Unmet needs in people with high-grade glioma: Defining criteria for stepped care intervention.

BACKGROUND: We aimed to define levels of unmet supportive care needs in people with primary brain tumour and reach expert consensus on feasibility of addressing patients' needs in clinical practice. METHODS: We conducted secondary analysis of a prospective cohort study of people diagnosed with high-grade glioma (n = 116) who completed the Supportive Care Needs Survey-SF34 during adjuvant chemoradiation therapy. Participants were allocated to one of three categories: no need ('no need' for help on all items), low need ('low need' for help on at least one item, but no 'moderate' or 'high' need), or moderate/high need (at least one 'moderate' or 'high' need indicated). Clinical capacity to respond to the proportion of patients needing to be prioritised was assessed. RESULTS: Overall, 13% (n = 5) were categorised as no need, 23% (n = 27) low need, and 64% (n = 74) moderate/high need. At least one moderate/high need was reported in the physical and daily living domain (42%), and psychological (34%) domain. In recognition of health system capacity, the moderate/high need category was modified to distinguish between: moderate need ('moderate' need indicated for at least one item but 'high' need was not selected for any item) and high need (at least one 'high' need indicated). Results revealed 24% (n = 28) moderate need and 40% (n = 46) high need. Those categorised as high need indicated needing assistance navigating the health system and information. CONCLUSIONS: Using four step allocations resulted in 40% of patients indicating high need. Categories may facilitate appropriate triaging, and guide stepped models of healthcare delivery.

[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Local hero: A phase II study of local therapy only (stereotactic radiosurgery and / or surgery) for treatment of up to five brain metastases from HER2+ breast cancer. (TROG study 16.02).

Introduction, A decade ago, stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) was emerging as preferred treatment for oligometastatic brain metastases. Studies of cavity SRS after neurosurgery were underway. Data specific to metastatic HER2 breast cancer (MHBC), describing intracranial, systemic and survival outcomes without WBRT, were lacking. A Phase II study was designed to address this gap. Method, Adults with MHBC, performance status 0-2, ≤ five BrM, receiving/planned to receive HER2-targeted therapy were eligible. Exclusions included leptomeningeal disease and prior WBRT. Neurosurgery allowed ≤6 weeks before registration and required for BrM >4 cm. Primary endpoint was 12-month requirement for WBRT. Secondary endpoints; freedom from (FF-) local failure (LF), distant brain failure (DBF), extracranial disease failure (ECDF), overall survival (OS), cause of death, mini-mental state examination (MMSE), adverse events (AE). Results, Twenty-five patients accrued Decembers 2016-2020. The study closed early after slow accrual. Thirty-seven BrM and four cavities received SRS. Four cavities and five BrM were observed. At 12 months: one patient required WBRT (FF-WBRT 95 %, 95 % CI 72-99), FFLF 91 % (95 % CI 69-98), FFDBF 57 % (95 % CI 34-74), FFECDF 64 % (95 % CI 45-84), OS 96 % (95 % CI 74-99). Two grade 3 AE occurred. MMSE was abnormal for 3/24 patients at baseline and 1/17 at 12 months. Conclusion, At 12 months, SRS and/or neurosurgery provided good control with low toxicity. WBRT was not required in 95 % of cases. This small study supports the practice change from WBRT to local therapies for MHBC BrM.

Utility of 68Ga-DOTATATE PET-MRI for Gamma Knife® stereotactic radiosurgery treatment planning for meningioma.

OBJECTIVES: To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. METHODS: Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. RESULTS: The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. CONCLUSION: The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. ADVANCES IN KNOWLEDGE: This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.

Reliability and validity of the telephone-based version of the Montgomery-Asberg depression rating scale for assessing depression in individuals with primary brain tumour.

This study aimed to examine interrater reliability and construct validity of the Montgomery-Asberg Depression Rating Scale (MADRS) semi-structured interview for assessing depression in adults with a primary brain tumour.Fifty adults with a primary brain tumour (mean age = 45.86, SD = 12.48) reporting at least mild distress (Distress Thermometer [DT] ≥ 4) were recruited from a multidisciplinary brain tumour clinic and administered a telephone-based cognitive screener, MADRS, Depression Anxiety Stress Scales (DASS) depression subscale and Generalised Anxiety Disorder-7 (GAD-7). Audiotaped interviews were transcribed and then scored by two independent raters.Interrater reliability for the MADRS total score was excellent (ICC = 0.98) and ranged from good to excellent (ICC = 0.83-0.96) for MADRS items. The MADRS total score was significantly associated with the DT, DASS depression, and GAD-7 (r = 0.50-0.76, p < 0.001), thus providing evidence of construct validity. Individuals with poorer cognitive function reported higher levels of depression.The findings provide psychometric support for the MADRS as a semi-structured interview for assessing depression after brain tumour. Further research investigating the sensitivity and specificity of the MADRS is recommended.

