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INTRODUCTION: Despite an increasing aging population, older adults (≥ 65 years) with primary brain tumors (PBTs) are not routinely assessed for geriatric vulnerabilities. Recent reports of geriatric assessment (GA) in patients with glioblastomas demonstrated that GA may serve as a sensitive prognosticator of overall survival. Yet, current practice does not include routine evaluation of geriatric vulnerabilities and the relevance of GA has not been previously evaluated in broader cohorts of PBT patients. The objective of this descriptive study was to assess key GA constructs in adults with PBT dichotomized into older versus younger groups. MATERIALS AND METHODS: A cross-sectional analysis of data collected from 579 participants with PBT recruited between 2016 and 2020, dichotomized into older (≥ 65 years, n = 92) and younger (≤ 64 years, n = 487) from an ongoing observational trial. GA constructs were evaluated using socio-demographic characteristics, Charlson Comorbidity Index (CCI), polypharmacy (>5 daily medications), Karnofsky Performance Status (KPS), Neurologic Function Score (NFS), and patient-reported outcome assessments including general health, functional status, symptom burden and interference, and mood. Descriptive statistics, t-tests, chi-square tests, and Pearson correlations were used to evaluate differences between age groups. RESULTS: Older participants were more likely to have problems with mobility (58% vs. 44%), usual activities (64% vs 50%) and self-care (38% vs 26%) compared to the younger participants (odds ratios [ORs] = 1.3–1.4, ps

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Purpose:To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma.Patients and Methods:This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden.Results:Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12–24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2_5347T>C (rs2470890) polymorphism was associated with higher AUCinf value.Conclusions:Zotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib.

Cognitive reserve (CR) has been proposed to account for functional outcome differences in brain pathology and its clinical manifestations. The purpose of our paper is to systematically review the effects of CR on cognitive outcomes in individuals with neurodegenerative and structural CNS diseases. We performed a systematic search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsychInfo using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Seventeen studies met the predetermined inclusion criteria and were selected for review. Education level was the most commonly used measure for CR, and various neuropsychological tests were used to measure cognitive outcomes. Regardless of the CNS disease of the individuals, almost all of the studies reported a positive association between CR and cognitive outcomes when they were evaluated cross-sectionally. However, when evaluated longitudinally, CR had either no effect on, or a negative association with, cognitive outcomes. Based on studies across a broad spectrum of CNS diseases, our findings suggest that CR may serve as a predictor of cognitive outcomes in individuals with CNS diseases. However, studies to date are limited by a lack of imaging analyses and standardized assessment strategies. The ability to use a standardized measure to assess the longitudinal effects of CR may allow for the development of more targeted treatment methods, resulting in improved disease outcomes for individuals.

BACKGROUND PBT patients experience high levels of distress and anxiety symptoms at the time of neuroimaging, yet few non-pharmacological interventions are available. This phase 2 clinical trial interim analysis explored feasibility of a VR relaxation intervention for a PBT population. METHODS PBT patients seen at NIH were recruited to participate in this single arm trial conducted via telehealth. English-speaking, adult patients with upcoming neuroimaging who can self-report symptoms and have reported distress on previous MD Anderson Symptom Inventory-Brain Tumor assessments were eligible. Exclusion criteria include recent surgery or seizures, anxiety disorders, nausea, or visual deficits. The primary intervention consisted of a brief VR session done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention, as well as 1 week and 4 weeks later, with self-directed VR use over 1 month. A qualitative phone interview was also completed to assess patient satisfaction. RESULTS Fifty-five patients were screened and approached with 40 (73%) responding to initial reach-out and 20 ultimately enrolling (9 declines, 11 screen fails). Decline reasons included: no distress/anxiety (30%), treatment-related toxicities (11%), and unknown (59%). Seven (64%) failed screening due to exclusionary anxiety disorders (36% GAD, 18% PTSD, 9% claustrophobia). Of those enrolled, 65% were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS ( > 80), 65% had high-grade tumors, and most were on active treatment. All enrolled patients completed the VR intervention and participation period, PROs questionnaires, weekly check-ins, and qualitative interview. Most patients (90%) reported frequent VR use with 7 mild adverse effects reported (headache, dizziness, nausea, neck pain). CONCLUSION These findings suggest that this intervention is feasible for this population with high enrollment and study completion, though incidence of anxiety disorders was higher than anticipated and a comprehensive evaluation of this cohort is planned.

Sleep-wake disturbances are among the most common and severe symptoms in primary brain tumor (PBT) patients. Currently, no studies have quantified their physiological sleep measurements or compared these assessments to established patient reported outcome measures (PROs). Smart wearable devices, such as Fitbits, continuously monitor patient behaviors at home and provide detailed physiological measurements of sleep, activity, and heart rate. We hypothesized that smart wearable devices can accurately determine physiological sleep disturbances and circadian disruptions and will complement established PROs in a PBT patient population. This observational, cross-sectional trial monitors sleep and circadian rhythm variables using Fitbit smart wearable devices worn for 1 month. Additionally, participants will answer PROs questionnaires (PROMIS Sleep Disturbance and Sleep Related Impairment-Short Forms, Sleep Hygiene Index, Morningness-Eveningness questionnaire, and Consensus Sleep Diary) at study entry and during the last week on-study. The present study is a planned interim analysis of 54 patients to assess feasibility, including evaluation of enrollment, attrition, study parameter completion and data missingness. 73 PBT patients were screened and approached. Of these patients, 54 (74%) were enrolled on study and 19 (26%) declined participation (8 lacked interest, 3 discomfort wearing watches, 3 lacked smart phone, 2 unable to wear device at work, 2 unable to attend consent calls, 1 pregnancy and 1 cognitive complication). The accrued patients were 56% male, 56%³ 50 years of age, and 81% had a KPS³ 90. Patients represented different stages of treatment: 6% of patients were newly diagnosed, 24% on active treatment (11% 1st recurrence, 13% 2nd recurrence), and 70% were on imaging surveillance. Feasibility was confirmed as there were no deviations reported and 100% of PROs and study timepoints completed. Quantified Fitbit data including percent time worn and physiologic sleep parameters will be reported. Study enrollment for efficacy measures continues.

BACKGROUND Precision health approaches to managing symptom burden in primary brain tumor (PBT) patients are imperative to improving patient outcomes and quality of life. Network Analysis (NA) identifies complex symptom co-severity patterns across large patient cohorts. Unsupervised clustering unbiasedly stratifies patients into clinically relevant subgroups based on symptom patterns. This is the first study to use NA and unsupervised clustering to explore PBT patients’ clinical and demographic determinants of symptom burden. METHODS Symptom severity data reported using the MDASI-BT from a two-institutional cohort of 1,128 PBT patients was analyzed. Gaussian Graphical Model networks were constructed for the entire cohort and for subgroups identified by unsupervised clustering. Network characteristics were analyzed and compared using permutation-based statistical tests. RESULTS NA on the entire cohort revealed that the majority of PBT patients experience symptoms on four core dimensions that drive overall symptom burden: cognitive, physical, focal neurologic, and affective. These dimensions substantially overlap with factor groupings defined during initial construct validation of the MDASI-BT. Fatigue/drowsiness scored the highest in all network centrality measures, indicating a pivotal role in the symptom experience. Unsupervised clustering identified four patient subgroups: PC1 (n = 683), PC2 (n = 244), PC3 (n = 92), and PC4 (n = 109). Moderately accurate networks could be constructed for PC1 and PC2, but not for PC3 and PC4 due to their small size. The PC1 network closely resembles the all-patient network, and these patients have the highest interference scores among the subgroups with fatigue/drowsiness as the primary driver. PC2 represents an older subgroup in which cognitive symptoms drive symptom burden. CONCLUSIONS This novel study identified clinically relevant subgroups of patients with unique symptom burdens. With further validation, our approach may inform more personalized and effective symptom management by identifying symptoms to prioritize for targeting in individual patients.

