorphic xanthoastrocytoma (PXA) (n = 1). Next-generation sequencing using a brain tumor-targeted gene panel, microsatellite instability (MSI) testing, Sanger sequencing for germline MMR gene mutation, immunohistochemistry of MMR proteins, and clinicopathological and survival analysis were performed. There were many accompanying mutations, suggesting a high tumor mutational burden (TMB) in 77%, but TMB was absent in one case of GBM, IDH-wildtype, DMG, and PXA, respectively. MSH2, MLH1, MSH6, and PMS2 mutations were found in 31%, 31%, 31% and 7% of patients, respectively. MSI-high and MSI-low were found in 50% and 8% of these gliomas, respectively and 34% was MSI-stable. All Lynch syndrome-associated GBMs had MSI-high. In addition, 77% (10/13) had histopathologically multinucleated giant cells. The progression-free survival tended to be poorer than the patients with no MMRD gliomas, but the number and follow-up duration of our patients were insufficient to get statistical significance. In the present study, we found that the most common MMRD primary brain tumor was GBM IDH-wildtype. The genetic profile of MMRD GBM was different from that of conventional GBM. MMRD gliomas with TMB and MSI-H may be sensitive to immunotherapy but resistant to temozolomide. Our findings can help develop better treatment options.

Chemoattraction of Neoplastic Glial Cells with CXCL10, CCL2 and CCL11 as a Paradigm for a Promising Therapeutic Approach for Primary Brain Tumors

Chemoattraction is a normal and essential process, but it can also be involved in tumorigenesis. This phenomenon plays a key role in glioblastoma (GBM). The GBM tumor cells are extremely difficult to eradicate, due to their strong capacity to migrate into the brain parenchyma. Consequently, a complete resection of the tumor is rarely a possibility, and recurrence is inevitable. To overcome this problem, we proposed to exploit this behavior by using three chemoattractants: CXCL10, CCL2 and CCL11, released by a biodegradable hydrogel (GlioGel) to produce a migration of tumor cells toward a therapeutic trap. To investigate this hypothesis, the agarose drop assay was used to test the chemoattraction capacity of these three chemokines on murine F98 and human U87MG cell lines. We then studied the potency of this approach in vivo in the well-established syngeneic F98-Fischer glioma-bearing rat model using GlioGel containing different mixtures of the chemoattractants. In vitro assays resulted in an invasive cell rate 2-fold higher when chemokines were present in the environment. In vivo experiments demonstrated the capacity of these specific chemoattractants to strongly attract neoplastic glioblastoma cells. The use of this strong locomotion ability to our end is a promising avenue in the establishment of a new therapeutic approach in the treatment of primary brain tumors.

EPID-17. COMPARATIVE EPIDEMIOLOGY OF PRIMARY BRAIN TUMORS AMONG ADOLESCENTS AND YOUNG ADULTS (AYA)

INTRODUCTION We utilized national registry data to evaluate the unique epidemiology of primary adolescent and young adult (AYA) brain tumors according to the WHO2016 classification. METHODS AYA patients (15≤age≤39) presenting between 2004-2017 with a brain tumor were identified by ICD-O-3 coding from the National Cancer Database (comprising >70% of newly-diagnosed cancers in the U.S.), and compared to pediatric and adult populations. Epidemiology and overall survival (estimated by Kaplan-Meier techniques and multivariable Cox regression) were assessed by WHO2016 tumor type. RESULTS 108,705 AYA brain tumor patients were identified (56.9% female), compared to 23,928 pediatric (46.8% female) and 748,272 adult (55.6% female) patients. Among the 69.4% of AYA brain tumors with pathological diagnosis, diffuse gliomas (31.4%), sellar tumors (19.2%), and meningiomas (15.3%) predominated in both sexes. Diffuse glioma (31.4%), sellar (19.2%), cranial nerve (7.3%), and mesenchymal non-meningothelial (4.1%) tumors represented a greater proportion of AYA brain tumors than in either pediatric or adult populations. A majority of all intracranial GCTs (59.2%) and neuronal & mixed neuronal-glial tumors (51.6%) presented during AYA. Although the prevalence of diffuse gliomas was similar between AYAs and adults, AYA gliomas were more likely to be grade 2-3 astrocytomas (38.9% vs 14.3%) and oligodendrogliomas (19.3% vs 4.3%) than in adults. GBMs represented 76.0% of adult diffuse gliomas vs. only 25.7% of AYA diffuse gliomas, but with a similar prevalence of MGMT promoter methylation (40.8% vs 38.4%). Notably, 50.7% of AYA PCNSLs were associated with HIV/AIDS, vs only 7.1% in adults (p< 0.001). CONCLUSIONS The distribution, epidemiology, and survival outcomes of primary brain tumors in the AYA population are distinct from their pediatric and adult counterparts. Notably, AYA infiltrative gliomas were more often of lower grade than adults and AYA PCNSL were far more likely to be associated with HIV/AIDS. Primary brain tumors in AYA patients require specialized management.

CTNI-55. THE CDK4/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS

BACKGROUND Medical therapies for recurrent brain tumors are limited. Abemaciclib is a small molecule CDK4/6 inhibitor that has demonstrated antitumor activity in multiple cancer types and crosses the blood-brain barrier. METHODS We conducted a phase II trial of single-agent abemaciclib in patients with recurrent primary brain tumors utilizing a novel CNS basket trial design with multiple tumor types accrued to separate cohorts including patients with recurrent IDH-wildtype gliomas (Cohort A), any recurrent gliomas requiring cytoreductive surgery (Cohort B), and any other recurrent primary brain tumors (Cohort C) including IDH-mutant gliomas, meningiomas, and other tumor types. In all patients, abemaciclib was administered orally at 200mg twice daily for each 28-day cycle. In cohort B abemaciclib was administered 4-7 days prior to surgery then resumed after recovery. Neuroimaging disease assessments were performed every two cycles. Cohorts were individually assessed for efficacy, tumoral molecular characteristics, and exploratory biomarker analyses. Next generation sequencing was performed on patients who had prior surgery. RESULTS To date, a total of 61 patients have enrolled and initiated treatment with abemaciclib. Cohort A enrolled 9 patients with IDH-wildtype WHO grade II and III astrocytomas. Cohort B enrolled 10 patients with astrocytomas of varying IDH-status. Cohort C is a diverse group of 42 patients including 22 treatment-refractory meningiomas, 10 IDH-mutant gliomas (5 astrocytomas, 5 oligodendrogliomas), 3 ependymomas, 3 primary CNS lymphomas, 2 pituitary tumors, 1 glioneuronal rosette forming tumor, and 1 diffuse midline glioma. A total of 7 grade 3 toxicities occurred in 6 patients: fatigue (3), neutropenia (2), colitis (1) and seizure (1); no grade 4 toxicities occurred. CONCLUSIONS We present the results of a novel CNS basket trial looking at the efficacy of abemaciclib across multiple recurrent primary brain tumors. Efficacy results will be presented, highlighting an update on promising results in the 22 patients with recurrent meningiomas.