The Montgomery Asberg Depression Rating Scale can be used to reliably assess depression in individuals with primary brain tumour.Individuals with poorer cognitive function may be at greater risk of developing depression after brain tumour.Semi-structured interviews such as the Montgomery Asberg Depression Rating Scale may support clinicians to distinguish depressive symptoms from effects of the illness, thus helping to identify individuals who most warrant psychological support.

Cost-utility analysis of a telehealth psychological support intervention for people with primary brain tumor: Telehealth Making Sense of brain tumor.

OBJECTIVE: To undertake an economic evaluation of a telehealth psychological support intervention for patients with primary brain tumor (PBT). METHODS: A within-trial cost-utility analysis over 6 months was performed comparing a tailored telehealth-psychological support intervention with standard care (SC) in a randomized control trial. Data were sourced from the Telehealth Making Sense of Brain Tumor (Tele-MAST) trial survey data, project records, and administrative healthcare claims. Quality-adjusted life years (QALYs) were calculated based on the EuroQol-5D-5L. Non-parametric bootstrapping with 2000 iterations was used to determine sampling uncertainty. Multiple imputation was used for handling missing data. RESULTS: The Tele-MAST trial included 82 participants and was conducted in Queensland, Australia during 2018-2021. When all healthcare claims were included, the incremental cost savings from Tele-MAST were -AU$4,327 (95% CI: -$8637, -$18) while incremental QALY gains were small at 0.03 (95% CI: -0.02, 0.08). The likelihood of Tele-MAST being cost-effective versus SC was 87% at a willingness-to-pay threshold of AU$50,000 per QALY gain. When psychological-related healthcare costs were included only, the incremental cost per QALY gain was AU$10,685 (95% CI: dominant, $24,566) and net monetary benefits were AU$534 (95% CI: $466, $602) with a 65% likelihood of the intervention being cost-effective. CONCLUSIONS: Based on this small randomized controlled trial, the Tele-MAST intervention is a cost-effective intervention for improving the quality of life of people with PBT in Australia. Patients receiving the intervention incurred significantly lower overall healthcare costs than patients in SC. There was no significant difference in costs incurred for psychological health services.

Individuals' perceptions of health and well-being in the context of stereotactic radiosurgery for benign brain tumour: A longitudinal qualitative investigation.

BACKGROUND AND OBJECTIVES: Treatment-related outcomes after Gamma Knife Stereotactic Radiosurgery (GKSRS) for benign brain tumour are well-established; yet patient reported outcomes have been largely overlooked. This study explored individuals' perspectives of their health and well-being prior to and following GKSRS. METHOD: Twenty adults (65% female) aged 24-71 years with benign brain tumour were recruited from a major metropolitan hospital and assessed approximately one week prior to, two weeks after, and at three months following GKSRS. They completed telephone-based interviews focusing on general health, symptoms, and well-being. Interviews were transcribed and analysed using thematic analysis. RESULTS: Three major themes characterized individuals' perceptions of their health and well-being. "Understanding my Illness and Treatment" reflected individuals' efforts to make sense of their illness and symptoms to reduce ambiguity and increase sense of control. "Experiencing Gamma Knife" related to expectations of the procedure, outcomes, daily impacts, and emotional reactions. "Adjusting one's Mindset and Coping" characterised how peoples' approaches to coping with their illness were altered over time. CONCLUSIONS: Coping and adjustment is highly individualistic in the context of GKSRS. Over time, most individuals were able to make sense of their illness, adjust their mindset and utilize behavioural strategies and support systems to cope with the long-term effects.

Management Paradigm of Central Nervous System Metastases in NSCLC: An Australian Perspective.