High-grade gliomas (HGG) are rare brain tumors that cause disproportionate suffering and mortality. Palliative care, whose aim is to relieve the symptoms and stressors of serious illness, may benefit patients with HGG and their families. In this review, we summarize the extant literature and provide recommendations for addressing the symptom management and communication needs of brain tumor patients and their caregivers at key points in the illness trajectory: initial diagnosis; during upfront treatment; disease recurrence; end-of-life period; and after death during bereavement.Patients with HGG experience highly intrusive symptoms, cognitive and functional decline, and emotional and existential distress throughout the disease course. The caregiver burden is also substantial during the patient's illness and after death. There is limited evidence to guide the palliative management of these issues. Palliative care is likely to benefit patients with HGG, yet further research is needed to optimize the delivery of palliative care in neuro-oncology.

BACKGROUND Financial toxicity (FT) refers to the negative financial impact of cancer. Research exploring FT in patients with CNS tumors is limited to more common diagnoses or within single institutions. Total income, work interference and symptom burden are all key parameters when investigating FT in patients with rare CNS tumors. METHODS A web-based study of 210 participants’ responses to financial, clinical, symptom burden (MDASI-BT/MDASI-SP), depression and anxiety (PROMIS-Depression/Anxiety), work interference (SF-36) and general health status (EQ-5D-3L) is reported using descriptive statistics and tests of associations. RESULTS Patients were white (93%) employed (48%) females (72%), with median age of 47 (19-75). The most common diagnosis was ependymoma (80%). Original tumor location was the brain in 83 (40%) and spine in 115 (55%). Median time from tissue diagnosis was 48 months (0 – 402). Income was lower than the poverty level in 6% and lower than the median U.S. in 23%. A change in work due to their tumor was reported by 60%, with the majority stopping work (31%). One-third reported lack of access to health-care services and 10% required home care services. Difficulty walking was reported by 42% and difficulty in performing activities due to physical health by over 60%. Anxiety and depression scores aligned with the average for the U.S. population; however, 21% were taking antidepressants and 42% reported not being able to complete work or activities due to depression. Half of all patients reported moderate-severe pain, fatigue, and weakness with higher symptom burden and depression associated with change in work status (p < 0.003). CONCLUSION Patients with rare CNS tumors report an impact of their tumor diagnosis on activities/work patterns, with an associated higher symptom burden. Future studies exploring financial impact in patients with rare CNS tumors and targeted programs to address these outcomes are needed.

Glioblastoma (GBM) is the most aggressive primary brain malignancy with < 45% living a year beyond diagnosis which drops to 7% at five years. However, there have been reports of long-term survivors (LTS) living three to ten years beyond diagnosis. Few studies have reported on molecular factors in tumors from LTS cohorts. We identified GBM (IDH1/2 wildtype) patients living at least 3 years post diagnosis (N=25), including 16 with pre-treatment tumor tissue, from our Natural History Study. Available pre- or post-treatment tumors were analyzed with targeted panel sequencing and methylation analysis for classification, MGMT promoter status and copy number changes. Classical clinical prognostic features such as limited resection or older age did not preclude long-term survival as patients with tumor biopsy (n=1) or subtotal resection (n= 5) and patients > 60 were included in the LTS cohort. Furthermore, tumors with molecular features typically associated with poor prognosis were also in this GBM LTS group. MGMT promoter was unmethylated in 17% of tumors; EGFRvIII mutation in 13%, EGFR amplification in 33%, CDKN2A homozygous loss in 30% and complete chromosome 7 gain with 10 loss in 55%. Additionally, the methylation classifier found a higher-than-expected incidence of mesenchymal tumors (29%) and RTK II (57%). Tumors had a higher percent of TP53 mutations (44%) but lower pTERT (76%) compared to TCGA. These data suggest an individual patient’s prognosis cannot easily be predetermined based on classical clinical and molecular data. This underscores the need for further analyses to discover additional factors leading to their unexpected, prolonged survival and elucidate the role of factors typically associated with poor prognosis. Future work will include RNA-sequencing and germline whole genome sequencing to determine tumor specific gene expression and identify any possible genomic alterations that confer improved survival.

SIGNIFICANCE AND AIMS Financial toxicity (FT) after a cancer diagnosis is the consequence of decreased earnings and increased spending. In patients with primary central nervous system (PCNS) tumors, the correlation between FT and factors such as symptom burden, psychological distress, and health-related quality of life has not been extensively studied. We assessed employment status and several patient illness factors in a PCNS tumor cohort. METHODS Patient and disease characteristics and patient-reported outcomes (PROs) were collected from adults diagnosed with PCNS tumors between 9/2016-12/2019. Descriptive statistics and regression analyses were used to describe PROs. RESULTS Of 277 patients, 77 (28%) reported being unemployed due to tumor diagnosis. They reported difficulty walking (64%) and performing usual activities (64%). This group had lower general health status (p< 0.001) and higher tumor-related symptom severity (p=0.004) than employed patients. Unemployed patients reported high symptom burden with an average of 6 moderate-severe symptoms for those with brain tumors and 10 for those with spine tumors. Both brain and spine tumor patients who were unemployed reported increased mood-related interference (p=0.020), as well as moderate-severe anxiety (30%) and depression (25%) compared to employed patients (15% vs 8%, respectively). Unemployed brain tumor patients reported worse scores in cognitive and neurologic symptom subscales (p< 0.001). CONCLUSIONS AND IMPLICATIONS These data provide indirect evidence that financial toxicity that correlates with high symptom burden across several domains and lower health-related quality of life. Future research work will include the COST questionnaire to further evaluate the implications of FT in the PCNS tumor patient population.

