Landscape and impact of mind-body, cognitive-behavioral, and physical activity interventions in adolescent and adult brain tumor patients: A systematic review.

Background: The use of mind-body, cognitive-behavioral, and physical activity interventions have shown efficacy for improving symptom burden and functional limitations in other cancers; however, these strategies have not been widely implemented within neuro-oncology. This systematic review describes the current landscape and the impact of these interventions on adolescent and adult patients with brain tumors, which may guide the development of future interventions. Methods: A systematic search of PubMed, Embase, and Web of Science was performed using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines with predefined eligibility criteria. Twenty-nine studies met the inclusion criteria and were selected for review. Results: There was promising evidence for the feasibility and efficacy of mind-body and physical activity interventions for improving mood and quality of life, as well as enhanced physical functioning following aerobic and strength-based interventions. Results were mixed for cognitive-behavioral interventions, likely due to underpowered analyses. Interventions tested in pediatric patients also showed improvements in fatigue, mood, and quality of life, though these individuals represented a small proportion of the pooled sample. Conclusions: Findings suggest that mind-body and physical activity interventions can improve both physical and psychological health for patients with brain tumors, though additional well-designed clinical trials are needed to better establish efficacy.

Assessing sleep in primary brain tumor patients using smart wearables and patient-reported data: Feasibility and interim analysis of an observational study.

Background: Sleep-wake disturbances are common and disabling in primary brain tumor (PBT) patients but studies exploring longitudinal data are limited. This study investigates the feasibility and relationship between longitudinal patient-reported outcomes (PROs) and physiologic data collected via smart wearables. Methods: Fifty-four PBT patients ≥ 18 years wore Fitbit smart-wearable devices for 4 weeks, which captured physiologic sleep measures (eg, total sleep time, wake after sleep onset [WASO]). They completed PROs (sleep hygiene index, PROMIS sleep-related impairment [SRI] and Sleep Disturbance [SD], Morningness-Eveningness Questionnaire [MEQ]) at baseline and 4 weeks. Smart wearable use feasibility (enrollment/attrition, data missingness), clinical characteristics, test consistency, PROs severity, and relationships between PROs and physiologic sleep measures were assessed. Results: The majority (72%) wore their Fitbit for the entire study duration with 89% missing < 3 days, no participant withdrawals, and 100% PRO completion. PROMIS SRI/SD and MEQ were all consistent/reliable (Cronbach's alpha 0.74-0.92). Chronotype breakdown showed 39% morning, 56% intermediate, and only 6% evening types. Moderate-severe SD and SRI were reported in 13% and 17% at baseline, and with significant improvement in SD at 4 weeks (P = .014). Fitbit-recorded measures showed a correlation at week 4 between WASO and SD (r = 0.35, P = .009) but not with SRI (r = 0.24, P = .08). Conclusions: Collecting sleep data with Fitbits is feasible, PROs are consistent/reliable, > 10% of participants had SD and SRI that improved with smart wearable use, and SD was associated with WASO. The skewed chronotype distribution, risk and impact of sleep fragmentation mechanisms warrant further investigation. Trial Registration: NCT04 669 574.

The relationship between social determinants of health and neurocognitive and mood-related symptoms in the primary brain tumor population: A systematic review.

Social determinants of health (SDOH) impact cancer-related health outcomes, including survival, but their impact on symptoms is less understood among the primary brain tumor (PBT) population. We conducted a systematic review to examine the relationships between SDOH and neurocognitive and mood-related symptoms among the PBT population. PubMed, EMBASE, and CINAHL were searched using PROGRESS criteria (place of residence, race/ethnicity, occupation, gender/sex, religion, education, socioeconomic status, and social capital) on March 8th, 2022. Two individuals screened and assessed study quality using the NHLBI Assessment Tool for Observational Cohort and Cross-sectional Studies. Of 3006 abstracts identified, 150 full-text articles were assessed, and 48 were included for a total sample of 28 454 study participants. Twenty-two studies examined 1 SDOH; none examined all 8. Four studies measured place of residence, 2 race/ethnicity, 13 occupation, 42 gender, 1 religion, 18 education, 4 socioeconomic status, and 15 social capital. Fifteen studies assessed neurocognitive and 37 mood-related symptoms. While higher education was associated with less neurocognitive symptoms, and among individuals with meningioma sustained unemployment after surgery was associated with depressive symptoms, results were otherwise disparate among SDOH and symptoms. Most studies were descriptive or exploratory, lacking comprehensive inclusion of SDOH. Standardizing SDOH collection, reducing bias, and recruiting diverse samples are recommended in future interventions.

