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OBJECTIVE: High self-efficacy is associated with improved self-care and reduced symptoms in cancer patients but has not been fully interrogated in adults with central nervous system (CNS) cancers. We aimed to identify the relationship between self-efficacy levels in managing emotions (SEMEM) and social interactions (SEMSI) by examining sample characteristics and symptom burden. METHODS: Sample characteristics and patient-reported outcome (PRO) measures addressing self-efficacy (PROMIS SEMEM & SEMSI) and symptom burden (MDASI BT or SP) were collected in a novel web-based study of 158 adult patients diagnosed with rare CNS tumors. RESULTS: The sample was predominantly female (73%), diagnosed with an ependymoma (66%), and had a median age of 45 (19-75). Low SEMEM was associated with a longer duration of symptoms before surgery (r = -0.26) and female gender (92%) among brain tumor (BT) participants and in spinal cord tumors (SCT), those with lower education (r = 0.29). Reporting low SEMSI was associated with being married (42%), lower education (r = 0.22), and a prolonged time with symptoms before surgery (r = 0.29) in those with BTs, with no associations identified in SCT. More severe mood-related interference (including mood, enjoyment of life, and relationship with others) was associated with lower SEMEM among both locations (r = -0.61 brain, r = -0.28 spine) and SEMSI in BT participants (r = -0.54). CONCLUSIONS: Low self-efficacy was linked to a prolonged time between symptom onset and initial surgery, education, gender, and marital status and was associated with higher mood-related interference. Understanding characteristics associated with low self-efficacy underscores a need for future studies to tailor interventions that enhance self-efficacy.
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Neoplasias do Sistema Nervoso Central , Autoeficácia , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias do Sistema Nervoso Central/psicologia , Neoplasias do Sistema Nervoso Central/terapia , Adulto Jovem , Medidas de Resultados Relatados pelo Paciente , InternetRESUMO
Background: Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a reduced sense of accomplishment, which commonly arises from chronic workplace stress in the medical field. Given the higher risk of burnout in younger age groups reported in some studies, the Society for Neuro-Oncology (SNO) Young Investigator (YI) and Wellness Committees combined efforts to examine burnout in the SNO YI membership to better understand and address their needs. Methods: We distributed an anonymous online survey to SNO members in 2019. Only those meeting the definition of a YI were asked to complete the survey. The survey consisted of questions about personal and professional characteristics as well as the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) questionnaire. Statistical analyses included descriptive statistics, univariate and multivariate analyses, and incorporation of previously defined burnout profiles. Results: Data were analyzed for 173 participants who self-identified as YI. Measures of burnout showed that YI members scored higher on emotional exhaustion and depersonalization compared to normative population but similar to those in a prior SNO general membership survey. With respect to burnout profiles, 30% of YI respondents classified as overextended and 15% as burnout. Organizational challenges were the most common contributors to stress. Conclusions: Similar to results from a previous survey completed by general SNO membership, the prevalence of burnout among neuro-oncology clinical and research YI is high, and is mainly characterized by overextension, warranting interventions at institutional and organizational levels.
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Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS). Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTSâ =â 23) or <3 years (NSTSâ =â 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTSâ =â 23; NSTSâ =â 74) and methylation analysis (NLTSâ =â 18; NSTSâ =â 28). Pre-surgical MRI scans for a subset of LTS (Nâ =â 14) and STS control (Nâ =â 28) matched on sex, age, and extent of resection were analyzed. Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers. Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.
