Rehabilitation in People Living with Glioblastoma: A Narrative Review of the Literature.

Glioblastoma is the most common primary malignant brain tumor. While preliminary data point to the positive effects of rehabilitation for patients with glioblastoma, there are unique challenges for clinicians working with this population, including limited life expectancy and/or rapid neurological deterioration. The aim of this article is to review the literature on rehabilitation of adults with glioblastoma, including the feasibility of interventions, their effectiveness, as well as the current clinical practice. The reviewed literature suggests that rehabilitation has been found beneficial for improving the functional prognosis and quality of life of adults with glioblastoma and is desired by patients. We summarize the qualitative evidence regarding healthcare professionals' and patients' perspectives on the use of supportive care services. We conclude there is a need for the design of effective rehabilitation programs for patients with glioblastoma, as well as for the development of glioblastoma-specific clinical guidelines for rehabilitation practitioners.

Living with an artificial eye: qualitative insights into patient and family member experiences.

PURPOSE: Artificial eye users (AEUs) can experience a negative impact on psychological and emotional wellbeing, including reduced social functioning, which may be a consequence of living with one eye removed, and/or of having a prosthetic eye. This may have wider consequences for their families. We aimed to explore what it means to live with a prosthetic eye, for both AEUs and their families-and how any quality of life (QoL) issues impact on their day-to-day functioning. METHODS: A subset of AEUs and their family members taking part in a feasibility randomised controlled trial comparing hand-painted to digitally printed artificial eyes were invited for semi-structured interviews. Transcripts were analysed using reflexive thematic analysis. Qualitative results related to trial participation are covered elsewhere. Here, we focus on QoL and day-to-day functioning. RESULTS: Twelve AEUs (eight males) and five spouses (one male) who had worn artificial eyes for 2-65 years took part, and four themes were identified. (1) Impact on day-to-day life: AEUs and their spouses have to adapt to (partial) sight loss, reduced levels of confidence, and social withdrawal. (2) Impact on psychological and emotional wellbeing: distress among AEUs and their spouses can be severe and prolonged, highlight unmet support needs. (3) Challenges with treatment experiences: AEUs experienced negative impact of fragmentation of care and long waiting times. (4) Worries about the future: AEUs mentioned fragility of remaining sight, and concerns around potential need for further treatment. CONCLUSION: Patients and their family members experience negative impact of being an AEU on their everyday lives and quality of life. There is a potential role for psychosocial support services in supporting AEUs and their families even long after eye loss.

Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) - protocol for a multi-centre open-label randomised trial.

INTRODUCTION: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM. METHODS AND ANALYSIS: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival. ETHICS AND DISSEMINATION: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines. TRIAL REGISTRATION NUMBER: ISRCTN60524.

Patient and caregiver return to work after a primary brain tumor.

Background: Studies focusing on the return to work (RTW) experiences of patients with a brain tumor (BT) are scarce. We aimed to explore, in-depth, the occupational expectations, experiences, and satisfaction of patients who RTW after a BT diagnosis and treatment, those not able to, and their family caregivers. Methods: This multicenter, cross-sectional study utilized semi-structured interviews and reflexive thematic analysis. Interviews were conducted with adults diagnosed with primary BT, in employment/self-employed before diagnosis, currently in follow-up care, and also with their caregivers. Results: In total, 23 interviews (17 patients/6 caregivers) took place. Five themes were developed: (1) Early (adjustments and) expectations: "Thought I would be back at work the following Monday"; pre-treatment patients wanted to be better informed about potential recovery time and side-effects. (2) Drivers to RTW: "Getting my life back on track"; RTW was seen as a symbol of normality and also dictated by financial pressures. (3) Experiences returning to work: "It's had its ups and downs": patients who had successfully returned were supported by employers financially, emotionally, and practically. (4) Required support: "He had surgery and that was it": suggested support included a back-to-work scheme and comprehensive financial support. (5) Caring and paid work: The "juggling act": carer's work was significantly impacted; often reducing/increasing their working hours while managing increasing caring demands. Conclusions: Future research focusing on RTW in neuro-oncology populations is needed. Interventions should be developed to improve employer/employee communication, and increase knowledge about BT care and possibilities for RTW, to support patients and caregivers towards sustained employment.

Depression and anxiety in glioma patients.