The sex-dependent impact of PER2 polymorphism on sleep and activity in a novel mouse model of cranial-irradiation-induced hypersomnolence.

Background: Hypersomnolence is a common and disruptive side effect of cranial radiotherapy and is associated with fatigue and disturbances in mood and cognition in primary brain tumor (PBT) patients. The biological underpinnings of this effect are not understood. Our laboratory has previously found that the presence of a single nucleotide polymorphism (rs934945, G-E mutation) in the PERIOD2 (PER2) clock gene was associated with a decreased likelihood of fatigue in PBT patients. Here, we aim to understand the effects of PER2 polymorphism on radiation susceptibility within a murine model of cranial-irradiation-induced hypersomnolence (C-RIH). Methods: Male and female transgenic mice were generated using CRISPR-Cas9, replacing the endogenous mouse PER2:CRY1 binding domain with its human isoform with (hE1244 KI) or without the SNP rs934945 (hG1244 KI). Activity and sleep were monitored continuously 10 days before and after cranial irradiation (whole brain, 15Gy, single fraction). Behavioral assessments measuring anxiety, depression, and working memory were used to assess mood and cognitive changes 2 months postradiation. Results: During their active phase, hE1244 knock-ins (KIs) had less radiation-induced suppression of activity relative to hG1244 KIs and female hE1244 KIs saw a reduction of hypersomnolence over 10 days. hE1244 KIs displayed less anxiety behavior and were more ambulatory within all behavioral tests. Conclusions: The PER2 rs934945 polymorphism had long-lasting behavioral effects associated with radiation toxicity, particularly in sleep in females and the activity of all animals. Our findings shed light on biological mechanisms underlying C-RIH.

Feasibility and preliminary efficacy of a virtual reality intervention targeting distress and anxiety in primary brain tumor patients at the time of clinical evaluation: Study protocol for a phase 2 clinical trial.

BACKGROUND: Primary brain tumor (PBT) patients experience higher levels of distress and anxiety than other solid tumor patients, particularly at the time of clinical evaluation when uncertainty about disease status is high ("scanxiety"). There is promising evidence supporting use of virtual reality (VR) to target psychological symptoms in other solid tumor patients, though PBT patients have not been studied extensively in this context. The primary aim of this phase 2 clinical trial is to establish the feasibility of a remote VR-based relaxation intervention for a PBT population, with secondary aims designed to determine preliminary efficacy of improving distress and anxiety symptoms. METHODS: PBT patients (N = 120) with upcoming MRI scans and clinical appointments who meet eligibility will be recruited to participate in a single arm trial conducted remotely through the NIH. Following completion of baseline assessments, participants will complete a 5-min VR intervention via telehealth using a head-mounted immersive device while under supervision of the research team. Following the intervention, over the course of 1 month patients can use VR at their discretion with follow-up assessments done immediately post-VR intervention, as well as 1 week and 4 weeks later. Additionally, a qualitative phone interview will be conducted to assess patient satisfaction with the intervention. DISCUSSION: Use of immersive VR is an innovative interventional approach to target distress and scanxiety symptoms in PBT patients who are at high risk for experiencing these symptoms leading into their clinical appointments. Findings from this study may inform design of a future multicenter randomized VR trial for PBT patients and may aid in development of similar interventions for other oncology populations. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04301089), registered 9 March 2020.

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

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

Feasibility and preliminary efficacy of a virtual reality intervention targeting distress and anxiety in primary brain tumor patients at the time of clinical evaluation: Study protocol for a phase 2 clinical trial.

Background: Primary brain tumor (PBT) patients experience higher levels of distress and anxiety than other solid tumor patients, particularly at the time of clinical evaluation when uncertainty about disease status is high ("scanxiety"). There is promising evidence supporting use of virtual reality (VR) to target psychological symptoms in other solid tumor patients, though PBT patients have not been studied extensively in this context. The primary aim of this phase 2 clinical trial is to establish the feasibility of a remote VR-based relaxation intervention for a PBT population, with secondary aims designed to determine preliminary efficacy of improving distress and anxiety symptoms. Methods: PBT patients (N=120) with upcoming MRI scans and clinical appointments who meet eligibility will be recruited to participate in a single arm trial conducted remotely through the NIH. Following completion of baseline assessments, participants will complete a 5-minute VR intervention via telehealth using a head-mounted immersive device while under supervision of the research team. Following the intervention, over the course of 1 month patients can use VR at their discretion with follow-up assessments done immediately post-VR intervention, as well as 1 week and 4 weeks later. Additionally, a qualitative phone interview will be conducted to assess patient satisfaction with the intervention. Discussion: Use of immersive VR is an innovative interventional approach to target distress and scanxiety symptoms in PBT patients who are at high risk for experiencing these symptoms leading into their clinical appointments. Findings from this study may inform design of a future multicenter randomized VR trial for PBT patients and may aid in development of similar interventions for other oncology populations. Trial Registration: clinicaltrials.gov (NCT04301089), registered 9 March 2020.