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Background: Gliosarcoma, an isocitrate dehydrogenase wildtype (IDH-WT) variant of glioblastoma, is defined by clonal biphasic differentiation into gliomatous and sarcomatous components. While the transformation from a glioblastoma to gliosarcoma is uncommon, the subsequent transformation to osteosarcoma is rare but may provide additional insights into the biology of these typically distinct cancers. We observed a patient initially diagnosed with glioblastoma, that differentiated into gliosarcoma at recurrence, and further evolved to osteosarcoma at the second relapse. Our objective was to characterize the molecular mechanisms of tumor progression associated with this phenotypic transformation. Methods: Tumor samples were collected at all 3 stages of disease and RNA sequencing was performed to capture their transcriptomic profiles. Sequential clonal evolution was confirmed by the maintenance of an identical PTEN mutation throughout the tumor differentiation using the TSO500 gene panel. Publicly available datasets and the Nanostring nCounter technology were used to validate the results. Results: The glioblastoma tumor from this patient possessed mixed features of all 3 TCGA-defined transcriptomic subtypes of an IDH-WT glioblastoma and a proportion of osteosarcoma signatures were upregulated in the original tumor. Analysis showed that enhanced transforming growth factor-ß (TGF-ß) and bone morphogenic protein signaling was associated with tumor transformation. Regulatory network analysis revealed that TGF-ß family signaling committed the lineage tumor to osteogenesis by stimulating the expression of runt-related transcription factor 2 (RUNX2), a master regulator of bone formation. Conclusions: This unusual clinical case provided an opportunity to explore the modulators of longitudinal sarcomatous transformation, potentially uncovering markers indicating predisposition to this change and identification of novel therapeutic targets.
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PURPOSE: We aimed to identify health-related quality of life (HRQOL) latent classes among primary central nervous system tumor (PCNST) long-term survivors (LTS) and to evaluate differences between classes in survivor sociodemographic characteristics, clinical characteristics, and symptoms to guide the development of survivorship care programs tailored to unique class needs. METHODS: Data from 298 PCNST LTS reporting HRQOL on the EQ-5D-3L were analyzed using latent profile analysis. Correlations and independent group t-tests were performed to identify differences between identified HRQOL classes by sociodemographic, clinical characteristics, and symptoms. RESULTS: Sample mean age was 48 years, 54% were male, 82% Caucasian, 56% employed, 60% had a high-grade glioma, and 52% had a KPS ≥ 90. Two HRQOL classes, good (61%) and poor (39%), were identified. The good HRQOL class reported no problems with self-care and few problems with mobility or usual activities. Thirty-eight percent reported anxiety and depression and 21% pain. Over 94% of the poor HRQOL class had at least moderate problems with mobility and usual activities, and over 50% had pain, self-care issues, anxiety, and depression. Older age (φ = 0.21), unemployment (φ = 0.30), spine tumors (φ = 0.18), active treatment (φ = 0.20), tumor recurrence (φ = 0.28), and poorer KPS scores (φ = 0.61) were associated with membership in the poor HRQOL class. CONCLUSIONS: In the poor PCNST LTS HRQOL class, an overwhelming majority faced significant physical challenges, and the good HRQOL class experienced mood-related disturbance but limited physical challenges. These HRQOL profiles can be used to guide survivorship programs and tailored interventions.
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Neoplasias do Sistema Nervoso Central , Qualidade de Vida , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Nível de Saúde , Recidiva Local de Neoplasia , Sobreviventes , Dor , Neoplasias do Sistema Nervoso Central/terapia , Inquéritos e QuestionáriosRESUMO
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.
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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.
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Neoplasias Encefálicas , Terapia de Exposição à Realidade Virtual , Adulto , Humanos , Masculino , Feminino , Estudos de Viabilidade , Ansiedade/etiologia , Ansiedade/terapia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapiaRESUMO
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.
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Neoplasias Encefálicas , Terapia de Exposição à Realidade Virtual , Humanos , Terapia de Exposição à Realidade Virtual/métodos , Estudos de Viabilidade , Ansiedade/etiologia , Ansiedade/terapia , Transtornos de Ansiedade , Neoplasias Encefálicas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
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.
