MD Anderson Symptom Inventory-Brain Tumor Research Articles

Abstract 6304: Seizure self-report and monitoring: Agreement between patient and clinician report and implications for care in patients with IDH-mutant and IDH-wild type gliomas

Abstract Primary brain tumor (PBT) patients commonly experience seizures, which can be measured and monitored by a variety of tools. Here, we explore the concordance between 2 tools and their use in reporting seizures over time among PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong). Patients complete the M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT), which measures symptom severity (including seizure) within the last 24 hours from 0-10; and, as part of the same visit, pairs of clinicians and patients complete the Seizure Control Composite Index (RANO-SCCI), which includes the questions ‘Have you ever had a seizure’ (RANO-SCCIQ1) and ‘Have you had a seizure since your last clinic visit’ (RANO-SCCIQ2). Responses to each measure are reported in aggregate and by IDH status. Participants included 89 patients with gliomas who were primarily white (84%) males (62%) with a median age of 48 years (range: 27-78) and KPS ≥ 90 (85%). Based on patient reports, 65% endorsed ever having a seizure (RANO-SCCIQ1), 17% had a recent seizure (RANO-SCCIQ2), and 12% had a seizure within the last 24 hours (MDASI-BT). For the RANO-SCCIQ1 data, patients and clinicians generally agreed except for 6 pairs (7%) where clinicians indicated a seizure but patients did not. Of the 59 who reported recent seizures (RANO-SCCIQ2), two pairs (3%) disagreed, with patients indicating a recent seizure but clinicians not endorsing a seizure had occurred. Good overall agreement (86%) was observed between the RANO-SCCIQ2 and MDASI-BT for both clinician and patient responses, with 3 and 2 paired disagreements respectively, in which seizures were indicated in the last 24 hours but not recorded as a recent seizure on the (RANO-SCCIQ2). Comparing clinician report of seizures in those with IDH-mutated (n=39) to IDH-wildtype (n=15) tumors, 85% (33/39) versus 47% (7/15) reported ever having a seizure and 7 of 33 (21%) with IDH-mutant and 1 of 7 (14%) with IDH-wild type (IDH-WT) tumors respectively reported a seizure since the last visit. Disparities in recognition of seizures between patient and clinician highlights a need for patient education to increase awareness of events and recognition of ongoing risk. Although those with IDH-mutated tumors are at higher risk of having seizures, nearly half of those with IDH-WT reported ever having seizures, underscoring the need for all patients to be educated on recognizing and assessing seizure symptoms. Citation Format: Hope Miller, Ewa Grajkowska, Alvina Acquaye-Mallory, Anna Choi, Jennifer Reyes, Mark R. Gilbert, Edward K. Avila, Terri S. Armstrong, Elizabeth Vera. Seizure self-report and monitoring: Agreement between patient and clinician report and implications for care in patients with IDH-mutant and IDH-wild type gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6304.

Abstract 6305: Evaluating clinical and sociodemographic risk for symptom-related functional interference in the primary brain tumor population

Abstract Purpose: Primary brain tumors have a high propensity for causing physical and activity-related disabilities due to the location within the brain and use of targeted treatments resulting in significant symptom burden. In other cancers, physical function impacts mood, quality of life, and even mortality. This exploratory study aims to identify factors associated with activity-related functional interference in a cross-sectional cohort of 584 primary brain tumor patients enrolled in a natural history study (NCT03251989, PI: T.S. Armstrong). Methods: Sociodemographic (age, race, ethnicity, income, education, employment, body mass index [BMI]) and disease-related clinical data were collected at study entry. Activity-related interference (work, walking, and general activity) and health status were reported via the MD Anderson Symptom Inventory-Brain Tumor. Activity-related interference means ≥ 2 were categorized as moderate/severe. Logistic regression assessed univariate associations with moderate/severe interference, with sig. <0.05. Results: This sample had a median age of 49 years (range 18-85), and was mostly male (57%), with a high-grade tumor (grade 3/4) (74%), glioblastoma (39%), on active treatment (21%) and prior tumor recurrence (49%). Risk factors for moderate/severe activity-related interference included: ≥ 2 surgeries (OR = 1.55, 95% CI [1.11, 2.18], P = 0.011), ≥ 2 radiation treatments (OR = 2.87, 95% CI [1.59, 5.17], P < 0.001), currently on active treatment (OR = 1.47, 95% CI [0.97, 2.22], P = 0.066), disease progression (OR = 1.87, 95% CI [1.24, 2.84], P = 0.003), prior recurrence (OR = 1.57, 95% CI [1.13, 2.19], P = 0.007), and poor KPS (OR = 3.61, 95% CI [2.55, 5.12], P < 0.001), but not tumor grade (OR = 1.05, 95% CI [0.72, 1.54], P = 0.790). Sociodemographic risk factors for moderate/severe activity-related interference included: less than a high school education (OR = 2.03, 95% CI [1.18, 3.51], P = 0.011), on disability (OR = 3.20, 95% CI [1.79, 5.71], P < 0.001), or unemployed (OR = 3.81, 95% CI [2.34, 6.19], P < 0.001), an annual income less than $49,999 (OR = 2.62, 95% CI [1.28, 5.35], P = 0.008), or childhood in a rural area (OR = 1.87, 95% CI [1.24, 2.84], P = 0.003), but not BMI, smoking status, or past physical activity in the 10 years prior to report. Conclusion: As expected, activity-related interference is associated with disease and treatment associated clinical characteristics, with significant risk derived from sociodemographic factors such as education, childhood environment, employment, and household income. Future studies should further explore these associations longitudinally to identify individuals at the highest risk of activity-related interference due to their brain tumor as well as interventions designed for those who may be socioeconomically disadvantaged. Citation Format: Bennett Ann McIver, Tara S. Davis, Kimberly Reinhart, Elizabeth Vera, Anna Choi, Tricia Kunst, Morgan Johnson, Ewa Grajkowska, Hope Miller, Terri S. Armstrong, Michelle L. Wright. Evaluating clinical and sociodemographic risk for symptom-related functional interference in the primary brain tumor population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6305.

