Brain Tumor Center Research Articles

DDDR-23. DECODING GLIOBLASTOMA DRUG RESISTANCE DYNAMICS USING NOVEL MICROFLUIDIC EX VIVO MODELS

Abstract Glioblastoma (GBM) is clinically challenging due to its aggressive nature and limited treatment options. Current standard of care involves surgical resection and chemoradiation with temozolomide (TMZ). GBM, however, often returns post-treatment fueled by its complex biology and the presence of resilient GBM stem cells. Compounding the issue is the blood-brain barrier, which poses a formidable obstacle to drug delivery into the brain. Understanding the molecular dynamics post-therapy within the brain, influenced by the tissue microenvironment, is key for developing more effective therapeutic strategies. Unfortunately, existing research models have fallen short in capturing the complexity of GBM and its response to treatment. While animal models have been a mainstay in GBM research, their ability to predict human responses has been called into question, highlighted by the disappointing results seen in clinical trials. We are therefore advancing bioprinting-based approaches for modeling various components of the tumor microenvironment to gain insight into mechanisms of drug resistance. We report on the development of three novel microfluidic platforms to investigate and interrogate GBM biology. First, we have developed a novel microfluidic model of GBM, termed GlioFlow-3D, produced through a combination of 3D printing methods. GlioFlow-3D mimics specific aspects of the perivascular niche, including protection from circulating TMZ. Second, we have adapted GlioFlow-3D as part of a platform to investigate advanced ultrasound techniques for delivering novel therapeutics into the human brain. Third, we are developing a novel approach aimed at exploring the relationship between the brain extracellular matrix and tumoral cells using bioprinting of living tumor organoids obtained from patients with a history of recurrence. By integrating bioprinting technologies with patient-derived models to create novel ex vivo platforms, we aim to obtain new insights into the intricate dynamics of drug resistance in GBM, ultimately paving the way for more effective therapeutic strategies. Funding: The Brain Tumor Center Research Award (UCGNI) The ARC Project - CCHMC and UC joint Research Award

Predicting therapeutic clinical trial enrollment for underrepresented patients in neuro-oncology using supervised machine learning.

1614 Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.

Can targeting TSP-1 with gabapentin enhance survival in glioblastoma? A 20-year retrospective cohort study.

2048 Background: Molecularly-defined cellular subpopulations of glioblastoma secrete high levels of the synaptogenic protein thrombospondin-1 (TSP-1) which promotes functional integration of tumor into neural circuity. A greater extent of glioma-neuronal crosstalk portends worse survival for patients. In preclinical studies, gabapentin was shown to inhibit TSP-1, in turn disrupting neuronal synaptogenesis and neuronal activity-dependent glioblastoma proliferation; however, clinical survival data is lacking. We aim to determine whether treatment with gabapentin is associated with improved survival and reduced serum TSP-1 in a retrospective cohort of patients with IDH-wildtype glioblastoma. Methods: Newly-diagnosed, IDH-wildtype glioblastoma patients who received care at the UCSF Brain Tumor Center between 1997-2017 were included in this study. Kaplan-Meier curves and multivariate Cox proportional-hazards models, controlled for age, MGMT promoter methylation status, preoperative tumor volume, and extent of resection, were used for survival analyses. Differences in serum TSP-1 measured by ELISA for gabapentin treated patients and matched non-gabapentin treated controls were assessed using unpaired two-tailed student’s t-test. Control samples were matched 2:1 by age, tumor volume, and extent of resection. After 2005, patients were treated with chemoradiation with concurrent and adjuvant temodar. Results: Among 379 adult patients with glioblastoma, 36 (9.5%) were treated with gabapentin. The median daily dose of gabapentin was 600 mg (IQR: 300-900 mg). There were no significant differences between gabapentin treated and non-gabapentin treated patients by age (0.06), sex (p=0.14), or race (p=0.52). Median overall survival for gabapentin treated and non-gabapentin treated patients was 20.8 months (IQR: 11.7 - 32.1) and 14.7 months (IQR: 8.9-23.5), respectively (p= 0.02). On Kaplan-Meier survival analysis, overall survival was longer for gabapentin treated patients compared with non-gabapentin treated patients (p=0.005). In the multivariate Cox proportional-hazards model, gabapentin use was associated with decreased hazard of death (HR 0.67, p=0.030). Mean serum TSP-1 in gabapentin-treated patients was significantly lower than in the matched control group (10181 ng/ml vs 17015 ng/ml, p=0.017). Conclusions: Gabapentin use is associated with a survival benefit for patients with glioblastoma, possibly mediated through a reduction in TSP-1. This promising result lays the foundation for future prospective studies to further evaluate TSP-1 as a circulating prognostic biomarker as well as to explore the therapeutic benefits of gabapentin as a life-prolonging treatment for patients with newly diagnosed glioblastoma.