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BACKGROUND AND OBJECTIVES: Financial toxicity significantly affects many patients, especially cancer survivors. We evaluated the association of unemployment as a major contributor to financial toxicity with patient-reported outcomes (PROs) assessing multiple illness experience domains in a primary CNS tumor (PCNST) cohort. METHODS: Patient and disease characteristics and PROs measuring symptom burden, interference, psychologic distress, functional impairment, and health-related quality of life (HRQOL) from participants enrolled in an institutional review board-approved observational study at the US NIH's Neuro-Oncology Branch were collected between September 2016 and December 2019. Descriptive statistics, tests of association, and comparison of group mean values were used to describe and evaluate PROs. RESULTS: Of the 277 participants diagnosed with a PCNST, 57% were male and 43% were female. Participants reported their race as White, non-Hispanic (78%); White, Hispanic/Latino (9%); Asian (7%); Black (4%); Native Hawaiian/Pacific Islander (1%); and other (2%) with 8% missing. The median age of the overall cohort was 45 years (range 18-74). Hispanic participants in the overall sample were 2.3 times more likely, and in the brain tumor group 3.2 times more likely, to report unemployment (p = 0.043, odds ratio [OR] 2.3, 95% CI 1.0-5.4 and p = 0.008, OR 3.2, 95% CI 1.3-7.9, respectively). 77 (28%) individuals unemployed due to tumor reported more functional impairment with walking, washing, dressing, and performing usual activities and reduced HRQOL (p < 0.001). More unemployed participants in the total sample reported moderate-to-severe depressive symptoms (25%) than those employed (8%) (χ2(1) = 13.9, p < 0.001, OR 3.7, 95% CI 1.8-7.8) and more moderate-to-severe anxiety symptoms (30%) than those employed (15%) (χ2(1) = 7.8, p = 0.005, OR 2.4, 95% CI 1.3-4.5). Unemployed participants with brain tumor reported on average 3 more symptoms as moderate-to-severe compared with those employed (t(83) = -4.0, 95% CI [Formula: see text] difference -5 to -2, p < 0.001, Hedge g = 0.70). DISCUSSION: Being unemployed due to a PCNST strongly correlated with high symptom burden, functional impairment, psychological distress, and reduced HRQOL, which may be impediments to returning to work that warrant intervention. Lack of employer-based health insurance and reduced earnings are financial sequelae of unemployment superimposed on the physical, social, and cognitive effects of living with a PCNST. Innovations to screen for and address financial toxicity and its contributing factors are needed.
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Neoplasias Encefálicas , Qualidade de Vida , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Emprego , Ansiedade , Transtornos de AnsiedadeRESUMO
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.
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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.
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The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, "High-grade neuroepithelial tumor with MN1 alteration" (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with MN1-altered primary CNS tumors diagnosed via genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.
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PURPOSE: Preclinical data showed that prophylactic, low-dose temozolomide (TMZ) significantly prevented breast cancer brain metastasis. We present results of a phase I trial combining T-DM1 with TMZ for the prevention of additional brain metastases after previous occurrence and local treatment in patients with HER2+ breast cancer. PATIENTS AND METHODS: Eligible patients had HER2+ breast cancer with brain metastases and were within 12 weeks of whole brain radiation therapy (WBRT), stereotactic radiosurgery, and/or surgery. Standard doses of T-DM1 were administered intravenously every 21 days (3.6 mg/kg) and TMZ was given orally daily in a 3+3 phase I dose escalation design at 30, 40, or 50 mg/m2, continuously. DLT period was one 21-day cycle. Primary endpoint was safety and recommended phase II dose. Symptom questionnaires, brain MRI, and systemic CT scans were performed every 6 weeks. Cell-free DNA sequencing was performed on patients' plasma and CSF. RESULTS: Twelve women enrolled, nine (75%) with prior SRS therapy and three (25%) with prior WBRT. Grade 3 or 4 AEs included thrombocytopenia (1/12), neutropenia (1/12), lymphopenia (6/12), and decreased CD4 (6/12), requiring pentamidine for Pneumocystis jirovecii pneumonia prophylaxis. No DLT was observed. Four patients on the highest TMZ dose underwent dose reductions. At trial entry, 6 of 12 patients had tumor mutations in CSF, indicating ongoing metastatic colonization despite a clear MRI. Median follow-up on study was 9.6 m (2.8-33.9); only 2 patients developed new parenchymal brain metastases. Tumor mutations varied with patient outcome. CONCLUSIONS: Metronomic TMZ in combination with standard dose T-DM1 shows low-grade toxicity and potential activity in secondary prevention of HER2+ brain metastases.