Abstract 7448: Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients

Abstract Background: Primary brain tumors (PBT) are associated with neurocognitive symptoms as a direct result of the tumor or its treatment. IDH-mutant gliomas are associated with longer survival, but with higher incidence of seizures and neurocognitive symptoms.​ Correlations between cytokines and neuroinflammation have been reported in other structural brain lesions but have not been evaluated in PBT. Here, we investigate elevated peripheral blood levels of proteins (cytokine levels) in a cross-sectional cohort (n=47) of adult, IDH-mutant PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong) versus healthy subjects (n=32) and the correlations between cytokine levels and patient-reported outcomes (PROs). Methods: Patient-reported symptoms and activity-related interference were collected via the MD Anderson Symptom Inventory-Brain Tumor at study entry. Serum samples were stored at -80°C for batch processing and used for biomarker analysis. Ten cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) were quantified in duplicate using an immunoassay (V-Plex/Proinflammatory, Meso Scale Discovery [MSD], Rockville, MD). Lab personnel were blinded to diagnosis and patient clinical status. Mean concentration (pg/mL) levels or ‘present or not detectable’ values were used. Descriptive statistics, Mann-Whitney tests, and Spearman correlations were conducted at p <0.05. Results: The patient sample was mostly male (62%), White (70%), employed (64%), had no prior recurrence (62%), high grade (3-4) tumors (70%), and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The healthy subject sample was mostly female (53%) and White (72%), with an average age of 46 years (SD: 19; median: 50; range: 19-78). Five cytokines (IFN-γ, IL-6, IL-8, IL-10, and TNF-α) were detectable in patients and healthy subjects with levels of IL-6, IL-10, and TNF-α higher in patients than healthy subjects. Serum levels of IL-10 (mean rank=50.7 vs 24.3, p<0.001) and TNF-α (mean rank=50.6 vs 24.2, p<0.001) were higher in PBT patients when compared to healthy subjects. Only IL-10, but not other cytokines, positively correlated with severity of patient-reported symptoms [pain (r=0.290, p=0.048), numbness/tingling (r=0.302, p=0.039)], and activity-related interference, including work (r=0.323, p=0.027), and walking (r=0.402, p=0.005). Conclusions: Higher IL-10 levels and detection differences in other cytokines, may indicate a reduction in immune-mediating processes and heightening inflammation in patients. Future analysis will include replication of this work in a larger cohort across PBT types to evaluate risk, explore mechanisms, and associations with treatment types. Citation Format: Kaitlynn A. Slattery, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, McKenzie C. Kauss, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7448.

Abstract 7453: Psychometric analysis of Neuro-QoL Perceived Cognitive Function tool in primary brain tumor patients