INTRODUCTION Standard and experimental therapies for patients with rare CNS tumors are scarce. Nivolumab (PD-1 inhibitor) is approved for several non-CNS cancers. This ongoing Phase II trial (NCT03173950) will determine the efficacy of nivolumab in adults with recurrence/progression of one of 11 selected rare primary CNS tumors. Efficacy is measured by Disease Control Rate (DCR; confirmed CR/PR or durable SD for ≥ 6 months) in 2 cohorts: heavily and non-heavily pretreated patients (heavily pretreated: ≥ 3 prior therapies; non-heavily pretreated: ≤ 2). We report efficacy and safety results of a preplanned interim analysis in the heavily pretreated cohort. METHODS Eligibility includes recurrence/progression of an eligible tumor; age ≥ 18 years; tumor tissue available for histopathology, molecular and immune profiling; KPS ≥ 70; and no steroids at study entry. A total of 150 evaluable patients will be enrolled (75 to each cohort). Prior therapies include radiation and/or standard or investigational drugs. Nivolumab treatment is 240 mg IV every 2 weeks (4 doses); then 480 mg every 4 weeks (14 additional doses). Interim analysis was planned when sample size reached 32 in each cohort. RESULTS As of March 10, 2021, DCR exceeded the minimum required for interim analysis in the heavily pretreated cohort. Among 30 patients, 4 achieved SD > 6 months (medulloblastoma, anaplastic ependymoma, myxopapillary ependymoma, metastatic atypical meningioma). Safety profile (related AEs): grade 3 = 7; grade 4 = 1. Most frequent grade 3-5 AEs regardless of attribution: tumor progression (6); anemia, hydrocephalus, lymphopenia (3 each); cerebral edema, headache (2 each). CONCLUSION DCR exceeded the “go” boundary (i.e., > 2) in the heavily pretreated cohort. Nivolumab showed safety profile consistent with other studies. This cohort will continue to stage 2 and complete total accrual of 75 patients. The trial is currently being expanded to 10 additional sites across the BTTC/NCI-CONNECT consortium.

BACKGROUND Participation in mentorship programs for early career physicians is crucial to developing key skills and professional networks, but availability and opportunities for mentorship may be hampered by racial, ethnic and gender leadership disparities in medicine. A 6-month virtually facilitated peer mentorship program for women and diverse early career faculty was developed and piloted through the Society for Neuro-Oncology (SNO) Women & Diversity Committee. METHODS We designed and conducted a 6-month pilot open to SNO’s multidisciplinary early career members, leveraging peer-mentoring sessions with mid-to late-career physician mentors. A curriculum with online resources was provided and group assignments were based on time-zones and interests. Pre- and post-participation surveys assessed mentee experience and descriptive statistics assessed participant demographics and survey results. Results/ CONCLUSION Twenty mentee applicants participated in 5 groups. Mentees were 90% women, 60% from diverse racial and ethnic backgrounds. Most were aged 31-40 (75%) and junior faculty (50%) in neuro-oncology (65%). Five mentors (2 female) practiced either neuro-oncology (3), neurosurgery (1) or radiation oncology (1). The proportion of mentees with a signature talk increased from 15% to 71% during the pilot. A large majority (64%) reported a positive impact of the program on their profile, career and networking, and reported participation was worthwhile (86%), and worth recommending to others (93%). Feedback themes included personal growth, peer support, networking, job opportunities, desire for late career female mentors, and scheduling constraints. The virtual environment during a global pandemic allowed participants to connect, creating a venue to discuss topics such as work-life balance, burnout, and self-advocacy. We did not have 100% post pilot follow up despite multiple attempts, limiting complete understanding of the pilot. This virtual mentorship pilot program proved feasible and of value in development of early career women and diverse individuals. A resource toolkit has been designed to scale and diffuse.

BACKGROUND Seizures are a common symptom in patients with CNS tumors. The RANO-Seizure Control Composite Index (RANO-SCCI) was developed to monitor seizures over time by patients and clinicians. We describe the use of the RANO-SCCI as part of the NCI NOB-Natural History Study. METHODS Patients completed a RANO-SCCI prior to their clinic appointment with results shared with clinicians who then completed a RANO-SCCI as part of the same appointment. Seizure reports were tallied by respondent type and further by tumor type and grade. Concordance between patient and clinician report was also investigated. RESULTS One hundred fifty-seven patients underwent 250 clinical evaluations. Participants were primarily white (82%) males (57%) with median age 47 years (range: 19 – 78). Most had high grade (60%) primary brain (86%) tumors, were in surveillance (76%), with no prior recurrence (57%) and KPS ≥ 90 (76%). Half of patients and 62% of clinicians reported the patient ever having a seizure. The 12% discordance were all where the patient did not report a seizure, but clinicians did. There was good agreement on seizure reporting since last visit (74% patients, 78% clinicians), and anti-seizure medication use (51% patients, 57% clinicians). Seizures were reported more frequently in patients with high-grade tumors (WHO Grade 3 or 4) (60% patients, 76% clinicians) versus low-grade (WHO Grade 1 or 2) (51% patients, 59% clinicians), and among patients with oligodendrogliomas (71% patients, 85% clinicians) versus non-oligodendroglioma tumors (54% patients, 68% clinicians). CONCLUSIONS The RANO-SCCI was used for self-report and clinician report of seizure activity. A higher frequency was reported among oligodendroglioma and high-grade tumors. Disparities between patient and clinician responses may reveal a limitation in the patient’s ability to recognize and assess their seizure symptoms. Further work will investigate reporting congruence and associations with clinical and demographic characteristics.

BACKGROUND The median overall survival of patients with glioblastoma (GBM) is 10-12 months and the five-year survival ranges from 5-10%. Favorable clinical and molecular prognostic markers have been described in the literature, although an individual patient’s prognosis cannot easily be predetermined on these features as shown in the NOB-LTS project by Briceno et al. (SNO 2021). Until now, no radiologic characteristics have been correlated with better patient outcomes. We reviewed eighteen MRI features to determine if these could aid the identification of long-term survivors (LTS). METHODS From the NOB-LTS cohort of our Natural History Study, 16 long-term survivals (LTS; ≥ 3 years survival post-diagnosis) were matched based on sex, age, and extent of resection to 32 control (STS, < 3 years survival post-diagnosis) patients with NGS-confirmed IDH-wt glioblastoma. Pre-surgical MRIs (T1, T1 post-contrast, T2, T2/FLAIR, DWI, ADC) were reviewed by three blinded reviewers and analyzed based on pre-set criteria. RESULTS T1 hypointensity occurred commonly in the LTS (71%) vs STS (29%) while central heterogeneous signal occurred commonly in the STS (73%) vs LTS (50%) patients. Restricted diffusion was seen in 82% of STS and 70% of LTS cases. No difference was seen in irregular enhancement, peripheral and grey matter enhancement on T1 post-contrast images. Evaluation of T2/FLAIR images showed no difference in the number of lobes involved, presence of mass effect, heterogeneity of the signal or the perilesional signal abnormality or involvement of grey matter. CONCLUSION Our results suggest that pre-surgical MRI might be a useful prognostic tool as T1 hypointensity more frequently, and T1 central heterogeneity less commonly seen in the LTS group. These imaging findings may provide additional insights regarding the differences in tumor biology between LTS and STS. Further validation and correlation with histological/molecular characteristics are planned to better predict patient outcomes with newly diagnosed glioblastoma.

