Lifestyle coaching is feasible in fatigued brain tumor patients: A phase I/feasibility, multi-center, mixed-methods randomized controlled trial.

Background: There are no effective treatments for brain tumor-related fatigue. We studied the feasibility of two novel lifestyle coaching interventions in fatigued brain tumor patients. Methods: This phase I/feasibility multi-center RCT recruited patients with a clinically stable primary brain tumor and significant fatigue (mean Brief Fatigue Inventory [BFI] score ≥ 4/10). Participants were randomized in a 1-1-1 allocation ratio to: Control (usual care); Health Coaching ("HC", an eight-week program targeting lifestyle behaviors); or HC plus Activation Coaching ("HC + AC", further targeting self-efficacy). The primary outcome was feasibility of recruitment and retention. Secondary outcomes were intervention acceptability, which was evaluated via qualitative interview, and safety. Exploratory quantitative outcomes were measured at baseline (T0), post-interventions (T1, 10 weeks), and endpoint (T2, 16 weeks). Results: n = 46 fatigued brain tumor patients (T0 BFI mean = 6.8/10) were recruited and 34 were retained to endpoint, establishing feasibility. Engagement with interventions was sustained over time. Qualitative interviews (n = 21) suggested that coaching interventions were broadly acceptable, although mediated by participant outlook and prior lifestyle. Coaching led to significant improvements in fatigue (improvement in BFI versus control at T1: HC=2.2 points [95% CI 0.6, 3.8], HC + AC = 1.8 [0.1, 3.4], Cohen's d [HC] = 1.9; improvement in FACIT-Fatigue: HC = 4.8 points [-3.7, 13.3]; HC + AC = 12 [3.5, 20.5], d [HC and AC] = 0.9). Coaching also improved depressive and mental health outcomes. Modeling suggested a potential limiting effect of higher baseline depressive symptoms. Conclusions: Lifestyle coaching interventions are feasible to deliver to fatigued brain tumor patients. They were manageable, acceptable, and safe, with preliminary evidence of benefit on fatigue and mental health outcomes. Larger trials of efficacy are justified.

A virtual multi-disciplinary meeting is a cost-effective method of triaging referrals to a regional musculoskeletal oncology service.

BACKGROUND AND AIMS: In 2010, a virtual sarcoma referral model was implemented, which aims to provide a centralised multidisciplinary team (MDT) to provide rapid advice, avoiding unnecessary appointments and providing a streamlined service. The aim of this study is to examine the feasibility of this screening tool in reducing the service burden and expediting patient journey. METHODS AND RESULTS: All referrals made to a single tertiary referral sarcoma unit from January 2010 to December 2018 were extracted from a prospective database. Only 26.0% events discussed required review directly. 30.3% were discharged back to referrer. 16.5% required further investigations. 22.5% required a biopsy prior to review. There was a reduction in the rate of patients reviewed at the sarcoma clinic, and a higher discharge rate from the MDT in 2018 versus 2010 (p < 0.001). This gives a potential cost saving of 670,700 GBP over the 9 year period. CONCLUSION: An MDT meeting which triages referrals is cost-effective at reducing unnecessary referrals. This can limit unnecessary exposure of patients who may have an underlying diagnosis of cancer to a high-risk environment, and reduces burden on services as it copes with increasing demands during the COVID-19 pandemic.

Geriatric assessment of glioblastoma patients is feasible and may provide useful prognostic information.

BACKGROUND: Glioblastoma (GBM) is the most common and most lethal primary brain tumor in adults. Clinical trials in older patients with GBM have explored the use of single and multimodality treatment regimens with modest survival benefits; however, trial criteria are commonly based on chronological age and do not reflect the heterogeneity of this cohort. Geriatric assessment (GA) techniques predict survival and treatment tolerance in other tumor sites and thus may objectively guide the decision-making process, but data are lacking in the neuro-oncology cohort. METHODS: We performed a prospective, multicenter feasibility study involving patients age 65 years or older with newly diagnosed GBM. A modified GA was undertaken in the outpatient setting prior to starting treatment. Feasibility was determined primarily by recruitment rate, alongside data completeness, impact on clinic time, and acceptability to patients and staff. Factors associated with survival were explored using Cox regression models. RESULTS: Fifty patients were recruited within a prespecified time period with a recruitment rate of 82% (target 80%). Data completeness was greater than 80% in all except one assessment. Median overall survival was 9.5 months (95% confidence interval [CI] 5.0-14.0 months). Among the GA screening factors analyzed, a baseline impaired Montreal Cognitive Assessment (hazard ratio [HR] = 2.7, 95% CI 1.128-6.530) and impairment in instrumental activities of daily living (HR = 2.9 95% CI 0.983-8.541) were associated with poorer survival. CONCLUSION: In the first study of this kind among elderly GBM patients, we have shown that undertaking a neurologically focused GA screen is feasible and may provide useful prognostic information.