Abstract Cognitive dysfunction is commonly reported but variable in course and severity in the primary brain tumor (PBT) population. Brief, reliable, and sensitive measures of patient-reported outcomes (PRO) of cognitive symptoms on function are needed for clinical care and research. This study aims to assess the reliability and validity of the Neuro-QoL Perceived Cognitive Function tool (NQC) and explore associations with symptoms and objective testing of cognitive dysfunction in a cohort of PBT patients enrolled in a natural history study (NCT02851706: PI T. Armstrong). Patient sample characteristics and PROs, including NQC (<40 = moderate/severe (MS) dysfunction), a symptom burden measure (MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), scores ≥5 = MS) and the Montreal Cognitive Assessment ((MoCA), scores ≤ 25 indicating cognitive impairment (range: 0-30)) were collected. Descriptive statistics and a psychometric analysis consisting of bivariate correlations, Cronbach’s alpha, and factor analyses using principal axis factoring with nonorthogonal rotation were performed. Cohen’s kappa and correlation were used to assess agreement between objective and subjective measures of cognitive function. The cohort included 327 patients who completed the NQC at study entry [median age: 47 years (range: 18-85), primarily white (78%) males (55%) with high-grade tumors (73%), 65% with a Karnofsky Performance Status (KPS) ≥ 90 (good), and 29% reporting MS cognitive dysfunction]. Factor analysis of the NQC identified two underlying factor groupings: concentration/focus and executive function with Cronbach’s alphas of 0.92 and 0.91 that are interpretable and provided adequate fit for the data. While the NQC was moderately correlated with several MDASI-BT symptom factors, it was highly associated with the cognitive factor (r = -.646). To assess agreement, a subset of patients also completed the MoCA (n=172). These were primarily male (58%), white (79%), had high-grade tumors (67%), and a good KPS score (67%). In this subset, 24% had MS cognitive dysfunction as measured by the NQC while 44% were cognitively impaired using the MoCA resulting in a kappa agreement of 0.07. The correlation between the MoCA score and NQC T-score was -0.292. Understanding the impact and prevalence of cognitive symptoms, objective cognitive testing, and perceived impact is essential for PBT patient care and identifying supportive care interventions. Select NQC psychometric properties demonstrate reliability and validity in this population, with strong agreement with self-report of cognitive symptoms but weaker correlation with objective testing, highlighting the variability in perceived impact. Future research in cognitive function will explore the use of objective testing and perceived impact, its predictors in select populations (i.e., IDH-mutant tumors), and examine its association with biomarkers. Citation Format: Morgan L. Johnson, Elizabeth Vera, Kimberly Reinhart, Hope Miller, Anna Choi, Tricia Kunst, Bennett McIver, Ewa Grajkowska, Michelle L. Wright, Terri S. Armstrong, Tito Mendoza. Psychometric analysis of Neuro-QoL Perceived Cognitive Function tool in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7453.

Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001.

Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT. An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated. The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P = .03), whereas patients living < 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48-0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76-2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43-0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78-1.50, P = .48). Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.

Differences in Symptom Burden in Primary Brain Tumor Patients Based on Sex, Race, and Ethnicity: a Single-Center Retrospective Study.

Symptom burden affects quality of life and prognosis in primary brain tumor (PBT) patients. Knowing whether symptom burden varies based on sex, race, or ethnicity may affect the interpretation of the relationship between symptoms and survival may reveal issues with applying the tools to measure symptom burden to different groups and may identify inequities in symptom management that need to be addressed at a system level. To determine whether symptoms in PBT patients vary across demographic groups, we conducted a retrospective chart review of symptom burden collected as part of routine care in a diverse population. Patient demographics and scores on the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) module were extracted from the electronic medical record for patients seen in the Inova Neuro-oncology Clinic between March 2021 and June 2022. MDASI-BT scores were compared based on side of tumor, sex, race, and ethnicity for the entire population and for the subset with gliomas. We included 125 people, of whom 85 had gliomas. For both the entire group and the subgroup with gliomas, about 40% were female and about 40% were non-White race. No differences in symptom burden were seen between males and females. Pain and numbness/tingling symptom burden were higher in both the entire population and the glioma subgroup for people of Hispanic/Latino/Spanish ethnicity and for people of races other than White or Middle Eastern self-identification. Pain, weakness, and numbness/tingling varied significantly across racial and ethnic groups. Further research is needed to validate this finding in other populations and determine its cause.