Abstract 1006: Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma

Abstract Introduction: Despite the enactment of the 1993 NIH Revitalization Act to improve accrual of women and minorities in clinical trials, these groups remain underrepresented. This study aims to uncover drivers of therapeutic clinical trial enrollment that are unique to women and minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997-2017 were identified in a prospective registry. Dividing the cohort into subgroups by gender and NIH-designated minority status, factors associated with therapeutic clinical trial enrollment on univariate logistic regression (p<0.2) were selected for multivariate logistic regression. Results: There were 351 trial participants (41% women, 12% minority) and 627 non-trial participants (44% women, 17% minority). Among women only, seizure at presentation (OR 2.10, p=0.008) was associated with increased odds of trial enrollment. In contrast, among men only, higher median household income (OR 1.09 per $10,000 increase, p=0.006), higher WHO tumor grade (OR 1.89, p=0.045), and occupational status according to the International Standard Classification of Occupations [professionals (e.g., physicians) vs managers (e.g., supervisory positions), OR 2.87, p=0.043] were associated with increased odds of trial enrollment. Among both women and men, lack of insurance (women: OR 0.49, p=0.02; men: OR 0.55, p=0.031) and no treatment with chemotherapy (women: OR 0.18, p=0.001; men: OR 0.34, p=0.002) were associated with decreased odds of clinical trial enrollment, whereas higher KPS (women: 90 vs <80, OR 3.16, p=0.003; men: 90 vs <80, OR 3.15, p=0.002) was associated with increased odds of trial enrollment. Among NIH-designated minority patients, older age (OR 0.66 per 10-year increase, p=0.033) and non-English preferred language (OR: 0.30, p=0.035) were associated with decreased odds of trial enrollment on univariate analysis, but not on multivariate analysis. Among non-minority patients, lack of insurance (OR 0.58, p=0.008) and no chemotherapy treatment (OR 0.25, p<0.001) were associated with decreased odds of trial enrollment, whereas seizure at presentation (OR 1.80, p=0.001), higher neighborhood household income (OR 1.07 per $10,000 increase, p=0.004), higher WHO grade (4 vs 2-3, OR 1.86, p=0.015), higher KPS (90 vs <80, OR 3.21, p<0.0001), and lower extent of tumor resection (80-89% vs 100%, OR 2.16, p=0.047) were associated with increased odds of trial enrollment. Conclusion: Drivers of trial enrollment differed for women and minority patients with glioma. Non-English-speaking minority patients may face additional barriers to trial enrollment requiring targeted interventions. Our findings can revitalize and tailor efforts to recruit women and minority patients to therapeutic clinical trials in neuro-oncology. Citation Format: Mulki Mehari, Gayathri Warrier, Sheantel Reihl, Abraham Dada, Aymen Kabir, Mikias Negussie, Cesar Nava Gonzales, Ugonma Chukwueke, Alyx Porter, Shawn Hervey-Jumper. Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma [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 1006.

Abstract TP229: Stroke Rate and Associated Factors in Individuals With Primary Brain Gliomas and Brain Radiation Therapy: A Retrospective Cohort Study

Background/Objectives: The risk of stroke in individuals with brain gliomas may be increased due to several possible factors including chemotherapy, radiation-induced toxicity, and concomitant vascular risks. We report on the stroke rate and associated factors following brain tumor diagnosis and radiation therapy. Design: This is a retrospective cohort study, from a single tertiary academic brain tumor center, of patients with brain gliomas diagnosed between 2004-2021 who received brain radiation therapy during their treatment. Chi-square test was used to calculate the odds ratios. Results: Among a total of 912 patients with primary gliomas who received radiation therapy, stroke subsequently occurred in 93 patients (10.2%). Strokes were ischemic in 72.0% (N=67), intracerebral hemorrhage (ICH) in 25.8% (N=24), and subarachnoid hemorrhage in 2.2% (N=2). Individuals who sustained a stroke were 44.1% female and had a mean age of 54.2 years (range 21-84) at the time of stroke diagnosis. Of those who had a stroke, 64.5% (N=60) were also taking bevacizumab at the time of stroke. Median time from initiation of radiation therapy to stroke was 653 days (range 0-3788). Median radiation dose was 5940 cGy (range 1800-6000). The following factors were associated with a higher odd of having a stroke: radiation necrosis (OR 4.51; 95% CI 1.98-10.29, P=0.0003); hypertension (OR 1.82; 95% CI 1.17-2.82, P=0.008); hyperlipidemia (OR 5.50; 95% CI 3.45-8.78, P<0.0001); and diabetes (OR 2.19; 95% CI 1.25-3.84, P=0.007). Among stroke patients, 80.6% had strokes on the same side as radiation therapy. Those who were taking bevacizumab were more likely to have an ICH (31.7% vs. 15.1%, OR 2.60, 95% CI 0.87-7.77, P=0.09) as compared to other stroke types. Conclusions: Individuals with primary brain gliomas undergoing radiation therapy who were subsequently diagnosed with a stroke had higher rates of comorbid vascular risk factors and radiation necrosis.

