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The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma–extracellular signal–regulated kinase–MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been successful in treating many adult cancers. Despite advances in other cancer types, the morbidity and survival outcomes of patients with glioma have remained relatively stagnant. Recently, there has been recognition that MAPK dysregulation is almost universally present in paediatric and adult gliomas. These findings, accompanying broad molecular characterization of gliomas, has aided prognostication and offered opportunities for clinical trials testing targeted agents. The use of targeted therapies in this disease represents a paradigm shift, although the biochemical complexities has resulted in unexpected challenges in the development of effective BRAF inhibitors. Despite these challenges, there are promising data to support the use of BRAF inhibitors alone and in combination with MEK inhibitors for patients with both low-grade and high-grade glioma across age groups. Safety and efficacy data demonstrate that many of the toxicities of these targeted agents are tolerable while offering objective responses. Newer clinical trials will examine the use of these therapies in the upfront setting. Appropriate duration of therapy and durability of response remains unclear in the glioma patient cohort. Longitudinal efficacy and toxicity data are needed. Furthermore, access to these medications remains challenging outside of clinical trials in Australia and New Zealand. Compassionate access is limited, and advocacy for mechanism of action-based drug approval is ongoing.

BACKGROUND Adolescents and young adults (AYAs) diagnosed with cancer experience physical, cognitive, and psychosocial effects from cancer treatment that can negatively affect their ability to remain engaged in education or work through cancer treatment and in the long-term. Disengagement from education or work can have lasting implications for AYAs’ financial independence, psychosocial wellbeing, and quality of life. Australian AYAs with cancer lack access to adequate specialist supports for their education and work needs, and report preference for online support that they can access from anywhere, in their own time. However, it remains unclear what online resources exist that are tailored to support AYAs with cancer in reaching their educational or work goals. OBJECTIVE This study aimed to determine (1) what online resources exist for Australian AYAs with cancer, to support return to education or work, and (2) identify the degree to which existing resources are age-specific, cancer-specific, culturally inclusive, evidence-based, are co-designed with AYAs, use age-appropriate language, and are easy to find. METHODS We conducted an environmental scan by searching Google with English search terms in August 2022 to identify information resources about employment and education for AYAs ever diagnosed with cancer. Data extraction was conducted in Microsoft Excel and the following were assessed: understandability and actionability (using the Patient Education and Materials Tool; PEMAT), readability (using the Sydney Health Literacy Lab (SHeLL) editor), and whether the resource was easy to locate, evidence-based, co-designed with AYA, and culturally inclusive of Aboriginal and Torres Strait Islander peoples. The latter was assessed using seven criteria previously developed by members of the research team. RESULTS We identified 24 online resources comprised of 20 written text resources and 12 video resources. Most resources (87.5%) were published by non-government organisations (NGOs) in Australia, Canada, the USA, and the UK. Seven resources focused on education, eight focused on work, and nine focused on both education and work. Evaluation of resources demonstrated poor understandability and actionability. Resources were rarely evidence-based or co-designed by AYAs, were difficult to locate online, and were largely not inclusive of Aboriginal and Torres Strait Islander populations. CONCLUSIONS Although online resources for AYAs with cancer are often available through the websites of hospitals or NGOs, this environmental scan suggests they would benefit from more evidence-based and actionable resources that are available in multiple formats (e.g., text and audio-visual) and tailored to be age-appropriate and culturally inclusive.

This study aimed to scope the psychological support practices of Australian health professionals providing supportive care to adults with primary brain tumor.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.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.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.

Automated brain tumour segmentation from post-operative images is a clinically relevant yet challenging problem. In this study, an automated method for segmenting brain tumour into its subregions has been developed. The dataset consists of multimodal post-operative brain scans (T1 MRI, post-Gadolinium T1 MRI, and T2-FLAIR images) of 15 patients who were treated with post-operative radiation therapy, along with manual annotations of their tumour subregions. A 3D densely-connected U-net was developed for segmentation of brain tumour regions and extensive experiments were conducted to enhance model accuracy. A model was initially developed using the publicly available BraTS dataset consisting of pre-operative brain scans. This model achieved Dice Scores of 0.90, 0.83 and 0.78 for predicting whole tumour, tumour core, and enhancing tumour subregions when tested on BraTS20 blind validation dataset. The acquired knowledge from BraTS was then transferred to the local dataset. For augmentation purpose, the local dataset was registered to a dataset of MRI brain scans of healthy subjects. To improve the robustness of the model and enhance its accuracy, ensemble learning was used to combine the outputs of all the trained models. Even though the size of the dataset is very small, the final model can segment brain tumours with a high Dice Score of 0.83, 0.77 and 0.60 for whole tumour, tumour core and enhancing core respectively.

IntroductionGlioblastoma (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 analysisMAGMA 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 disseminationThe 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 numberACTRN12620000048987.

We aim to conduct a scoping review of the literature and clinical practice resources to identify existing evidence and guidelines for care coordination for people with primary brain tumours and their caregivers.

The aim of this project was to determine research priorities, barriers, and enablers for adult primary brain tumour research in Australia and New Zealand. Consumers, health professionals, and researchers were invited to participate in a two-phase modified Delphi study. Phase 1 comprised an initial online survey (n = 91) and then focus groups (n = 29) which identified 60 key research topics, 26 barriers, and 32 enablers. Phase 2 comprised two online surveys to (1) reduce the list to 37 research priorities which achieved consensus (>75% 2-point agreement) and had high mean importance ratings (n = 116 participants) and (2) determine the most important priorities, barriers, and enablers (n = 90 participants). The top ten ranked research priorities for the overall sample and sub-groups (consumers, health professionals, and researchers) were identified. Priorities focused on: tumour biology, pre-clinical research, clinical and translational research, and supportive care. Variations were seen between sub-groups. The top ten barriers to conducting brain tumour research related to funding and resources, accessibility and awareness of research, collaboration, and process. The top ten research enablers were funding and resources, collaboration, and workforce. The broad list of research priorities identified by this Delphi study, together with how consumers, health professionals, and researchers prioritised items differently, and provides an evidence-based research agenda for brain tumour research that is needed across a wide range of areas.