JS01.5.A PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA. A CERN STUDY

Abstract BACKGROUND Most adults with ependymoma undergo tumor resection at the time of diagnosis, which may be followed by radiation. At recurrence, re-resection and/or (re)-irradiation may be given, however, there are few established chemotherapy treatments. A previous retrospective report of 8 patients treated with carboplatin and bevacizumab showed a high response rate with 6 patients demonstrating an imaging response (Green, Neurology 2009). We sought to further investigate this regimen with a prospective trial. MATERIAL AND METHODS We performed a prospective phase 2 study in the CERN Adult Clinical Trials Network. Adult patients with recurrent or progressive ependymoma were enrolled to receive carboplatin (AUC =4-5) every 4 weeks for up to 6 cycles and bevacizumab at 10mg/kg every 2 weeks for one year, with the option to continue until progression or toxicity. The primary endpoint was 12-month PFS rate and &amp;gt;50% defined efficacy. Serial symptom burden measurement at baseline and at the time of disease evaluation using MD Anderson Symptom Inventory-brain tumor (MDASI-BT) or MDASI-Spine patient-reported outcomes (PROs) were used to evaluate the clinical impact of PFS. RESULTS A total of 22 patients with median age of 45 years were accrued and treated; 11 were women. WHO grade was 3 in 13 patients and grade 2 in 9 patients (3 with myxopapillary ependymoma) Ten patients had only spinal cord disease, 3 had both spinal cord and brain involvement and 9 patients had brain involvement alone (6 supratentorial, 3 infratentorial). Previous treatments included radiotherapy in all 22 patients and alkylating chemotherapy in 9 patients. Treatment was well tolerated with expected myelotoxicities and hypertension. The Kaplan-Meier calculated 12-Month PFS rate was 76.4% (95%CI 52.2%, 89.4%), median PFS = 18 months (95%CI 12.2, +∞). There were 2 partial responses (9.1%). Brain tumor responders (objective response or stable disease) showed reduction while non-responders had an increase in both neurologic and cognitive symptoms but similar report of other symptoms. Spine tumor responders and non-responders both showed worsening disease-related symptoms; autonomic symptoms worsened in responders. Activity related interference worsened for all patients. CONCLUSION This treatment regimen was safe and met the primary efficacy endpoint of 12-month PFS rate. The improvement in disease-related symptoms in brain tumor patients supports that the achieved disease stability was clinically meaningful, but the increased activity-related interference suggests that treatment-associated symptoms may impact work, general activity, and walking ability during treatment. Improvements in spine tumor disease-associated symptoms were not seen. A confirmatory trial is warranted to further investigate the findings and to determine if there are differences in response amongst ependymoma subtypes and tumor location.

Fatigue and Its Contributing Factors in Chinese Patients with Primary Pituitary Adenomas.

Pituitary adenomas (PAs) refers to a group of benign tumors that develop in the pituitary gland and are often characterized by fatigue. However, fatigue has not been documented in any Chinese research involving people with primary PA. The study sought to examine the prevalence, predictors, and correlation of fatigue with the quality of life (QoL) among PA patients in China. In total, 203 primary PA patients were included in this cross-sectional study. A series of questionnaires were administered, including the Multidimensional Fatigue Inventory (MFI), M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT), Short-Form 36 Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). Data analysis was accomplished by Pearson or Spearman correlations, linear regression, and simple path analysis. Severe fatigue prior to the initial diagnosis and preparation for surgery affected 50% of PA patients. Depression, sleep disturbance, and MDASI-BT symptom total scores were independently able to predict patient fatigue. Sleep disturbance mediates the influence of depression on fatigue (IE sleep = 0.296, 95% CI: LB = 0.148 to UB = 0.471). Chinese patients with primary PA often report experiencing fatigue. Depression and poor sleep quality were shown to be significant contributors to PA patients' fatigue. Depression affects PA patients' fatigue directly or indirectly. Medical professionals should take a proactive approach to PA patients suffering from fatigue before initial diagnosis and preoperative preparation to determine necessary interventions early, thus reducing fatigue and ultimately enhancing their QoL.

Relationship between RANO-PRO Working Group standardised priority constructs and disease progression among malignant glioma patients: A retrospective cohort study.

Recognising the importance of clinical outcomes assessments (COAs), the Response Assessment in Neuro-Oncology-Patient Reported Outcome (RANO-PRO) Working Group recommended inclusion of core symptoms and functions in clinical care or research for malignant glioma patients. This study evaluated the association of the recommended symptoms (pain, perceived cognition, seizures, aphasia, symptomatic adverse events) and functions (weakness, walking, work, usual activities) with disease progression in these patients. In this retrospective cohort study, patients with malignant glioma were included from the US National Cancer Institute Neuro-Oncology Branch Natural History Study (NOB-NHS) which follows primary central nervous system tumour patients aged 18 years and older throughout their disease trajectory. The M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT), EQ-5D-3L, Karnofsky Performance Status (KPS), and Neurologic Function scores (NFS) were evaluated in relation to disease progression by chi-square tests, independent- and paired-samples t-tests, adjusted for multiple comparisons at first assessment and over time to a second assessment. Radiographic disease progression was determined on the interpretation of the imaging study by a radiologist and neuro-oncologist using standard criteria as part of clinical trial participation or routine standard of care. The priority constructs were evaluated to provide initial evidence of their relevance, relationship to disease status over time, and sensitivity to change in a diverse group of patients with malignant glioma. Seven hundred and sixty-five patients had enrolled into the NOB-NHS between September 1, 2016 and January 31, 2020. Three hundred and thirty-six patients had a diagnosis of a malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, and gliosarcoma) and were included in the current study. The sample was 64% male (n=215), 36% female (n=121), median age of 52 years (IQR=18.75), 82% White (n=276), and 65% had tumour recurrence (n=219). One hundred and fifty-four (46%) had radiographic disease progression. Difficulty remembering, fatigue, and weakness were worse in the group whose imaging was interpreted as radiographic disease progression versus stable disease, as well as the functions of walking, work, activity, and self-care (1.1 < difference < 1.8). Patients with disease progression were four times more likely to have a poor KPS (≤80) and worse NFS. Among patients with disease progression at a second assessment (n=112), all symptoms, except seizures, worsened between first assessment and disease progression and up to 22% of patients (n=25) reported worsening mobility, self-care, and usual activity; 46% (n=51) and 35% (n=30) had worsened KPS and NFS, respectively. On average, 4 symptoms or functions (SD=3) were reported as moderate-to-severe and 30% (n=33) and 23% (n=26) had a change to moderate-to-severe fatigue and walking, respectively, at time of disease progression. Over 7% of patients with worsening (n=7 of 100) reported every symptom and function as having changed the most severely including seizures with fatigue and activity reported as the top symptom and function, respectively. The identified core symptoms and functions worsened at the time of progression, supporting the relevance and sensitivity of the priority constructs identified by the RANO-PRO Working Group for clinical care and clinical trials for malignant glioma patients. The Natural History Study is supported by Intramural Project 1ZIABC011786-03.