Abstract A080: Engagement and experience with clinical trial counseling in adult glioma patients: A single institution, mixed-methods study

Abstract Introduction: Participation in a clinical trial offers the promise for high-quality medical care for patients with cancer, particularly glioma; however, disparities exist in the accrual of underserved patient populations, including minority patients. A multi-pronged approach for increasing the accrual of underrepresented patients to meet NIH-defined benchmarks includes optimizing patient trial education and counseling. This study seeks to assess the perceptions of the trial counseling process and barriers to trial enrollment among a diverse population of patients with low-and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center from 2020 to 2022 participated in supervised interviews and completed a validated survey, Service Evaluation of Patient Experience of Clinical Trials and Factors Influencing Clinical Trial Entry (SPECIFIC). Thematic analysis, descriptive statistics, and Chi-square tests were used for analysis. Results: One hundred and thirty-six patients completed the SPECIFC questionnaire. There were 44 trial participants (TPs), and 92 non-trial participants (NTPs). Compared to NTPs, TPs were on average 49.8 years old (NTPs 54.6, p=.11) and white (86.3% v. 70%, p=.009). Four core themes emerged from patient perspectives, either as facilitators or barriers to clinical trial participation: 1) Cancer Awareness/Knowledge of Scientific Research 2) Flexible Lifestyle/Affordability 3) Consistency with Values/Faith/Belief System 4) Existing Family/Community Support. Both TPs and NTPs overwhelmingly agreed that clinical trials help improve treatments for cancer. However, compared to 100% of TPs, only 57% of NTPs believed trials offered the best treatment available (p=.001). TPs were more likely to be referred to our institution specifically to enroll in a trial (p=.003), have done prior research on specific experimental treatments (p=.002), have had more than two appointments with the neurosurgeon/neuro-oncologist, and report receiving the most counseling directly from an MD level provider (p=.01). When evaluating the trial counseling process, 93% of TPs reported willingness to consent the same day, but 5% endorsed feeling pressure to participate. TPs were satisfied with the quality of the patient information sheet, with 88% rating the information sheet as good or excellent and 88% reporting that the information sheet was easy to understand. While 14% of TPs believed the information sheet was too long, 27% and 41% desired more information about the trial therapeutic and participation requirements, respectively. Conclusion: Overwhelmingly, trial participants were confident in the information they received and were willing to begin clinical trial enrollment on the same day of receiving information. Interventions to improve the quality and equitable delivery of patient trial education must be paired with other validated multi-dimensional strategies to reach target accrual benchmarks of underserved patient populations to therapeutic clinical trials. Citation Format: Mulki Mehari, Sheantel Reihl, Ramin Morshed, Jasleen Kaur, Mikias Negussie, Ugomma Chukwueke, Alyx Porter, Valy Fontil, Shawn Hervey-Jumper. Engagement and experience with clinical trial counseling in adult glioma patients: A single institution, mixed-methods study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A080.

TMIC-21. SPHINGOSINE-1-PHOSPHATE RECEPTOR 3 (S1PR3) IN THE GLIOBLASTOMA TUMOR MICROENVIRONMENT MAY PLAY A ROLE IN IMMUNOSUPPRESSION

Abstract Glioblastoma remains an intractable clinical problem with few efficacious treatments and poor patient outcomes because of the challenge in treating the tumor cells that have invaded into the normal brain. These invasive tumor cells typically remain after standard-of-care surgical resection and likely persist to generate recurrent tumors. In our previous studies of the glioma tumor microenvironment (TME), we identified sphingosine-1-phosphate receptor 3 (S1PR3) as upregulated in glioma TME regions with increased fluid flow. In order to efficiently study S1PR3 in the normal brain/ glioblastoma tumor interface, we engaged the Wake Forest University Brain Tumor Center of Excellence to construct a tissue microarray (TMA) including glioblastoma tissue cores specifically of the normal brain/ tumor interface as determined by pathologist review. The TMA included FFPE tissue cores from 42 GBM patients (average age 67.7 ± 10.9 years, 25 male, 17 female). Immunohistochemistry to detect S1PR3 was performed using an antibody that targets the amino-terminal domain followed by spatial profiling using neuroscience, neuroinflammation, and immune antibody panels (Akoya Biosciences). Preliminary analyses of the spatial profiling revealed 34 evaluable tissue cores, with no difference in the percentage of neurons, glial cells, vascular cells, or T cells between the S1PR3 positive and negative cores, however a significant difference in the percentage of M1 macrophages/ antigen presenting cells was found between the two groups (S1PR3-positive 0.646 ± 0.569%, n=13; S1PR3-negative 2.95 ± 3.28%, n=21, p=0.0178 two-tailed t-test. These findings suggest that the presence of S1PR3 may be associated with reduced M1 macrophages/ antigen presenting cells and therefore S1PR3 may contribute to glioblastoma tumor associated immunosuppression.