BackgroundGlioma accounts for approximately 80% of malignant adult brain cancer and its most common subtype, glioblastoma, has one of the lowest 5-year cancer survivals. Fifty risk-associated variants within 34 glioma genetic risk regions have been found by genome-wide association studies (GWAS) with a sex difference reported for 8q24.21 region. We conducted an Australian GWAS by glioma subtype and sex.MethodsWe analyzed genome-wide data from the Australian Genomics and Clinical Outcomes of Glioma (AGOG) consortium for 7 573 692 single nucleotide polymorphisms (SNPs) for 560 glioma cases and 2237 controls of European ancestry. Cases were classified as glioblastoma, non-glioblastoma, astrocytoma or oligodendroglioma. Logistic regression analysis was used to assess the associations of SNPs with glioma risk by subtype and by sex.ResultsWe replicated the previously reported glioma risk associations in the regions of 2q33.3 C2orf80, 2q37.3 D2HGDH, 5p15.33 TERT, 7p11.2 EGFR, 8q24.21 CCDC26, 9p21.3 CDKN2BAS, 11q21 MAML2, 11q23.3 PHLDB1, 15q24.2 ETFA, 16p13.3 RHBDF1, 16p13.3 LMF1, 17p13.1 TP53, 20q13.33 RTEL, and 20q13.33 GMEB2 (P < .05). We also replicated the previously reported sex difference at 8q24.21 CCDC26 (P = .0024) with the association being nominally significant for both sexes (P < .05).ConclusionsOur study supports a stronger female risk association for the region 8q24.21 CCDC26 and highlights the importance of analyzing glioma GWAS by sex. A better understanding of sex differences could provide biological insight into the cause of glioma with implications for prevention, risk prediction and treatment.

BackgroundTemozolomide offers minimal benefit in patients with glioblastoma with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status, hence, the need for novel therapies. This study evaluated whether veliparib, a brain-penetrant poly(ADP-ribose) polymerase (PARP) inhibitor, acts synergistically with radiation and temozolomide.MethodsVERTU was a multicenter 2:1 randomized phase II trial in patients with newly diagnosed glioblastoma and MGMT-unmethylated promotor status. The experimental arm consisted of veliparib and radiotherapy, followed by adjuvant veliparib and temozolomide. The standard arm consisted of concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide. The primary objective was to extend the progression-free survival rate at six months (PFS-6m) in the experimental arm.ResultsA total of 125 participants were enrolled, with 84 in the experimental arm and 41 in the standard arm. The median age was 61 years, 70% were male, 59% had Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 87% underwent macroscopic resection. PFS-6m was 46% (95% confidence interval [CI]: 36%-57%) in the experimental arm and 31% (95% CI: 18%-46%) in the standard arm. Median overall survival was 12.7 months (95% CI: 11.4-14.5 months) in the experimental arm and 12.8 months (95% CI: 9.5-15.8 months) in the standard arm. The most common grade 3-4 adverse events were thrombocytopenia and neutropenia, with no new safety signals.ConclusionThe veliparib-containing regimen was feasible and well tolerated. However, there was insufficient evidence of clinical benefit in this population. Further information from correlative translational work and other trials of PARP inhibitors in glioblastoma are still awaited.

The rapid rise in cancer incidence within the world's poorest nations highlights the need for equitable access to evidence-based cancer care. It has been previously demonstrated that radiotherapy is a cost-effective and necessary tool in cancer treatment. However, globally there is a growing divide between demand and supply of radiotherapy services. In low- and middle-income countries, this resource gap is particularly problematic. By region, the Asia-Pacific has been demonstrated to have the highest absolute deficit in radiotherapy services. Radiation oncologists in Australia and New Zealand are geographically well positioned to assist departments within the Asia-Pacific to help to reduce these inequities. The Asia-Pacific Radiation Oncology Special Interest Group (APROSIG) aims to support oncology professionals in the Asia-Pacific to develop safe and sustainable cancer services. Members have already contributed to multiple projects throughout the region, supported by grants and departmental funding. However, the backbone of support comes from volunteers sharing their time and expertise. The Australasian oncological community has the skills and knowledge to help not only those within our borders but also beyond. Such efforts provide the potential to develop valuable clinical, educational, research and leadership experiences whilst establishing networking opportunities throughout the most populated regions of the world. More options for growth and work in global health must be investigated, encouraging future trainees to consider a role within the global cancer community. Without prompt and continued action, the resource deficit is likely to grow and the inequity in accessing radiotherapy and other cancer services further magnified.

Radiomics is a field of medical imaging analysis that focuses on the extraction of many quantitative imaging features related to shape, intensity and texture. These features are incorporated into models designed to predict important clinical or biological endpoints for patients. Attention for radiomics research has recently grown dramatically due to the increased use of imaging and the availability of large, publicly available imaging datasets. Glioblastoma multiforme (GBM) patients stand to benefit from this emerging research field as radiomics has the potential to assess the biological heterogeneity of the tumour, which contributes significantly to the inefficacy of current standard of care therapy. Radiomics models still require further development before they are implemented clinically in GBM patient management. Challenges relating to the standardisation of the radiomics process and the validation of radiomic models impede the progress of research towards clinical implementation. In this manuscript, we review the current state of radiomics in GBM, and we highlight the barriers to clinical implementation and discuss future validation studies needed to advance radiomics models towards clinical application.

ObjectivesSymptoms of raised intracranial pressure (ICP) in recurrent high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on ICP symptoms. Acetazolamide reduces ICP when used in other clinical non-cancer settings. The aim of the study was to explore whether the addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent HGG.MethodsParticipants had recurrent HGG with any of dexamethasone recommencement, dose increase or dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide or placebo for 8 weeks. Standardised protocols were used for dexamethasone dosing, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stable Karnofsky Performance Status Secondary endpoints included toxicity and feasibility.ResultsThirty participants (15 per group) were enrolled (mean age 58 years) from seven Australian sites. The mean baseline dexamethasone dose was 6.2 mg. Mean duration on study treatment was 38 days (placebo group) and 31 days (acetazolamide group) with nine participants (30%) completing all study treatments (six placebo, three acetazolamide). Study withdrawal was due to adverse events (n=6; one placebo, five acetazolamide) and disease progression (n=6 (three per arm)). Four participants (13%) (two per arm) were stable responders. Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: five participants (33%), six events, two related).ConclusionsThe study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction.Trial registration numberACTRN12615001072505.

This study explores healthcare professionals (HCPs)’ perception and current management of sleep disturbance (SD) in people with malignant brain tumours and their caregivers. We aimed to identify barriers to effective management of SD in neuro-oncology care. We conducted semi-structured interviews with 11 HCPs involved in neuro-oncology care. The study was underpinned by the Capability Opportunity Motivation-Behaviour (COM-B) model within the Behavioural Change Wheel (BCW) guiding topic selection for the exploration of underlying processes of HCPs’ behaviours and care decisions for SD management. Data were analysed thematically using a framework synthesis, and subsequently mapped onto the BCW to identify barriers for effective management and recommend potential interventions. We identified four themes: HCPs’ clinical opinions about SD, the current practice of SD management in neuro-oncology clinics, gaps in the current practice, and suggested areas for improvements. HCPs perceived SD as a prevalent yet secondary issue of low priority in neuro-oncology care. SD was unrecognised, and inadequately managed in usual clinical settings. Interventional options included modifying the use of corticosteroids or prescribing sedatives. When mapped onto the BCW, themes identified main barriers as a lack of awareness among HCPs about SD warranting care, due to the absence of screening tools and limited knowledge and resources for therapeutic interventions. Multidisciplinary HCPs need training in the routine use of appropriate sleep assessment tools, and access to clear management pathways. More professional resources are needed to educate staff in implementing appropriate interventions for people with malignant brain tumours who are experiencing SD.