NCOG-47. SYMPTOMATOLOGY OF PRIMARY BRAIN TUMOR PATIENTS AT CLINICAL TRIAL INITIATION: SNAPSHOT FROM THE NCI NOB-NATURAL HISTORY STUDY

Abstract Clinical trial endpoints include response/survival, but also treatment tolerance and clinical benefit. Few reports exist on the frequency and type of disease-related symptoms and functions and treatment-associated symptomatic toxicities at clinical trial initiation. The MD Anderson Symptom Inventory-Brain Tumor self-reports from patients at baseline of a clinical trial initiation were retrospectively evaluated for the presence of severe ratings ( ≥ 7 for symptom, ≥ 6 for interference) of Reeve's toxicity symptoms (TS) (pain, fatigue, nausea, insomnia, anxiety, dyspnea, anorexia, depression, vomiting, neuropathy, constipation, diarrhea) and RANO-COA Collaborative core disease-related symptoms (DRS) (pain, perceived cognition, difficulty communicating, seizure, physical function, role/social functioning). A total of 137 baseline assessments from 132 patients for 10 clinical trials were evaluated. Patients were primarily white (82%) males (67%), with median age 48 years (range: 19-76), initiating treatment for a recurrent (86%) high grade (95%) tumor. Thirty-six percent reported severe TS (range: 1-9) and 48% reported DRS (range: 1-8), both with a median of 2 symptoms. All 12 TS and 7 DRS were reported as severe (TS range: 3%-23%); DRS range: 1%-25%); most common were fatigue (23%), insomnia (12%), and anxiety (10%) for TS, and role/social function-work (25%), physical function-walking (24%), and role/social function-usual activity (20%) for DRS. Those ≤ 4 weeks since recurrence more frequently reported TS (53%) or DRS (62%). TS were more common if treatment initiation closely followed a previous treatment (0-4 weeks: 45%). Baseline symptom occurrence and functional limitations and their severity at clinical trial initiation are critical to understanding tolerability and clinical benefit. For TS, baseline adjustments are warranted for anticipated symptomatic toxicities. High disease-related symptom severity necessitates symptom management and supportive care approaches for patients entering clinical trials and promotes symptomatic improvement measures as trial endpoints along with traditional measures such as tumor reduction and prolongation of survival outcomes.

INNV-21. FEASIBILITY OF A VIRTUAL REALITY (VR) INTERVENTION TARGETING DISTRESS AND ANXIETY IN PRIMARY BRAIN TUMOR (PBT) PATIENTS AT THE TIME OF NEUROIMAGING: INTERIM ANALYSIS OF A PHASE 2 CLINICAL TRIAL

Abstract 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 ( &amp;gt; 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.

Exploring the prevalence and burden of sleep disturbance in primary brain tumor patients.

Sleep disturbance (SD) is common in patients with cancer and has been associated with worse clinical outcomes. This cross-sectional study explored the prevalence of SD in a primary brain tumor (PBT) population, identified associated demographic and clinical characteristics, and investigated co-occurrence of SD with other symptoms and mood disturbance. Demographic, clinical characteristics, MD Anderson Symptom Inventory-Brain Tumor, and Patient Reported Outcome Measurement Information System Depression and Anxiety Short-Forms were collected from PBT patients at study entry. Descriptive statistics, Chi-square tests, and independent t-tests were used to report results. The sample included 424 patients (58% male, 81% Caucasian) with a mean age of 49 years (range 18-81) and 58% with high-grade gliomas. Moderate-severe SD was reported in 19% of patients and was associated with younger age, poor Karnofsky Performance Status, tumor progression on MRI, and active corticosteroid use. Those with moderate-severe SD had higher overall symptom burden and reported more moderate-severe symptoms. These individuals also reported higher severity in affective and mood disturbance domains, with 3 to 4 times higher prevalence of depressive and anxiety symptoms, respectively. The most frequently co-occurring symptoms with SD were, drowsiness, and distress, though other symptoms typically associated with tumor progression also frequently co-occurred. PBT patients with moderate-severe SD are more symptomatic, have worse mood disturbance, and have several co-occurring symptoms. Targeting interventions for sleep could potentially alleviate other co-occurring symptoms, which may improve life quality for PBT patients. Future longitudinal work examining objective and detailed subjective sleep reports, as well as underlying genetic risk factors, will be important.