AbstractGlioma patients carry the burden of having both a progressive neurological disease and cancer, and may face a variety of symptoms, including depression and anxiety. These symptoms are highly prevalent in glioma patients (median point prevalence ranging from 16-41% for depression and 24-48% for anxiety when assessed by self-report questionnaires) and have a major impact on health-related quality of life and even overall survival time. A worse overall survival time for glioma patients with depressive symptoms might be due to tumor progression and/or its supportive treatment causing depressive symptoms, an increased risk of suicide or other (unknown) factors. Much is still unclear about the etiology of depressive and anxiety symptoms in glioma. These psychiatric symptoms often find their cause in a combination of neurophysiological and psychological factors, such as the tumor and/or its treatment. Although these patients have a particular idiosyncrasy, standard treatment guidelines for depressive and anxiety disorders apply, generally recommending psychological and pharmacological treatment. Only a few nonpharmacological trials have been conducted evaluating the efficacy of psychological treatments (eg, a reminiscence therapy-based care program) in this population, which significantly reduced depressive and anxiety symptoms. No pharmacological trials have been conducted in glioma patients specifically. More well-designed trials evaluating the efficacy of nonpharmacological treatments for depressive and anxiety disorders in glioma are urgently needed to successfully treat psychiatric symptoms in brain tumor patients and to improve (health-related) quality of life.

The experience of interval scans for adults living with primary malignant brain tumors.

PURPOSE: People with primary malignant brain tumors (PMBT) undergo anti-tumor treatment and are followed up with MRI interval scans. There are potential burdens and benefits to interval scanning, yet high-quality evidence to suggest whether scans are beneficial or alter outcomes of importance for patients is lacking. We aimed to gain an in-depth understanding of how adults living with PMBTs experience and cope with interval scanning. METHODS: Twelve patients diagnosed with WHO grade III or IV PMBT from two sites in the UK took part. Using a semi-structured interview guide, they were asked about their experiences of interval scans. A constructivist grounded theory approach was used to analyze data. RESULTS: Although most participants found interval scans uncomfortable, they accepted that scans were something that they had to do and were using various coping methods to get through the MRI scan. All participants said that the wait between their scan and results was the most difficult part. Despite the difficulties they experienced, all participants said that they would rather have interval scans than wait for a change in their symptoms. Most of the time, scans provided relief, gave participants some certainty in an uncertain situation, and a short-term sense of control over their lives. CONCLUSION: The present study shows that interval scanning is important and highly valued by patients living with PMBT. Although interval scans are anxiety provoking, they appear to help people living with PMBT cope with the uncertainty of their condition.

Communication in the context of glioblastoma treatment: A qualitative study of what matters most to patients, caregivers and health care professionals.

BACKGROUND: Patients with glioblastoma have a poor prognosis and treatment is palliative in nature from diagnosis. It is therefore critical that the benefits and burdens of treatments are clearly discussed with patients and caregivers. AIM: To explore experiences and preferences around glioblastoma treatment communication in patients, family caregivers and healthcare professionals. DESIGN: Qualitative design. A thematic analysis of semi-structured interviews. SETTING/PARTICIPANTS: A total of 15 adult patients with glioblastoma, 13 caregivers and 5 healthcare professionals were recruited from Leeds Teaching Hospitals NHS Trust. RESULTS: Four themes were identified: (1) Communication practice and preferences. Risks and side-effects of anti-tumour treatments were explained clearly, with information layered and repeated. Treatment was often understood to be 'the only option'. Understanding the impact of side-effects could be enhanced, alongside information about support services. (2) What matters most. Patients/caregivers valued being well-supported by a trusted treatment team, feeling involved, having control and quality of life. Healthcare professionals similarly highlighted trust, maintaining independence and emotional support as key. (3) Decision-making. With limited treatment options, trust and control are crucial in decision-making. Patients ultimately prefer to follow healthcare professional advice but want to be involved, consider alternatives and voice what matters to them. (4) Impact of COVID-19. During the pandemic, greater efforts to maintain good communication were necessary. Negative impacts of COVID-19 were limited, caregivers appeared most disadvantaged by pandemic-related restrictions. CONCLUSIONS: In glioblastoma treatment communication, where prognosis is poor and treatmentwill not result in cure, building trusting relationships, maintaining a sense of control and being well-informed are identified as critical.

Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: A longitudinal study spanning two decades.

BACKGROUND: While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients' long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis). METHODS: Participants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS]), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. RESULTS: Thirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers' HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients' mental health improved (P < .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. CONCLUSIONS: While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent.

The effects of SmartCare© on neuro-oncology family caregivers' distress: a randomized controlled trial.

