NCOG-49. UNMET NEEDS AND WISH FOR SUPPORT OF FAMILY CAREGIVERS OF PRIMARY BRAIN TUMOUR PATIENTS

BACKGROUND Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it may lead to significant burden. To develop support it is therefore vital to distinguish between unmet needs, and an actual wish for support. Study aims: 1) identify the presence and magnitude of caregivers’ unmet needs; 2) examine associations between unmet needs and wish for support; 3) evaluate perceived usefulness of caregiver needs screening in clinical practice. METHODS Family caregivers of primary brain tumour patients were recruited and asked to complete an adapted version of the Caregiver Needs Screen (CNS) which consisted of 33 common issues in neuro-oncology caregiving (scale 0-10), and the wish for support (yes/no). Participants ranked (0-7) their experience of using the CNS with a study-specific evaluation questionnaire. Descriptive and correlational analyses were applied. RESULTS Caregivers (N=79) reported between 1-33 unmet needs (M=17.20, sd=7.98) but did not always wish for support (range 0-28, M=4.71, sd=6.63). Most distressing items were changes in patient’s memory or concentration (M=5.75, SD=3.29), followed closely by patient’s fatigue (M=5.58, SD= 3.43), and recognising signs of disease progression (M=5.23, SD= 3.15). A weak correlation was found between the total number of unmet needs and wish for support (r=0.296, p=0.014). Caregivers most often wished for support with recognising disease progression (N=24, 34.78%), and least often with managing spiritual issues (N=0, 0%). Caregivers evaluated the CNS tool positively (mean item scores ranging 4.19-6.21 out of 7). CONCLUSIONS Family caregivers experience distress resulting from many neuro-oncology specific needs, but this is not directly related to a wish for support. Caregiver needs screening could be useful to tailor support to suit caregivers’ preferences in clinical practice.

Inhibition of ATR prevents macropinocytosis driven retraction of neurites and opposes invasion in GBM

Glioblastoma (GBM) is the most common and aggressive type of primary brain tumour and remains incurable despite decades of research. GBM are characterised by highly infiltrative growth patterns that contribute to the profound cognitive and neurological symptoms experienced by patients, and to inevitable recurrence following treatment. Novel treatments that reduce infiltration of the healthy brain have potential to ameliorate clinical symptoms and improve survival. Here, we report a novel role of the Ataxia telangiectasia and Rad 3 related kinase (ATR) in supporting the invasive properties of GBM cells through the regulation of macropinocytosis-driven internalisation of integrin adhesion receptors. We demonstrate that inhibition of ATR opposes GBM migration in vitro, and correspondingly reduces infiltrative behaviour in orthotopic mouse models. These results indicate that ATR inhibition, in addition to its use as a radiosensitiser, may be effective in reducing GBM infiltration and its associated symptoms.

Identification of five important genes to predict GBM subtypes

Background Glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, has been classified into three subtypes: classical, mesenchymal and proneural. While the original classification relied on an 840 gene-set, further clarification on true GBM subtypes uses a 150-gene signature to accurately classify GBM into the three subtypes. We hypothesized whether a machine learning approach could be used to identify a smaller gene-set to accurately predict GBM subtype. Methods Using a supervised machine learning approach, extreme gradient boosting (XGBoost), we developed a classifier to predict the three subtypes of glioblastoma (GBM): classical, mesenchymal and proneural. We tested the classifier on in-house GBM tissue, cell lines and xenograft samples to predict their subtype. Results We identified the five most important genes for characterizing the three subtypes based on genes that often exhibited high Importance Scores in our XGBoost analyses. On average, this approach achieved 80.12% accuracy in predicting these three subtypes of GBM. Furthermore, we applied our five-gene classifier to successfully predict the subtype of GBM samples at our centre. Conclusion Our 5-gene set classifier is the smallest classifier to date that can predict GBM subtypes with high accuracy, which could facilitate the future development of a five-gene subtype diagnostic biomarker for routine assays in GBM samples.

Challenges and Prospects for Designer T and NK Cells in Glioblastoma Immunotherapy

Glioblastoma (GBM) is the most prevalent, aggressive primary brain tumour with a dismal prognosis. Treatment at diagnosis has limited efficacy and there is no standardised treatment at recurrence. New, personalised treatment options are under investigation, although challenges persist for heterogenous tumours such as GBM. Gene editing technologies are a game changer, enabling design of novel molecular-immunological treatments to be used in combination with chemoradiation, to achieve long lasting survival benefits for patients. Here, we review the literature on how cutting-edge molecular gene editing technologies can be applied to known and emerging tumour-associated antigens to enhance chimeric antigen receptor T and NK cell therapies for GBM. A tight balance of limiting neurotoxicity, avoiding tumour antigen loss and therapy resistance, while simultaneously promoting long-term persistence of the adoptively transferred cells must be maintained to significantly improve patient survival. We discuss the opportunities and challenges posed by the brain contexture to the administration of the treatments and achieving sustained clinical responses.

