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Background and ObjectivesFinancial 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.MethodsPatient 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.ResultsOf 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 andp= 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% CIdifference−5 to −2,p< 0.001, Hedgeg= 0.70).DiscussionBeing 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.

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

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.

Introduction There is a trend towards arthroscopically treating shoulder instability with glenoid deficiency. Despite this, there remains the option for treatment through an open technique. Multiple bone augmentation options are available for recurrent anterior shoulder instability. Objective To provide a systematic review of recent studies for recurrent anterior shoulder instability necessitating glenoid bone augmentation specifically through open procedures using coracoid bone or free bone blocks [iliac crest bone autograft/allograft or distal tibia allograft (DTA)]. Methods PubMed, Cochrane, EMBASE, and Google Scholar were searched for studies reporting open glenoid bone augmentation procedures with iliac crest, tibia, or coracoid bones within 10 years. Extracted data included study/patient characteristics, techniques, prior surgeries, prior dislocations, radiographic findings, range of motion (ROM), recurrent instability, patient-reported outcomes, and complications. Results 92 met inclusion criteria (5693 total patients). Six were studies of iliac crest bone, four of DTA, and 84 using the coracoid bone. 29 studies measured postoperative arthritis showing no development or mild arthritis. 26 studies reported postoperative graft position. 62 studies reported ROM noting decline in internal/external rotation. 87 studies measured postoperative instability with low rates. Rowe Scores with noted improvement across 31/59 (52.5%) studies were seen. Common post operative complications included infection, hematoma, graft fracture, nerve injury, pain, and screw-related irritation. Conclusion Despite a trend towards arthroscopic management of recurrent anterior shoulder instability with glenoid deficiency, open procedures continue to provide satisfactory outcomes. Additionally, studies have demonstrated safe and efficacious use of free bone block graft options in the primary and revision setting.

Glioblastoma (GBM) has a median survival of less than 18 months with infrequent long-term survival (LTS). Reports on LTS to date have not identified distinct molecular or clinical/imaging characteristic in long ( >3 years) versus short (< 3 year) survivors. We identified IDH wildtype GBM patients living ≥ 3 years post diagnosis (LTS, Nf25) and a control cohort (STS, Nf76) from our Natural History Study. Available tissue was analyzed with targeted panel sequencing (Nf25) and methylation analysis (Nf21) for classification, MGMT promoter (MGMTp) status and copy number changes. Median survival and age for LTS and STS was 54mo and 48yrs, and 16mo and 56yrs, respectively. LTS were more likely to be female (2.8x) or have a GTR (2.9x) but 83% less likely to be white. MGMTp was 10x more likely to be methylated in LTS tumors (95% CI [2.6, 39.6]), yet was unmethylated in 17%. LTS were 63% and 90% less likely to have TERTp or EGFR amplification (95% CI [0.14, 0.97] and [0.04, 0.29]). Core pathway review showed 21% of LTS had at least one alteration in p53, RB and RTK/PI3K with RTK/PI3K the most common (46%) . Methylation classifier identified 74% as GBM (STS=96%) with most the RTK II subtype (53%; STS=41%) and despite classic histologic features, indicated a non-GBM diagnosis in three cases (14%).Although uncommon, there are LTS with molecularly confirmed GBM. Remarkably, not all had MGMTp methylation, were young or had extensive tumor resection. Clinical estimates of outcome in GBM patients should consider the possibility of long-term survival even with established poor prognostic factors. Imaging characteristics in a subset of these cases are reported in a separate abstract. Additional interrogation of tumor from LTS may uncover additional determinants of response and outcomes.

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.