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

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

Discovery of clinical and demographic determinants of symptom burden in primary brain tumor patients using network analysis and unsupervised clustering.

Background: Precision health approaches to managing symptom burden in primary brain tumor (PBT) patients are imperative to improving patient outcomes and quality of life, but require tackling the complexity and heterogeneity of the symptom experience. Network Analysis (NA) can identify complex symptom co-severity patterns, and unsupervised clustering can unbiasedly stratify patients into clinically relevant subgroups based on symptom patterns. We combined these approaches in a novel study seeking to understand PBT patients' clinical and demographic determinants of symptom burden. Methods: MDASI-BT symptom severity data from a two-institutional cohort of 1128 PBT patients were analyzed. Gaussian Graphical Model networks were constructed for the all-patient cohort and subgroups identified by unsupervised clustering based on co-severity patterns. Network characteristics were analyzed and compared using permutation-based statistical tests. Results: NA of the all-patient cohort revealed 4 core dimensions that drive the overall symptom burden of PBT patients: Cognitive, physical, focal neurologic, and affective. Fatigue/drowsiness was identified as pivotal to the symptom experience based on the network characteristics. Unsupervised clustering discovered 4 patient subgroups: PC1 (n = 683), PC2 (n = 244), PC3 (n = 92), and PC4 (n = 109). Moderately accurate networks could be constructed for PC1 and PC2. The PC1 patients had the highest interference scores among the subgroups and their network resembled the all-patient network. The PC2 patients were older and their symptom burden was driven by cognitive symptoms. Conclusions: In the future, the proposed framework might be able to prioritize symptoms for targeting individual patients, informing more personalized symptom management.

The link between psychological distress and survival in solid tumor patients: A systematic review.

PURPOSE: Research has demonstrated that solid tumor patients experience high levels of psychological distress at the time of diagnosis. While distress has been associated with many adverse clinical outcomes, little is known about how this symptom may influence the disease trajectory for cancer patients, affecting outcomes such as progression, recurrence, and survival. The purpose of this systematic review was to explore the literature linking distress with survival in solid tumor patients, which may guide future work exploring clinical outcomes as a function of distress. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with predefined eligibility criteria. Thirteen studies met the inclusion criteria and were selected for review. RESULTS: Findings from this review demonstrated a weak-to-moderate relationship between cancer patients' experience of distress and overall survival, with most included studies (11/13) finding at least one predictive analysis to be significant when controlling for confounders. However, significant heterogeneity in the literature, particularly with study sample characteristics and varying methodologies, made direct comparisons across studies challenging. CONCLUSION: Findings from this review suggest that psychological distress may have an impact on disease-related outcomes, including (but not limited to) survival. Future work should consider performing disease-specific analyses controlling for key prognostic factors to better understand the nuanced relationship between distress and clinical outcomes, which may allow further understanding of the biological underpinnings of this relationship and enable the development of targeted interventions for improving distress.

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

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: The Natural History Study is supported by Intramural Project 1ZIABC011786-03.

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

Background: 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. Methods: 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. 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. Conclusions: 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.

Histological analysis of sleep and circadian brain circuitry in cranial radiation-induced hypersomnolence (C-RIH) mouse model.

Disrupted sleep, including daytime hypersomnolence, is a core symptom reported by primary brain tumor patients and often manifests after radiotherapy. The biological mechanisms driving the onset of sleep disturbances after cranial radiation remains unclear but may result from treatment-induced injury to neural circuits controlling sleep behavior, both circadian and homeostatic. Here, we develop a mouse model of cranial radiation-induced hypersomnolence which recapitulates the human experience. Additionally, we used the model to explore the impact of radiation on the brain. We demonstrated that the DNA damage response following radiation varies across the brain, with homeostatic sleep and cognitive regions expressing higher levels of γH2AX, a marker of DNA damage, than the circadian suprachiasmatic nucleus (SCN). These findings were supported by in vitro studies comparing radiation effects in SCN and cortical astrocytes. Moreover, in our mouse model, MRI identified structural effects in cognitive and homeostatic sleep regions two-months post-treatment. While the findings are preliminary, they suggest that homeostatic sleep and cognitive circuits are vulnerable to radiation and these findings may be relevant to optimizing treatment plans for patients.

