Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

PURPOSE: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. METHODS: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. RESULTS: Fifty-five patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). CONCLUSION: This interim analysis supports feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. TRIAL REGISTRATION: NCT04301089 registered on 3/9/2020.

The relationship between prior psychiatric diagnosis and brain cancer diagnosis in the U.S. military health system.

PURPOSE: Prior research suggested the increased likelihood of brain cancer diagnosis following certain psychiatric diagnoses. This association may result from detection bias or suggest an early sign for brain cancer. This study investigated whether psychiatric illness may be an early manifestation of brain cancer while considering potential effects of detection bias. METHODS: This case-control study used the data from the Department of Defense's Central Cancer Registry and the Military Health System Data Repository. Four cancer-free controls and one negative-outcome control (cancers not associated with psychiatric illness) were matched to each brain cancer case diagnosed from 1998 to 2013 by age, sex, race, and military status. The groups were compared in the likelihood of having a pre-existing psychiatric diagnosis using conditional logistic regression. RESULTS: We found a significant association of psychiatric illnesses with brain cancer (Odds Ratio (OR) = 2.63, 95% confidence interval (CI) = 2.18-3.16) and other cancers (OR = 1.80, 95% CI = 1.49-2.19), compared to non-cancer controls. The association was stronger for psychiatric diagnoses within three months before cancer (brain cancer: OR = 26.77, 95% CI = 15.40-46.53; other cancers: OR = 4.12, 95% CI = 1.96-8.65). The association with psychiatric disorders within 3 months were higher for small brain tumors (OR = 128.32, 95% CI = 17.28-952.92 compared to non-cancer controls) while the OR was 2.79 for other cancers (95% CI = 0.86-8.99 compared to non-cancer controls). CONCLUSION: Our findings suggest an association between diagnosed psychiatric illnesses and subsequent brain cancer diagnosis, which may not be solely explained by detection bias. Psychiatric illness might be a sign for early detection of brain cancer beyond the potential effects of detection bias.

Survival among patients with glioma in the US Military Health System: A comparison with patients in the Surveillance, Epidemiology, and End Results program.

BACKGROUND: Glioma is the most common malignant brain cancer. Accessibility to health care is an important factor affecting cancer outcomes in the US general population. The US Military Health System (MHS) provides universal health care to its beneficiaries. It is unknown whether this universal health care has translated into improved survival outcomes among MHS beneficiaries with glioma. This study compared the overall survival of patients with glioma in the MHS with the overall survival of patients with glioma in the general population. METHODS: The MHS cases were identified from the Department of Defense's Automated Central Tumor Registry (ACTUR). Glioma cases from the general population were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. SEER cases were matched 2:1 to ACTUR cases by age, sex, race, histology, and diagnosis year. All cases had histologically confirmed glioma diagnosed between January 1, 1987, and December 31, 2013. A Kaplan-Meier analysis was conducted to compare survival between the ACTUR and SEER cases. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The study included 2231 glioma cases from ACTUR and 4462 cases from SEER. ACTUR cases exhibited significantly better overall survival than SEER cases (HR, 0.74; 95% CI, 0.67-0.83). The survival advantage of the ACTUR patients was observed in most subgroups stratified by age, sex, race, diagnosis year, and histology. For glioblastoma, the survival advantage was observed in both the pre- and post-temozolomide periods. CONCLUSIONS: Universal MHS health care may have translated into improved survival outcomes in glioma. Future studies are warranted to identify factors contributing to the improved survival.

Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) are being investigated in clinical trials for patients with glioblastoma. While these therapies hold great promise, management of the patients receiving such treatment can be complicated due to the challenges in recognizing immune-related adverse events caused by checkpoint inhibitor treatment. Brain imaging changes that are the consequence of an inflammatory response may be misinterpreted as disease progression leading to inappropriate premature cessation of treatment. The aim of this study was to, by way of a series of cases, underscore the challenges in determining the nature of contrast-enhancing masses that develop during the treatment of patients with glioblastoma treated with ICPIs. CASE PRESENTATION: We reviewed the clinical course and management of 4 patients on ICPIs who developed signs of tumor progression on imaging. These findings were examined in the context of Immunotherapy Response Assessment in Neuro-Oncology (iRANO) guidelines. Although all 4 patients had very similar imaging findings, 2 of the 4 patients were later found to have intense inflammatory changes (pseudoprogression) by pathologic examination. CONCLUSIONS: A high index of suspicion for pseudoprogression needs to be maintained when a patient with brain tumor on immunotherapy presents with worsening in an area of a pre-existing tumor or a new lesion in brain. Our findings strongly suggest that pathological diagnosis remains the gold standard for distinguishing tumor progression from pseudoprogression in patients receiving immunotherapy. There is a large unmet need to develop reliable non-invasive imaging diagnostic techniques. TRIAL REGISTRATION: ClinicalTrials.gov NCT02311920. Registered 8 December 2014.

Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report.

A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism.

Advances in the treatment of newly diagnosed glioblastoma.

Glioblastoma is a refractory malignancy with limited treatment options at tumor recurrence. Only a small proportion of patients survive 2 years or longer with the current standard of care. Gene expression profiling can segregate newly diagnosed patients into groups with different prognoses, and these biomarkers are being incorporated into a new generation of personalized clinical trials. Using the experience from recently completed large scale, multi-faceted, randomized glioblastoma clinical trials, a new clinical trial paradigm is being established to move promising therapies forward into the newly diagnosed treatment setting. Upcoming trials using the immune check-point inhibitors are an example of this changing paradigm and these and other immunotherapies have potential as promising new treatment modalities for newly diagnosed GB patients.

Effects of Traumatic Amputation on ß-Trace Protein and ß2-Microglobulin Concentrations in Male Soldiers.

BACKGROUND: Serum creatinine (SCr) levels are decreased following traumatic amputation, leading to the overestimation of glomerular filtration rate (GFR). ß-Trace protein (BTP) and ß2-microglobulin (B2M) strongly correlate with measured GFR and have not been studied following amputation. We hypothesized that BTP and B2M would be unaffected by traumatic amputation. METHODS: We used the Department of Defense Serum Repository to compare pre- and post-traumatic amputation serum BTP and B2M levels in 33 male soldiers, via the N Latex BTP and B2M nephelometric assays (Siemens Diagnostics, Tarrytown, N.Y., USA). Osterkamp estimation using DEXA scan measurements was used to establish percent estimated body weight loss (%EBWL). Results were analyzed for small (3-5.9% EBWL), medium (6-13.5%), and large (>13.5%) amputation subgroups; and for a control group matched 1:1 to the 12 large amputation subjects. Paired Student's t test was used for comparisons. RESULTS: Mean serum BTP levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. BTP appeared to decrease following large %EBWL amputation (p = 0.05). Mean serum B2M levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. B2M appeared to increase following large %EBWL amputation (p = 0.05). CONCLUSIONS: BTP and B2M levels are less affected than SCr by amputation, and should be considered for future study of GFR estimation. BTP and B2M changes following large %EBWL amputation require validation and may offer insight into non-GFR BTP and B2M determinants as well as increased cardiovascular disease and mortality following amputation.

Promising response to vemurafenib and cobimetinib treatment for BRAF V600E mutated craniopharyngioma: a case report and literature review.

Craniopharyngiomas are tumors that arise from the remnants of Rathke's pouch along the nasopharynx to the diencephalon. Current standard of care includes maximal surgical resection versus adjuvant radiation if a maximal resection is unfeasible. Pharmacological therapy with MAPK targeted agents is an emerging therapeutic option for tumors with BRAF V600E mutations. We report a 45-year-old male with a strictly third ventricle papillary craniopharyngioma with a BRAF V600E mutation. After initial surgery with subtotal resection, the patient demonstrated durable response to targeted BRAF and MEK inhibitor therapy with vemurafenib and cobimetinib. Our report suggests that targeted therapy may reduce the need for radiation and impact surgical interventions in select cases.