The incidence of distal lower extremity fractures in National Basketball Association (NBA) athletes continues to increase. There is a paucity of data regarding return-to-play (RTP) rates and performance after sustaining foot fractures in these athletes. The purpose of this study is to quantify RTP rates and performance in NBA players after sustaining a foot fracture.Sixty-two NBA athletes suffered foot fractures between 2005 and 2021 according to publicly accessible online data. Each athlete was matched to a control player based on age at start of career, age at index injury year, body mass index (BMI), and position played. Performance statistics from 3 seasons prior and 3 seasons following the index injury season were recorded.We found that players who suffered foot fracture injuries are expected to make a full recovery and reach their previous level of performance within three years. 100% of players treated nonoperatively returned to play; meanwhile only 90% of players who were treated operatively returned to play. This difference is statistically significant.NBA athletes have a high RTP rate after sustaining a foot fracture. Players may experience an initial decrease in playing time and performance when returning to play, however, these variables were found to return to baseline over time. After three seasons, player statistics returned to baseline in mostly every category, including player efficiency rating (PER). We found that players are expected to make a full recovery and return to their previous level of performance, regardless of whether they were treated operatively or not. Players treated nonoperatively returned to play at a rate of 100% meanwhile those treated operatively returned at a rate of 90%. Therefore, it is our recommendation that players opt for nonoperative treatment when possible.

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 Mild cognitive impairment (MCI) commonly occurs in primary CNS tumor patients (PCTP). Our group and others have reported on the Montreal Cognitive Assessment (MoCA) as an MCI screening tool. Several abbreviated MoCA protocols have been developed for telehealth administration in other neurological diseases, with varied literature on scoring and clinical utility. We compared MoCA Full and 5-minute scores to assess utility in neuro-oncology. METHODS 71 PCTP completed the MoCA Full (abnormal: < 26/30) assessing: visuospatial/executive functioning, naming, memory, attention, language, abstraction, delayed recall, and orientation. Full scores were retrospectively recoded to the Pendlebury MoCA 5-minute protocol (abnormal: < 10/12) assessing: memory, delayed recall, and orientation. Correlation was assessed using Pearson’s coefficient. Disagreements between tests were examined using t-test and chi-square test. RESULTS Patients were primarily White (83%), college-educated (71%) males (54%) diagnosed with glioblastoma (20%), with average age of 43 years (range: 19-75), KPS > 80 (57%), prior radiation treatment (78%), and imaging surveillance at time of testing (79%). MoCA Full and 5-minute mean scores were 25.3 (SD: 4.8) and 9.9 (SD: 2.3), respectively. MCI was indicated in 32% (n= 23) of patients using MoCA Full and 27% (n= 19) using MoCA 5-minute. Where the protocols disagreed, MCI was detected only by MoCA Full in 6 patients (8%), and MoCA 5-minute in 2 patients (3%). Visuospatial/executive (p= 0.025) and abstraction (p< 0.001) subdomain scores, unique to MoCA Full, were significantly associated with MCI detected only by the MoCA Full; other subdomains, patient characteristics, and total score were not significant. The MoCA versions were highly correlated (r= 0.90). CONCLUSION High correlation and agreement between MoCA Full and 5-minute scores in this neuro-oncology patient population highlight potential telehealth utility of the MoCA 5-minute. Future prospective assessment of the MoCA 5-minute is warranted to describe optimal scoring threshold and utility in neuro-oncology.

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.

To assess the safety and effectiveness of Schlemm canal stenting for reducing intraocular pressure (IOP) in combination with cataract surgery in the United States cohort of the HORIZON study.Twenty-six clinical sites in the U.S.Prospective clinical trial.Eyes with mild to moderate primary open-angle glaucoma (POAG) on 1 to 4 medications, significant cataract, and an unmedicated diurnal IOP between 22 mm Hg and 34 mm Hg after medication washout were randomized 2:1 to receive the Hydrus microstent or no further treatment after successful cataract surgery. Patients were followed for 24 months. Medication washout and diurnal IOP measurements were repeated at 12 months and 24 months.Two hundred nineteen eyes were randomized to microstent implantation and 112 patients to phacoemulsification only. At 24 months, the diurnal IOP was reduced by 20.0% or more in a greater proportion of eyes in the microstent group (78.5% versus 54.5%; P .001). The mean change in the number of medications was -1.2 ± 0.9 (SD) in the microstent group and -0.8 ± 1.1 in the phaco-only group (P .001), and 78.5% of eyes and 39.2% of eyes, respectively, were medication free (difference 38.8%; P .001).Implantation of a Schlemm canal microstent after phacoemulsification significantly reduced diurnal IOP and medication use compared with phacoemulsification only in patients with mild to moderately severe POAG. The combination procedure was equivalent to cataract surgery alone in terms of visual acuity outcomes and the rate of adverse ocular events.