Background Sleep is an important element in health-related quality of life of cancer patients and caregivers. This study aimed to explore the experience of sleep disturbance in people with malignant brain tumors (BT) and their family caregivers. Methods Participants were recruited from ambulatory neuro-oncology clinics. Semi-structured interviews were conducted with 24 patients (67% with high-grade gliomas) and 14 caregivers. Data were analyzed thematically using a framework synthesis. Results We identified six themes relating to perceptions of the nature, impact, causal factors, and interventions for sleep disturbance, beliefs about sleep and impact, and personal coping strategies. Participants described their sleep disturbance in terms of insomnia symptoms; most commonly difficulties initiating and maintaining sleep. Participants had varied views on causal factors including the BT diagnosis and treatment and caregiver burden. However, excessive thinking and BT-related anxiety were evident in both patients and caregivers. The described impact on daytime functioning due to non-restful sleep and fatigue appeared to be significant and many participants needed daytime naps, although they understated the impact on individual functioning. Some participants were reluctant to seek help from clinicians for sleep disturbance due to previous experiences where sleep disturbance was overlooked, or because they held negative views toward pharmacological interventions. Participants reported various coping strategies, ranging from relaxation-promoting techniques to behaviors to distract thinking at night that may instead disturb sleep. Conclusions Psychological factors contribute to sleep disturbance in patients with BT and caregivers. This population may benefit from information about sleep disturbance and interventions targeting anxiety.

Background Emerging evidence supports the clinical impact of sleep disturbance (SD) on cancer patients. This study aimed to determine the prevalence and predictors of SD in people with malignant brain tumors and caregivers, and explore any relationship between the patient-caregiver dyad’s sleep. Methods Eighty-one adults with primary malignant (91%) or metastatic (9%) brain tumors and their family caregivers (n = 44) completed a series of self-report questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index, and the drowsiness item of The MD Anderson Symptom Inventory-Brain Tumor in an Australian ambulatory neuro-oncology setting. Participants were grouped by the PSQI cutoff (SD > 5), and binary logistic regression analyses were performed to identify risk factors. Results Of patients, 53% reported SD and 15% of those clinically significant insomnia, and 27% reported moderate to severe daytime drowsiness. Whereas anxiety, depression, fatigue, pain, neurocognitive symptoms, and antiemetic use were higher in patients with SD, fatigue and KPS were strong predictors of SD. In caregivers, 55% reported poor sleep and 13% clinical insomnia. Anxiety, caregiver burden, and comorbid illness were significantly associated with caregivers’ SD. The individual’s SD did not affect the chance of the other member of the patient-caregiver dyad experiencing SD. Conclusions More than half the sample had sleep disturbance, which was linked to many concomitant symptoms, such as fatigue in patients and anxiety in caregivers, potentially contributing to distress and functional impairment. Understanding underlying mechanisms of SD, the potential use of these clinical predictors in care settings, and options for management is warranted.

Sleep disturbance is easily overlooked in subspecialty consultations and may remain untreated during and after initial treatment of malignant brain tumours (BT). This study aimed to explore perceptions of healthcare professionals (HCPs) actively engaged in neuro-oncology care towards sleep disturbance in adults with primary or secondary BT and to identify facilitators and barriers to assessment and management of sleep disturbance. A survey was conducted to explore HCPs’ perceptions about their knowledge, skills, and confidence in managing sleep disturbance in people with BT. The survey also explored their beliefs, motivation, and perceived role in managing sleep disturbance, and views on contributing external factors that impacted management. Seventy-three interdisciplinary HCPs with average of 9.3 years of clinical experience in neuro-oncology participated. Fifty-five percent of participants were medical or radiation oncologists. Participants reported a high observed prevalence of sleep disturbance, especially in inpatient settings, during initial treatment, and after tumour progression or recurrence. Only 20% of participants reported routinely reviewing sleep-related symptoms during consultations. General symptom screening questions were perceived as helpful to identify sleep disturbance. Almost all respondents (92%) viewed corticosteroids as the most relevant risk factor, followed by psychological distress. The most frequent clinical responses were offering verbal advice and prescribing medication. The lack of time, resources, and training for managing sleep issues were commonly reported barriers. Overall, participants perceived sleep disturbance as highly prevalent in neuro-oncology and positively viewed the importance of managing this symptom. Practical barriers to management were reported that future interventions can target.

An extensive body of scholarship focuses on cultural diversity in health care, and this has resulted in a plethora of strategies to “manage” cultural difference. This work has often been patient-oriented (i.e., focused on the differences of the person being cared for), rather than relational in character. In this study, we aimed to explore how the difference was relational and coproduced in the accounts of cancer care professionals and patients with cancer who were from migrant backgrounds. Drawing on eight focus groups with 57 cancer care professionals and one-on-one interviews with 43 cancer patients from migrant backgrounds, we explore social relations, including intrusion and feelings of discomfort, moral logics of rights and obligation, and the practice of defaulting to difference. We argue, on the basis of these accounts, for the importance of approaching difference as relational and that this could lead to a more reflexive means for overcoming “differences” in therapeutic settings.

Background The goal of a clinical quality registry is to deliver immediate gains in survival and quality of life by delivering timely feedback to practitioners, thereby ensuring every patient receives the best existing treatment. We are developing an Australian Brain Cancer Registry (ABCR) to identify, describe, and measure the impact of the variation and gaps in brain cancer care from the time of diagnosis to the end of life. Methods To determine a set of clinical quality indicators (CQIs) for the ABCR, a database and internet search were used to identify relevant guidelines, which were then assessed for quality using the AGREE II Global Rating Scale. Potential indicators were extracted from 21 clinical guidelines, ranked using a modified Delphi process completed in 2 rounds by a panel of experts and other stakeholders, and refined by a multidisciplinary Working Group. Results Nineteen key quality reporting domains were chosen, specified by 57 CQIs detailing the specific inclusion and outcome characteristics to be reported. Conclusion The selected CQIs will form the basis for the ABCR, provide a framework for achievable data collection, and specify best practices for patients and health care providers, with a view to improving care for brain cancer patients. To our knowledge, the systematic and comprehensive approach we have taken is a world first in selecting the reporting specifications for a brain cancer clinical registry.