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS). Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTS = 23) or <3 years (NSTS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTS = 23; NSTS = 74) and methylation analysis (NLTS = 18; NSTS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed. Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers. Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.

Association of Employment Status With Symptom Burden and Health-Related Quality of Life in People Living With Primary CNS Tumors.

BACKGROUND AND OBJECTIVES: Financial toxicity significantly affects many patients, especially cancer survivors. We evaluated the association of unemployment as a major contributor to financial toxicity with patient-reported outcomes (PROs) assessing multiple illness experience domains in a primary CNS tumor (PCNST) cohort. METHODS: Patient and disease characteristics and PROs measuring symptom burden, interference, psychologic distress, functional impairment, and health-related quality of life (HRQOL) from participants enrolled in an institutional review board-approved observational study at the US NIH's Neuro-Oncology Branch were collected between September 2016 and December 2019. Descriptive statistics, tests of association, and comparison of group mean values were used to describe and evaluate PROs. RESULTS: Of the 277 participants diagnosed with a PCNST, 57% were male and 43% were female. Participants reported their race as White, non-Hispanic (78%); White, Hispanic/Latino (9%); Asian (7%); Black (4%); Native Hawaiian/Pacific Islander (1%); and other (2%) with 8% missing. The median age of the overall cohort was 45 years (range 18-74). Hispanic participants in the overall sample were 2.3 times more likely, and in the brain tumor group 3.2 times more likely, to report unemployment (p = 0.043, odds ratio [OR] 2.3, 95% CI 1.0-5.4 and p = 0.008, OR 3.2, 95% CI 1.3-7.9, respectively). 77 (28%) individuals unemployed due to tumor reported more functional impairment with walking, washing, dressing, and performing usual activities and reduced HRQOL (p < 0.001). More unemployed participants in the total sample reported moderate-to-severe depressive symptoms (25%) than those employed (8%) (χ2(1) = 13.9, p < 0.001, OR 3.7, 95% CI 1.8-7.8) and more moderate-to-severe anxiety symptoms (30%) than those employed (15%) (χ2(1) = 7.8, p = 0.005, OR 2.4, 95% CI 1.3-4.5). Unemployed participants with brain tumor reported on average 3 more symptoms as moderate-to-severe compared with those employed (t(83) = -4.0, 95% CI [Formula: see text] difference -5 to -2, p < 0.001, Hedge g = 0.70). DISCUSSION: Being unemployed due to a PCNST strongly correlated with high symptom burden, functional impairment, psychological distress, and reduced HRQOL, which may be impediments to returning to work that warrant intervention. Lack of employer-based health insurance and reduced earnings are financial sequelae of unemployment superimposed on the physical, social, and cognitive effects of living with a PCNST. Innovations to screen for and address financial toxicity and its contributing factors are needed.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

Purpose: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. Methods: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. Results: 55 patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). Conclusion: This interim analysis confirmed feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. Trial Registration: NCT04301089 registered on 3/9/2020.

Chronic daily headache in U.S. soldiers after concussion.