PurposeClinically evaluate intraocular pressure (IOP) measurements taken with a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann prism examining measurement differences correlated to central corneal thickness (CCT) and corneal hysteresis (CH) values.DesignProspective, open-label, randomised, controlled, multicentre reference device accuracy analysis.MethodsA GAT and a modified surface GAT prism measured IOP on 243 unique eyes. The study design and methodology complied with International Standard Organization (ISO) tonometer evaluation guidelines, except the inclusion of thin (600 µm) corneas. All eyes were randomised to IOP measurement by one of five standard Goldmann prisms and five modified prisms. Pressures were measured by six investigators, two times with each prism for a total of 1936 IOP measurements. Analysis included a multiple linear regression including CCT and CH correlation.ResultsThe difference in IOP measurements of the standard and modified Goldmann prisms correlated well to CCT particularly in thin (600 µm) corneas (R2=0.404, p=0.007). Corneal hysteresis (CH) also significantly correlated to the difference in prism measurements (R2=0.125, p=0.039). There was no significant overall mean IOP bias between the two prisms (+0.43 mm Hg in modified, p=0.19).DiscussionThe paired IOP measurement difference between GAT and a modified surface Goldmann replacement prism indicated a statistically significant correlation to CCT and CH. A simple modified replacement prism for any Goldmann-type tonometer may significantly improve IOP measurement accuracy by minimising corneal biomechanical errors associated with CCT and CH.Trial registration numberNCT02990169 and NCT02989909.

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.

Objective To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months. Design Prospective, multicenter, single-masked, randomized controlled trial. Participants Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. Methods Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. Main Outcome Measures The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events. Results A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%–27.8%, P Conclusions This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.

Shoulder pain is a common secondary complication of amyotrophic lateral sclerosis (ALS) that can contribute to functional decline and decreased participation in daily activities. The purpose of this study was to assess the effectiveness of an educational brochure aimed at improving knowledge regarding shoulder pain and dysfunction in people with ALS. Participants completed a preintervention survey with questions regarding their knowledge of how ALS may affect their shoulders. After completing the presurvey, they were mailed a brochure that described shoulder health and range of motion and stretching exercises. Four weeks after receiving the brochure, participants were then asked to determine the effectiveness of the educational materials in terms of impact on shoulder-related knowledge and self-efficacy with regard to prevention of shoulder pain and dysfunction. More than 50% of participants reported pain, decreased range of motion, or weakness in at least one shoulder since being diagnosed with ALS. All participants were interested in receiving educational materials, and all agreed that the brochure was easy to interpret and understand, with most (87%) reporting that it was helpful. Educational brochures are one strategy to improve awareness about shoulder health and to educate patients with ALS about exercises that may help reduce shoulder pain and dysfunction.