Life-prolonging central nervous system active systemic therapies for metastatic NSCLC have increased the complexity of managing brain metastases (BMs). Australian medical oncologists, radiation oncologists, and neurosurgeons discussed the evidence guiding the diverse clinical approaches to the management of BM in NSCLC. The Australian context is broadly applicable to other jurisdictions; therefore, we have documented these discussions as principles with broader applications. Patient management was stratified according to clinical and radiologic factors under two broad classifications of newly diagnosed BMs: symptomatic and asymptomatic. Other important considerations include the number and location of metastases, tumor histotypes, molecular subtype, and treatment purpose. Careful consideration of the pace and burden of symptoms, risk of worsening neurologic function at a short interval, and extracranial disease burden should determine whether central nervous system active systemic therapies are used alone or in combination with local therapies (surgery with or without radiation therapy). Most clinical trial evidence currently focuses on historical treatment options or a single treatment modality rather than the optimal sequencing of multiple modern therapies; therefore, an individualized approach is key in a rapidly changing therapeutic landscape.

Evaluation of the telehealth making sense of brain tumor psychological support intervention for people with primary brain tumor and their caregivers: A randomized controlled trial.

OBJECTIVE: This pragmatic randomized control trial aimed to evaluate clinical efficacy of the Making Sense of Brain Tumour program delivered via videoconferencing (Tele-MAST) for improving mental health and quality of life (QoL) relative to standard care in individuals with primary brain tumor (PBT). METHOD: Adults with PBT experiencing at least mild distress (Distress Thermometer ≥4) and caregivers were randomly allocated to the 10-session Tele-MAST program or standard care. Mental health and QoL were assessed pre-intervention, post-intervention (primary endpoint), and 6-weeks and 6-months follow-up. The primary outcome was clinician-rated depressive symptoms on the Montgomery-Asberg Depression Rating Scale. RESULTS: 82 participants with PBT (34% benign, 20% lower-grade glioma, 46% high-grade glioma) and 36 caregivers were recruited (2018-2021). Controlling for baseline functioning, Tele-MAST participants with PBT had lower depressive symptoms at post-intervention (95% CI: 10.2-14.6, vs. 15.2-19.6, p = 0.002) and 6-weeks post-intervention (95% CI: 11.5-15.8 vs. 15.6-19.9, p = 0.010) than standard care, and were almost 4 times more likely to experience clinically reduced depression (OR, 3.89; 95% CI: 1.5-9.9). Tele-MAST participants with PBT also reported significantly better global QoL, emotional QoL and lower anxiety at post-intervention and 6-weeks post-intervention than standard care. There were no significant intervention effects for caregivers. At 6-months follow-up participants with PBT who received Tele-MAST reported significantly better mental health and QoL relative to pre-intervention. CONCLUSIONS: Tele-MAST was found to be more effective for reducing depressive symptoms at post-intervention than standard care for people with PBT but not caregivers. Tailored and extended psychological support may be beneficial for people with PBT.

Access to psychosocial support for people with brain tumor and family members: Healthcare professional perspectives.

OBJECTIVES: Ongoing access to psychosocial support is important to maintain the well-being of people with brain tumor (PwBT) and their families; yet, there is limited knowledge of psychosocial care access. This qualitative study aimed to develop an understanding of psychosocial support pathways specific to PwBT from the perspectives of Australian healthcare professionals. METHODS: Semi-structured interviews were conducted with 21 healthcare professionals working in hospital and community services supporting PwBT and their family members. Transcribed interviews were coded and analyzed thematically. RESULTS: The three major themes identified were: (1) Challenges in fitting people into the care system within existing pathways; (2) Benefits of longer-term care coordination and interdisciplinary connections; and (3) Brain tumor affects the whole family. Despite established psychosocial care pathways, service access varied and lacked continuity for individuals with lower-grade glioma and benign tumors across the illness trajectory. CONCLUSIONS: Healthcare professionals recognize the need for improved access to care coordination and multidisciplinary psychosocial care tailored to the varying needs of PwBT and their families.

Prevalence and management of sleep disturbance in adults with primary brain tumours and their caregivers: a systematic review.

PURPOSE: The aims of this systematic review were to (1) examine the prevalence, severity, manifestations, and clinical associations/risk factors of sleep disturbance in primary brain tumour (PBT) survivors and their caregivers; and (2) determine whether there are any sleep-focused interventons reported in the literature pertaining to people affected by PBT. METHODS: This systematic review was registered with the international register for systematic reviews (PROSPERO: CRD42022299332). PubMed, EMBASE, Scopus, PsychINFO, and CINAHL were electronically searched for relevant articles reporting sleep disturbance and/or interventions for managing sleep disturbance published between September 2015 and May 2022. The search strategy included terms focusing on sleep disturbance, primary brain tumours, caregivers of PBT survivors, and interventions. Two reviewers conducted the quality appraisal (JBI Critical Appraisal Tools) independently, with results compared upon completion. RESULTS: 34 manuscripts were eligible for inclusion. Sleep disturbance was highly prevalent in PBT survivors with associations between sleep disturbance and some treatments (e.g., surgical resection, radiotherapy, corticosteroid use), as well as other prevalent symptoms (e.g., fatigue, drowsiness, stress, pain). While the current review was unable to find any sleep-targeted interventions, preliminary evidence suggests physical activity may elicit beneficial change on subjectively reported sleep disturbance in PBT survivors. Only one manuscript that discussed caregivers sleep disturbance was identified. CONCLUSIONS: Sleep disturbance is a prevalent symptom experienced by PBT survivors, yet there is a distinct lack of sleep-focused interventions in this population. This includes a need for future research to include caregivers, with only one study identified. Future research exploring interventions directly focused on the management of sleep disturbance in the context of PBT is warranted.