Patient reported function and symptom burden in breast cancer patients with CNS metastases.

e18635 Background: Central nervous system (CNS) metastases are associated with decreased quality of life for patients with metastatic breast cancer (MBC). Collecting patient-reported outcome (PRO) data can identify patient needs and inform patient-focused interventions. IMPACT the Brain is a care coordination program that aims to improve access to multidisciplinary care for patients with MBC and CNS metastases. The purpose of this study is to report baseline PRO data obtained as part of this program. Methods: Patients with MBC and CNS metastases are referred for enrollment in the program. PROs and caregiver assessments are collected on a voluntary basis at baseline and every 3 months. We performed a retrospective review of the baseline PRO data to determine: (1) type and severity of cancer-related symptoms reported by patients and (2) degree of burden reported by caregivers. The PROMIS Cancer Function Brief 3D Profile measures physical function (PF), fatigue (Fat), and social participation (Soc) in patients with cancer; 50.0 is the population mean and higher scores indicate a greater degree of a trait. The MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) measures severity of cancer-related symptoms including interference with daily life. A score &gt; 4 represents moderate symptoms and &gt; 6 severe symptoms. The mean of the interference items represents overall symptom distress. The Short Form Zarit Burden Interview (ZBI-12) evaluates caregiver burden; a score ≥ 10 suggests mild burden while &gt; 20 suggests high burden. PRO scores were summarized using descriptive statistics. Results: Sixty patients were referred and 54 (90%) enrolled; median age was 53 years (range 31-81). 47 questionnaires were collected at baseline from 32 participants. Average PROMIS T-scores were 37.0 for PF (31.9-51.2), 59.9 for Fat (48.9-66.8), and 42.3 for Soc (32.8-57.1). Participants reported greatest difficulty with performing heavy housework and completing usual work. The mean symptom severity score reported on the MDASI-BT (n = 20) was 2.82 (SD 1.56). Fatigue was the most severe symptom (mean 5.2, SD 2.7) and 25% of patients reported moderate symptoms. The mean interference score was 3.9 (SD 2.66), with 20% of patients reporting moderate and 30% reporting severe overall symptom distress. 65% of caregivers (n = 17) had at least mild caregiver burden on the ZBI-12. Of those, almost half (45.5%) had a score consistent with high burden. Conclusions: Collecting baseline PROs was feasible and provided valuable information about the patient experience. Symptoms experienced by patients with MBC and CNS metastases, particularly fatigue, interfere with ability to carry out usual activities. The distress caused by these symptoms may not correlate with the severity reported by the patient. Given the prevalence of burden experienced by caregivers, further work is needed to explore relationships among symptom distress, symptom severity, and caregiver burden.

Assessing mobility in primary brain tumor patients: A descriptive feasibility study using two established mobility tests.

Patients with primary brain tumors (PBT) face significant mobility issues related to their disease and/or treatment. Here, the authors describe the preliminary utility and feasibility of two established mobility measures, the Timed-Up-and-Go (TUG) and Five-Times Sit-to-Stand (TSS) tests, in quickly and objectively assessing the mobility status of PBT patients at a single institution's neuro-oncology clinic. Adult patients undergoing routine PBT care completed the TUG/TSS tests and MD Anderson Symptom Inventory-Brain Tumor module (MDASI-BT), which assessed symptom burden and interference with daily life, during clinic visits over a 6-month period. Research staff assessed feasibility metrics, including test completion times/rates, and collected demographic, clinical, and treatment data. Mann-Whitney tests, Kruskal-Wallis tests, and Spearman's rho correlations were used to interrogate relationships between TUG/TSS test completion times and patient characteristics. The study cohort included 66 PBT patients, 59% male, with a median age of 47 years (range: 20-77). TUG/TSS tests were completed by 62 (94%) patients. Older patients (P < .001) and those who were newly diagnosed (P = .024), on corticosteroids (P = .025), or had poor (≤80) KPS (P < .01) took longer to complete the TUG/TSS tests. Worse activity-related (work, activity, and walking) interference was associated with longer TUG/TSS test completion times (P < .001). The TUG/TSS tests are feasible for use among PBT patients and may aid in clinical care. Older age, being newly diagnosed, using corticosteroids, poor (≤80) KPS, and high activity-related interference were associated with significant mobility impairment, highlighting the tests' potential clinical utility. Future investigations are warranted to longitudinally explore feasibility and utility in other practice and disease settings.