OBJECTIVE: To determine the prevalence and characteristics of, and factors associated with, chronic daily headache (CDH) in U.S. soldiers after a deployment-related concussion. METHODS: A cross-sectional, questionnaire-based study was conducted with a cohort of 978 U.S. soldiers who screened positive for a deployment-related concussion upon returning from Iraq or Afghanistan. All soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury Program that included a history, physical examination, 13-item self-administered headache questionnaire, and a battery of cognitive and psychological assessments. Soldiers with CDH, defined as headaches occurring on 15 or more days per month for the previous 3 months, were compared to soldiers with episodic headaches occurring less than 15 days per month. RESULTS: One hundred ninety-six of 978 soldiers (20%) with a history of deployment-related concussion met criteria for CDH and 761 (78%) had episodic headache. Soldiers with CDH had a median of 27 headache days per month, and 46/196 (23%) reported headaches occurring every day. One hundred seven out of 196 (55%) soldiers with CDH had onset of headaches within 1 week of head trauma and thereby met the time criterion for posttraumatic headache (PTHA) compared to 253/761 (33%) soldiers with episodic headache. Ninety-seven out of 196 (49%) soldiers with CDH used abortive medications to treat headache on 15 or more days per month for the previous 3 months. One hundred thirty out of 196 (66%) soldiers with CDH had headaches meeting criteria for migraine compared to 49% of soldiers with episodic headache. The number of concussions, blast exposures, and concussions with loss of consciousness was not significantly different between soldiers with and without CDH. Cognitive performance was also similar for soldiers with and without CDH. Soldiers with CDH had significantly higher average scores on the posttraumatic stress disorder (PTSD) checklist compared to soldiers with episodic headaches. Forty-one percent of soldiers with CDH screened positive for PTSD compared to only 18% of soldiers with episodic headache. CONCLUSIONS: The prevalence of CDH in returning U.S. soldiers after a deployment-related concussion is 20%, or 4- to 5-fold higher than that seen in the general U.S. population. CDH following a concussion usually resembles chronic migraine and is associated with onset of headaches within the first week after concussion. The mechanism and number of concussions are not specifically associated with CDH as compared to episodic headache. In contrast, PTSD symptoms are strongly associated with CDH, suggesting that traumatic stress may be an important mediator of headache chronification. These findings justify future studies examining strategies to prevent and treat CDH in military service members following a concussive injury.

Posttraumatic headache in military personnel and veterans of the iraq and afghanistan conflicts.

OPINION STATEMENT: Headaches, particularly migraine, are common in US servicemembers (SMs) who are deployed to or have returned from theaters of combat operations in Iraq and Afghanistan. Concussions and exposure to explosive blasts may be a significant contributor to the increased prevalence of headaches in military veterans. Concussions, usually due to blast exposure, occur in approximately 20% of deployed SMs, and headaches are a common symptom after a deployment-related concussion. Posttraumatic headaches (PTHAs) in US SMs usually resemble migraines, and posttraumatic stress disorder (PTSD) and depression are common comorbidities. Treatment of PTHAs in SMs is based upon the treatment setting, whether the headaches are acute or chronic, the headache phenotype, and associated comorbidities. No randomized, controlled clinical trials evaluating the efficacy of therapies for PTHAs have been completed. Pharmacologic and nonpharmacologic management strategies should be selected on an individual basis. Acute therapy with NSAIDs or triptans and prophylactic therapy in acute and chronic settings using valproate, nortriptyline, amitriptyline, propranolol, topiramate, or botulinum toxin are discussed. Triptans and topiramate may be particularly effective in SMs with PTHA. Management of PTHA and other features of the posttraumatic syndrome should be multidisciplinary whenever possible.

Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.

ONC206 is an imipridone derivative that is being developed clinically as a single agent given orally in a first-in-human trial (NCT04541082). This ongoing clinical trial requires pharmacokinetic analysis of ONC206 to fully characterize its pharmacologic profile. There is currently no published bioanalytical method for ONC206 quantitation. To understand the clinical pharmacokinetics of ONC206, a sensitive yet simple uHPLC-MS/MS method for quantitation of ONC206 in human plasma was developed. Protein-precipitation allowed rapid and sensitive bioanalytical measurement of ONC206 in human plasma. A Phenomenex Kinetex C18 (50 ×2.1 mm, 1.3 µm, 100 Å) analytical column achieved symmetrical and sharp chromatography peaks of ONC206 and the internal standard, [2H]7-ONC206, which were detected using multiple reaction monitoring. The assay calibration range was 1-500 ng/mL and was best fit by a linear regression model (r2 > 0.99732 ± 0.0010). The method proved accurate (< ± 9% deviation), precise (<11%CV), selective and specific with no interference and low inter-lot matrix variability. ONC206 demonstrated excellent short-term, long-term, and multiple freeze-thaw cycle stability in solution and human plasma. This fully validated method was used to quantitate ONC206 plasma concentrations from patients enrolled in the aforementioned clinical trial at the NCI to demonstrate its clinical applicability.