PURPOSE: Patients with primary malignant brain tumors have high symptom burden and commonly rely on family caregivers for practical and emotional support. This can lead to negative mental and physical consequences for caregivers. We investigated effectiveness of an 8-week nurse-led online needs-based support program (SmartCare©) with and without online self-guided cognitive behavioral therapy (CBT) for depression compared to enhanced care as usual (ECAU) on depressive symptoms, caregiving-specific distress, anxiety, mastery, and burden. METHODS: Family caregivers scoring ≥ 6 on a depressive symptoms inventory were randomized to three groups: ECAU plus self-guided CBT and SmartCare©; ECAU plus SmartCare©; ECAU only. Primary outcomes (depressive symptoms; caregiving-specific distress) and secondary outcomes (anxiety, caregiver mastery, and caregiver burden) were assessed online. Intention to treat (ITT) and per protocol (PP) analyses of covariance corrected for baseline scores were performed for outcomes at 4 months. RESULTS: In total, 120 family caregivers participated. Accrual and CBT engagement were lower than expected, therefore intervention groups were combined (n = 80) and compared to ECAU (n = 40). For depressive symptoms, no statistically significant group differences were found. Caregiving-specific distress decreased in the intervention group compared with ECAU (ITT: p = 0.01, partial ɳ2 = 0.08; PP: p = 0.02, partial ɳ2 = 0.08). A trend towards improvement in mastery for the intervention group compared with ECAU was identified (ITT: p = 0.08, partial ɳ2 = 0.04; PP: p = 0.07, partial ɳ2 = 0.05). CONCLUSIONS: SmartCare©, with or without self-guided CBT, reduced caregiving-specific distress with a trend towards improving mastery. SmartCare© has the potential to improve the lives of families coping with a brain tumor diagnosis. TRIAL REGISTRATION NUMBER: NCT02058745; 10 February 2014.

The Added Value of Family Caregivers' Level of Mastery in Predicting Survival of Glioblastoma Patients: A Validation Study.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive brain tumor. Patients commonly rely on family caregivers for physical and emotional support. We previously demonstrated that caregiver mastery measured shortly after diagnosis was predictive of GBM patient survival, corrected for known predictors of survival (n = 88). OBJECTIVE: The aims of this study were to verify the contribution of caregiver mastery and investigate the added value of mastery over other predictors to predict 15-month survival. METHODS: Data collected for a longitudinal study (NCT02058745) were used. Multivariable Cox regression analyses were performed for models with known clinical predictors (patient age, Karnofsky Performance Status, type of surgery, O6-methylguanine-DNA-methyltransferase promotor methylation status), with and without adding caregiver mastery to predict mortality. The added value of each model in discriminating between patients with the lowest and highest chances of survival at 15 months was investigated through Harrell's concordance index. RESULTS: In total, 41 caregiver-patient dyads were included. When evaluating solely clinical predictors, Karnofsky Performance Status and patient age were significant predictors of mortality (hazard ratio [HR], 0.974; 95% confidence interval [CI], 0.949-1.000; and HR, 1.045; 95% CI, 1.002-1.091, respectively). Adding caregiver mastery, these clinical predictors remained statistically significant, and mastery showed an HR of 0.843 (95% CI, 0.755-0.940). The discriminative value improved from C = 0.641 (model with known clinical predictors) to C = 0.778 (model with mastery), indicating the latter is superior. CONCLUSIONS: We confirm that caregiver mastery is associated with GBM patient survival. IMPLICATIONS FOR PRACTICE: Incorporating support and guidance for caregivers into standard care could lead to benefits for caregiver well-being and patient outcomes.

Long-term health-related quality of life and neurocognitive functioning after treatment in skull base meningioma patients.