Introduction: The increasing prevalence of obesity has been linked to increased risk of cancers such as prostate, breast and endometrium, but its role in thyroid cancer is not clearly established. Since prevalence of obesity-related metabolic disturbances (dyslipidemia, dysglycemia) varies among individuals, it has been suggested that poor metabolic health, rather than obesity (defined by BMI), plays a role in thyroid cancer. We performed a retrospective review of our thyroid cancer cohort to evaluate the association between metabolic health and severity of thyroid cancer. Objectives: 1. Association between dyslipidemia and stages of thyroid cancer 2. Association between dysglycemia and stages of thyroid cancer. Methodology: The Scripps Clinic Thyroid Cancer Cohort includes 656 patients diagnosed with thyroid cancer from 2017-2020 in the Scripps Health System. IRB approval for our study was obtained in January 2020. Inclusion criteria: 1. Confirmed thyroid cancer on surgical pathology 2. First available lipid profile at least 6 months prior to diagnosis 3. First available HbA1c at least 6 months prior to diagnosis. A total of 214 patients with an available lipid profile were included in the analysis. Of those, 148 had an available HbA1c. Definitions used: 1. Dyslipidemia - total cholesterol >=200 mg/dl or HDL =150 mg/dl. 2. Dysglycemia - HbA1c >=5.7%. Thyroid cancer stages were compared in patients with and without dyslipidemia and dysglycemia. Subgroup analysis was performed for patients above age of 55 years (n=103) due to difference in AJCC staging. Results: A larger proportion of dyslipidemic patients (28.4% vs 18.1%) had stage 2-4 thyroid cancer, but the difference was not statistically significant (p 0.07). A larger proportion of dysglycemic patients (36.3% vs 15.6%) had stage 2-4 thyroid cancer, a statistically significant difference (p 0.003). Similar findings were noted on subgroup analysis: a larger proportion of dyslipidemic (15.2% vs 8.2%) patients had Stage 3-4 thyroid cancer without statistical significance (p 0.1), while a statistically significant higher percentage of dysglycemic patients (20% vs 2.7%, p 0.01), had stage 3-4 thyroid cancer. A larger proportion of advanced thyroid cancer cases was noted in patients with both dyslipidemia and dysglycemia as compared to patients with only one abnormality or none. Conclusions: 1. Poor metabolic health, particularly dysglycemia, is associated with advanced stages of thyroid cancer, especially in the >=55 years age group. Dysglycemia with dyslipidemia confers highest probability of advanced thyroid cancer. 2. Mechanisms by which dysglycemia affects thyroid cancer severity requires further rigorous study. 3. Based on our study, we recommend a thorough discussion regarding risk of advanced thyroid cancer in patients with poor metabolic health and thyroid nodules.

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 Goldmann applanation tonometry (GAT) error relative to intracameral intraocular pressure (IOP) has not been examined comparatively in both human cadaver eyes and in live human eyes. Futhermore, correlations to biomechanical corneal properties and positional changes have not been examined directly to intracameral IOP and GAT IOP. Methods Intracameral IOP was measured via pressure transducer on fifty-eight (58) eyes undergoing cataract surgery and the IOP was modulated manometrically on each patient alternately to 10, 20, and 40 mmHg. IOP was measured using a Perkins tonometer in the supine position on 58 eyes and upright on a subset of 8 eyes. Twenty one (21) fresh human cadaver globes were Intracamerally IOP adjusted and measured via pressure transducer. Intracameral IOP ranged between 5 and 60 mmHg. IOP was measured in the upright position with a Goldmann Applanation Tonometer (GAT) and supine position with a Perkins tonometer. Central corneal thickness (CCT) was also measured. Results The Goldmann-type tonometer error measured on live human eyes was 5.2 +/−1.6 mmHg lower than intracameral IOP in the upright position and 7.9 +/− 2.3 mmHg lower in the supine position (p

BACKGROUND: The Glioma International Case-Control (GICC) study is the largest study to date examining genetic and environmental risk factors for adult gliomas. Inverse associations have been repeatedly confirmed for allergies, atopic skin diseases, and viral infections. Evaluations of these risk factors specifically ependymoma has not been completed, due to the rarity compared to other glioma types. Therefore, the purpose of this report is evaluating the associations of these confirmed glioma risk factors with ependymomas. METHODS: Adult ependymoma patients (n=128) enrolled in the NOB-ROS and NHS completed a risk factor questionnaire adapted from the GICC study via a web-based portal. Survey sections related to history of asthma/allergies, common infectious diseases, and regular antihistamine/anti-inflammatory use were examined. Ependymoma patients exposed to these factors were calculated and compared to control (n=1,534) and glioma cases (n=1,339) from a published report (Scheurer, 2011). Odds ratios were calculated for ependymoma using the published controls to compare risk factor effects between ependymoma and glioma cases. RESULTS: The sample was mostly female (62%), median age=45, white (95%), diagnosed with an ependymoma (52%)in the spine (66%). Ependymoma patients were: less likely to have history of asthma/allergy (41%) than controls (66%; OR 0.36, p