Associations of meaning of illness with psychosocial, clinical, and immunological characteristics in patients with Leptomeningeal metastasis

BackgroundLeptomeningeal metastasis (LM) creates symptoms related to both the disease within the nervous system and treatment toxicities. Biologic processes, such as inflammation and behavioral processes, such as the meaning ascribed to illness (Meaning of Illness: MoI), can impact physical and psychosocial symptoms. The aim of this study was to understand the relationships among MoI, physical and psychosocial symptoms, and inflammation in patients with LM. MethodsThirty enrolled participants completed the MD Anderson Symptom Inventory-Brain Tumor with spine experimental symptoms added. Meaning of illness, quality of life (QoL), and depression were captured by validated instruments. Interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum and cerebrospinal fluid (CSF) were measured by ELISA. Correlations were performed to assess relationships among the variables. ResultsParticipants were primarily white (73%), female (63%). Median age was 54 years (34–83). Breast (50%) and lung (20%) were most common diagnosis. Higher MoI scores were associated with better QoL (p < .01) and fewer depressive symptoms (p < .01). All CSF samples contained IL-6 and all but one sample had elevated IL-6. Higher levels of IL-6 in the CSF were associated with greater symptom burden (p < .01) and interference of symptoms in daily life (p = .02) but not MoI. ConclusionsMoI was associated with QoL and depression. High levels of IL-6 in the CSF were associated with more severe symptoms. This study provides the groundwork for future research, including interventional studies to improve QoL in patients with LM.

QOLP-02. PATIENT-REPORTED OUTCOMES FOLLOWING PERTUZUMAB PLUS HIGH-DOSE TRASTUZUMAB IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER (MBC) AND CENTRAL NERVOUS SYSTEM (CNS) PROGRESSION POST-RADIOTHERAPY

Abstract Effective therapies are needed for the treatment of patients with HER2-positive MBC who develop brain metastases. In the open-label, phase II PATRICIA study (NCT02536339), 40 patients with HER2-positive MBC with CNS metastases and CNS progression post-radiotherapy (median age 48 years [range, 34–69]; prior CNS treatment [whole brain radiotherapy 71%, stereotactic radiosurgery 59%, both 31%]) were enrolled to receive pertuzumab plus high-dose trastuzumab (6-mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Following a median (range) treatment duration of 4.5 (0.3–37.3) months, the CNS-confirmed objective response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria (primary endpoint) was 11% (95% confidence interval: 3.03, 25.42), and the clinical benefit rate at 4 months was 68%, indicating sustained clinical stability. Patient-reported outcomes (PROs) were evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), which includes sub-scales for symptom severity (average of 13 core symptom and 9 brain-tumor specific items) and symptom interference (average of 6 interference-with-life items representing overall symptom distress). Among 36 patients included in the PRO analyses, mean (standard deviation [SD]) symptom severity scores at baseline and weeks 12 and 28 were 1.65 (1.62), 2.24 (2.14), and 1.94 (2.55), respectively. Mean (SD) symptom interference scores at baseline and weeks 12 and 28 were 2.51 (2.63), 2.81 (3.39), and 1.76 (2.43), respectively. Mean (SD) changes in symptom severity and interferences scores from baseline to week 12 were 0.34 (1.54) and 0.33 (3.08), respectively. On average, patients who did not achieve stable disease or better in the CNS following treatment had worsened symptom severity and symptom interference scores over 12 weeks, while those with stable disease or better in the CNS exhibited stable or improving scores. Pertuzumab plus high-dose trastuzumab provided clinical benefit to the majority (68%) of patients in PATRICIA, without a decrement in quality of life.

Exploring sleep disturbance among adults with primary or secondary malignant brain tumors and their caregivers.