INNV-30. DEVELOPMENT AND IMPLEMENTATION OF A NOVEL, BRIEF NEUROCOGNITIVE SCREENING AND REHABILITATION SERVICE IN A CLINICAL NEURO-ONCOLOGY SETTING

Abstract BACKGROUND Although neurocognitive dysfunction is common in patients with brain tumors, existing screening methods (e.g., Montreal Cognitive Assessment) lack sensitivity for detecting neurocognitive difficulties. Moreover, existing neurocognitive screens provide only modest clinical utility for characterizing individual neurocognitive strengths/weaknesses critical for treatment planning. METHODS Beginning in February 2023, the Alvord Brain Tumor Center at the University of Washington Medical Center (UWMC) implemented the Rehabilitation Neuropsychology Screening Service (RNSS). The RNSS is an internal outpatient service staffed by a rehabilitation neuropsychologist from the Department of Rehabilitation Medicine at UWMC. Neuro-oncologists and advanced practice providers placed referrals to the RNSS based on clinical need and cognitive symptoms. On average, 1-2 referrals per week were received. RESULTS Patients referred to the RNSS have included those with high- and low-grade gliomas with varying degrees of everyday functioning status (e.g., independence at home, goals to return to work/school) and neurocognitive symptoms. The goal of the RNSS is to explore inclusion and exclusion criteria that optimize patient experience and outcomes while maximizing outreach to patients in need of neurorehabilitation services. The RNSS includes brief, repeatable neuropsychological testing (90-minutes) and patient-reported outcomes (e.g., mood, quality of life). A separate feedback appointment is then held with patients to describe personal neurocognitive strengths/weaknesses and provide neurorehabilitation strategies or rehabilitation resources/referrals based on findings. In select cases, RNSS has served as a triage stage for stepped care towards referrals to a more comprehensive neuropsychological evaluation. CONCLUSION The development and implementation of this novel approach to neurocognitive screening and rehabilitation, including the rationale, workflow of patient care, and expected outcomes, is described. With additional quality assessment/improvement, the RNSS may serve as a model for integrating neurorehabilitation services into existing neuro-oncology clinics, and may be an additional guide for patients and families towards neurorehabilitation resources and education.

Treatment Complications of Venous Thromboembolism in Patients with Central Nervous System Tumors

Introduction: In the last decade, landmark studies have been conducted in patients with cancer-associated venous thromboembolism (CA-VTE), helping to guide treatment decisions of anticoagulant therapy. Although these trials outlined new treatment opportunities, they either completely excluded or included only a small number of patients with primary brain tumors or central nervous system (CNS) metastasis. Additionally, there are very limited data on complication rates of anticoagulants in patients with spinal metastasis. Consequently, there is an ongoing knowledge gap for safe and effective anticoagulation options for patients with acute VTE in this high-risk patient population. Methods: We conducted a single institution IRB-approved retrospective study evaluating the rates of hemorrhage and recurrent thromboses in patients with CA-VTE and a diagnosis of a primary brain tumor or brain and/or spinal metastases. Our investigation was conducted at The Preston Robert Tisch Brain Tumor Center and the Center for Brain and Spine Metastasis at Duke between 2017 and 2021. The cohort was built through identifying patients by ICD-10 codes searched within the electronic medical records. Inclusion criteria consisted of patients ≥ 18 years of age, a history of confirmed primary brain tumor or brain and/or spinal metastases prior to VTE, treatment with anticoagulation or an inferior vena cava (IVC) filter, and followed up at least once since starting treatment beyond 1 month of VTE diagnosis . We compared complication event rates and the anticoagulant selected for treatment. Data obtained included patient demographic information, medical and social histories, cancer-related history, VTE history and treatment, recurrent thrombotic and hemorrhagic events, and patient mortality. Results: We identified 3584 total patients during the study timeframe. Eight hundred and twenty-five patients were included and 2759 were excluded for not meeting our inclusion criteria. Of the 825 included patients, 766 were treated with either apixaban (348/766; 45%), rivaroxaban (178/766; 23%), or enoxaparin (240/766; 31%) for their initial CA-VTE (Table 1). The other 59 patients were treated with another anticoagulant or received an IVC filter without anticoagulation. The median age for our cohort of 766 patients was 61.0 (20.0 - 87.0). There was no significant statistical association between relevant past medical histories of obesity or hypertension among the 3 anticoagulant groups. There was no significant statistical association between the 3 anticoagulant cohorts and primary brain tumors, or brain and/or spinal metastases ( p= 0.06). Although it trended towards significance, there was no statistically significant difference in the proportion of patients receiving anti-VEGF inhibitors at time of initial VTE among the 3 anticoagulant cohorts ( p = 0.052). When looking at our primary outcomes of recurrent thrombosis, major hemorrhage, or clinically relevant non-major bleeding, 171 individual patients experienced a total of 188 unique events that occurred during treatment with apixaban, rivaroxaban, or enoxaparin (Table 2). Of the 171 unique patients, enoxaparin use was the most common (80/171; 47%), followed by apixaban (61/171; 36%), rivaroxaban (28/171; 16%), and a small percentage (2/171; 1%) were treated with a combination of apixaban, rivaroxaban, or enoxaparin during their unique event. When excluding the 2 patients with multiple anticoagulant treatments, there was no statistical difference among anticoagulant rates and any event of recurrent thrombosis, major hemorrhage, clinically relevant non-major bleeding, or any multiple events ( p = 0.07). Conclusions: We present the largest unique data set comparing anticoagulant use in a known high-risk patient population of primary brain tumors, brain and/or spinal metastases. Our data demonstrate up to 22% of patients with CA-VTE and primary brain tumors, brain and/or spinal metastases have a subsequent hemorrhagic or recurrent thrombotic complication during treatment with apixaban, rivaroxaban, or enoxaparin for their initial event. However, our data did not demonstrate a statistically significant difference in complication rates between these 3 anticoagulants. These findings indicate a need for future large-scale prospective investigations to determine optimal treatment in this high-risk patient population.