BACKGROUND: A unified data collection system for interrogating the clinical trajectory of patients and their molecular pathology is of significant diagnostic, research, and therapeutic importance. The NCI-NHS follows primary CNS tumor patients throughout their disease. A targeted NGS panel was developed for clinical screening of mutations in 56 genes, 21 copy number alterations, and 25 gene fusion pairs using archived FFPE tissue. Due to the nature of study, available specimens range in age and source, posing a considerable challenge to obtaining an adequate quality and quantity of nucleic acid for genomic analysis. METHODS: Tumor blocks or unstained slides were received for macrodissection of neuro-pathologist scored tumor tissue. DNA and RNA were extracted, using the Qiagen AllPrep FFPE Kit on a semi-automated QIAcube instrument, and sequenced on Ion Torrent NGS platform. RESULTS: Tissue material from 227 patients was submitted, 17(8%) were rejected for low tumor content (

BACKGROUND: Survivorship is an important area of cancer care and research. There are limited studies exploring the experience of long term survivors of CNS tumors. A recent review of quality of life in adults with CNS tumors underscored the need for studies exploring patient outcomes, including mood disturbance. This report explores mood disturbance in CNS tumor patients living greater than 5 years from diagnosis. METHODS: Patients enrolled on the NOB-NHS were included. PROMIS depression/anxiety measures were completed at study entry. T-scores >60 were considered significant. Independent sample t-tests, chi-square and Fishers Exact tests were used to identify associations with mood disturbance. Significance level was set at 0.05. RESULTS: 132 patients, primarily white (84%), males (58%), with median age 49 (22–81), were included with 59% having low grade tumors; oligodendroglioma (19%) was the most common diagnosis, 30% underwent gross total resection, 33% had had a recurrence and 27% had a poor KPS (80). Five percent were on corticosteroids and 20% on psychotropic medications. Overall, 14% and 18% reported significant depression and anxiety respectively, with 10% reporting both. More non-white [29% vs 11%; X2 (1) = 4.4, p

Primary CNS tumor patients are highly symptomatic, with 40% of brain tumor patients reporting 3 moderate-severe symptoms. The five most commonly reported are fatigue, drowsiness, difficulty remembering, disturbed sleep in brain and in spine patients, pain, numbness, leg weakness, and autonomic dysfunction (bowel and sexual dysfunction). Twenty-five percent reported interference with activity and mood. These reports are limited to primarily white patients, with limited studies exploring in more diverse samples. Fifty patients self-identified as non-white are included in this report of symptom burden (MD Anderson Symptom Inventory-Brain and Spine Tumor), depression and anxiety (PROMIS measures). Descriptive statistics, and standardized classification of severe symptoms and mood are used to describe the sample characteristics Chi-square and Fishers exact test were used to identify associations. Significance level was set at p< 0.05. The majority of patients were male(62%), Black/African American(38%). Median age 40(range 14–69), 44% had a gross total resection at diagnosis. Glioblastoma was the most common diagnosis(40%) with 1/3 having a poor(KPS 80) and a recurrence, and 56% having completed treatment. All spine and 34% of brain tumor patients had at least three symptoms rated as moderate-severe. The top five among brain tumor patients were weakness in arms/legs, fatigue, disturbed sleep, difficulty remembering, and feeling irritable and 57% reported moderate-severe activity related interference from symptoms. Fourteen percent of patients reported having moderate-severe depression and anxiety symptoms at study entry. Diagnosis other than glioblastoma was associated with depression symptoms (X2(1)= 5.4, p< 0.04), but no associations between clinical and demographic factors were found with interference, depression, or anxiety. Minority populations are highly symptomatic, but differences in symptoms reported as most severe were found when compared to historical data which is a restricted patient demographic. Future studies exploring symptom prevalence, underlying risk and treatment in diverse populations are warranted.