Are patients with brain tumours being given timely DVLA advice?

Aims Over 11,000 patients are diagnosed with a primary brain tumour annually in the UK, with many more being diagnosed with a secondary brain tumour. UK law stipulates that all individuals with a brain tumour must inform the Driver and Vehicle Licensing Agency (DVLA) and may be required to surrender their driving license depending on their specific tumour and symptoms. Despite this guidance, we found that patients continue to arrive at the neuro-oncology clinic without the correct DVLA advice being given. This can potentially lead to patients with brain tumours continuing to drive on the public highway, which poses a severe hazard as the risk of seizures could endanger the public. This retrospective study looks to review what information was provided to patients with brain tumours upon initial diagnosis and determine the adequacy of this; ultimately aiming to improve the quality of information given to future neuro-oncology patients. Method A structured questionnaire was designed, asking patients who have been treated for a brain tumour at the Queen Elizabeth Hospital in Birmingham about any information they received about driving when they were first diagnosed. The questionnaire comprised of 11 questions designed to gather an understanding of what information was given to patients about driving. The study secured local audit approval. 75 patients identified from the weekly neuro-oncology MDT list were contacted. All patients included in this audit were required to stop driving and inform the DVLA about their condition as per the DVLA guidelines. Their responses were collated and analysed. Using this data, we determined if there were inadequacies in the information that was given to these patients about driving, and how this process may be improved in the future. Results 60 patients (80%) possessed driving licenses when first diagnosed and 17% of these (n=10) were not told to stop driving; 8 of whom were diagnosed in primary/secondary care. 39 patients (65%) were first diagnosed in primary/secondary care, however, only 21% of these (n=8) were told to stop driving by primary/secondary care consultants. The remaining 31 patients (81%) were only told to stop driving after referral to tertiary care, by consultant neurosurgeons at the Queen Elizabeth Hospital. Conversely, of the 12 patients first diagnosed at the Queen Elizabeth Hospital, 85% were told to stop driving at diagnosis, suggesting a notable difference in informing patients between primary/secondary care and tertiary care. Patients also commented on the quality of the information received, as 10 individuals (21%) mentioned needing more information about getting their license back, and 5 individuals (11%) mentioning being given conflicting or incorrect information from different members of the MDT. Conclusion The results show that in practice, there are inconsistencies about mandatory DVLA advice which should be clearly provided to patients with a new diagnosis of a brain tumour. Only 78% of patients were told to stop driving at diagnosis, suggesting that the remainder could be liable to continue driving despite their diagnosis. Furthermore, many patients diagnosed in primary/secondary care are not being told to stop driving until after referral to tertiary care which can take weeks, causing delays in them being given this information, which can pose risks to themselves and the public. These delays may be alleviated by giving patients a simplified resource when they are first diagnosed which clearly explains the driving rules. We therefore propose developing a one-page resource based on DVLA guidance and distributing this to patients and referring healthcare professionals at first diagnosis. A subsequent re-audit can evaluate if this intervention improves the current situation.

Static permeability assessment method to distinguish brain tumour recurrence from pseudoprogression

Aims It is common to have adjuvant chemo-radiotherapy after primary brain tumour resection. It is a known side effect that enhancing lesion could be seen in radiation territory after treatment, termed as pseudoprogression. It has been a difficult task to distinguish brain between tumour recurrence from pseudoprogression after radiotherapy. Timing of occurrence of these can overlap. It is important to distinguish the two as management is completely different. Early intervention in recurrence could improve survival time while pseudoprogression could be self-limiting. Surgical resection of pseudoprogression could be counter-productive. The radiological approach has been relying on multimodality investigation and close follow up. It has come to our institution notice that there is a new technique which could distinguish the two conditions efficiently. That's static permeability assessment method, also known as treatment response assessment maps (TRAMs). Our experience with it so far has been beneficial. Method This is a retrospective case series review of primary brain tumour treatment in our neurosurgical institution in 2020. Two high resolution 3D T1-weighted brain MRI images were acquired after a standard dose of gadolinium based contrast agent was injected. The first acquisition began five minutes after injection, and the second began 60 – 105 minutes post contrast injection. The TRAMs technique is based on image subtraction that is post processed after acquisition. The resultant subtracted image set was mapped to grey scale values, where voxels showing contrast clearance were light grey/white, and those showing contrast accumulation were dark grey/black. The zero value (i.e. no clearance or accumulation) was therefore mid-grey. Those with contrast clearance is associated with tumour recurrence. TRAMs images were compared to serial follow up imaging and histopathology results to determine the diagnostic accuracy of the technique. Results We have identified 21 patients in this period who had concern of either of pseudoprogression or tumour recurrence/progression. There were 6 females and 15 males, mean age 51. There were 14 glioblastoma multiforme (GBM), 5 astrocytoma, 1 oligodendroglioma and 1 post radiotherapy arteriovenous malformation. 17 cases were found to have clear cut recurrence, pseudoprogression or mixture of both in TRAMS. These findings are backed up by histology or repeated follow up scan. 4 cases were considered as equivocal. In retrospect, these cases have challenging interpretation due to poor case selection. TRAMs could distinguish high grade transformation as well as detecting recurrence. In some difficult cases, it is found that both pseudoprogression and recurrence could happen together. Conclusion TRAMs is a useful adjunct to the multimodalities of diagnostic techniques in tricky situation. This has provided an efficient and easy to use tool for radiologists to come up with the answer. We are the first independent centre to report on this technique. This is still early days and fine-tuning of its use is still undergoing. It is clear this has saved precious resources and has given patients more suitable care. We think it would be beneficial for us to share our experience with others and hope to get future collaboration with other centres.