The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

OBJECTIVE: It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. MATERIALS AND METHODS: Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. RESULTS: The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. CONCLUSION: Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

A survival analysis of GBM patients in the West of Scotland pre- and post-introduction of the Stupp regime.

OBJECTIVE: It is now accepted that the concomitant administration of temozolomide with radiotherapy (Stupp regime), in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM), significantly improves survival and this practice has been adopted locally since 2004. However, survival outcomes in cancer can vary in different population groups, and outcomes can be affected by a number of local factors including socioeconomic status. In the West of Scotland, we have one of the worse socioeconomic status and overall health record for a western European country. With the ongoing reorganisation and rationalisation in the National Health Service, the addition of prolonged courses of chemotherapy to patients' management significantly adds to the financial burden of a cash stripped NHS. A survival analysis in patients with GBM was therefore performed, comparing outcomes of pre- and post-introduction of the Stupp regime, to justify the current practice. MATERIALS AND METHODS: Prospectively collected clinical data were analysed in 105 consecutive patients receiving concurrent chemoradiotherapy (Stupp regime) following surgical treatment of GBM between December 2004 and February 2009. This was compared to those of 106 consecutive GBM patients who had radical radiotherapy (pre-Stupp regime) post-surgery between January 2001 and February 2006. RESULTS: The median overall survival for the post-Stupp cohort was 15.3 months (range, 2.83-50.5 months), with 1-year and 2-year overall survival rates of 65.7% and 19%, respectively. This was in comparison with the median overall pre-Stupp survival of 10.7 months, with 1-year and 2-year survival rates of 42.6% and 12%, respectively (log-rank test, p < 0.001). Multivariate Cox regression analysis showed that independent prognostic factors for better survival were younger age, greater extent of surgical resection and a post-operative chemoradiotherapy regime. CONCLUSION: Significant survival benefit has been achieved, following the introduction of the Stupp regime, in GBM patients in the West of Scotland.

The frequency, longitudinal course, clinical associations, and causes of emotional distress during primary treatment of cerebral glioma.

BACKGROUND: Relatively little is known about the frequency, longitudinal course, independent associations, and reported causes of emotional distress in adults with primary cerebral glioma. We aimed to describe these features in an observational study. METHODS: This was a twin-center prospective cohort study. Eligible adults were those with a new histological diagnosis of glioma who were receiving active management. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and problem checklist. Subjects were sampled at 3 timepoints: T1 (shortly after starting chemo/radiotherapy), T2 (3 months later), and T3 (6 months later). RESULTS: T1 n = 154; T2 n = 103; T3 n = 83. Significant distress was present in 36.4 ± 7.6% at T1, 35.9 ± 9.3% at T2, and 33.7 ± 10.2% at T3. Longitudinally, subjects with high distress at T1 (median Distress Thermometer score = 8; interquartile range [IQR] 7-9) remained highly distressed on follow-up (T2 median = 8, IQR 6-8; T3 median = 7, IQR 5-8) (Friedman test P = .304). Younger age, functional impairment, and concurrent major depressive disorder were independently associated with high distress (logistic regression χ(2) for model = 39.882, P < .001, R(2) = 0.312). The most frequently reported causes of distress were worry, fatigue, sleep difficulties, and sadness. Emotional difficulties were among the most common causes of distress at all 3 timepoints. CONCLUSIONS: At each timepoint, one-third of patients reported significant emotional distress, which persisted during follow-up among those initially highly distressed. Young, functionally impaired, and depressed glioma patients may particularly benefit from increased support.

Screening for major depressive disorder in adults with glioma using the PHQ-9: a comparison of patient versus proxy reports.