Background The Response Assessment in Neuro-Oncology Patient-Reported Outcome (RANO-PRO) working group aims to provide guidance on the use of PROs in brain tumor patients. PRO measures should be of high quality, both in terms of relevance and other measurement properties. This systematic review aimed to identify PRO measures that have been used in brain tumor studies to date. Methods A systematic literature search for articles published up to June 25, 2020 was conducted in several electronic databases. Pre-specified inclusion criteria were used to identify studies using PRO measures assessing symptoms, (instrumental) activities of daily living [(I)ADL] or health-related quality of life (HRQoL) in adult patients with glioma, meningioma, primary central nervous system lymphoma, or brain metastasis. Results A total of 215 different PRO measures were identified in 571 published and 194 unpublished studies. The identified PRO measures include brain tumor-specific, cancer-specific, and generic instruments, as well as instruments designed for other indications or multi- or single-item study-specific questionnaires. The most frequently used instruments were the EORTC QLQ-C30 and QLQ-BN20 (n = 286 and n = 247), and the FACT-Br (n = 167), however, the majority of the instruments were used only once or twice (150/215). Conclusion Many different PRO measures assessing symptoms, (I)ADL or HRQoL have been used in brain tumor studies to date. Future research should clarify whether these instruments or their scales/items exhibit good content validity and other measurement properties for use in brain tumor patients.

11039 Background: Participation in mentorship programs for early career physicians may be crucial to developing key skills and professional networks to navigate racial, ethnic and gender leadership disparities in medicine. A 6-month virtual facilitated peer mentorship program was developed and piloted through the Society for Neuro-Oncology (SNO) Women & Diversity Committee. The evaluation of the program’s feasibility to positively impact early career physicians, investigators and trainees is presented here. Methods: We designed and conducted a virtual mentoring program pilot open to SNO’s multidisciplinary members in residency, fellowship, or early career phase, leveraging peer-mentoring sessions with mid-to late-career physician mentors. A curriculum with online resources was provided recommending groups meet for 6 sessions: 3 involving the mentor and 3 dedicated to peer-mentoring. Group assignments were based on time-zones and interests. Pre- and post-participation surveys assessed mentee experience. Descriptive statistics were used to assess participant demographics and survey results. Results: Our call for participation was broad; all 20 mentee applicants participated in 5 groups. Mentees were 90% women and 60% were from diverse racial and ethnic backgrounds. Most were aged 31-40 (75%) and junior faculty (50%) in neuro-oncology (65%). The 5 senior mentors (3 men and 3 of diverse race and ethnic backgrounds) practiced either neuro-oncology (3), neurosurgery (1) or radiation oncology (1). The proportion who reporting having a signature lecture increased from 15% to 62% during the pilot. A large majority reported their participation was worthwhile (85%), that they would participate again (92%) and would recommend it to others (92%). Feedback themes included positive personal growth, peer support, networking and job opportunities, access to CV reviews, lack of and desire for late career female mentors, and virtual scheduling constraints. While the pilot was limited by several variables, it was timely to connect participants in Q3 of 2020 early in the COVID-19 global pandemic. The virtual meeting environment created a venue to share and discuss topics such as work-life balance, burnout, leading through change and social connection. Despite not achieving 100% professional concordance, participants found the experience worthwhile. The tools and curriculum of topics provided was implemented differently across groups, leading to varied experiences. Finally, we did not have 100% post pilot follow up despite multiple attempts limiting our complete understanding of the pilot. Conclusions: This virtual mentorship pilot program proved feasible and of value in development of early career women and diverse individuals. A resource toolkit has been designed to scale and diffuse.

Recognizing the importance of clinical outcomes assessments (COA), the RANO-PRO Working Group recommends inclusion of core symptoms/functions in clinical care/research for malignant glioma patients. This study evaluated the association between the recommended symptoms (pain, perceived cognition, seizures, aphasia, treatment-specific symptoms) and functions (physical: weakness, walking; and role/social: work, usual activities) and disease progression in these patients. MDASI-Brain Tumor and EQ-5D-3L scores, Karnofsky Performance Status (KPS), and Neurologic Function Score (NFS) were evaluated in relation to disease progression by chi-square tests, independent- and paired-samples t-tests, adjusted for multiple comparisons. Our sample included 336 patients with malignant glioma; 82% white, 64% male, median age=52 (21-79). Imaging study revealed disease progression for 46% of patients. All symptoms except seizures and difficulty concentrating were worse in the group whose imaging showed disease progression versus stable disease, as well as the functions of walking, work, activity, and self-care (0.8 < difference < 1.8). Patients with disease progression were 4 times more likely to have a poor KPS (≤ 80) and worse NFS. Among patients with disease progression (n=112), all symptoms, except seizures, worsened from first assessment to time of progression. Up to 22% of patients reported worsening mobility, self-care, and usual activity; 46% and 35% had worsened KPS and NFS, respectively. Seven symptoms and functions were each individually reported by at least 10% of patients as having worsened the most. Worsening of symptoms and functions was not observed among patients with stable disease, except in difficulty understanding. Identified core symptoms/functions worsen at the time of progression demonstrating the relationship between priority constructs and a traditional tumor response measure while highlighting the importance of longitudinal collection of COA. The pattern of worsening was observed via both patient- and clinician-reported outcomes, emphasizing the utility of COA in clinical care and clinical trials.

Cognitive dysfunction (CD) is common among primary brain tumor (PBT) patients and adds to the overall symptom burden. Standardized assessments able to be incorporated into routine clinical in-person and telehealth care are needed. Here, we report the feasibility, utility, and satisfaction with use of the Montreal Cognitive Assessment (MoCA) in telehealth and clinical settings by trained clinical providers. Feasibility and provider satisfaction were assessed through survey responses, and patient performance on the MoCA, after a reliability check, was reported through descriptive statistics. Seventy-nine MoCAs on 71 patients were completed in clinic (n=55) or telehealth (n=24). Majority of patients were white (83%) males (54%) with high grade PBTs (66%), and half of patients had completed at least a college education. In clinic, providers (n=9) reported the MoCA took 5-20 minutes to complete, was easy to incorporate into routine practice (78%), believed it was accurate in assessing cognition (67%), and was useful in determining treatment (88%). The average in-person MoCA score was 25 (range: 6 to 30), with 31% of scores classified as abnormal (≤26). In telehealth, providers (n=11) found the administration of the MoCA prior to attending participation in the telehealth visit helpful (75%), discussed the results with their clinical team (75%) and patient (63%), and believed the MoCA was accurate in assessing cognition remotely (63%). On average, patients took 13 minutes (9-22) to complete testing, with three tests discordant on reliability scoring and one patient unable to complete testing. The average telehealth MoCA score was 26 (12-30), with 29% of scores classified as abnormal. Overall, testing was feasible in both clinical and telehealth settings, and providers reported satisfaction with its use. Future studies should evaluate validity in a larger sample and include analysis of relevant cut-off scores, impact of disease, tumor treatment, and genomic predispositions.