BACKGROUND VERTU was a randomized phase II trial evaluating veliparib, a brain-penetrant PARP inhibitor, combined with radiotherapy and temozolomide, for patients with newly diagnosed MGMT-unmethylated glioblastoma. As part of planned correlative work after study completion, we assessed genome-wide DNA methylation patterns to predict methylation class, glioblastoma subtype and MGMT status. METHODS Patients were randomized 2:1 to experimental (60Gy/30 fractions with veliparib 200mg bid, then temozolomide 150-200mg/m2 D1-5 + veliparib 40mg bid D1-7 Q28D for 6 cycles) versus standard arm (60Gy/30 fractions with temozolomide 75mg/m2 daily, then temozolomide 150-200mg/m2 D1-5 Q28D for 6 cycles). The primary objective to improve 6-month progression-free survival (PFS-6m) was not met (doi: 10.1093/neuonc/noab111). Methylation data were generated using the Illumina Infinium Methylation EPIC bead chip array. Tumor tissues were categorized using the Heidelberg methylation-based classifier. RESULTS Methylation data were successfully generated for 98/125 patients (poor quality DNA [n = 12], no consent [n = 11], insufficient tissue [n = 4]). Those with classifier scores below 0.5 (n = 25), tumor microenvironment only (n = 6) and rediagnosis as pleomorphic xanthoastrocytoma (n = 1) were excluded, leaving n = 66. Methylation classes were GBM RTK II (n = 23, PFS-6m 43% [95%CI 23-62]), RTK I (n = 20, PFS-6m 50% [95%CI 27-69]), MES (n = 20, PFS-6m 40% [95%CI 19-60]), MID (n = 2) and G34 (n = 1). Glioblastoma subtypes were mesenchymal (n = 28, PFS-6m 50% [95%CI 30-66]), proneural (n = 24, PFS-6m 50% [95%CI 29-68]) and classical (n = 14, PFS-6m 36% [95%CI 13-59]). MGMT status were unmethylated (n = 58, PFS-6m 48% [95%CI 35-60]) and methylated (n = 8, PFS-6m 38% [95%CI 9-67]). There was no evidence of interaction between treatment arm and methylation class (excluding GBM MID and G34, P = 0.45), glioblastoma subtype (P = 0.68) or MGMT status (P = 0.52). CONCLUSIONS Genome-wide DNA methylation patterns in VERTU identified a spectrum of methylation-defined subgroups, reflecting tumoral heterogeneity. This may have utility for future clinical trials and practice. The effect of veliparib in VERTU appeared to be consistent across subgroups. ACTRN12615000407594.

BACKGROUND Accurate and repeatable imaging segmentation of glioblastomas is important for effective radiomics modelling of clinical endpoints such as survival and treatment response. Manual and even automated segmentation are prone to variability. The primary objective of this study is to evaluate the repeatability of manually segmented glioblastomas on MRI which will serve as quality assurance for a quantitative MRI radiomics repeatability study. METHODS MRI datasets from n=19 patients with recurrent glioblastoma extracted from The Cancer Imaging Archive (RIDER Neuro MRI dataset) comprised of test-retest scans (time-point 1 and 2) acquired on average 2 days apart. The MRI protocol consisted of dynamic contrast-enhanced 3D FLASH using 0.1mmol/kg Magnevist intravenous injection at 3cc/second (TR 3.8ms, TE 1.8ms, 5mm slices, flip angle 25°), contrast-enhanced 3D FLASH (TR 8.6ms, TE 4.1ms, 1mm slices, flip angle 20°) and contrast-enhanced 3D FLAIR (TR 6000ms, TE 353ms, TI 2200ms, 1mm slices, flip angle 180°) on a 1.5T magnet. Contrast enhancing tumour from n=38 MRI scans were manually segmented by a radiologist slice by slice using contrast-enhanced 3D FLASH T1-weighted images on MIM software (v6.9.5). All cases at time-point 1 were contoured before contouring commenced for time-point 2 in the same order. Repeatability and spatial overlap was assessed by Dice similarity coefficient (DSC), Hausdorff distance (HD) and centroid shift. RESULTS A comparison of time-point 1 and 2 demonstrated the median DSC for n=19 cases was 0.84 (interquartile range 0.07), mean HD was only 0.1cm and mean centroid shift was 0.2cm. CONCLUSION High repeatability and spatial overlap of manually segmented contrast enhancing regions of recurrent glioblastoma were achieved on serial MRI. This substantiates a high level of repeatability which forms a core component of an MRI radiomics platform under development.

BACKGROUND Nivolumab is a PD-1 inhibitor with known safety profile. An increase in mutations as we age is well documented in glioblastoma and other cancers. Higher mutational load is associated with increased response to nivolumab in extracranial malignancies. NUTMEG examined the activity of nivolumab added to temozolomide in glioblastoma patients aged ≥ 65 years. METHODS NUTMEG was an international multicenter phase II trial for newly diagnosed glioblastoma patients aged ≥ 65 years, randomized 2:1 to experimental (40Gy/15 fractions with temozolomide 75mg/m2, then 6 cycles of temozolomide 150-200mg/m2 D1-5 Q28D + nivolumab 240mg D1,15 Q28D C1-4 and 480mg D1 Q28D C5-6) versus standard arm (40Gy/15 fractions with temozolomide 75mg/m2, then 6 cycles of temozolomide alone 150-200mg/m2 D1-5 Q28D), stratified by age, ECOG status, MGMT status and resection extent. RESULTS 103 patients were enrolled (69 in experimental arm, 34 in standard arm). Median age was 73 years, 36% ECOG 0, 57% MGMT-unmethylated and 51% gross macroscopic resection. Median follow-up is 31 months to date, with 77 deaths (surviving patients to continue follow-up and final results will be presented). Median overall survival was 11.8 months in the experimental arm versus 12.0 months in the standard arm (HR 0.95 95%CI 0.59-1.53 for experimental relative to control). Six-month progression-free survival rate using mRANO was 64% in the experimental arm versus 49% in the standard arm (HR 0.81 95%CI 0.51-1.26). Grade 3/4 adverse events were reported in 46% of experimental arm (7% lung infection, 7% thromboembolic events, 6% fatigue, 6% muscle weakness) and in 29% of control arm (9% fatigue, 6% seizure, 6% thromboembolic events). CONCLUSIONS There was insufficient evidence of clinical benefit with nivolumab in this population. No new safety signals were identified. Central imaging review is underway and correlative studies will characterize the immune landscape, including mutational load, neoantigen and other immune markers. NCT04195139.

Purpose High-grade disease accounts for ~ 70% of all glioma, and has a high mortality rate. Few modifiable exposures are known to be related to glioma risk or mortality. Methods We examined associations between lifetime physical activity and physical activity at different ages (15–18 years, 19–29 years, 30–39 years, last 10 years) with the risk of glioma diagnosis, using data from a hospital-based family case–control study (495 cases; 371 controls). We followed up cases over a median of 25 months to examine whether physical activity was associated with all-cause mortality. Physical activity and potential confounders were assessed by self-administered questionnaire. We examined associations between physical activity (metabolic equivalent [MET]-h/wk) and glioma risk using unconditional logistic regression and with all-cause mortality in cases using Cox regression. Results We noted a reduced risk of glioma for the highest (≥ 47 MET-h/wk) versus lowest ( Conclusion Our findings are consistent with previous research that suggested physical activity during adolescence might be protective against glioma. Engaging in physical activity during adolescence has many health benefits; this health behavior may also offer protection against glioma.