"Hey, I'm still here!": Maintaining, managing and rebuilding social connections after brain tumour.

It is well recognized that social networks can buffer the adverse effects of chronic illness on psychological wellbeing. However, the functional impairments associated with brain tumour often affect social participation, which may reduce people's capacity to draw upon their social capital for support. This qualitative phenomenological study aimed to understand how brain tumour influences people's ability to manage, maintain, and rebuild their social networks. Participants were 20 individuals (65% female) aged 22-69 years with diverse types of primary brain tumour (50% high grade or malignant) who were on average 35 months post-diagnosis. Two semi-structured interviews, conducted three months apart, comprised a Social Identity Mapping exercise and questions exploring changes in social groups since diagnosis. Two overarching and interrelated themes emerged: engaging and connecting and then versus now. An interplay of barriers, facilitators and strategies influenced people's ability to engage and connect with their social groups, which in turn influenced whether they experienced stability; maintenance and expansion; loss and rebuilding; or loss and shrinkage of their social networks over time. These novel findings highlight the need to develop interventions that specifically focus on enhancing individuals' abilities to maintain or rebuild their social networks.

Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature.

PURPOSE: Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup. METHODS: Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed. RESULTS: 41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80-90% were ECOG 0-1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0-2% Grade 3 radionecrosis rates. CONCLUSION: HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.

Benefits of supportive strategies for carers of people with high-grade glioma: a systematic review : Strategies for addressing the needs of high-grade glioma carers.

PURPOSE: To systematically review and examine current evidence for the carer-reported benefits of supportive care strategies for carers of adults with high-grade glioma (HGG). METHODS: Four databases (CINAHL, EMBASE, PubMed, PsycINFO) were searched for articles published between January 2005 and April 2022 that assessed strategies for addressing the supportive care needs of carers of adults with HGG (WHO grade 3-4). Study selection and critical appraisal were conducted independently by three authors (DJ/MC, 2021; DJ/RJ 2022). Data extraction was conducted by one author (DJ) and checked by a second author (RJ). Results were synthesised narratively. RESULTS: Twenty-one studies involving 1377 caregivers were included, targeting the carer directly (n = 10), the patient-carer dyad (n = 3), or focused on people with HGG + / - their carers (n = 8). A paucity of high-quality evidence exists for effective and comprehensive support directly addressing outcomes for carers of adults with HGG. Strategies that demonstrated some benefits included those that built carer knowledge or provided emotional support, delivered by health professionals or through peer support. Supportive and early palliative care programmes have potential to reduce unmet carer needs while providing ongoing carer support. CONCLUSION: Strategies incorporating an educational component, emotional support, and a regular needs assessment with corresponding tailored support are most valued by carers. Future practice development research should adopt a value-based approach and exceed evaluation of efficacy outcomes to incorporate evaluation of the experience of patients, carers, and staff, as well as costs.

Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations.

INTRODUCTION: Gamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations. METHODOLOGY: A retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar's test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model. RESULTS: Thirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12-13). The median follow-up duration from GKSRS was 809 days (IQR 536-960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008-0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004-1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074-0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS. CONCLUSION: GKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

Multi-Arm GlioblastoMa Australasia (MAGMA): protocol for a multiarm randomised clinical trial for people affected by glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) 'neoadjuvant' chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform. METHODS AND ANALYSIS: MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023.Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment.The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive/prognostic biomarkers and health utilities and incremental cost-effectiveness ratio.The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention. ETHICS AND DISSEMINATION: The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBER: ACTRN12620000048987.

Telehealth cancer-related fatigue clinic model for cancer survivors: a pilot randomised controlled trial protocol (the T-CRF trial).