CNS tumor patients are highly symptomatic causing interference with activity and worse quality of life. Social distancing due to the COVID-19 pandemic increased demands on the patient, caregivers, clinicians, and the health care system. The NCI’s Neuro-Oncology Branch Natural History Study (NHS) systematically collected patient-reported outcomes (PROs) provide insight into how these challenges influenced symptom burden and interference during the COVID year. METHODS: Patient and disease characteristic as well as patient-reported symptoms and interference (MDASI-BT/-SP) and general health status (EQ-5D-3L) from 3/2020-2/2021) were compared to NHS normative sample collected prior to 3/2020. RESULTS: The sample (n = 178) was primarily White (82%), male (55%), median age of 45 (range 18 – 79) and KPS ³ 90 (51%). The majority had high-grade (70%) brain (83%) tumors (BT) with ≥ 1 prior recurrence (60%) and 25% were on active treatment. Clinical visits were primarily conducted via telehealth (64%) and 20% of all patients were diagnosed with progression at the time of assessment. Most commonly reported moderate-severe symptoms among BT patients were fatigue (30%), difficulty remembering (28%), feeling drowsy (22%). Among spinal cord tumor patients, fatigue (39%), pain (35%) and numbness/tingling in arms/legs/trunk (35%) were most frequently reported. These symptoms were reported in similar frequencies by the normative sample. Nearly half of the COVID year sample (48%) reported moderate-severe activity-related interference. Reported problems with mobility (38%), self-care (19%), pain/discomfort (40%), and usual activities (50%) were similar in both groups except for increased mood disturbance (53%) was reported during the COVID year. CONCLUSION: These findings support CNS tumor patients remained highly symptomatic with significant impact on health-related quality of life during the COVID year. Clinicians should develop timely individual care plans to help BT patients navigate their disease course. Evaluation of risk associated with more severe symptoms and functional limitations are ongoing.

Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, survivorship care plans, and improving communication among all stakeholders in an individual patient's care as the means to elevate health-related quality of life. The merits of these survivorship care provisions in the field of neuro-oncology and its patients' exigent need for more patient-centric care focused on living with their illness are discussed. Since 2014 there has been a mandate within the United States for adult cancer patients treated with curative intent to receive survivorship care plans, comprising a treatment summary and a follow-up plan, intended to facilitate patients' care after initial diagnosis and upfront treatment. Several cancer-specific survivorship care plans have been developed and endorsed by health care professional organizations and patient advocacy groups. A survivorship care plan specific for neuro-oncology has been collaboratively developed by a multidisciplinary and interprofessional committee; it is endorsed by the Society for Neuro-Oncology Guidelines Committee. It is available as open access for download from the Society for Neuro-Oncology website under "Resources": https://www.soc-neuro-onc.org/SNO/Resources/Survivorship_Care_Plan.aspx. Survivorship care offers an opportunity to begin directly addressing the range of issues patients navigate throughout their illness trajectory, an oncology initiative to which neuro-oncology patients both need and deserve equitable access.

Gliomatosis cerebri (GC) is a controversial entity no longer recognized as a histopathologic-defined diagnosis, characterized by diffuse, commonly bilateral infiltration of cerebral hemispheres. The purpose of this report is to describe clinical, imaging, patient-reported outcomes (PRO’s) and pathologic characteristics of clinically-defined cases from a large natural history study cohort (N=769). Of 19 patients, 10 male, 16 white, mean age at diagnosis 43 (19-70), seventeen presented as primary GC, while 2 developed GC after treatment. Ten patients were IDH-WT, 7 IDH-M, and 2 IDH undetermined. The majority (7/10) IDH-WT patients presented acutely (5 with seizures), whereas, 3 had a protracted presentation of 2 weeks-3months with 6/10 having enhancing tumors and 8/10 undergoing biopsy only. On histopathologic review, 4 were anaplastic astrocytoma (AA), 3 GBMs, 2 grade II astrocytoma, and 1 histone-mutated glioma. Nearly all (9/10) IDH-WT patients received radiation with concurrent and adjuvant temozolomide. 7/10 IDH-WT patients had a survival of only 1.5yrs or less from diagnosis. Of the 7 IDH-M patients, 4 had protracted presentations of 1 month-5 years. 6/7 had non-enhancing tumors at presentation. 4 had biopsy only and 3 underwent partial resection. 3 were AA, 2 grade II astrocytoma, 1 grade II oligodendroglioma, and 1 grade IV astrocytoma. 3/7 received radiation with concurrent and adjuvant temozolomide, 3/7 chemotherapy alone, and 1 RT alone. All 7 IDH-M patients survived 3+ years from diagnosis (range 3-10+ yrs). Both patients who developed GC later, were IDH-M, with prolonged survival (3.5yrs and the other still alive 10+yrs). PRO's at time of last clinical assessment revealed GC patients to be highly symptomatic with mean overall symptom burden, depression, and anxiety higher than our overall glioma population. GC patients have a varied clinical course mandating further investigation to enable better prognostic definition to refine treatments based on the varying clinical and molecular characteristics.

BACKGROUND Primary CNS tumors are associated with uncertainty likely contributing to mood disturbance that is common throughout the disease trajectory. The intersection of the COVID-19 pandemic with a CNS tumor diagnosis may further impact the anxiety/depression experienced in this population. This study assessed key anxiety/depression symptoms in patients with CNS tumors prior to and during the COVID year. METHODS Patient reported outcomes (PROs), including the PROMIS Anxiety and Depression Short Forms and EQ-5D-3L, were collected at the time of clinical or telehealth evaluation from the COVID year (March 2020-February 2021) and were compared to assessments through February 2020 (a NOB-normative sample), reflecting what we would typically see in our regular clinic evaluations. RESULTS The COVID sample (N = 178) was primarily White (82%), male (55%), median age of 45 (range 18–79), and KPS ³ 90 (50%). The majority had high grade (70%) brain (83%) tumors with ³ 1 prior recurrence (60%) and 25% were on active treatment. Visits were primarily conducted via telehealth (64%) and 20% had progression at assessment. Compared to the NOB-normative sample, patients reported significantly higher depression scores (moderate-severe, 17% vs. 12%, p < 0.05), but not anxiety (18% vs. 16%). Eleven percent reported both moderate-severe anxiety and depressive symptoms (8% pre-COVID). Overall health assessed by the EQ-5D-3L was similar to the normative sample in all dimensions, apart from impact of moderate/extreme mood disturbance, which was more prevalent in the COVID year (53% vs. 43%, p < 0.05%). CONCLUSION Patients with CNS tumors are at risk for significant symptoms of depression and anxiety; this risk was heightened during the COVID year. Further evaluation of clinical factors associated with risk are underway. These findings highlight the need for assessments and interventions that can be administered via telehealth to address the mental health needs of this vulnerable population. Radiobiology