Background Translating outcomes achieved by clinical trials into routine care is crucial to improving outcomes of glioblastoma (GBM). This study examines the extent to which an advance in treatment for GBM has translated into meaningful, population-level survival benefits in New South Wales (NSW), Australia. Methods This retrospective cohort study used linked population-based cancer registry, admitted patient, and mortality datasets. The cohort (n = 2604) included NSW residents aged ≥18 years with a histologically confirmed GBM and a surgical resection between July 2001 and December 2012. The study outcome was all-cause survival, examined using multivariable proportional hazard models. The main study factor was period of surgery, categorized into 4 periods corresponding to different eras in temozolomide (TMZ) use. Survival was examined over time by age (≤70 and >70 years) and for a subcohort selected to approximate the seminal European Organisation for Research and Treatment of Cancer (Stupp) protocol trial cohort. TMZ use was estimated using aggregate prescription claims data. Results Median survival in 2001-2003, 2004-2006, 2007-2009, and 2010-2012 was 7.4, 9.0, 9.8, and 10.6 months, and risk-adjusted 2-year survival was 8.2%, 13.8%, 15.5%, and 18.3%, respectively. Survival improved for those aged ≤70 years and those aged >70 years. In the proxy trial subcohort, median and 2-year survival were 14.3 months and 27.3%, respectively. The volume of TMZ prescribed annually increased rapidly from 2005. Conclusions Introduction of TMZ into standard care in 2005 coincided with improvements in survival and a rapid increase in TMZ prescribing. Optimization of care has continued to improve survival of people with GBM in subsequent years.

Subacute changes following breast radiotherapy have been demonstrated in discrete areas of the left ventricle (LV), with recent guidelines being developed to help determine dose to subvolumes of the LV. This study aims to determine doses to the 17 segments of the LV as per the American Heart Association (AHA) and other cardiac subvolumes, and to correlate mean heart (MHD) dose with various subvolume dosimetric indices. These results may direct focus to specific left ventricular segments in studies of radiation-related heart disease incorporating surveillance imaging, help to determine more precise dose response relationships, and potentially aid prediction of late radiation effects.The heart and cardiac subvolumes of 29 patients treated with tangential radiotherapy for left breast cancer were contoured. Delineation of cardiac subvolumes (cardiac chambers, cardiac valves and the 17 segments of the LV) was undertaken using a novel contouring method on planning CT data reformatted into the cardiac axis. Individual segments were then combined to determine doses to the basal, mid and apical left ventricular regions, and the anterior, septal, inferior and lateral ventricular walls. Radiotherapy doses (including maximum, mean, D1cc, V25) were determined. Correlation analyses were performed between MHD and various substructure dosimetric indices.Twenty five patients received tangential breast free breathing radiotherapy alone, and four patients received regional nodal irradiation including the internal mammary chain with deep inspiration breath hold (DIBH). For patients receiving breast only radiation, the median mean heart radiation dose was 2.62 Gy (range 1.52-3.90 Gy), and a heterogeneous dose distribution to the LV was noted, with the apical region receiving the highest median mean dose (14.99 Gy) compared with the mid and basal regions (3.10 Gy and 1.51 Gy respectively). The anterior LV wall received the highest median mean dose (9.21 Gy) with the remaining walls receiving similar mean doses (range 1.79-3.05 Gy). The anterior LV apical segment (segment 13) and apex (segment 17) received the highest individual median mean segment doses (26.73 Gy and 30.02 Gy respectively). Apical segments received the highest median mean doses (segments 13, 14, 15, 16), followed by the mid anterior (segment 7) and anteroseptal (segment 8) segments. Segments receiving the highest doses remained unchanged between the DIBH cohort and free breathing cohort. MHD showed a high correlation with the anterior wall r = 0.71, p 0.05 and entire left ventricle r = 0.82, p 0.05, but correlations varied from weak to high when MHD was correlated with segments receiving highest doses (range r = 0.43-0.76), p 0.05.In the setting of breast cancer radiotherapy, there are substantial RT dose variations within specific LV segments, with mid and apical anterior ventricular segments (segments 7, 13) and the apical region of the LV (segments 13, 14, 15, 16, 17) being consistently exposed to the highest radiation doses. Determining segmental and regional RT doses to the left ventricle may help guide focus in diagnostic cardiology in the post radiotherapy setting.

BACKGROUND Grade 2 and 3 (G2/3) gliomas are the second largest group of brain tumors in adults. Although the prognosis for G2/3 gliomas at the time of relapse mirror those of glioblastoma, there are few trials in this space. METHODS LUMOS was a national multi-center pilot study for patients with relapsed G2/3 gliomas designed to match contemporaneous tissue obtained at the time of disease progression with subsequent targeted therapies. The objective was to establish the feasibility of a precision oncology, umbrella approach to obtain and type tissue within a useful timeframe. As a key feature of LUMOS, a multidisciplinary Molecular Tumor Advisory Panel (MTAP) with subspecialty neuro-oncology expertise was formed to interpret the complex genomic information and provide a simplified recommendation to the treating physician. RESULTS Ten patients (median age 42: range 32-62; four G2 astrocytoma, one G3 astrocytoma, three G2 oligoendroglioma, one G3 oligodendroglioma, one mixed tumor) were enrolled in the study. Eight patients had biopsies within 6 months of study entry whilst two underwent a biopsy during the study. All patients had potentially targetable alterations (10 IDH, 3 FGFR, 2 PIK3K, CCND3, NRAS, CDK4, PRPRZ1-MET fusion and MET amplification). Matched therapies were delivered for two patients via compassionate access outside the study. The median turnaround time (TAT) of MTAP reports was 6.2 weeks (range 4.2-9.7 weeks) but 4.6 weeks when lag time for shipping was removed. CONCLUSION LUMOS confirmed that this design was feasible with good turnaround times. The MTAP facilitated education and support for treating physicians. Thes findings support moving to a larger study using contemporaneous and longitudinal tissue samples matched with targeted therapies as part of a comprehensive umbrella study design. Delivery and interpretation of molecular data is a challenge shared across oncology which may be mitigated with a neuro-oncology specific molecular tumor board.