OBJECTIVE: Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL) and possibly neurocognitive dysfunction. As the survival of meningioma patients is near normal, long-term neurocognitive and HRQOL outcomes are important to evaluate, including evaluation of the impact of specific tumor location and treatment modalities on these outcomes. METHODS: In this multicenter cross-sectional study including patients 5 years or more after their last tumor intervention, Short-Form Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20 questionnaires were used to assess generic and disease-specific HRQOL. Neurocognitive functioning was assessed with standardized neuropsychological assessment. SBM patient assessments were compared with those of 1) informal caregivers of SBM patients who served as controls and 2) convexity meningioma patients. In addition, the authors compared anterior/middle SBM patients with posterior SBM patients and anterior/middle and posterior SBM patients separately with controls. Multivariable and propensity score regression analyses were performed to correct for possible confounders. RESULTS: Patients with SBM (n = 89) with a median follow-up of 9 years after the last intervention did not significantly differ from controls (n = 65) or convexity meningioma patients (n = 84) on generic HRQOL assessment. Statistically significantly but not clinically relevantly better disease-specific HRQOL was found for SBM patients compared with convexity meningioma patients. Anterior/middle SBM patients (n = 62) had significantly and clinically relevantly better HRQOL in SF-36 and EORTC QLQ-BN20 scores than posterior SBM patients (n = 27): physical role functioning (corrected difference 17.1, 95% CI 0.2-34.0), motor dysfunction (-10.1, 95% CI -17.5 to -2.7), communication deficit (-14.2, 95% CI -22.7 to -5.6), and weakness in both legs (-10.1, 95% CI -18.8 to -1.5). SBM patients whose primary treatment was radiotherapy had lower HRQOL scores compared with SBM patients who underwent surgery on two domains: bodily pain (-33.0, 95% CI -55.2 to -10.9) and vitality (-18.9. 95% CI -33.7 to -4.1). Tumor location and treatment modality did not result in significant differences in neurocognitive functioning, although 44% of SBM patients had deficits in at least one domain. CONCLUSIONS: In the long term, SBM patients do not experience significantly more sequelae in HRQOL and neurocognitive functioning than do controls or patients with convexity meningioma. Patients with posterior SBM had poorer HRQOL than anterior/middle SBM patients, and primary treatment with radiotherapy was associated with worse HRQOL. Neurocognitive functioning was not affected by tumor location or treatment modality.

Pilot study of smartphone-based health outcome tracking (OurBrainBank) for glioblastoma patients.

BACKGROUND: Patients with glioblastoma (GBM) typically have high symptom burden impacting on quality of life. Mobile apps may help patients track their condition and provide real-time data to clinicians and researchers. We developed a health outcome reporting app (OurBrainBank [OBB]) for GBM patients. Our primary aim was to explore the feasibility and take-up of OBB. Secondary aims were to examine the potential value of OBB app usage for patient well-being and clinical research. METHODS: Participants (or caregiver proxies) completed baseline surveys and tracked 10 health outcomes over time. We evaluated usage and engagement, and relationships between clinical/sociodemographic variables and OBB use. Participant satisfaction and feedback were described. To demonstrate usefulness for clinical research, health outcomes were compared with corresponding items on a validated measure (EQ-5D-5L). RESULTS: From March 2018 to February 2021, OBB was downloaded by 630 individuals, with 15 207 sets of 10 health outcomes submitted. Higher engagement was associated with being a patient rather than a caregiver (χ 2(2,568) = 28.6, P < .001), having higher self-rated health scores at baseline (F(2,460) = 4.8, P = .009) and more previous experience with mobile apps (χ 2(2,585) = 9.6, P = .008). Among the 66 participants who completed a feedback survey, most found health outcome tracking useful (average 7/10), and would recommend the app to others (average 8.4/10). The OBB health outcomes mapped onto corresponding EQ-5D-5L items, suggesting their validity. CONCLUSIONS: OBB can efficiently collect GBM patients' health outcomes. The long-term goal is to create a unique database of thousands of deidentified GBM patients, with open access to qualified researchers.

Unmet support needs in teenage and young adult childhood brain tumour survivors and their caregivers: "it's all the aftermath, and then you're forgotten about".

PURPOSE: Teenage and young adult (TYA) survivors of childhood brain tumours and their family caregivers can experience many late effects of treatment that can hamper the transition to living independent lives. Yet, their long-term supportive care needs are largely unknown. We investigated the supportive care needs of TYA survivors and their caregivers and explored the role and perceived use of support. METHODS: Face-to-face semi-structured interviews were conducted with survivors aged 16-30 (n = 11) who were ≥ 5 years after diagnosis and caregivers (n = 11). Interviews were recorded and transcriptions thematically analysed. RESULTS: Four themes emerged: (1) preferences for support and support services (unmet needs). Concerns regarding mental health, employment and financial uncertainty, the desire to live independently, and lack of support were emphasised. (2) Decline in support. Caregivers noted a drop-off in support available when transitioning to adult services. (3) Reasons for not obtaining adequate support. Several barriers to accessing support were raised, including distance and aging out of services. (4) The role of long-term hospital-based follow-up care. Participants highlighted the importance of, and reassurance from, long-term follow-up care but noted a more all-inclusive approach is required. CONCLUSIONS: Even many years after diagnosis, TYA childhood brain tumour survivors and their caregivers continue to have unmet supportive care needs. Both TYA survivors and their caregivers can benefit from support to meet their unique needs and improve long-term quality of life. Understanding unmet needs and recognising what services are required due to the late effects of treatment is critical to improving long-term quality of survival.