P08.04.B DOES PSYCHO-ONCOLOGICAL CARE AFFECT HEALTH-RELATED QUALITY OF LIFE AND PATIENT AND CAREGIVER SATISFACTION IN IDH WILD-TYPE GLIOMA? - A PROSPECTIVE STUDY

Abstract BACKGROUND Isocitrate dehydrogenase wild-type (IDHwt) gliomas are uncurable primary tumors of the brain and impose a high burden on affected patients and caregivers. In addition to neurological symptoms, changes in cognition and personality are common and should be diagnosed and treated early. About 75% of patients with brain tumors suffer from psychosocial distress at their first consultation. Health-related quality of life (HR-QoL) is significantly reduced by anxiety and negative mood, following glioma diagnosis. Brain tumor diagnosis also affects caregivers negatively. Recent publications show that caregiver and patient satisfaction influence each other, with caregivers generally being less satisfied than patients. In addition to specific tumor and symptomatic therapy, psycho-oncological care is an important element in a comprehensive treatment approach and may lead to increased HR-QoL and patient and caregiver satisfaction. However, there are few prospective datasets focusing on these aspects. MATERIAL AND METHODS We investigated the impact of psycho-oncological care on HR-QoL and patient and caregiver satisfaction in a large brain tumor center. Data from the regional brain tumor registry and electronic medical charts were used to compile the prospective patient cohort. Standardized questionnaires were used to investigate HR-QoL (EORTC QLQ C-30 and BN-20) and satisfaction (EORTC PATSAT-C33). Univariable and multiple linear regression analysis was applied to test the influence of psycho-oncological care on both aspects. RESULTS A homogenous cohort of 61 patients was investigated, of whom 29 (47.5%) received psycho-oncological care. We analyzed 141 EORTC QLQ-C30, 139 EORTC QLQ-BN20, 129 EORTC PATSAT-C33 questionnaires from patients, and 115 EORTC PATSAT-C33 questionnaires from caregivers. We show that patients who received at least one psycho-oncological consultation had significantly worse role functioning (p = 0.001) and a negatively influenced global health status (p = 0.038). Psycho-oncological care had no significant correlation with the satisfaction of patients. Caregivers of patients with psycho-oncological care documented inferior satisfaction with information exchange of doctors (p = 0.036). CONCLUSION We conclude that receiving psycho-oncological care is associated with changes in HR-QoL and patient and caregiver satisfaction. Utmost efforts should be made to integrate intensively and frequently psycho-oncological care on a daily-practice basis. It will be subject of future prospective studies to investigate kind and frequency of interventions that are suited to improve HR-QoL and treatment satisfaction in patients with IDHwt gliomas and their caregivers, and how to complement supportive therapies better to achieve optimal psychosocial outcomes for these patients and their caregivers.

SPCR-12 A PROCESS IMPROVEMENT FOR INCREASING DEPRESSION AND ANXIETY SCREENING IN PATIENTS WITH BRAIN TUMORS

Abstract Anxiety and depression are highly prevalent in patients with brain tumors. These conditions significantly affect quality of life and are associated with worsened survival. The Alvord Brain Tumor Center at UW did not have a process to screen patients for anxiety and depression. In response to this, a quality improvement project was developed to identify barriers and facilitators to mood screening and to introduce a new standard process for screening. We formed an interdisciplinary mood screening committee in the clinic to ensure a collaborative process with each profession’s voice accounted. The new process for mood screening consisted of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) being automatically sent to all return patients’ MyChart accounts 24 hours before their scheduled appointment, repeating up to every six months. Upon completion of the questionnaires, the results would immediately file into the patient’s electronic medical record. The new process was implemented and we collected data from clinic visits over two weeks to determine its impact. Of all patients eligible for screening, 18% completed the screenings as a result of the new screening process, compared to the baseline 15% who had already completed the screenings in the last six months at other clinics within the health system, effectively doubling the number of patients in the clinic with mood screening in the last 6 months. Among those with MyChart accounts, the total response rate to the screenings was 24%. The automaticity of the process will help ensure an ongoing baseline standard for patients to be screened. In the future, an additional process will be developed to ensure that those without access to MyChart have equal opportunity for screening and treatment of mood disorders.