Evaluation of the key geriatric assessment constructs in primary brain tumor population - a descriptive study.

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 < 0.05), while older participants were less likely to report feeling distressed (OR = 0.4, p < 0.05). Older participants also had higher CCI and were more likely to have polypharmacy (OR = 1.7, ps < 0.05). Increasing age strongly correlated with worse KPS score (r = -0.232, OR = 1.4, p < 0.001) and worse NFS (r = 0.210, OR = 1.5, p < 0.001). No differences were observed in overall symptom burden, symptom interference, and anxiety/depression scores. DISCUSSION: While commonly used GA tools were not available, the study employed patient- and clinician-reported outcomes to identify potential future research directions for the use of GA in the broader neuro-oncology population. Findings illustrate missed opportunities in neuro-oncology practice and underscore the need for incorporation of GA into routine care of this population. Future studies are warranted to further evaluate the prognostic utility of GA and to better understand functional aging outcomes in this patient population.

The Montreal Cognitive Assessment (MoCA) in neuro-oncology: A pilot study of feasibility and utility in telehealth and in-person clinical assessments.

Background: Cognitive impairments are a common burden for patients with primary CNS tumors. Neuropsychological assessment batteries can be too lengthy, which limits their use as an objective measure of cognition during routine care. The purpose of this study was to evaluate the feasibility and utility of the brief Montreal Cognitive Assessment (MoCA) in routine in-person and telehealth visits (as a result of the global COVID-19 pandemic) with neuro-oncology patients. Methods: Seventy-one adults with primary CNS tumors completed MoCA testing in person (n = 47) and via telehealth (n = 24). Correlation analysis and patient-reported outcomes (PROs), including symptom burden and interference, perceived cognition, general health status, and anxiety and depression, were included in this study. Feasibility was assessed through a provider satisfaction questionnaire. Results: Patients were primarily White (83%), college-educated (71%) males (54%) with high-grade tumors (66%). The average total score on the MoCA administered in person was 25 (range: 6-30), with 34% classified as abnormal, and the average total score via telehealth was 26 (range: 12-30), with 29% classified as abnormal. Providers reported satisfaction in using the MoCA during routine clinical care, both in person and via telehealth. Lower MoCA scores correlated with worse symptom severity, KPS, age, education, and previous treatment. Conclusions: The MoCA was feasible in clinical and telehealth settings, and its relationship to clinical characteristics and PROs highlights the need for both objective and patient-reported measures of cognition to understand the overall cognitive profile of a patient with a CNS tumor.

High-grade gliomas.

OPINION STATEMENT: High-grade gliomas (HGGs) should be treated with maximal, safe surgical resection followed by 57-60 Gy of partial-field external beam or intensity-modulated radiotherapy to a 2 cm margin surrounding the resection cavity. The standard of care for newly diagnosed glioblastoma includes concurrent temozolomide (TMZ) during radiotherapy and adjuvant TMZ for six or more cycles. The optimal role of chemotherapy in anaplastic gliomas is unresolved. Carefully selected patients with anaplastic gliomas can be treated with combination chemotherapy (procarbazine, lomustine, vincristine; PCV) or TMZ as initial therapy after surgical resection, adjuvant therapy after radiotherapy, or at recurrence in patients with anaplastic glioma. Patients with recurrent glioblastoma can be treated with intravenous bevacizumab or dose-intense regimens of TMZ, but selection of optimal candidates for either therapy is unresolved. Other currently available targeted biologic agents are not part of routine management of patients with HGGs. Combination therapeutic trials of antiangiogenic and other targeted agents are ongoing in patients with HGGs. The way forward for patients with HGGs will involve treatments targeting the molecular abnormalities that are important to tumor initiation and growth. All patients with HGGs should be evaluated for clinical trial eligibility at diagnosis and upon recurrence.