BACKGROUND Survival outcomes for patients with newly diagnosed glioblastoma have not changed significantly since the introduction of concurrent temozolomide with post-surgical radiation followed by adjuvant temozolomide. METHODS Multi-Arm Glioblastoma Australasia (MAGMA) is a recently initiated phase III multi-arm, multi-centre randomized trial for patients with newly diagnosed glioblastoma, led by the Australian Cooperative Trials Group for Neuro-Oncology (COGNO), that will concurrently test multiple treatment questions. Initially, a partial factorial design will be implemented to compare the current standard of care with either or both of (1) neoadjuvant temozolomide and (2) aduvant temozolomide continued beyond six months until progression. MAGMA will transition to a multi-arm multi-stage (MAMS) design as additional tratment question are introduced. Treatment allocation to each question will be balanced (1:1) using minimisation over several stratification factors, including study site, age, IDH-mutation status, surgical extent and randomization to the prior treatment question(s). The primary outcome is overall survival. Secondary outcomes include progression-free survival (measured by mRANO), time to first non-temozolomide systemic treatment, clinically significant toxicity as measured by Grade 2/4 adverse events, and health-related quality of life measures. Parsimonious data collection and a streamlined assessment schedule have been incorporated to mitigate the burden of data collection (such as low grade toxicity from temozolomide), and to encourage participation in regional and rural settings. A consortium model has been adopted to foster neuro-oncology expertise and infrastructure and share academic credit and future design opportunities. PROGRESS Recruitment commenced in September 2020. To date, 60 patients have been recruited from an initial sample size target of 250 patients for each of these initial two treatment questions. Of these 60 patients, 45 have been randomized in Question 1 (neoadjuvant chemotherapy) whilst 50 randomized in Question 2 (prolonged adjuvant chemotherapy). To date, 14 of the 27 intended sites are open to recruitment.

Background Subclinical left ventricular dysfunction detected by 2‐dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Methods and Results Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy‐naïve women with left‐sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within‐patient dose–response association between the segment‐specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received. Conclusions Radiotherapy for left‐sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose–response relationship with radiotherapy dose received. Radiotherapy‐induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy‐related cardiotoxicity in patients with breast cancer. Long‐term outcomes in patients with asymptomatic strain reduction require further investigation.

Introduction Mongolia has a population of 3.3 million and is classified by the WHO as a lower middle-income country. Cancer is now a major public health issue and one of the leading causes of mortality. Within the framework of an existing national cancer control plan, the National Cancer Centre of Mongolia (NCCM) aimed to implement 3D conformal radiation planning and linac-based treatment delivery. Methods In 2018, an opportunity arose for collaboration between the Mongolia Society for Radiation Oncology (MOSTRO), the National Cancer Centre Mongolia (NCCM), the Asia-Pacific Radiation Oncology Special Interest Group (APROSIG) of the Royal Australian and New Zealand College of Radiologists (RANZCR) and the Asia-Pacific Special Interest Group (APSIG) of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) and radiation therapists (RTTs) from a range of Australian centres. We describe here the results to date of this collaboration. Results Despite a number of significant technical and practical barriers, successful linac commissioning was achieved in 2019. Key factors for success included a leadership receptive to change management, stable bureaucracy and health systems, as well as a synchronised effort, regional cooperation and mentorship. Conclusion Future directions for ongoing collaborative efforts include a continued focus on education, practical training in radiotherapy planning and delivery and postgraduate education initiatives. Radiotherapy safety and quality assurance remain an ongoing priority, particularly as technological advances are sequentially implemented.

This study explores healthcare professionals (HCPs)' perception and current management of sleep disturbance (SD) in people with malignant brain tumours and their caregivers. We aimed to identify barriers to effective management of SD in neuro-oncology care.We conducted semi-structured interviews with 11 HCPs involved in neuro-oncology care. The study was underpinned by the Capability Opportunity Motivation-Behaviour (COM-B) model within the Behavioural Change Wheel (BCW) guiding topic selection for the exploration of underlying processes of HCPs' behaviours and care decisions for SD management. Data were analysed thematically using a framework synthesis, and subsequently mapped onto the BCW to identify barriers for effective management and recommend potential interventions.We identified four themes: HCPs' clinical opinions about SD, the current practice of SD management in neuro-oncology clinics, gaps in the current practice, and suggested areas for improvements. HCPs perceived SD as a prevalent yet secondary issue of low priority in neuro-oncology care. SD was unrecognised, and inadequately managed in usual clinical settings. Interventional options included modifying the use of corticosteroids or prescribing sedatives. When mapped onto the BCW, themes identified main barriers as a lack of awareness among HCPs about SD warranting care, due to the absence of screening tools and limited knowledge and resources for therapeutic interventions.Multidisciplinary HCPs need training in the routine use of appropriate sleep assessment tools, and access to clear management pathways. More professional resources are needed to educate staff in implementing appropriate interventions for people with malignant brain tumours who are experiencing SD.

BACKGROUND Despite the acceptability and efficacy of e–patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging. OBJECTIVE This pragmatic trial implemented the PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer. METHODS Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals. RESULTS From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877). CONCLUSIONS Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12616000615482; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370633 INTERNATIONAL REGISTERED REPORT RR2-10.1186/s12885-018-4729-3

Sleep disturbance is easily overlooked in subspecialty consultations and may remain untreated during and after initial treatment of malignant brain tumours (BT). This study aimed to explore perceptions of healthcare professionals (HCPs) actively engaged in neuro-oncology care towards sleep disturbance in adults with primary or secondary BT and to identify facilitators and barriers to assessment and management of sleep disturbance.A survey was conducted to explore HCPs' perceptions about their knowledge, skills, and confidence in managing sleep disturbance in people with BT. The survey also explored their beliefs, motivation, and perceived role in managing sleep disturbance, and views on contributing external factors that impacted management.Seventy-three interdisciplinary HCPs with average of 9.3 years of clinical experience in neuro-oncology participated. Fifty-five percent of participants were medical or radiation oncologists. Participants reported a high observed prevalence of sleep disturbance, especially in inpatient settings, during initial treatment, and after tumour progression or recurrence. Only 20% of participants reported routinely reviewing sleep-related symptoms during consultations. General symptom screening questions were perceived as helpful to identify sleep disturbance. Almost all respondents (92%) viewed corticosteroids as the most relevant risk factor, followed by psychological distress. The most frequent clinical responses were offering verbal advice and prescribing medication. The lack of time, resources, and training for managing sleep issues were commonly reported barriers.Overall, participants perceived sleep disturbance as highly prevalent in neuro-oncology and positively viewed the importance of managing this symptom. Practical barriers to management were reported that future interventions can target.

