Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

INTRODUCTION: Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma. METHODS AND ANALYSIS: Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups. ETHICS AND DISSEMINATION: Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available. TRIAL REGISTRATION NUMBER: COMET study ID 1508.

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients?

BACKGROUND: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery. METHODS: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression. RESULTS: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months. CONCLUSIONS: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

Treatment Outcomes of Incidental Intracranial Meningiomas: Results from the IMPACT Cohort.

BACKGROUND: Incidental findings such as meningioma are becoming increasingly prevalent. There is no consensus on the optimal management of these patients. The aim of this study was to examine the outcomes of patients diagnosed with an incidental meningioma who were treated with surgery or radiotherapy. METHODS: Single-center retrospective cohort study of adult patients diagnosed with an incidental intracranial meningioma (2007-2015). Outcomes recorded were postintervention morbidity, histopathologic diagnosis, and treatment response. RESULTS: Out of 441 patients, 44 underwent treatment. Median age at intervention was 56.1 years (interquartile range [IQR], 49.6-66.5); patients included 35 women and 9 men. The main indication for imaging was headache (25.9%). Median meningioma volume was 4.55 cm3 (IQR, 1.91-8.61), and the commonest location was convexity (47.7%). Six patients underwent surgery at initial diagnosis. Thirty-eight had intervention (34 with surgery and 4 with radiotherapy) after a median active monitoring duration of 24 months (IQR, 11.8-42.0). Indications for treatment were radiologic progression (n = 26), symptom development (n = 6), and patient preference (n = 12). Pathology revealed World Health Organization (WHO) grade 1 meningioma in 36 patients and WHO grade 2 in 4 patients. The risk of postoperative surgical and medical morbidity requiring treatment was 25%. Early and late moderate adverse events limiting activities of daily living occurred in 28.6% of patients treated with radiotherapy. Recurrence rate after surgery was 2.5%. All meningiomas regressed or remained radiologically stable after radiotherapy. CONCLUSIONS: The morbidity after treatment of incidental intracranial meningioma is not negligible. Considering most operated tumors are WHO grade 1, treatment should be reserved for those manifesting symptoms or demonstrating substantial growth on radiologic surveillance.

A prognostic model to personalize monitoring regimes for patients with incidental asymptomatic meningiomas.

BACKGROUND: Asymptomatic meningioma is a common incidental finding with no consensus on the optimal management strategy. We aimed to develop a prognostic model to guide personalized monitoring of incidental meningioma patients. METHODS: A prognostic model of disease progression was developed in a retrospective cohort (2007-2015), defined as: symptom development, meningioma-specific mortality, meningioma growth or loss of window of curability. Secondary endpoints included non-meningioma-specific mortality and intervention. RESULTS: Included were 441 patients (459 meningiomas). Over a median of 55 months (interquartile range, 37-80), 44 patients had meningioma progression and 57 died (non-meningioma-specific). Forty-four had intervention (at presentation, n = 6; progression, n = 20; nonprogression, n = 18). Model parameters were based on statistical and clinical considerations and included: increasing meningioma volume (hazard ratio [HR] 2.17; 95% CI: 1.53-3.09), meningioma hyperintensity (HR 10.6; 95% CI: 5.39-21.0), peritumoral signal change (HR 1.58; 95% CI: 0.65-3.85), and proximity to critical neurovascular structures (HR 1.38; 95% CI: 0.74-2.56). Patients were stratified based on these imaging parameters into low-, medium- and high-risk groups and 5-year disease progression rates were 3%, 28%, and 75%, respectively. After 5 years of follow-up, the risk of disease progression plateaued in all groups. Patients with an age-adjusted Charlson comorbidity index ≥6 (eg, an 80-year-old with chronic kidney disease) were 15 times more likely to die of other causes than to receive intervention at 5 years following diagnosis, regardless of risk group. CONCLUSIONS: The model shows that there is little benefit to rigorous monitoring in low-risk and older patients with comorbidities. Risk-stratified follow-up has the potential to reduce patient anxiety and associated health care costs.

Quality improvement of neuro-oncology services: integrating the routine collection of patient-reported, health-related quality-of-life measures.

BACKGROUND: Brain cancer has a strong impact on health-related quality of life (HRQoL), and its evaluation in clinical practice can improve the quality of care provided. The aim of this project was to integrate routine collection of HRQoL information from patients with brain tumor or metastasis in 2 specialized United Kingdom tertiary centers, and to evaluate the implementation process. METHODS: Since October 2016, routine collection of electronic self-reported HRQoL information has been progressively embedded in the participating centers using standard questionnaires. During the first year, the project was implemented, and the process evaluated, through regular cycles of process evaluation followed by an action plan, monitoring of questionnaire completion rates, and assessment of patient views. RESULTS: Main challenges encountered included reluctance to change usual practice and limited resources. Key measures for success included strong leadership of senior staff, involvement of stakeholders in project design and evaluation, and continuous strategic support to professionals. Final project workflow included 6 process steps, 1 decision step, and 4 outputs. Questionnaires were mostly self-completed (75.1%), and completion took 6-9 minutes. Most patients agreed that the questionnaire items were easy to understand (97.0%), important for them (93.0%), and helped them think what they wanted to discuss in their clinical consultation (75.4%). CONCLUSIONS: Integrating HRQoL information as a routine part of clinical assessments has the potential to enhance individually tailored patient care in our institutions. Challenges involved in innovations of this nature can be overcome through a systematic approach involving strong leadership, wide stakeholder engagement, and strategic planning.

Defining unmet clinical need across the pathway of brain tumor care: a patient and carer perspective.

OBJECTIVE: The aim of this study was to determine the experience of patients with brain tumors and their carers across distinct parts of their treatment pathway and identify their views on potential service gaps in need of addressing. METHODS: A structured survey was administered at patient workshops across the UK and online through a charity newsletter. Answers to closed questions were analyzed using descriptive statistics, and open questions were examined using techniques of inductive content analysis. RESULTS: A total of 136 survey responses were received, representing patients with a variety of diagnoses and geographical locations (30 counties). There was a wide range of opinions on the provision of current neuro-oncology services. Key themes identified included a perceived lack of information provision, a gap in postdischarge psychological and neuropsychological supports, and an unmet willingness for involvement in research. CONCLUSION: This national survey enhances our knowledge of current patient and carer experience within neuro-oncology services. A number of areas of unmet clinical need are highlighted providing a basis for informing future patient-centered service improvements and research.