Establishing anchor-based minimally important differences for the EORTC QLQ-C30 in glioma patients.

BACKGROUND: Minimally important differences (MIDs) allow interpretation of the clinical relevance of health-related quality of life (HRQOL) results. This study aimed to estimate MIDs for all European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) scales for interpreting group-level results in brain tumor patients. METHODS: Clinical and HRQOL data from three glioma trials were used. Clinical anchors were selected for each EORTC QLQ-C30 scale, based on correlation (>0.30) and clinical plausibility of association. Changes in both HRQOL and the anchors were calculated, and for each scale and time period, patients were categorized into one of the three clinical change groups: deteriorated by one anchor category, no change, or improved by one anchor category. Mean change method and linear regression were applied to estimate MIDs for interpreting within-group change and between-group differences in change over time, respectively. Distribution-based methods were applied to generate supportive evidence. RESULTS: A total of 1687 patients were enrolled in the three trials. The retained anchors were performance status and eight Common Terminology Criteria for Adverse Events (CTCAE) scales. MIDs for interpreting within-group change ranged from 4 to 12 points for improvement and -4 to -14 points for deterioration. MIDs for between-group difference in change ranged from 4 to 9 for improvement and -4 to -16 for deterioration. Most anchor-based MIDs were closest to the 0.3 SD distribution-based estimates (range: 3-10). CONCLUSIONS: MIDs for the EORTC QLQ-C30 scales generally ranged between 4 and 11 points for both within-group mean change and between-group mean difference in change. These results can be used to interpret QLQ-C30 results from glioma trials.

The long-term caregiver burden in World Health Organization grade I and II meningioma: It is not just the patient.

BACKGROUND: Little is known about long-term caregiver burden in meningioma patients. We assessed meningioma caregiver burden, its association with informal caregiver's well-being and possible determinants. METHODS: In this multicenter cross-sectional study, informal caregivers completed the Caregiver Burden Scale (five domains and total score). Patients completed a disease-specific health-related quality of life (HRQoL) questionnaire focusing on symptoms (EORTC QLQ-BN20) and underwent neurocognitive assessment. Both groups completed a generic HRQoL questionnaire (SF-36) and the Hospital Anxiety, and Depression Scale. We assessed the association between caregiver burden and their HRQoL, anxiety and depression. Furthermore, we assessed determinants for the caregiver burden. Multivariable regression analysis was used to correct for confounders. RESULTS: One hundred and twenty-nine informal caregivers were included (median 10 years after patients' treatment). Caregivers reported burden in ≥1 domain (34%) or total burden score (15%). A one-point increase in total caregiver burden score was associated with a clinically relevant decrease in caregiver's HRQoL (SF-36) in 5/8 domains (score range: -10.4 to -14.7) and 2/2 component scores (-3.5 to -5.9), and with more anxiety (3.8) and depression (3.0). Patients' lower HRQoL, increased symptom burden, and increased anxiety and depression were determinants for higher caregiver burden, but not patients' or caregivers' sociodemographic characteristics, patients' neurocognitive functioning, or tumor- and treatment-related characteristics. CONCLUSIONS: Ten years after initial treatment, up to 35% of informal caregivers reported a clinically relevant burden, which was linked with worse HRQoL, and more anxiety and depression in both patients and caregivers, emphasizing the strong interdependent relationship. Support for meningioma caregivers is therefore warranted.

Determinants and predictors for the long-term disease burden of intracranial meningioma patients.