Background The literature describing the incidence of sleep difficulty in CNS cancers is very limited, with exploration of a sleep difficulty symptom trajectory particularly sparse in people with advanced disease. We aimed to establish the prevalence and longitudinal trajectory of sleep difficulty in populations with CNS cancers receiving palliative care nationally, and to identify clinically modifiable predictors of sleep difficulty. Methods A consecutive cohort of 2406 patients with CNS cancers receiving palliative care from sites participating in the Australian national Palliative Care Outcomes Collaboration were evaluated longitudinally on patient-reported sleep difficulty from point-of-care data collection, comorbid symptoms, and clinician-rated problems. Multilevel models were used to analyze patient-reported sleep difficulty. Results Reporting of mild to severe sleep difficulties ranged from 10% to 43%. Sleep scores fluctuated greatly over the course of palliative care. While improvement in patients’ clinical status was associated with less sleep difficulty, the relationship was not clear when patients deteriorated. Worsening of sleep difficulty was associated with higher psychological distress (P < .0001), greater breathing problems (P < .05) and pain (P < .05), and higher functional status (P < .001) at the beginning of care. Conclusions Sleep difficulty is prevalent but fluctuates widely in patients with CNS cancers receiving palliative care. A better-tailored sleep symptom assessment may be needed for this patient population. Early interventions targeting psychological distress, breathing symptoms, and pain for more functional patients should be explored to see whether it reduces sleep difficulties late in life.

The FIG study is a prospective non-randomised study now recruiting up to 210 newly diagnosed GBM participants across ten Australian sites. Study outcomes will address the role of [18F] fluoroethyl-L-tyrosine positron emission tomography (FET-PET) in radiotherapy (RT) planning, evaluation of post-treatment changes versus disease progression and prognostication. We describe here the methodology and preliminary outcomes for site credentialing. Eligible participants with GBM undergo FET-PET imaging at three time-points: FET-PET1-post-operative pre-chemo-RT, FET-PET2 acquired one month post-chemo-RT and FET-PET3 (+/-FDG-PET) triggered when clinical and/or radiological (MRI) progression is suspected. Dynamic and static FET-PET images are analysed qualitatively and quantitatively. Radiotherapy is as per standard care with the treating Radiation Oncologist (RO) blinded to FET-PET1. Site nuclear medicine (NM) physicians are required to delineate a biological target volume (BTV) based on FET-PET1 with hybrid RT volumes derived post-hoc. Pre-trial NM quality assurance comprises certification from the Australasian Radiopharmaceutical Trials Network encompassing FET-PET radiochemistry Quality Control and PET camera calibration. Site and central integrated workflows incorporating multi-modality image registration, target volume/region of interest contouring and analysis have been developed. NM benchmarking involves delineation of FET-PET BTVs in 3 cases with another 3 cases addressing response criteria interpretation harmonized across FET-PET, FDG-PET and MRI. Site ROs complete 3 cases involving standard and hybrid target volume delineation based on pre-derived FET-PET volumes. All NM and RO credentialing cases undergo central expert review. To date, of six sites which have submitted full credentialing data, 19/21 RO and 6/6 planning cases were passed. Of 72 NM cases, 18/72 (25%) required resubmission, primarily related to ensuring standardisation of background regions and time activity curve interpretation. The FIG study will be pivotal in establishing the role of FET-PET in GBM management. The robust NM and RO credentialing program will build capacity and expertise in FET-PET production, acquisition and image interpretation.

Purpose To determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57 (95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52 (95% CI 0.48-0.56) for MRI supine, 0.56 (95% CI 0.53-0.59) for CT prone and 0.55 (95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41 (95% CI 0.36-0.46) for supine and 0.38 (0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images.

ObjectivesTo improve the experiences of people from diverse cultural backgrounds, there has been an increased emphasis on strengthening cultural awareness and competence in healthcare contexts. The aim of this focus-group based study was to explore how professionals in cancer care experience their encounters with migrant cancer patients with a focus on how they work with cultural diversity in their everyday practice, and the personal, interpersonal and institutional dimensions therein.DesignThis paper draws on qualitative data from eight focus groups held in three local health districts in major metropolitan areas of Australia. Participants were health professionals (n=57) working with migrants in cancer care, including multicultural community workers, allied health workers, doctors and nurses. Focus group discussions were audio recorded and transcribed in full. Data were analysed using the framework approach and supported by NVivo V.11 qualitative data analysis software.ResultsFour findings were derived from the analysis: (1) culture as merely one aspect of complex personhood; (2) managing culture at the intersection of institutional, professional and personal values; (3) balancing professional values with patient values and beliefs, and building trust and respect; and (4) the importance of time and everyday relations for generating understanding and intimacy, and for achieving culturally competent care.ConclusionsThe findings reveal: how culture is often misconstrued as manageable in isolation; the importance of a renewed emphasis on culture as interpersonalandinstitutional in character; and the importance of prioritising the development of quality relationships requiring additional time and resource investments in migrant patients for enacting effective intercultural care.

Toxicity to cardiac and coronary structures is an important late morbidity for patients undergoing left-sided breast radiotherapy. Many current studies have relied on estimates of cardiac doses assuming standardised anatomy, with a calculated increase in relative risk of 7.4% per Gy (mean heart dose). To provide individualised estimates for dose, delineation of various cardiac structures on patient images is required. Automatic multi-atlas based segmentation can provide a consistent, robust solution, however there are challenges to this method. We are aiming to develop and validate a cardiac atlas and segmentation framework, with a focus on the limitations and uncertainties in the process. We present a probabilistic approach to segmentation, which provides a simple method to incorporate inter-observer variation, as well as a useful tool for evaluating the accuracy and sources of error in segmentation. A dataset consisting of 20 planning computed tomography (CT) images of Australian breast cancer patients with delineations of 17 structures (including whole heart, four chambers, coronary arteries and valves) was manually contoured by three independent observers, following a protocol based on a published reference atlas, with verification by a cardiologist. To develop and validate the segmentation framework a leave-one-out cross-validation strategy was implemented. Performance of the automatic segmentations was evaluated relative to inter-observer variability in manually-derived contours; measures of volume and surface accuracy (Dice similarity coefficient (DSC) and mean absolute surface distance (MASD), respectively) were used to compare automatic segmentation to the consensus segmentation from manual contours. For the whole heart, the resulting segmentation achieved a DSC of [Formula: see text], with a MASD of [Formula: see text] mm. Quantitative results, together with the analysis of probabilistic labelling, indicate the feasibility of accurate and consistent segmentation of larger structures, whereas this is not the case for many smaller structures, where a major limitation in segmentation accuracy is the inter-observer variability in manual contouring.

In this article, we focus on developing a critical sociology of ‘cultural and linguistic diversity’ as evident in cancer care praxis, drawing on the perspectives of cancer care health professionals. Set within the context of increasing efforts on the part of healthcare providers to ‘accommodate difference’ and ‘incorporate diversity’, we aimed to utilise participants’ accounts of practice to ask: how do we and how should we think about and operationalise ‘culture’ (if at all) in cancer care settings. Drawing on eight focus groups with doctors, nurses, allied health staff and multicultural community workers, here we explore their accounts of: othering and over-simplification; the role of absences in biographical reciprocity; intimacy, care and carelessness; and entanglements of culture with other aspects of the person. Based on their accounts, we argue for a broadening of the examination of the nexus of culture and care, to focus on the problematics of othering, intimacy, reciprocity and complexity.