Outcome of glioblastoma patients after intensive care unit admission with invasive mechanical ventilation: a multicenter analysis

PurposePatients with glioblastoma are exposed to severe symptoms and organs failures (e.g., coma or acute respiratory failure), that may require intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). However, only limited data are available concerning the prognosis of patients with glioblastoma receiving IMV. We sought to describe the reasons for ICU admission, and outcomes of patients with glioblastoma requiring IMV for unplanned critical complications.MethodsIn this retrospective analysis, four certified interdisciplinary brain tumor centers performed a retrospective review of their electronic data systems. All patients with glioblastoma admitted to an in-house ICU and receiving IMV between January 2015 and December 2019 were included. Clinical and prognostic factors as well as relevant outcome parameters were evaluated by group comparisons and Kaplan Meier survival curves.ResultsWe identified 33 glioblastoma patients with a duration of IMV of 9.2 ± 9.4 days. Main reasons for ICU admission were infection (n = 12; 34.3%) including 3 cases of Pneumocystis jirovecii pneumonia, status epilepticus (31.4%) and elevated intracranial pressure (22.9%). In-hospital mortality reached 60.6%. Younger age, low number of IMV days, better Karnofsky Performance Status Scale before admission and elevated intracranial pressure as cause of ICU admission were associated with positive prognostic outcome.ConclusionWe conclude that less than 50% of patients with glioblastoma have a favorable short-term outcome when unplanned ICU treatment with IMV is required. Our data mandate a careful therapy guidance and frequent reassessment of goals during ICU stay.

Neurofibromatosis

While the Neurofibromatoses have been observed and classified by their phenotypes for several centuries, their great variability constitutes a considerable challenge in diagnostics and therapy selection. This article focuses on highlighting the three most frequent sub-types NF1, NF2 and NF3. All three NF types are outlined by the following measures: the history of their clinical detection, the typical appearance, the underlying genetic constitution and its consequences, the official diagnostic criteria, the mandatory diagnostic steps and finally the treatment opportunities and specific risks. About 50% of NF patients have a positive family history and the other 50% are the first symptomatic generations and suffer from new mutations. A considerable (unknown) number of patients do not exhibit a complete genetic NF constitution, but have a so-called mosaic sub-form with only a limited number of cells being genetically affected and prone to tumorous changes. The neurofibromatoses are neuro-cutaneous diseases with manifestations at the skin and nervous system, except for NF 3, where the skin and eyes are never affected. Skin and eye manifestations, especially pigmentation disturbances, mostly started early in childhood and adolescence. The underlying genetic constitutions, on chromosome 17 in NF1 and on chromosome 22 in NF2 and NF3, cause a defect in tumor suppressor genes and lead to excessive proliferation of Schwann cells. Major features are tumors of the peripheral nerves, including cranial and spinal nerves leading to tumors with considerable nerve, brain and spinal cord compression and resulting in pain, sensory and motor deficits. A further variable disease feature may be neuropathy with neuropathic pain, related to tumor formation or even independent of it.Although benign by histopathology and growing rather slowly, those tumors often cause progressive neurological deficit and loss of function. Loss of function may be prevented by adequate timing of therapy such as nerve decompression by microsurgical tumor resection or reduction, medication with immunotherapy or radiotherapy in selected cases. To date it is unknown why some tumors remained silent and stable while others progress and show periods of accelerated growth.As a consequence, NF patients need to be accompanied by a specialized interdisciplinary NF team at long-term, with a clear-cut standardized protocol for clinical and imaging controls along with counseling and support in decision-making.Further, NF patients may suffer from reactive depression due to the danger of losing essential neural functions, such as vision or audition or movement. And especially NF1 patients show characteristics of ADHS and other cognitive compromise in at least 50% of cases. As the neurofibromatosis belong to the so-called rare diseases, all patients with a suspicion or diagnosis of NF should get the opportunity to present to an interdisciplinary NF Center, mostly situated at University Hospitals, where competent counseling on the individual disease phenotype may be provided. Here the patients will be informed on the necessary diagnostic steps, their frequency as well as on practical steps in case of acute deterioration. Most NF centers are run by neurosurgeons or neurologists or pediatricians, working in a network with geneticists, neuro-radiologists, ophthalmologists, dermatologists, plastic and general surgeons, psychologists, psychiatrists and social work experts. They participate regularly in neuro-oncological tumor and sarcoma tumor boards, skull base tumor centers, comprehensive hearing centers, and deliver all the treatment opportunities provided by certified brain tumor centers, among those the inclusion in special diagnostic and treatment studies or the contact information to patient support groups.

Does the distance to the cancer center affect psycho-oncological care and emergency visits of patients with IDH wild-type gliomas? A retrospective study.

Malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas impose a high symptomatic and psychological burden. Wide distances from patients' homes to cancer centers may affect the delivery of psycho-oncological care. Here, we investigated, in a large brain tumor center with a rural outreach, the initiation of psycho-oncological care depending on spatial distance and impact of psycho-oncological care on emergency visits. Electronic patient charts, the regional tumor registry, and interviews with the primary care physicians were used to investigate clinical data, psycho-oncological care, and emergency unit visits. Interrelations with socio-demographic, clinical, and treatment aspects were investigated using univariable and multivariable binary logistic regression analysis and the Pearson's Chi-square test. Of 491, 229 adult patients of this retrospective cohort fulfilled the inclusion criteria for analysis. During the last three months of their lives, 48.9% received at least one psycho-oncological consultation, and 37.1% visited the emergency unit at least once. The distance from the cancer center did neither affect the initiation of psycho-oncological care nor the rate of emergency unit visits. Receiving psycho-oncological care did not correlate with the frequency of emergency unit visits in the last three months of life. We conclude that the distance of IDHwt glioma patients' homes from their cancer center, even in a rural area, does not significantly influence the rate of psycho-oncological care.