Proceedings of the Survivorship Care in Neuro-Oncology Workshop sponsored by the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT).

Background: Survivorship for those living with primary CNS cancers begins at diagnosis, continues throughout a person's life, and includes caregivers. Opportunities and challenges exist to advance survivorship care for those living with primary CNS cancers that necessitate stakeholder involvement. Methods: In June 2021, NCI-CONNECT convened a two-day virtual workshop about survivorship care in neuro-oncology. Two expert panels provided key recommendations and five working groups considered critical questions to identify strengths, weaknesses, opportunities, and threats to the advancement of survivorship care and developed recommendations and action items. Results: The following action items emanated from the workshop: seek endorsement of meeting report from stakeholder organizations; address barriers in access to survivorship care and provider reimbursement; advance survivorship research through NIH and private grant support; develop a survivorship tool kit for providers, people living with primary CNS cancers and their caregivers; provide accessible educational content for neuro-oncology, neurology, and oncology community providers about survivorship care in neuro-oncology; and establish core competencies for survivorship care for neuro-oncology providers to be included in training and standardized exams. Conclusions: Action items aim to address access and reimbursement barriers, expand patient and provider education, develop core competencies, and support survivorship research through funding and other supports.

A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer.

Background: Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. Methods: PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. Conclusion: We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.

Neurocognition and Health-Related Quality of Life Among Patients with Brain Tumors.

Patients with brain tumors experience great symptom burden across various domains of functioning, with associated decreases in health-related quality of life and general well-being. Impaired neurocognitive functioning is among the primary concerns of these patients. Unfortunately, most patients will experience such impairment at some point in the disease. However, impaired neurocognitive functioning, symptom burden, and well-being vary according numerous patient-, tumor-, and treatment-related factors. Recent work has furthered our understanding of these contributors to patient functioning and health-related quality of life and also points to various potential targets for prevention and intervention strategies, though more efficacious treatments remain needed.

Living with a central nervous system (CNS) tumor: findings on long-term survivorship from the NIH Natural History Study.

BACKGROUND: Primary central nervous system (CNS) tumors are often associated with high symptom burden and a poor prognosis from the time of diagnosis. The purpose of this study is to describe patient-reported outcomes (PRO) data from long-term survivors (LTS; ≥5-year survival post-diagnosis). METHODS: Clinical/treatment/molecular characteristics and PROs (symptom burden/interference (MDASI-BT/SP), perceived cognition (Neuro-QoL), anxiety/depression (PROMIS), and general health status (EQ-5D-3L)) were collected on 248 adult LTS between 9/2016 and 8/2019. Descriptive statistics and regression analysis were used to report results. RESULTS: Participants had a median age of 47 years (19-82) and were primarily White (83%) males (51%) with high-grade tumors (59%) and few mutations. Forty-two percent of the 222 brain tumor LTS reported no moderate-to-severe symptoms, whereas 45% reported three or more; most common symptoms were fatigue (40%), difficulty remembering (29%), and drowsiness (28%). Among spine tumor LTS (n = 42), nearly half reported moderate-to-severe weakness, pain, fatigue, and numbness/tingling, with 72% experiencing activity-related interference. Severe anxiety, depression, and cognitive symptoms were reported in up to 23% of the sample. Brain tumor LTS at higher risk for severe symptoms were more likely to be young, unemployed, and have poor KPS (Karnofsky Performance Status), whereas high symptom-risk spinal cord tumor LTS had poor KPS and received any tumor treatment. CONCLUSIONS: Findings indicate LTS fall into distinct cohorts with no significant symptoms or very high symptom burden, regardless of tumor grade or mutational profile. These LTS data demonstrate the need for survivorship care programs and future studies to explore the symptom trajectory of all CNS tumor patients for prevention and early interventions.

Use of virtual reality for symptom management in solid-tumor patients with implications for primary brain tumor research: a systematic review.