SIGNIFICANCE AND AIMS Past research in PBT patients has demonstrated that minorities may have a survival advantage compared to Whites for high-grade tumors, though little is known about their illness experience given their underrepresentation in clinical trials. This study explored differences in PROs across race-ethnicity within a large PBT cohort describing associated burden and risk for minority populations where data is scarce. METHODS Demographic, clinical characteristics, MDASI-Brain Tumor, PROMIS Depression and Anxiety Short-Forms, and Neuro-QoL Cognitive Function were collected from the most recent timepoint for PBT patients enrolled on the Natural History Study. Descriptive statistics, one-way ANOVA, and linear regression were used to report results. RESULTS The sample included 562 PBT patients (58% male, median age = 50 [18-85]) comprised of 79% White, 6% African American (AA), 10% Hispanic, and 5% Asian patients per self-report. Most patients had a high-grade glioma (60%), with 28% on active treatment and 44% with good KPS (90-100). Among the most commonly reported moderate-severe symptoms were fatigue ( > 40% in all groups), difficulty remembering (30-40% of Asians, AAs, and Whites), and disturbed sleep (44% in Asians, 29% in Hispanics), while hemiparesis was common only for AA patients (37%). There were no differences between groups with respect to symptom burden and interference, mood disturbance, or cognitive function. Race/ethnicity group was not predictive of overall symptom burden or interference, but for all groups, higher KPS predicted lower symptom and interference scores (p < .001 and p = .004, respectively). CONCLUSION While some symptoms were common across ethnoracial groups, there were differences in symptom patterns, suggesting there may be other factors driving their illness experience. Future exploration of socioeconomic and cultural factors that might contribute to the symptom burden of minorities is warranted, which may allow development of targeted interventions to improve clinical outcomes in these groups.

Primary brain tumor (PBT) patients experience high symptom burden and functional limitations, which may be impacted by the economic strain and mood disturbance during the COVID-19 pandemic. We assessed financial toxicity and associated patient reported outcomes (PROs) after one year of lockdown in a cohort of PBT patients. Patient and disease characteristics and PROs including FACIT-COST, MDASI-Brain Tumor, PROMIS-Anxiety/Depression short forms, and EQ-5D-3L were collected from 7/2020 to 5/2021 from participants in our Natural History Study. Descriptive statistics, Pearson correlations, and independent samples t-tests evaluated PRO relationships. The cohort included 112 PBT patients: 57% male, 87% white, mean age = 47 (range 25 – 80). Majority were married (65%), completed ≥ 4-year college degree (73%), earned annual family income ≥ $50,000 (68%) and living with a high-grade glioma (72%) complicated by recurrence (51%). Using FACIT-COST, 56% reported some financial hardship due to illness with a mean FACIT-COST of 28.3 (SD = 11.3, range: 0 - 44). Half of patients reported feeling moderately to extremely anxious or depressed. Non-Whites and Hispanics as well as those not currently working reported worse financial toxicity compared to White non-Hispanics and individuals currently working (21.4 vs 29.8 and 25.7 vs 30.4, respectively). Worse financial toxicity scores strongly correlated with worse overall symptom burden (r = -0.55) and interference (r = -0.42), worse anxiety (r = -0.39) and depression scores (r = -0.44), and worse overall HRQOL scores (r = –0.33)[all p< .01]. This is the first report of FACIT-COST in PBT patients to our knowledge and demonstrates that non-White individuals living with high grade glioma who are not currently working due to their tumor reported worse financial toxicity which was strongly correlated with higher symptom burden and interference with lower HRQOL. Future studies to assess financial toxicity longitudinally and post-pandemic using the FACIT-COST are needed.

Cross-sectional studies indicate that patients with gliomas report significant depressive/anxiety symptoms and symptom-related interference with daily activities at diagnosis and throughout the illness trajectory. Our study aimed to explore relationships between these mood disturbances and symptom interference with respect to progressive disease (PD) in glioma patients. Demographic, clinical characteristics, MDASI-Brain Tumor (interference items), and PROMIS Anxiety and Depression Short-Forms were collected at the time of imaging surveillance, before discussing imaging results. Comparisons between patients with/without PD and respective change scores were calculated at study entry and at subsequent assessments. Independent t-tests, Chi-square tests, and paired sample t-tests were used to report results. The sample included 438 glioma patients (62% male, 84% Caucasian, 82% high-grade) with median age of 51 years (range 18-82); 42% had PD with 60% reporting past recurrence(s); 45% had poor Karnofsky Performance Status (KPS); and median time from diagnosis was 2 years (range: 0-30). On average, patients with PD on imaging at time of assessment reported significantly greater anxiety (p = 0.008), depression (p < 0.001), and symptom interference (p < 0.001) than those with stable disease. Additionally, more patients with PD reported moderate-severe anxiety (25%) and depression (22%) than patients with stable disease (15% and 12%, respectively). When evaluating change scores, patients with PD reported worse symptom interference (p < 0.001) but stable mood disturbance, while patients with stable disease reported improved depression (p = 0.018) and unchanged anxiety symptoms compared to baseline. Although mood disturbance is higher for patients with PD, some of these patients do not experience worsening, but rather a continuation of ongoing psychological symptoms, which may portend a worse illness trajectory. Identifying these patients early in this trajectory to evaluate potential biologic correlates between mood and prognosis is warranted to validate these findings.

Prior reports suggest the low prevalence of primary central nervous system (PCNS) tumors and the healthcare setting where patients seek care can contribute to diagnostic delays, potentially affecting prognosis. This descriptive report highlights findings from patient-reported data at presentation collected from a sample of 623 PCNS tumor patients. Participants were White (88%), males (56%), median age at diagnosis 41 (2-79) with high grade (HG) (66%) brain tumors (BT) (89%). Among BT patients, 30% reported ≥ 3 concurrent symptoms at presentation including headaches (40%), seizures (30%), and memory problems or difficulty with balance/walking (20% each). Over half (57%) had symptoms for < 6 months before diagnosis and 60% presented to the Emergency Room. Sixty-five percent of HG BT patients had symptoms for < 6 months prior to diagnosis compared to low grade (LG) tumors (40%) and had surgery in < 1 month from presentation (68% vs 51%, p < 0.01). More HG BT patients presented with weakness in the arms/legs than LG BT (14% vs 8%). Among spine tumor (ST) patients, 45% reported ≥ 3 concurrent symptoms at presentation including back pain (65%), sensory changes (45%), and weakness (40%). Almost half (46%) were symptomatic for > 1 year before diagnosis, presented in an outpatient clinic (64%) with 41% having surgery < 1 month from presentation. Younger (40% vs 16%) and HG ST patients (56% vs 21%) more often reported symptoms for < 6 months before diagnosis. HG ST patients more often presented to Emergency Rooms (67% vs 25%) and had surgery < 1 month from presentation (60% vs 36%). Further analysis of symptom presentation and clinical course is ongoing. Tumor location, grade, patient age and healthcare setting were associated with the time from clinical presentation to diagnosis. Development of aids providing guidance on diagnostic evaluation/treatment to front-line healthcare providers is warranted.