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Neoplasias Encefálicas , Neoplasias da Mama , Ácidos Nucleicos Livres , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Temozolomida/uso terapêutico , Prevenção Secundária , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapêutico , Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundárioRESUMO
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.
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Abstract Objective: To analyze the lipid profile and cardiovascular risk of overweight and obese adolescents and correlate the findings with anthropometric measurements. Methods: This is a cross-sectional study on overweight and obese adolescents of both sexes (aged 14 to 18 years old). The collected variables were sex, weight, height, age, total cholesterol, triglycerides, High-density lipoprotein (HDL) and low-density lipoprotein (LDL). The Atherogenic Index of Plasma and Castelli Risk Indices I and II were calculated. These indices were classified into cutoff points to stratify cardiovascular risk. The anthropometric profile was evaluated by Z score according to Body Mass Index for age. Significance level was considered as p≤0.05. Results: A total of 146 adolescents participated in the study; the mean age was 16.4±1.1 years and most of them were girls (74.7%) and obese (52.7%). The prevalent dyslipidemias were high triglycerides (47.9%), LDL (26.7%), total cholesterol (37.7%), and low HDL (46.6%). Most adolescents presented increased atherogenic risk according to the Atherogenic Index of Plasma (55.5%); 15.1% presented high cardiovascular risk according to Castelli Risk Index I; and 13.7%, according to Castelli Risk Index II. Boys presented higher values of anthropometric measurements and Castelli Risk Indices I and II in relation to girls — who, conversely, presented higher values of HDL. There was a positive correlation of the Z score with Atherogenic Index of Plasma and a negative correlation with HDL. Conclusions: The adolescents of the study presented high prevalence of cardiovascular and atherogenic risk according to the evaluated indices. In addition, the increased cardiovascular risk was correlated with higher Body Mass Index.
RESUMO Objetivo: Analisar o perfil lipídico e os índices de risco cardiovascular de adolescentes com sobrepeso e obesidade e correlacionar os achados com medidas antropométricas. Métodos: Estudo transversal com adolescentes com sobrepeso ou obesidade de ambos os sexos (14 a 18 anos). Foram coletadas as variáveis: sexo, peso, altura, idade, colesterol total, triglicerídeos, lipoproteína de alta densidade (HDL-c) e lipoproteína de baixa densidade (LDL-c). Calcularam-se o índice aterogênico plasmático e os índices de Castelli I e II. Eles foram classificados em pontos de corte para estratificar o risco cardiovascular. O perfil antropométrico foi avaliado por meio do escore Z com base no índice de massa corporal para a idade. Considerou-se o nível de significância p≤0,05. Resultados: Foram incluídos 146 adolescentes, com média de idade de 16,4±1,1 anos, a maioria do sexo feminino (74,7%) e obesa (52,7%). As dislipidemias prevalentes foram: triglicerídeos (47,9%), LDL-c (26,7%), colesterol total (37,7%) elevado e HDL-c baixo (46,6%). A maioria apresentou risco aterogênico aumentado pelo índice aterôgenico plasmático (55,5%); 15,1% apresentaram alto risco cardiovascular segundo o índice de Castelli I e 13,7%, segundo o índice de Castelli II. Os meninos apresentaram valores superiores de medidas antropométricas e índices de Castelli I e II em relação às meninas, que, por outro lado, apresentaram valores superiores de HDL-c. Houve correlação positiva do escore Z com o índice aterôgenico plasmático e negativa com HDL-c. Conclusões: Os adolescentes do estudo apresentaram alta prevalência de risco cardiovascular e aterogênico conforme os índices avaliados. Além disso, o risco cardiovascular aumentado foi correlacionado com maior índice de massa corporal.