BACKGROUND: Body image is an important psychosocial issue in cancer patients, including those with primary brain tumors (PBT). Investment in physical appearance is associated with depression and quality-of-life (QoL) outcomes in non-CNS malignancies. Therefore, examination of body image investment is warranted to better understand factors involved in body image disturbance in the PBT population. METHODS: A cross-sectional survey of 100 PBT patients was conducted as part of an IRB approved prospective protocol. Participants completed the 10-item Body Image Scale (BIS), and the 20-item Appearance Schemas Inventory-Revised (ASI-R) which includes self-evaluative and motivational salience subscales. Potential BIS and ASI-R scores ranged from 0–30 and 1–5 respectively. Cronbach’s alpha assessed reliability. Pearson’s correlation coefficients assessed relationships between questionnaires. Significance level was p< 0.05. RESULTS: Patients were mostly male (56%) with a median age of 48 (range 23–74). Glioblastoma was the most common diagnosis (32%). Median time from initial diagnosis was 5 years (range 0–22), and 64% of patients had a KPS≥ 90. Median BIS score was 5 (range 0–27), ASI-R composite score was 2.9 (range 1.5–4.7), self-evaluative subscale score was 2.6 (range 1.2–4.5), and motivational subscale score was 3.4 (range 1.9–5.0). BIS was significantly correlated with ASI-R composite (r=0.53, 95%CI: 0.37 to 0.65), ASI-R self-evaluative (r=0.65, 95%CI: .52 to .75), but not ASI-R motivational (r=0.14, 95%CI: -0.06 to 0.33, p=0.17) scores. Increased severity of altered body image was correlated to increased negativity of the patient’s belief about their appearance. Cronbach’s alpha for the ASI-R composite, self-evaluative and motivational subscales were 0.87, 0.85, and 0.81 respectively. CONCLUSIONS: Body image and investment are important QoL issues for PBT patients. The ASI-R demonstrated good internal consistency in this population. While there was significant correlation between BIS and ASI-R composite and self-evaluative scores, this was not true with the motivational score.

BACKGROUND: Body image dissatisfaction is associated with difficulty coping and adjustment in patients with other solid tumors. Although PBT patients may be at increased risk due to the visible disfigurement and debilitating nature of the disease, there is limited research in this patient group. The purpose of this report is to present the qualitative analysis of data captured on the NOB-NHS Body Image Study. METHODS: 100 patients participated by completing structured questionnaires and open-ended responses. Seventy-two patients provided open-ended feedback exploring, How have the changes affected you? within the Feedback Form. Qualitative analysis software (MAXQDA) allowed for text coding of response data to identify recurrent themes. RESULTS: The sample was primarily white (82%), males (58%) median age=50 (range 23–74), diagnosed with glioblastoma (36%). Only 10 (8%) indicated no body image issues. Five dominant themes (lifestyle changes, symptom effects, negative & positive outlook, changes in appearance) characterized participant description of body image since their diagnosis. A number of patients (28%) expressed a hindrance within their lifestyle (altered mobility, independence, activity, and changes in relationships) contributing to this theme. Participants described symptom effects (weight gain, fatigue, pain, vision changes) contributing to dissatisfaction throughout the disease trajectory. Specific changes in appearance (hair loss, indentation on head, skin dryness) were also problematic factors affecting adjustment and coping. An ascribed negative outlook (9%) (self-conscious, feeling ashamed or vulnerable) magnified awareness of long-term permanent changes, but some (8%) described the implementation of a positive outlook (using exercise and hope) allowing for acceptance of these changes. CONCLUSION: These findings offer insight from the patients perspective on identified physical, mental and treatment-related factors regarding body image concerns and the scope of issues faced by PBT patients. Understanding patient concerns allows for a multidimensional approach in management of key areas with the goal of improving overall quality of life.

Purpose To clinically evaluate a modified surface Goldmann applanation tomometer (GAT) prism for intraocular pressure (IOP) accuracy, repeatability, and safety. Design Prospective, open-label, randomized, controlled, multicenter reference device reliability and validity analysis. Methods A GAT and a modified surface GAT prism measured IOP on 173 unique eyes. The study design and analysis complied with FDA 510(k) and ANSIZ80.10-2014 guidelines. All eyes were randomized to IOP measurement by 1 of 5 standard prisms or 5 modified prisms, each from a different manufacturing lot. Pressures were measured by 6 investigators, 2 times with each prism, for a total of 1384 IOP measurements. Analysis included Bland-Altman difference accuracy, intraoperator and interoperator IOP measurement, and manufactured lot repeatability. Results Bland-Altman indicated no IOP measurements pairs outside the ±5 mm Hg guidelines. Operator and manufactured lot repeatability F tests and 1-way ANOVAs indicated no statistical difference between the standard and modified prisms (all P > .10). The difference in IOP measurements of the standard and modified prisms correlated well to Dresdner central corneal thickness (CCT) correction (P = .01). Conclusion A modified surface replacement prism is statistically equivalent to a flat-surfaced prism. The modified surface prism indicated statistically significant correction for CCT requiring further testing outside the ANSI standard limits (0.500 mm