INTRODUCTION: Cancer-related fatigue (CRF) is one of the most common and debilitating adverse effects of cancer and its treatment reported by cancer survivors. Physical activity, psychological interventions and management of concurrent symptoms have been shown to be effective in alleviating CRF. This pilot randomised controlled trial (RCT) will determine the feasibility of a telehealth CRF clinic intervention (T-CRF) to implement evidence-based strategies and assess the impact of the intervention on CRF and other clinical factors in comparison to usual care. METHODS AND ANALYSIS: A parallel-arm (intervention vs usual care) pilot RCT will be conducted at the Princess Alexandra Hospital in Queensland, Australia. Sixty cancer survivors aged 18 years and over, who report moderate or severe fatigue on the Brief Fatigue Inventory and meet other study criteria will be recruited. Participants will be randomised (1:1) to receive the T-CRF intervention or usual care (ie, specialist-led care, with a fatigue information booklet). The intervention is a 24-week programme of three telehealth nurse-led consultations and a personalised CRF management plan. The primary objective of this pilot RCT is to determine intervention feasibility, with a secondary objective to determine preliminary clinical efficacy. Feasibility outcomes include the identification of recruitment methods; recruitment rate and uptake; attrition; adherence; fidelity; apathy; and intervention functionality, acceptability and satisfaction. Clinical and resource use outcomes include cancer survivor fatigue, symptom burden, level of physical activity, productivity loss, hospital resource utilisation and carer's fatigue and productivity loss. Descriptive statistics will be used to report on feasibility and process-related elements additional to clinical and resource outcomes. ETHICS AND DISSEMINATION: This trial is prospectively registered (ACTRN12620001334998). The study protocol has been approved by the Metro South Health and Hospital Services Human Research Ethics Committee (MSHHS HREC/2020/QMS/63495). Findings will be disseminated through peer-reviewed publications, national and international conferences and seminars or workshops. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ID: ACTRN12620001334998; Pre-results. Trial Version: Version 1.1. Last updated 10 December 2020.

Antibody-Based Formats to Target Glioblastoma: Overcoming Barriers to Protein Drug Delivery.

Glioblastoma (GB) is recognized as the most aggressive form of primary brain cancer. Despite advances in treatment strategies that include surgery, radiation, and chemotherapy, the median survival time (∼15 months) of patients with GB has not significantly improved. The poor prognosis of GB is also associated with a very high chance of tumor recurrence (∼90%), and current treatment measures have failed to address the complications associated with this disease. However, targeted therapies enabled through antibody engineering have shown promise in countering GB when used in combination with conventional approaches. Here, we discuss the challenges in conventional as well as future GB therapeutics and highlight some of the known advantages of using targeted biologics to overcome these impediments. We also review a broad range of potential alternative routes that could be used clinically to administer anti-GB biologics to the brain through evasion of its natural barriers.

Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes.

INTRODUCTION/PURPOSE: This study assessed long-term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). METHODS: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional-hazards modelling was performed with a P <0.05 for significance. RESULTS: 101 patients (435 melanoma BM) were treated with SRS between January-2015 and June-2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non-concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow-up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS-IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2-5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16-0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long-term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007-0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan-Meier analysis. CONCLUSION: Concurrent SRS-IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long-term outcomes for treatment response.

Scoping the psychological support practices of Australian health professionals working with people with primary brain tumor and their families.

OBJECTIVES: This study aimed to scope the psychological support practices of Australian health professionals providing supportive care to adults with primary brain tumor. METHOD: Health professionals from multidisciplinary organizations and cancer support services completed an online survey focused on psychological support for people with brain tumor (PwBT) and family members, and perceived barriers or gaps in support provision. RESULTS: 107 professionals, mainly from psychology (45%), nursing (20%), and social work (10%) backgrounds, completed the survey. Scope of practice differed according to discipline, with psychologists and nurses most likely to screen for psychological distress (71%-76%), and psychologists more typically providing at least one psychological support session (78%). Psychologists were more likely to screen for cognitive impairment (31%), whereas nurses and social workers more commonly provided family-based support (62%-73%). Psychological support was more frequently provided in the long-term management phase (78%) than early post-diagnosis/treatment (45%). System-level barriers to accessing psychological support were most frequently identified, which included limited resources and funding, insufficient staff time, lengthy waitlists and costs, poor service coordination, and lack of staff with brain tumor-specific training. CONCLUSIONS: The provision of psychological support for PwBT varies according to discipline, setting and management phase. Further research on different models of psychosocial care is needed to inform strategies to address organizational and policy factors impacting professionals' scope of practice.