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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.
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Background: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma. Methods: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity. Results: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02-3.27) and being female (OR, 4.45; 95% CI, 2.45-8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43-1.89). Conclusions: Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients.
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Background: Cognitive impairments are a common burden for patients with primary CNS tumors. Neuropsychological assessment batteries can be too lengthy, which limits their use as an objective measure of cognition during routine care. The purpose of this study was to evaluate the feasibility and utility of the brief Montreal Cognitive Assessment (MoCA) in routine in-person and telehealth visits (as a result of the global COVID-19 pandemic) with neuro-oncology patients. Methods: Seventy-one adults with primary CNS tumors completed MoCA testing in person (n = 47) and via telehealth (n = 24). Correlation analysis and patient-reported outcomes (PROs), including symptom burden and interference, perceived cognition, general health status, and anxiety and depression, were included in this study. Feasibility was assessed through a provider satisfaction questionnaire. Results: Patients were primarily White (83%), college-educated (71%) males (54%) with high-grade tumors (66%). The average total score on the MoCA administered in person was 25 (range: 6-30), with 34% classified as abnormal, and the average total score via telehealth was 26 (range: 12-30), with 29% classified as abnormal. Providers reported satisfaction in using the MoCA during routine clinical care, both in person and via telehealth. Lower MoCA scores correlated with worse symptom severity, KPS, age, education, and previous treatment. Conclusions: The MoCA was feasible in clinical and telehealth settings, and its relationship to clinical characteristics and PROs highlights the need for both objective and patient-reported measures of cognition to understand the overall cognitive profile of a patient with a CNS tumor.
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INTRODUCTION: Despite an increasing aging population, older adults (≥ 65 years) with primary brain tumors (PBTs) are not routinely assessed for geriatric vulnerabilities. Recent reports of geriatric assessment (GA) in patients with glioblastomas demonstrated that GA may serve as a sensitive prognosticator of overall survival. Yet, current practice does not include routine evaluation of geriatric vulnerabilities and the relevance of GA has not been previously evaluated in broader cohorts of PBT patients. The objective of this descriptive study was to assess key GA constructs in adults with PBT dichotomized into older versus younger groups. MATERIALS AND METHODS: A cross-sectional analysis of data collected from 579 participants with PBT recruited between 2016 and 2020, dichotomized into older (≥ 65 years, n = 92) and younger (≤ 64 years, n = 487) from an ongoing observational trial. GA constructs were evaluated using socio-demographic characteristics, Charlson Comorbidity Index (CCI), polypharmacy (>5 daily medications), Karnofsky Performance Status (KPS), Neurologic Function Score (NFS), and patient-reported outcome assessments including general health, functional status, symptom burden and interference, and mood. Descriptive statistics, t-tests, chi-square tests, and Pearson correlations were used to evaluate differences between age groups. RESULTS: Older participants were more likely to have problems with mobility (58% vs. 44%), usual activities (64% vs 50%) and self-care (38% vs 26%) compared to the younger participants (odds ratios [ORs] = 1.3-1.4, ps < 0.05), while older participants were less likely to report feeling distressed (OR = 0.4, p < 0.05). Older participants also had higher CCI and were more likely to have polypharmacy (OR = 1.7, ps < 0.05). Increasing age strongly correlated with worse KPS score (r = -0.232, OR = 1.4, p < 0.001) and worse NFS (r = 0.210, OR = 1.5, p < 0.001). No differences were observed in overall symptom burden, symptom interference, and anxiety/depression scores. DISCUSSION: While commonly used GA tools were not available, the study employed patient- and clinician-reported outcomes to identify potential future research directions for the use of GA in the broader neuro-oncology population. Findings illustrate missed opportunities in neuro-oncology practice and underscore the need for incorporation of GA into routine care of this population. Future studies are warranted to further evaluate the prognostic utility of GA and to better understand functional aging outcomes in this patient population.