Define the effectiveness of a topical non-steroidal anti-inflammatory drug (NSAID) added to topical steroid use after uncomplicated phacoemulsification for the prevention of pseudophakic cystoid macular edema (PCME) using a prospective, randomized, double-masked, placebo-controlled clinical study. Eyes (1000) were randomized to placebo (497) or nepafenac 0.3% (503) used once daily, post-operatively for 5 weeks at two ophthalmology clinics. Diagnosis of PCME was made by clinical, ocular coherence tomography (OCT), and with fluorescein angiography confirmation. Correlation of PCME to NSAID use and the presence of pre-operative risk factors for PCME were assessed including, contralateral PCME, diabetic retinopathy, retinal vein occlusion, macular hole, epiretinal membrane, macular degeneration, retinal detachment repair, and prostaglandin use. PCME was the most common complication associated with routine cataract surgery (4.2% with PCME risk factors, 2.0% with risk factors excluded). Topical nepafenac 0.3% significantly reduces the incidence of PCME compared to placebo when used after routine cataract surgery (p = .0001). When patients with pre-operative risk factors are excluded, the incidence of PCME between treatment and placebo groups is equivalent (p = 0.31). PCME relative risk (RR) was most significant in contralateral PCME (RR 19.5), diabetic retinopathy (RR 13.1), retinal vein occlusion (RR 12.9), macular hole (RR 7.7), and epiretinal membrane (RR 5.7). Prostaglandin use and previous retinal detachment were not shown to increase risk. Pseudophakic cystoid macular edema is common after phacoemulsification cataract surgery. Topical nepafenac 0.3% reduces PCME in patients with pre-operative risk factors for PCME compared to placebo but shows no benefit in patients without pre-operative risk factors. NIH ClincalTrials.gov retrospectively registered January 15, 2017, NCT03025945 .

PURPOSE To describe multicolor scanning laser imaging (MSLI) and conventional fundus photography findings in lipemia retinalis (LR). METHODS We report two LR cases. The first case is a 47-year-old diabetic woman with LR secondary to familial hypertriglyceridemia examined with MSLI, conventional fundus photography, and optical coherence tomography (OCT). The second case is a 39-year-old diabetic man with hypertriglyceridemia and LR. He was followed over time with conventional fundus photography of his retina until metabolic control was achieved. RESULTS In the first case, MSLI showed retinal arteries with an intense yellow and retinal veins with a pale yellow color. Fundus photography disclosed only mild pale red vessels. Optical coherence tomography detected macular edema and hyperreflective changes of retinal vessels. In the second case, fundus photography showed vessels with a pale red appearance that normalized after metabolic control of triglycerides. CONCLUSION We described the retinal findings in patients with LR using different image modalities. Specifically, we report the findings with MSLI not previously described. While regular fundus photography may show mild changes in LR, the MSLI modality may show more significant findings assisting in the diagnosis and follow-up of this disease.

PurposeThe aim of this study is to test a technological solution to two traditional limitations of information sharing between law enforcement agencies: data quality and privacy concerns.Design/methodology/approachEntity Analytics Software (EAS) was tested in two studies with North American law enforcement agencies. In the first test, duplicated cases held in a police record system were successfully identified (4.0 percent) to a greater extent than the traditionally used software program (1.5 percent). This resulted in a difference of 11,954 cases that otherwise would not have been identified as duplications. In the second test, entity information held separately by police and border officials was shared anonymously between these two organizations. This resulted in 1,827 alerts regarding entities that appeared in both systems; traditionally, this information could not have been shared, given privacy concerns, and neither agency would be aware of the relevant information held by the other. Data duplication resulted in an additional 1,041 alerts, which highlights the need to use technological solutions to improve data quality prior to and during information sharing.FindingsThe current study demonstrated that EAS has the potential to merge data from different technologically based systems, while identifying errors and reducing privacy concerns through anonymization of identifiers.Originality/valueWhile only one potential technological solution (EAS) was tested and organizations must consider the potential expense associated with implementing such technology, the implications resulting from both studies for improved awareness and greater efficiency support and facilitate information sharing between law enforcement organizations.