Purpose High-quality symptom management and supportive care are essential components of comprehensive cancer care. We aimed to describe the development of an evidence-based automated decisional algorithm for patients with cancer that had specific, actionable, clinical, evidence-based recommendations to improve patient care, communication, and management. Methods We reviewed existing literature and clinical practice guidelines to identify priority domains of patient care and potential clinical recommendations. Two multidisciplinary clinical advisory groups used a two-stage consensus decision-making approach to determine domains of care and patient-reported outcome (PRO) measures and subsequently developed automated algorithms with clear clinical recommendations amendable to intervention in clinical settings. Results Algorithms were developed to inform management of patient symptoms, distress, and unmet needs. Three PRO measures were chosen: Distress Thermometer and problem checklist, Edmonton Symptom Assessment Scale, and the Supportive Care Needs Survey–Screening Tool 9. PRO items were mapped to five domains of patient well-being: physical, emotional, practical, social and family, and maintenance of well-being. A total of 15 actionable clinical recommendations tailored to specific issues of concern were established. Conclusion Using automated algorithms and clinical recommendations provides a platform for streamlining and systematizing the use of PROs to inform risk-stratified guideline-informed care. The series of algorithms, which set out systematized care pathways for the clinical care of patients with cancer, can be used to potentially inform patient-centered care.

Aim Flurodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is routinely used in non-small-cell lung cancer. This study aims to assess the prognostic value of quantitative FDG-PET/CT parameters including standard uptake value (SUV), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) in non-small-cell lung cancer. Methods A retrospective review of 92 nonsurgical patients with pathologically confirmed stage I–III non-small-cell lung cancers treated with radical dose radiotherapy (≥50 Gy) was conducted. Metabolically active tumor regions on FDG-PET/CT scans were contoured manually. SUV, MTV and TLG were calculated for primary, nodal and whole-body disease. Univariate and multivariate (adjusting for age, sex, disease stage and primary tumor size in centimeters) Cox regression modeling were performed to assess the association between these parameters and both overall and progression-free survival (PFS). Results On univariate analysis, overall survival (OS) was significantly associated with primary MTV (P = 0.03), whole-body MTV (P = 0.02), whole-body maximum SUV (P = 0.05) and whole-body TLG (P = 0.03). PFS was significantly associated with primary MTV (P = 0.01), primary TLG (P = 0.04), whole-body MTV (P < 0.01) and whole-body TLG (P = 0.01). On multivariate analysis, OS was significantly associated with whole-body MTV (P = 0.05). PFS was significantly associated with whole-body MTV (P = 0.02) and whole-body TLG (P = 0.05). Conclusions Whole-body MTV was significantly associated with overall and PFS, and whole-body TLG was significantly associated with PFS on multivariate analysis. These two parameters may be significant prognostic factors independent of other factors such as stage. SUV was not significantly associated with survival on multivariate analysis.

Aim Innovative e-health strategies are emerging, to tailor and provide convenient, systematic and high-quality survivorship care for an expanding cancer survivor population. This pilot study tests the application of an e-health platform, “Healthy.me,” in a breast cancer survivor cohort at Liverpool and Macarthur Cancer Therapy Centres, New South Wales, Australia. Methods Fifty breast cancer patients were recruited to use the Healthy.me website, designed by the Centre of Health Informatics at the University of New South Wales, over a 4-month period. Telephone and online questionnaires were used at 1 and 4 months and a face-to-face feedback at study completion, to gather qualitative and quantitative data regarding feasibility of Healthy.me. Results Healthy.me was reported to be a useful online resource by most users. Usage declined from 76% at 1 month to 48% at 4 months. Breast cancer survivors enjoyed a variety of tailored information regarding health and life-style issues. Positive aspects of Healthy.me were the convenient access to trusted information, and interaction with their peers and healthcare professionals. Barriers to usage contributing to usage decline were lack of reported patient time to re-access information, limited content updates and technical factors. Conclusions This pilot study suggested the potential of an e-health strategy such as Healthy.me in addressing the needs of a growing breast cancer survivor population. Ongoing development of a more robust e-health resource and integration with primary care models is warranted.

Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12–15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication.

BACKGROUND TMZ offers minimal benefit in pts with de novo uMGMT GBM. V is synergistic with RT and TMZ in uMGMT preclinical GBM models, safe when combined with either RT or TMZ clinically, but the triplet (V+RT+TMZ) is poorly tolerated. VERTU tested V in pts with uMGMT GBM. METHODS VERTU is a randomized Phase 2 trial comparing Standard Arm (Arm A), RT (60Gy/30 fractions) + TMZ (75mg/m2 daily) followed by TMZ (150–200mg/m2D 1–5) every 28 days for 6 cycles vs Experimental Arm (Arm B), RT (60Gy/30 fractions) + V (200mg PO BID) followed by TMZ (150–200mg/m2D 1–5) + V (40mg bid, D 1–7) every 28 days for 6 cycles in pts with de novo uMGMT GBM according to centralised testing. RESULTS 125 pts were randomized 1:2 (41:84). The 2 groups were matched for age, sex, performance status and extent of resection. Median follow-up was 25.8 months and 91 pts had died. The 6-month Progression-Free Survival (6mPFS) for Arms A and B were 34% (95% CI 20–48) and 46% (95% CI 36–57) respectively. The median PFS for Arms A and B were 4.2m (95% CI 2.5–6.0) and 5.7m (95% CI 4.1–6.6) respectively (HR = 0.80, 95%CI 0.55–1.18). 55% of pts in both arms experienced Grade 3/4 adverse events (AEs) with no significant differences in frequency or severity between the arms. Most common Grade 3/4 AEs were thrombocytopenia, seizures, hyperglycaemia and diarrhoea. CONCLUSION VERTU demonstrated that a novel treatment strategy for patients with de novo uMGMT GBM was feasible and tolerable. The observed 6mPFS and PFS were similar in both arms. Overall survival and other endpoints will be presented. Central MRI review, biomarker analyses, including DNA repair and methylation signature analyses are ongoing. (ANZCTR#ACTRN12615000407594).

Poster: "2015 ASM / R-0116 / Relationship between CT-Derived Gross Tumour Volume (GTV) and the FDG-PET/CT-Derived Metabolic Tumour Volume (MTV): An Exploratory Study in Non-Small Cell Lung Cancer Patients Treated with Radical Radiotherapy " by: " A. Oar , M. Jameson, I. Ho-Shon, P. Phan, L. Holloway, D. Wang, J. Descallar, A. Pramana, S. Vinod, M. Field, E.-S. Koh; Sydney/AU"