INTRODUCTION: Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first assessed variables associated with impaired long-term health-related quality of life (HRQoL) and impaired neurocognitive function on group level (i.e. determinants). Next, prediction models were developed to predict the risk for long-term neurocognitive or HRQoL impairment on individual patient-level. METHODS: Secondary data analysis of a cross-sectional multicenter study with intracranial WHO grade I/II meningioma patients, in which HRQoL (Short-Form 36) and neurocognitive functioning (standardized test battery) were assessed. Multivariable regression models were used to assess determinants for these outcomes corrected for confounders, and to build prediction models, evaluated with C-statistics. RESULTS: Data from 190 patients were analyzed (median 9 years after intervention). Main determinants for poor HRQoL or impaired neurocognitive function were patients' sociodemographic characteristics, surgical complications, reoperation, radiotherapy, presence of edema, and a larger tumor diameter on last MRI. Prediction models with a moderate/good ability to discriminate between individual patients with and without impaired HRQoL (C-statistic 0.73, 95% CI 0.65 to 0.81) and neurocognitive function (C-statistic 0.78, 95%CI 0.70 to 0.85) were built. Not all predictors (e.g. tumor location) within these models were also determinants. CONCLUSIONS: The identified determinants help clinicians to better understand long-term meningioma disease burden. Prediction models can help early identification of individual patients at risk for long-term neurocognitive or HRQoL impairment, facilitating tailored provision of information and allocation of scarce supportive care services to those most likely to benefit.

Long-Term Disease Burden and Survivorship Issues After Surgery and Radiotherapy of Intracranial Meningioma Patients.

BACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE: To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS: In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS: At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (-2.11, 95% CI: -3.52 to -0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION: In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning.

Pharmacological treatment of depression in people with a primary brain tumour.

BACKGROUND: This is the second updated version of the Cochrane Review published in Issue 3, 2010 and first updated in Issue 5, 2013. People with a primary brain tumour often experience depression, for which drug treatment may be prescribed. However, they are also at high risk of epileptic seizures, cognitive impairment, and fatigue, all of which are potential adverse side effects of antidepressants. The benefit, or harm, of pharmacological treatment of depression in people with a primary brain tumour is unclear. OBJECTIVES: To assess the benefits and harms of pharmacological treatment of depression in people with a primary brain tumour. SEARCH METHODS: We updated the search to include CENTRAL, MEDLINE, Embase, and PsycINFO to September 2019. As in the original review, we also handsearched Neuro-Oncology, Journal of Neuro-Oncology, Journal of Neurology, Neurosurgery and Psychiatry, and Journal of Clinical Oncology: for the current update we handsearched the latest three years of articles from these journals (up to November 2019). SELECTION CRITERIA: We searched for all randomised controlled trials (RCTs), controlled clinical trials, cohort studies, and case-control studies of any pharmacological treatment of depression in people with a histologically diagnosed primary brain tumour. DATA COLLECTION AND ANALYSIS: No studies met the inclusion criteria. MAIN RESULTS: We found no eligible studies evaluating the benefits of any pharmacological treatment of depression in people with a primary brain tumour. AUTHORS' CONCLUSIONS: We identified no high-quality studies that investigated the value of pharmacological treatment of depression in people with a primary brain tumour. RCTs and detailed prospective studies are required to inform the effective pharmacological treatment of this common and important complication of brain tumours. Since the last version of this review none of the related new literature has provided additional information to change these conclusions.

Healthcare utilization and productivity loss in glioma patients and family caregivers: the impact of treatable psychological symptoms.

BACKGROUND: Gliomas are associated with significant healthcare burden, yet reports of costs are scarce. While many costs are unavoidable there may be treatable symptoms contributing to higher costs. We describe healthcare and societal costs in glioma patients at high risk for depression and their family caregivers, and explore relationships between costs and treatable symptoms. METHODS: Data from a multicenter randomized trial on effects of internet-based therapy for depressive symptoms were used (NTR3223). Costs of self-reported healthcare utilization, medication use, and productivity loss were calculated for patients and caregivers separately. We used generalized linear regression models to predict costs with depressive symptoms, fatigue, cognitive complaints, tumor grade (low-/high-grade), disease status (stable or active/progression), and intervention (use/non-use) as predictors. RESULTS: Multiple assessments from baseline through 12 months from 91 glioma patients and 46 caregivers were used. Mean overall costs per year were M = €20,587.53 (sd = €30,910.53) for patients and M = €5,581.49 (sd = €13,102.82) for caregivers. In patients, higher healthcare utilization costs were associated with more depressive symptoms; higher medication costs were associated with active/progressive disease. In caregivers, higher overall costs were linked with increased caregiver fatigue, cognitive complaints, and lower patient tumor grade. Higher healthcare utilization costs were related to more cognitive complaints and lower tumor grade. More productivity loss costs were associated with increased fatigue (all P < 0.05). CONCLUSIONS: There are substantial healthcare and societal costs for glioma patients and caregivers. Associations between costs and treatable psychological symptoms indicate that possibly, adequate support could decrease costs. TRIAL REGISTRATION: Netherlands Trial Register NTR3223.