BACKGROUND: Perception of body image is an important issue for cancer patients, as patients with body image concerns are susceptible to psychosocial consequences such as depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with similar heightened risk due to visible disfigurement and lifestyle alterations, such as in head and neck tumors, currently no data exists of this QoL issue in patients with primary brain tumors (PBT). METHODS: A cross-sectional survey of 100 PBT patients was conducted as part of an IRB approved prospective protocol using structured questionnaires. Participants completed the 10-item Body Image Scale (BIS) questionnaire to assess the prevalence of body image disturbance. Clinically significant body image disturbance was defined as a BIS score ≥ 10. Cronbach’s alpha was used to assess reliability. RESULTS: The median age was 48 (range 23–74), 86% were Caucasian, and 56% were male. Glioblastoma was the most common diagnosis (32%), with low grade tumors (I-II) representing 30% of the sample. Median time from initial diagnosis was 5 years (range 0–22), and 64% of patients had a KPS of ≥ 90. Overall, the median BIS score was 5 (range 0–27). The prevalence of clinically significant body image disturbance was 28% (95%CI: 19%-37%). Cronbach’s alpha for the BIS in this population was 0.91, with all 10 items contributing to its reliability. CONCLUSIONS: This is the first study to explore altered body image in PBT patients. Clinically significant body image disturbance was present in nearly 1/3 of patients, and was similar to other solid tumor patients felt to be at heightened risk. The BIS demonstrated good internal consistency. This data supports future research into the characteristics and etiology of this QoL issue among PBT patients.

BACKGROUND: The use of molecular diagnostics is an integral component of CNS cancer care. The NIH NOB PBTP includes 80 alterations (55 mutations/copy number variations and 25 gene fusions) identified as relevant to the primary CNS patient population. We have previously reported on the diagnostic utility. Identified therapeutic target results from the PBTP are reported here. METHODS: PBTP results from patients enrolled on the NOB NHS are reported. Targetable alterations were defined using the NCI MATCH trial list. The proportion of cases with identified alterations based on recognized diagnostic histology and recurrence are reported. RESULTS: 190/282 (67%) PBTPs reported significant alterations; 132 from initial diagnosis and 58 recurrent samples;10 had two sequential samples analyzed. Astrocytoma, grade 2–4 (126/190, 66%), was the most common histologic tumor type. Over 60% of cases had a unique alteration profile, appearing only once in the data set. At diagnosis 74% had 1–3 alterations. At recurrence 45% had >3, and 9% had > 7 alterations. New and increasing alterations were seen in 80% (8/10) of sequential cases, with 1 case showing an entirely different alteration pattern. Targetable alterations were identified in 87/190 (46%) PBTP results. Exclusively in astrocytomas, EGFR (19%), and CDK4/CDK6 (12%) were found. Less frequent were: BRAF (5%) (8 astrocytomas, 2 pleomorphic xanthoastrocytoma), FGFR (3%) (5 GBM, 1 rosette-forming glioneuronal tumor), MET (3%) (3 GBM, 1 anaplastic oligodenroglioma, 1 anaplastic ependymoma), PTCH1 (3%) (3 astrocytoma, 1 ependymoma, 1 medulloblastoma), NTRK (2%) (2 astrocytomas, 1 oligodendroglioma). CONCLUSIONS: The PBTP has demonstrated diagnostic and therapeutic utility, with actionable targets found in nearly half of analyzed samples. The profile and number of alterations was higher at recurrence, underscoring the need for contemporary resampling and analysis. Importantly, 2/3 of the results showed a unique alteration profile highlighting the unique nature of each patients tumor.