Re-operation for recurrent intracranial meningioma – is it worth it?

Aims Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma. Method Retrospective cohort study (1998-2018). Eligible patients had re-operation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each re-operation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS). Results Fifty-eight patients were eligible (38 female, mean age at 1st re-operation 56 years (SD=11.4)). Eleven patients (18.9%) had 2 re-operations and 3 patients (3.4%) had 3 re-operations. Median follow up was 125.5 months (IQR 73-191.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR 24.2–79.1) and 43.8 months (IQR 22.9–102.7), respectively. Fifteen patients (25.9%) had worse performance status after 1st re-operation, compared to 6.9% (n=4) after the primary operation (Figure 1). Complication rate was 32.8% (n=19) after the primary operation compared to 46.6% (n=27) after 1st re-operation. At primary operation, there were 29 (50%) grade 1, 26 (44.8%) grade 2, and 1 (1.7%) grade 3 tumours. Median RFS after first re-operation was 68 months (95% CI 45.5-90.5) (figure 2). Median OS was 312 months (95% CI 236.9-387.1) (Figure 3). Post-operative complications were a risk factor for worsened performance status following re-operation (OR 4.91, 95% CI 1.3-18.4). Conclusion Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.

ACE-Neuro: A Tailored Exercise Oncology Program for Neuro-Oncology Patients – Study Protocol

BackgroundPatients with primary brain tumours lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise – Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness.MethodsNeuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro or other cancer rehabilitation or physiatry resources. In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes, functional fitness, and physical activity. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching.ConclusionWe are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.

P12.06 Unmet needs and wish for support of informal caregivers of primary brain tumour patients

BACKGROUND Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it also commonly leads to significant burden. In developing support for caregivers, it is vital to distinguish between caregivers’ unmet needs, and their actual wish for support to resolve unmet needs. We aimed to 1) identify the presence and magnitude of unmet needs; 2) examine associations between unmet needs and desire for support; 3) evaluate perceived usefulness of caregiver needs screening in clinical practice. MATERIAL AND METHODS Family caregivers of patients with primary brain tumours were recruited and asked to complete an adapted version of the Caregiver Needs Screen (CNS). This covered the level of distress resulting from 33 common issues in neuro-oncology caregiving (scale 0–10), and wish for information or support for any issue (yes/no). In addition, participants were asked to rank (0–7) their experience of using the CNS based on items covering ‘ease of us’, ‘usefulness’ and ‘satisfaction’. Descriptive and correlational analyses were applied. RESULTS Caregivers (N=79) reported between 1–33 unmet needs (M=17.20, sd=7.98) but did not always wish for support for each need (range 0–28, M=4.71, sd=6.63). Most distressing items were patient’s fatigue (M=5.58), recognising signs of disease progression (M=5.23), changes in patients’ thinking or behaviour (M=5.04), patient distress or sadness (M=4.68), and changes in caregivers’ own emotional health (M=4.44). A weak correlation was found between the total number of unmet needs and the desire for support (r=0.296, p=0.014). Caregivers most often desired support with recognising disease progression (N=24), managing medications and side-effects (N=18), and least often with managing spiritual issues (N=0), communication with (grand)children (N=2) and communication with family members and friends (N=3). Caregivers evaluated the CNS tool positively (mean item scores ranging 4.19–6.21 out of 7). CONCLUSION Family caregivers of brain tumour patients experience distress resulting from many neuro-oncology specific needs, but this is not directly related to a wish for support or information. Caregiver needs screening could be useful to tailor support or information to suit caregivers’ preferences in clinical practice.