Karnofsky performance status (KPS) scale, a clinician-reported measure, is used to assess patients’ functional ability and as a metric for trial eligibility. Glioma patients often have a degree of neurologic deficit which can invariably affect performance status. There is little research comparing KPS, patient-reported cognitive outcomes, and objective cognitive outcomes. 273 primary brain tumor patients enrolled in the NOB Natural History Study were included in this report. We evaluated Pearson correlations between KPS (range 40-100), dichotomized as Good KPS (KPS ≥ 90) and Poor KPS (KPS ≤ 80), and MDASI-BT cognitive symptom factor, NeuroQoL Cognitive Function t-score, EQ-5D-3L index score, and objective MoCA test. The majority of patients were white (81%), male (58%) with a median 50 years of age (range 24-79). Most had high grade gliomas (74%), 22% were on active treatment, and 55% had prior tumor recurrences. Providers reported a poor KPS in 37% of patients. KPS correlated with the MDASI-BT cognitive symptoms (r = -0.32), NeuroQoL (r = 0.39), and EQ-5D-3L index score (r = 0.55) (all p < 0.01). Patients with poor KPS reported moderate-severe cognitive symptoms on the Neuro-QoL Cognitive Function (40%), moderate-severe difficulty remembering on the MDASI-BT (37%), and difficulty with usual activities on the EQ-5D-3L (83%). In a subset of 27 patients, MoCA scores were assessed but no significant correlation was found with KPS (r = 0.19, p = 0.352). Patient-reported and objective cognitive dysfunction was seen in up to 36% of those with good KPS. These data demonstrate that perceived cognitive testing is associated with poor KPS but may also occur in those with good performance status. The results underscore the need for alternative measures of cognitive functioning to further explore the impact in those with good KPS and the use of the MoCA in a larger sample.

BACKGROUND The utility of geriatric assessment (GA) has been evaluated in older adults diagnosed with solid tumors other than primary brain tumors (PBT). We assessed several key GA domains in adults with PBT receiving tumor-directed treatment. METHODS Patient and disease characteristics and key GA domains within patient-reported outcomes (PROs) including symptom burden (MDASI-BT), Anxiety/ Depression (PROMIS-short forms) and general health status (EQ-5D-3L) were systematically and prospectively collected between 9/2016–8/2019 from adults diagnosed with PBT. Descriptive statistics and regression analyses were used to assess PROs. RESULTS Of 581 participants, 92 were 65 – 85 years old (median age = 70 years; “older”) and 489 were ≤ 64 years (median age = 46 years; “younger”). Tumor grade distribution in the older group was 74% WHO grade III/IV, 26% WHO grade I/II; tumor types included gliomas and meningiomas with no tissue diagnosis in 3 patients. Older patients were 49% less likely to receive chemotherapy and twice as likely to have KPS ≤ 80 (p=0.003, OR=0.51, OR=1.98). More older patients reported problems with mobility (57% vs 44%), self-care (38% vs 26%), and usual activities (64% vs 51%) than younger patients. Charlson Comorbidity Index mean scores were significantly higher in older patients (3.5 vs 0.6, p< 0.001). The top 3 most frequently reported moderate-to-severe symptoms were similar in older vs younger groups: fatigue (44% vs 41%), feeling drowsy (29% vs 30%) and difficulty remembering (28% vs 29%). Feeling distressed was the only symptom whose frequency differed between the age groups (11% older vs 27% younger, p=0.001). CONCLUSION Older PBT patients had lower performance status, more co-morbidities and increased functional impairments, affirming that GA is relevant. Symptom burden was similarly high in both age groups. These findings support conducting GA concurrently in future symptom intervention and therapeutic clinical trials for adults with PBT receiving tumor-directed treatment.

Background Atypical meningioma is a World Health Organization grade II tumor with intermediate prognosis and risk of recurrence. Optimal management after gross total resection (GTR) is controversial, with observation versus adjuvant radiotherapy (RT) contentiously debated. Methods Pathologic review was performed of all atypical meningiomas diagnosed at our institution from 1988 to 2011. Retrospective chart review documented patient demographics, extent of surgical resection, history of radiation therapy, progression-free survival (PFS), and overall survival (OS). A supplemental systematic literature review was completed in which English-language articles published since 1979 comparing observation and RT after GTR of atypical meningioma were surveyed. Results Sixty-nine patients met inclusion criteria. Sixty-one underwent observation, and 8 received RT. Overall, 15 observation and 3 patients undergoing RT experienced tumor recurrence (5-year PFS 79% vs. 88%; P = 0.67); 19 observation and 2 patients undergoing RT died (5-year OS 89% vs. 83%; P = 0.68). Systematic review identified 9 preceding studies reporting extractable data comparing observation and RT outcomes after GTR. Recurrence was 18% and 19% after observation and RT ( P = 0.9); total survival was 84% and 93% ( P = 0.2). At 5 years, PFS was 81% after observation and 88% after RT ( P = 0.2), whereas survival was 87% after observation and 96% after RT ( P = 0.4). Conclusions Observation alone after GTR of atypical meningioma was not associated with increased risk of tumor recurrence or mortality. Although some preceding authors advocate for RT based on empiric experience, a systematic review also suggests that observation may provide equivalent PFS and OS to RT. Taken together, these findings indicate that observation after GTR may be a safe alternative to RT.

As cancer care has evolved so has the awareness of the issues cancer patients, their caregivers and families face during and after treatment, giving rise to the cancer survivorship care initiative. The body of research pertaining to quality of life, health-related quality of life, and multidimensional symptom burden of neuro-oncology patients and their caregivers has grown significantly, yielding a wealth of data and information indicating interventions and actions targeting symptoms and needs are both warranted and desired. The provision of survivorship care aiming to deliver care in a patient-centered, whole-person model offers a means by which these interventions and actions can be actualized. The research specific to survivorship care models and survivorship care plans and their delivery remains a large opportunity, one worth the careful consideration and participation of neuro-oncology healthcare providers for the benefit of their highly deserving patients and their caregivers and families.

TPS2072 Background: The majority of recurrent CNS tumors lack effective systemic therapy options following surgical resection and adjuvant radiotherapy. ONC201, the founding member of the imipridone class of small molecules, has induced durable tumor regressions in patients with diffuse midline glioma, H3 K27M-mutant (DMG H3K27M). ONC206, the second imipridone to enter clinical development, is a DRD2 antagonist and ClpP agonist that exhibits differentiated receptor pharmacology and gene expression profiles in tumors relative to ONC201. The compound is orally bioavailable, penetrates the blood-brain barrier, and exhibits anti-cancer efficacy without toxicity in several preclinical cancer models with pronounced efficacy in myc-overexpressing CNS tumors. Methods: A first-in-human, open label, dose escalation, and food effect Phase I study of oral ONC206 (NCT04541082) is currently enrolling. Patients must be 18 years or older and diagnosed with a recurrent, primary CNS neoplasm. Eligible diseases include recurrent glioblastoma, WHO Grade 2 and 3 infiltrating glial neoplasms, DMG H3K27M, ependymoma, medulloblastoma, malignant meningiomas, and other rare primary CNS neoplasms. Dose escalation, initially with weekly dosing, will follow a standard 3+3 design. After the MTD is established, a food effect cohort will enroll with a balanced, single-dose, two-arm, two-period, crossover design. The primary endpoint is to determine DLT during the first 28-day cycle. Secondary endpoints will include objective response rate by RANO criteria, overall and progression-free survival, and disease control rate. Exploratory biomarker analyses based on preclinical correlations with efficacy will include DRD2, DRD2 dimer, ClpP, DRD5, c-myc, and n-myc expression. Clinical trial information: NCT04541082.