Strokes in Patients with Primary Brain Tumors After Radiation Therapy: A Retrospective Cohort Study (P3-13.006)

<h3>Objective:</h3> To describe the characteristics and risk factors of patients who suffered strokes after radiation therapy for primary brain tumors. <h3>Background:</h3> Strokes can complicate the treatment of individuals with primary brain tumors due to several possible mechanisms including chemotherapy and radiation-induced toxicity as well as disease-specific etiologies. Little is known about the prevalence and risk factors of stroke in this population. <h3>Design/Methods:</h3> This is a retrospective cohort from a single tertiary academic brain tumor center of patients with primary brain tumors who also received radiation therapy. We report on the prevalence and types of strokes following brain tumor diagnosis and compare the risk factors among those with or without stroke. <h3>Results:</h3> We identified 443 patients with primary brain tumors who had received radiation therapy. 63 patients (14.2%), with 52.4% male and 47.6% female, mean age 57.46 (SD 12.46), were found to have suffered a stroke, 40 being ischemic (63.5%) and 23 hemorrhagic (36.5%), during their treatment course. Patients who had a stroke were more likely to have hyperlipidemia (66.7% vs. 30.6%, OR 4.91, 95% CI 2.78–8.67, P&lt;0.0001), diabetes mellitus (17.5% vs. 8.4%, OR 2.68, 9%% CI 2.67–5.67, P=0.01), hypertension (57.6% vs. 49.6%, OR 1.51, 95% CI 0.88–2.59, P=0.13), and obstructive sleep apnea (9.5% vs. 4.7%, OR 2.25, 95% CI 0.85–5.94, P=0.10). In the patients with stroke, 65.1% were on bevacizumab at the time of the stroke. Of the 62 patients with stroke in known locations, 82% had strokes on the same side as radiation with 53% having strokes in the same location of radiation therapy. <h3>Conclusions:</h3> Patients with primary brain tumors undergoing radiation therapy who were diagnosed with stroke had higher rates of comorbid vascular risk factors, with statistically significantly higher odds of hyperlipidemia and diabetes and more often had strokes on the same side and location as their radiation therapy. <b>Disclosure:</b> Dr. Ryan has nothing to disclose. Dr. Sugita has nothing to disclose. Eric Lipp, 10512 has nothing to disclose. Dr. El Husseini has nothing to disclose. Dr. Peters has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Vivacitas Oncology. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sapience. Dr. Peters has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NuVox Therapeutics. Dr. Peters has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Cordance Medical. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ONO Pharmaceutical. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Blue Earth Diagnostics. The institution of Dr. Peters has received research support from Novocure. The institution of Dr. Peters has received research support from Biomimetix. The institution of Dr. Peters has received research support from Servier. The institution of Dr. Peters has received research support from Varian. The institution of Dr. Peters has received research support from Sapience. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving as a Educational Lecturer with Eisai.

Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital.

The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.

The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients

Abstract Background Glioblastoma is an aggressive brain cancer with no possibility for cure. Treatment and survival have only improved slightly since 2005 when the current regime was implemented. The limited improvements in the treatment of glioblastoma may reflect our poor understanding of the disease. We hypothesize that systematically collected translational data will improve knowledge and hereby treatment. Methods We have been performing whole exome sequencing in glioblastoma tumor tissue since 2016 and whole genome sequencing (WGS) since 2020 with the aim of offering experimental treatment. Results We have sequenced 400+ GBM patients and from these 100+ are paired tumor samples from relapse surgery. To develop genomic profiling and to increase the information on each patient´s contribution, we have initiated the Neurogenome study as of June 2022. The Neurogenome protocol is a national, comprehensive, translational, and omic protocol. It is a continuation of 2 previous protocols from 2016 and forth in our department, but with more substudies added, focusing on the translational and clinical utility. We collect and analyze data from an out-patient clinic in a systematic approach to a number of subprojects ranging from basic science to applied clinical science, including clinical trials. Conclusions The protocol will act as a backbone for future projects in the national research center, Danish Comprehensive Cancer Center—Brain Tumor Center with the overall aim to select eligible patients for experimental treatment based upon genomic alterations. The article will present the Neurogenome setup and a presentation of selected projects that are based upon inclusion.