When screening for depression in glioma patients, the utility of proxy carer report is unknown. We studied how patients and proxies differed in the frequency, severity and agreement of reported depressive symptoms, the external validity of these reports, and whether patient-proxy agreement was associated with cognitive function. This was a cross-sectional study within a prospective cohort study of depression in glioma. Eligible patients were adults with a new diagnosis of cerebral glioma whose cohabiting partners chose to attend study interviews. Patients completed the Patient Health Questionnaire-9 (PHQ-9, maximum score 27) to screen for major depressive disorder. Proxies independently completed the PHQ-9 'for the patient'. A structured clinical interview for MDD was then given. From 55 couples attending, 41 participated (74 %). Patient-proxy total PHQ-9 score differed by 3 or more points in 26/41 cases (63.4 %). Disagreement within dyads ranged from -7 to +10 points. Proxies observed more individual depressive symptoms than patients reported (mean 2.7 vs 1.8 symptoms respectively, p = 0.013, Wilcoxon Rank Sum Test), and a greater severity of symptom burden (mean PHQ-9 score 8.4 vs 6.8 respectively, p = 0.016, Wilcoxon Rank Sum Test). Proxies were more reliable than patients on objective behavioural symptoms of depression. Dyadic agreement was not associated with severity of patient cognitive impairment. There was frequent disagreement between glioma patients and proxies reports of depressive symptoms. Proxies reported more depressive symptoms than patients, and were more reliable when reporting observable behavioural symptoms. When diagnosing depression in glioma, collateral history should be obtained.

Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments.

No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire-9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or "watchful waiting." At each of 3 interviews over a 6-month period, patients completed the screening questionnaires and received a structured clinical interview to diagnose MDD. Internal consistency, area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value, and positive likelihood ratio were calculated. A maximum of 154 patients completed the DT, 133 completed the HAD-D, and 129 completed the PHQ-9. The HAD-D and PHQ-9 showed good internal consistency (α ≥ 0.77 at all timepoints). Median AUCs were 0.931 ± 0.074 for the HAD-D and 0.915 ± 0.055 for the PHQ-9. The optimal threshold was 7+ for the HAD-D, but 8+ had similar operating characteristics. There was no consistently optimal PHQ-9 threshold, but 10+ was optimal in the largest sample. The DT was inferior to the multi-item instruments. Clinicians can screen for depression in well-functioning glioma patients using the HAD-D at the existing recommended lower threshold of 8+, or the PHQ-9 at a threshold of 10+. Due to a modest positive predictive value of either instrument, patients scoring above these thresholds need a clinical assessment to diagnose or exclude depression.

Frequency, clinical associations, and longitudinal course of major depressive disorder in adults with cerebral glioma.

PURPOSE: There is a need for high-quality evidence regarding the frequency, independent clinical associations, and longitudinal course of depression in patients with cerebral glioma. PATIENTS AND METHODS: This was a twin-center, prospective, observational cohort study with 6-month follow-up. Consenting adults with a new diagnosis of cerebral glioma received the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to diagnose major depressive disorder (MDD). Interviews occurred shortly after the start of radiotherapy (T1), with follow-up interviews 3 months later (T2) and 6 months later (T3). Independent associations between MDD and clinical variables were analyzed using logistic regression. RESULTS: One hundred fifty-five patients participated. The frequency of MDD was 13.5% ± 5.4% at T1 (n = 155); 14.8% ± 6.7% at T2 (n = 108); and 6.8% ± 5.3% at T3 (n = 88). Overall, 32 individuals were diagnosed with MDD during the study period (20.6% ± 6.4%). Inter-rater diagnostic agreement for MDD was good (κ = 0.81; 95% CI, 0.60 to 1.00). Independent predictors of MDD were functional impairment (odds ratio, 3.9; 95% CI, 1.5 to 10.8) and a previous history of depression (odds ratio, 2.7; 95% CI, 0.99 to 7.3). MDD persisted for at least 3 months in half of the patients with adequate follow-up, but many depressed patients also dropped out of the study as a result of clinical deterioration. CONCLUSION: In this longitudinal study, one in five patients with glioma developed clinical depression in the 6 months after starting radiotherapy. Patients with functional impairment or previous depression were at higher risk. MDD often persisted for at least 3 months. Clinicians should seek and treat depression in adults with glioma.