TPS2576 Background: Blockade of the dopamine receptor D2 (DRD2) has emerged as a therapeutic target in neuro-oncology. ONC201, a first-generation imipridone that antagonizes DRD2, has demonstrated clinical activity in Diffuse Midline Gliomas, H3K27M-mutant (DMGs). Treatment options beyond surgical resection and radiation therapy are limited for most recurrent and rare primary CNS neoplasms. DRD2 blockade holds promise as a therapeutic target in multiple primary CNS cancers. ONC206 is a next generation imipridone and a chemical analog of ONC201 that possesses favorable drug properties such as oral bioavailability, robust stability, and blood-brain barrier penetrance. ONC206 exhibits enhanced allosteric inhibition of DRD2 and nanomolar affinity/potency as a DRD2 antagonist with complete antagonism and specificity for DRD2. ONC206 demonstrated broad spectrum anti-cancer efficacy in vitro across most solid tumor types tested in a panel of > 1000 human cancer cell lines with nervous system tumors emerging as most responsive. In addition to its broad-spectrum activity in vitro, ONC206 efficacy has been demonstrated in xenograft mouse models. Methods: This is an open label, dose escalation, and food effect Phase I study of ONC206at the National Cancer Institute, Neuro-Oncology Branch. Adult patients 18 years and older with recurrent, primary CNS neoplasms will initially be accrued to the dose escalation portion of the study and evaluated for toxicity. Eligible diseases include recurrent glioblastoma, WHO Grade 2 and 3 infiltrating glial neoplasms, and rare primary CNS neoplasms in the NCI-CONNECT program: DMGs, ependymomas, medulloblastomas, and other rare CNS tumor types. The primary endpoint is to determine DLT during the first cycle (28 days). Dose escalation will proceed according to a standard 3+3 design. Both once weekly and more frequent dosing of ONC206 will be explored in the dose escalation scheme. After the MTD is established, food effect will be determined in a dedicated cohort using a balanced, single-dose, two-arm, two-period crossover design. Secondary endpoints will include objective response rate by RANO criteria, overall and progression-free survival, and disease control rate. Exploratory analysis of DRD2 and DRD5 expression, DRD2 dimerization, expression of MYC and N-MYC in tumor tissue in relation to clinical outcomes will also be performed.

Cancer patient survivorship has become a significant topic within oncology care for both adult and pediatric patients. Starting in 2005, the Institute of Medicine recommended the use of survivorship care plans to assist patients transitioning from active treatment to the posttreatment phase of their cancer care, a critical time for many patients. Since 2014 there has been a mandate within the United States for adult cancer patients treated with curative intent to receive survivorship care plans comprised of a treatment summary and a follow-up plan to facilitate a better understanding among patients of what to expect after treatment. In addition to a general oncology survivorship care plan, specific care plans have been created for breast, lung, prostate, and colon cancers, as well as lymphoma. A survivorship care plan specific to adult neuro-oncology has been developed by a multidisciplinary and interprofessional committee, with approval from the Society for Neuro-Oncology Guidelines Committee. It has been published in compendium with this review of survivorship care planning and available as a fillable PDF on the Society of Neuro-Oncology Guidelines Endorsement web page (https://www.soc-neuro-onc.org/SNO/Resources/Survivorship_Care_Plan.aspx). Implementation of this survivorship care plan provides a unique opportunity to begin addressing the range of survivorship issues our neuro-oncology patients navigate from diagnosis to end of life.

// Heather E. Leeper 1 , Alissa A. Caron 2 , Paul A. Decker 3 , Robert B. Jenkins 5 , Daniel H. Lachance 4 , Caterina Giannini 5 1 Neuro-Oncology, Advocate Medical Group, Park Ridge, IL 60068, USA 2 Experimental Pathology, Mayo Clinic SW, Rochester, MN 55905, USA 3 Biomedical Statistics and Informatics, Mayo Clinic SW, Rochester, MN 55905, USA 4 Neurology, Mayo Clinic SW, Rochester, MN 55905, USA 5 Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA Correspondence to: Caterina Giannini, e-mail: giannini.caterina@mayo.edu Keywords: diffuse gliomas, WHO grade II, IDH mutation, ATRX, 1p19q codeletion Received: March 12, 2015 Accepted: June 22, 2015 Published: July 03, 2015 ABSTRACT Background: Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated. Methods: We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003–2012). Results: IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors ( p = 0.003). All codeleted tumors ( n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different ( p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups ( p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only ( p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion. Conclusions: For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

International audience; The Response Assessment in Neuro-Oncology-Patient-Reported Outcome (RANO-PRO) working group is an international multidisciplinary collaboration that provides guidance on the use of patient-reported outcome (PRO) measures in clinical trials and practice for adult patients with brain tumours. Findings from both PROs and traditional outcome measures, such as survival, and clinical or radiological response, are essential to inform the research community, policy makers, physicians, and patients in the treatment decision-making process. Previous initiatives in oncology have focused on guidelines concerning the collection, analysis, interpretation, and reporting of PRO data. However, we recommend the application of appropriate PRO instruments, with respect to its content and measurement properties (ie, research question, content validity, and other measurement properties), in brain tumour research. PROs should be well defined and reliable to generate high-quality evidence, and our recommendations on the use of specific PRO measures could help to improve the quality of PRO evidence derived from neuro-oncological studies, and might add a new dimension in how the value of therapeutics is assessed in patients with brain tumours. In this Policy Review, we present the RANO-PRO working plan for the use of PROs in adults with brain tumours.

Sexual history taking is a core clinical skill for all physicians, yet many medical schools do not adequately address this important topic within the curriculum. This article describes a sexual-history-taking module that was initiated, designed, and presented by 2nd-year medical students for their peers as part of the required Introduction to Clinical Medicine (ICM) course.As part of this module, a group of 2nd-year medical students developed a large-group presentation and small-group role play cases to enhance students' basic sexual-history-taking skills in challenging situations, teach ways to ask nonjudgmental questions, and introduce legal issues that may arise. Under faculty supervision, the students recruited and trained peer and faculty facilitators and designed, developed, and analyzed the survey evaluation tools.Both the students and facilitators completed an anonymous questionnaire within 1 to 4 weeks of completing the activity. Of the 92 students completing an online survey, 92% rated the large group presentation good or excellent, and 89% rated the small-group role playing activities as good or excellent, as compared to overall ICM course ratings of 68% good or excellent. Facilitators were well prepared for their roles and reported that the students responded to them positively. Participating students reported that having students as teachers positively enhanced their small group learning experience. Students performed better on the sexual-history-taking questions on the final examination (97.5%) than on the final examination overall (89%).Medical students can successfully create and implement a curriculum module for their peers in a sensitive area such as sexual history taking. Due to changing responsibilities for students as they progress through medical school, sustainability may be challenging.