NQPC-15 DEVELOPMENT OF BRAIN TUMOR SURVIVORSHIP PROGRAM

Abstract Introduction Brain tumor patients suffer from psychological distress and various sequelae from the moment they are diagnosed with a brain tumor, during and after treatment. Although the number of brain tumor survivors is increasing as a result of improved treatment outcomes for brain tumors, the support system is not sufficient. We, in collaboration with the University of California San Francisco Brain Tumor Center, have established a multidisciplinary professional staff of physicians, nurses, pharmacists, rehabilitation therapists, nutritionists, and social workers to support brain tumor patients, their families, and care givers. The brain tumor survivorship program is designed to support brain tumor patients, their families, and caregivers. This report describes their efforts. Methods This program started in December 2021. We asked relevant departments in the hospital to cooperate with the program. In July 2022, the “Brain Tumor Survivorship Care Program 360” website was opened to the public. Results As of the end of August 2022, there were 9 participants, of which 7 were patients and 2 were care givers. Of these, two were patients being treated at other hospitals. Various information is provided on the website. Web meetings are also held to provide a place where participants can communicate directly with each other. When participants were asked about their requests for the program, many of them requested information on treatment, public services, and a place for communication among patients. Discussion Brain tumor patients face not only life-threatening but also painful symptoms associated with the impairment of their own physical motor and cognitive functions, which they had possessed until then. Through the survivorship program, we will continue to scientifically examine and develop a support system for the various survival-related issues that brain tumor patients and their families experience from diagnosis to the end of life.

Surveillance of Long-Term Complications after Brain Irradiation in Adult Brain Tumor Survivors

<h3>Purpose/Objective(s)</h3> As a consequence of treatment, brain tumor survivors may experience chronic symptoms, comorbidities, and psychosocial issues that impact their overall well-being, daily functioning, and quality of life. Commonly identified complications include cognitive dysfunction, vasculopathy, endocrinopathy, ophthalmic sequela, ototoxicity, physical disability, sleep disturbance, mood disorder, unemployment, financial toxicity, secondary malignancy, and care partner fatigue. While there are guidelines for childhood survivors of brain tumors, there are no standardized guidelines for screening, monitoring, and managing treatment-related complications for adult brain tumor survivors. This abstract outlines the results of our expert recommendations from a multidisciplinary panel of healthcare professionals for assessing, screening, and providing appropriate interventions during neuro-oncology survivorship to improve quality of life and health outcomes. <h3>Materials/Methods</h3> We examined the Children's Oncology Group Guideline (COG) recommendations as a foundation to establish guidelines for adult brain tumor survivors. The committee focused on intracranial brain tumors. We performed a literature search using PubMed, EMBASE, and CINAHL databases. The committee structured meetings based on the COG guidelines supplemented by the literature available for adult brain tumor complications. While reviewing the literature, experts in radiation oncology, neuropsychology, endocrinology, vascular neurology, otolaryngology, ophthalmology, sleep medicine, and rehabilitation medicine were invited to discuss and provide their perspectives and recommendations on screening and management of adult brain tumor survivors. <h3>Results</h3> Prior work identified common complications among brain tumor survivors include cognitive dysfunction, vasculopathy, endocrinopathy, ophthalmic sequela, ototoxicity, physical disability, sleep disturbance, mood disorder, unemployment, financial toxicity, and secondary malignancy. The Alvord Brain Tumor Center Survivorship Committee recommends routine screening using laboratory testing, subjective assessment of symptoms, and objective evaluations for patients with malignant brain tumors during patient clinical visits to appropriately monitor the complications of brain tumor treatments. <h3>Conclusion</h3> On-going thorough symptom assessment during survivorship is required due to the variability of onset and progressive nature of the medical complications of treatment. Early detection of the described complications optimizes health promotion and maximizes the quality of life. Effective monitoring and treatment should involve collaboration with primary care providers and may require referral to other specialties and support services to provide patient-centered care during neuro-oncology survivorship.

P13.03.A Radiomics for the non-invasive assessment of the PDL-1 expression in patients with non-small cell lung cancer brain metastases

Abstract BACKGROUND The expression level of programmed cell death ligand 1 (PDL-1) might be an indicator for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As intra-tumoral differences and discrepancies between the PDL-1 expression in the primary tumor and the brain metastases may occur, a method for a reliable non-invasive assessment of the intracranial PDL-1 expression would be of clinical value. We evaluated the potential of MRI radiomics for a non-invasive assessment of the PDL-1 expression in patients with NSCLC brain metastases. PATIENTS AND METHODS Fifty-three patients with brain metastases from NSCLC from two university brain tumor centers (group 1, 36 patients; group 2, 17 patients) underwent tumor resection with subsequent immunohistochemical assessment of the PDL-1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction from T1-weighted contrast-enhanced MRI, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using five-fold cross validation. Finally, the best performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses. RESULTS An intracranial PDL-1 expression was found by immunohistochemistry in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified tumor volume as a significant clinical feature for PDL-1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature including tumor volume yielded an AUC of 0.83 ± 0.18 in the training data (group 1). Finally, the classifier achieved an AUC of 0.84 in the external test data (group 2). CONCLUSION The developed radiomics classifiers allows a non-invasive assessment of the intracranial PD-L1 expression in patients with NSCLC brain metastases with a high diagnostic performance.