BACKGROUND: Primary brain tumors (PBTs) remain incurable, with a typically poor prognosis and significant symptom burden for patients. Virtual reality (VR) can potentially alleviate some of the negative aspects of illness by allowing individuals to escape to environments where they can experience more positive thoughts and emotions. Given promising findings for VR use in other clinical populations, there is increasing interest to use VR for symptomatic improvement in oncology patients. The purpose of this review was to analyze the literature of VR-related interventions for symptom management in adult PBT and other solid-tumor patients, which will guide development of future VR interventions in these populations. METHODS: A systematic search of EMBASE, PubMed, Scopus, and Web of Science was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with predefined eligibility criteria. Thirteen studies met the inclusion criteria and were selected for review. RESULTS: Findings showed promising evidence that VR can improve anxiety for solid-tumor patients, with mixed results reported for pain, distress, depression, and mood. There was significant heterogeneity in methodological approaches across the literature and the majority of studies were underpowered and lacked rigorous study designs. Qualitative findings demonstrated a high degree of participant satisfaction with VR use, with very few adverse side effects reported. CONCLUSIONS: Findings from this review suggest that VR can be used as an innovative delivery system for targeted interventions to improve symptoms in PBTs and other solid-tumor patient populations, though additional well-designed clinical trials are needed to better establish its efficacy.

Potential for identification of memory problems in the cancer clinic to enable improved treatment experience and outcomes: Mixed methods case study research.

PURPOSE: To inform improvement in cancer treatment experience and outcomes for people with dementia or milder cognitive impairment. People with dementia, compared to those without, experience more side effects from cancer treatment and have poorer outcomes including poorer survival. METHODS: The research was a mixed methods exploratory case study. Each case was a cancer treatment in a person with memory loss, a common symptom of dementia. Observations were conducted in 30 clinic sessions at one cancer centre between September 2014 and February 2015. Thirty-three encounters between people with a memory problem and a staff member were observed and ten consultations recorded. Interviews were conducted with five staff members and six people receiving cancer treatment, five accompanied by their carer. Analysis, informed by hermeneutic phenomenology, enabled the treatment pathway to be mapped and modelled to reveal sites for intervention. FINDINGS: Five potential sites of intervention were identified in the treatment pathway. Five actions at the sites of intervention that may improve patient experience and outcomes include, raising awareness of common problems for people with cognitive impairment receiving cancer treatment, encouraging disclosure of memory problems, staff training to identify memory problems and to know what to do, offering tools and techniques to aid self-management of memory problems, and addressing carer support needs. CONCLUSION: Embedding biomedical treatment of cancer within a dementia-friendly psychosocial system may enable safe cancer treatment for a greater number of people with dementia or milder cognitive impairment.

Tuning Second Coordination Sphere Interactions in Polypyridyl-Iron Complexes to Achieve Selective Electrocatalytic Reduction of Carbon Dioxide to Carbon Monoxide.

The development of noble-metal-free catalysts capable of electrochemically converting carbon dioxide (CO2) selectively into value-added compounds remains one of the central challenges in catalysis research. Here, we present a systematic study of Fe(II) complexes of the functionalized ligands bpyRPY2Me (bpyPY2Me = 6-(1,1-bis(pyridin-2-yl)ethyl)-2,2'-bipyridine) in the pursuit of water-stable molecular Fe complexes that are selective for the catalytic formation of CO from CO2. Taking advantage of the inherently high degree of tunability of this ligand manifold, we followed a bioinspired approach by installing protic functional groups of varying acidities (-H, -OH, -OMe, -NHEt, and -NEt2) into the ligand framework to systematically modify the second coordination sphere of the Fe center. This family of [(bpyRPY2Me)FeII] complexes was characterized using single-crystal X-ray analysis, 1H NMR spectroscopy, and mass spectrometry. Comparative catalytic evaluation of this set of compounds via voltammetry and electrolysis experiments identified [(bpyNHEtPY2Me)Fe]2+ in particular as an efficient, iron-based, non-heme CO2 electroreduction catalyst that displays significant selectivity for the conversion of CO2 to CO in acetonitrile solution with 11 M H2O. We propose that the NH group acts as a local proton source for cleaving the C-O bond in CO2 to form CO. Interestingly, the complex with the most acidic functional group in the second coordination sphere, [(bpyOHPY2Me)Fe]2+, favors formation of H2 over CO. Our results correlate the selectivity of water versus carbon dioxide reduction to the acidity of the second coordination sphere functional group and emphasize the continued untapped potential that synthetic molecular chemistry offers in the pursuit of next-generation CO2 reduction electrocatalysts.