Emerging evidence supports the clinical impact of sleep disturbance (SD) on cancer patients. This study aimed to determine the prevalence and predictors of SD in people with malignant brain tumors and caregivers, and explore any relationship between the patient-caregiver dyad's sleep. Eighty-one adults with primary malignant (91%) or metastatic (9%) brain tumors and their family caregivers (n = 44) completed a series of self-report questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index, and the drowsiness item of The MD Anderson Symptom Inventory-Brain Tumor in an Australian ambulatory neuro-oncology setting. Participants were grouped by the PSQI cutoff (SD > 5), and binary logistic regression analyses were performed to identify risk factors. Of patients, 53% reported SD and 15% of those clinically significant insomnia, and 27% reported moderate to severe daytime drowsiness. Whereas anxiety, depression, fatigue, pain, neurocognitive symptoms, and antiemetic use were higher in patients with SD, fatigue and KPS were strong predictors of SD. In caregivers, 55% reported poor sleep and 13% clinical insomnia. Anxiety, caregiver burden, and comorbid illness were significantly associated with caregivers' SD. The individual's SD did not affect the chance of the other member of the patient-caregiver dyad experiencing SD. More than half the sample had sleep disturbance, which was linked to many concomitant symptoms, such as fatigue in patients and anxiety in caregivers, potentially contributing to distress and functional impairment. Understanding underlying mechanisms of SD, the potential use of these clinical predictors in care settings, and options for management is warranted.

The prevalence of altered body image in patients with primary brain tumors: an understudied population

PurposeBody image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT).MethodsA cross-sectional survey of 100 PBT patients was conducted on an IRB approved prospective protocol using structured questionnaires. Participants completed the body image scale (BIS), Appearance Scheme Inventory Revised (ASI-R), MD Anderson Symptom Inventory Brain Tumor (MDASI-BT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Depression, Anxiety, and Psychosocial Impact Positive measures.ResultsThe prevalence of clinically significant body image dissatisfaction (BIS ≥ 10) was 28% (95% CI 19–37%), median BIS score was 5 (range 0–27). The median ASI-R composite score was 2.9 (range 1.5–4.7). BIS was significantly correlated with the ASI-R (r = 0.53, 95% CI 0.37 to 0.65). The mean PROMIS Depression score was 48.4 (SD = 8.9), PROMIS Anxiety score was 49.4 (SD = 9.9), and PROMIS Psychosocial Illness Impact Positive score was 48.9 (SD = 9.7). BIS was significantly correlated with age, and trended with BMI and sex. The PROMIS Psychosocial Illness Impact Positive and PROMIS Anxiety scores were the most strongly related to BIS.ConclusionsThis study, the first to explore altered body image in PBT patients, revealed clinically significant body image dissatisfaction in nearly 1/3 of patients, similar to other malignancies. These findings underscore the potential contribution of disease and treatment-related body image concerns on psychosocial wellbeing in patients with PBT.

A prospective evaluation of health-related quality of life after skull base re-irradiation.

To report cancer control outcomes and health-related quality of life (HRQoL) outcomes after highly conformal skull-based re-irradiation (re-RT). Patients planned for curative intent re-RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires. Thirty-nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow-up was 14 months. Progression free survival was 71% at 1-year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI-BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow-ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous. Conformal skull base re-RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.

ACTR-50. PRESERVATION OF NEUROCOGNITIVE FUNCTION &amp; PATIENT-REPORTED SYMPTOMS WITH HIPPOCAMPAL AVOIDANCE (HA) DURING WHOLE-BRAIN RADIOTHERAPY (WBRT) FOR BRAIN METASTASES: LONG-TERM RESULTS OF NRG ONCOLOGY CC001

Abstract BACKGROUND NRG-CC001 sought to evaluate the neuro-protective effects of avoiding the peri-hippocampal stem cell niche using intensity-modulated radiotherapy during WBRT. METHODS Patients with brain metastasis were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+ Memantine (M) (30Gy in 10 fractions). Standardized NCF tests and the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) were obtained at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure defined using the reliable change index. Pre-specified secondary endpoints included patient-reported symptoms using the MDASI-BT. Time to NCF was reported as cumulative incidence (with death without NCF failure as a competing risk); between-arms differences were tested using Gray’s test. Deterioration at discrete time-points were tested using chi-square tests. MDASI-BT symptom burden, interference, and cognitive and neurologic burden were analyzed using mixed effects models and t-tests within the model using Hochberg’s multiplicity adjustment. RESULTS A total of 518 patients were randomized from 7/2016 to 3/2018. Median follow-up for alive patients was 12.1 mos, with no difference between arms in terms of toxicity, overall survival or intracranial progression-free survival. HA-WBRT+M was associated with lower risk of NCF failure (adjusted HR=0.739, 95% CI: 0.577–0.945, p=0.0.016), with differences first noted at 4 mos in Trail Making Test Part-B (23.3% vs. 40.4% deteriorated, p=0.012). Age did not dilute treatment effect. HA-WBRT+M was associated with reduced cognitive symptom burden in an imputed model (estimate=-0.29, p=0.0425), and also reduced overall symptom burden (p&lt; 0.0001) and interference (p&lt; 0.0016) at 6 mos. CONCLUSIONS The addition of HA to WBRT+M preserved NCF and reduced patient reported cognitive symptom burden, overall symptom burden and symptom interference and should be considered standard of care for any patient fit enough to have WBRT. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.