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OBJECTIVES: Symptoms 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. METHODS: Participants 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. RESULTS: Thirty 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). CONCLUSIONS: The study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction. TRIAL REGISTRATION NUMBER: ACTRN12615001072505.

The SARS-CoV-2 pandemic has resulted in considerable consequences for many cancer patients, exacerbating pre-existing systemic health system limitations as well as creating new challenges. From socially distanced clinics and the widespread introduction of telehealth, to the halting of clinical trials and the reassessment of what constitutes “essential” treatment, care in oncology has abruptly changed. There is currently limited analysis of cancer patients’ experiences of the pandemic and its impacts on illness, wellness, and everyday life. Through semi-structured interviews with 54 people living with cancer during the 2020 phase of the SARS-CoV-2 pandemic in Australia, we explore how patients experience illness and care in reflecting upon a range of pandemic challenges, including delay, distance, and vulnerability. We find that in some cases, these pandemic conditions redefined the meaning of essential cancer care, reconfigured expectations around clinical trials, constructed new affective distances, and amplified dread and fear for people living with cancer.

BACKGROUND: Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities. METHODS: BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania. RESULTS: Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world's first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data. CONCLUSIONS: Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.

Background: The COVID-19 pandemic has forced rapid system-wide changes to be implemented within cancer care at an alarming pace. Clinical trials are a key element of comprehensive cancer care. Ensuring the continuing safe conduct of cancer clinical trials in the context of a pandemic is challenging. Method(s): We aimed to describe the COVID-19 pandemic response of a Cancer Care Clinical Research Unit (CRU) of a tertiary hospital in Queensland, Australia. We used a mixed methods approach for this case study. Emailed directives from CRU managers to all CRU staff sharing were qualitatively analysed and mapped against our unit activities over longitudinal time points. Data from patient recruitment and protocol deviations were analysed using descriptive statistics. Result(s): Mapping activity from 11 March to 30 September 2020 revealed rapid change during the first 2 weeks. Four key strategies to accommodate change were identified: supporting patients and families, introduction of telehealth, accessing investigational product, and social distancing. Early in the pandemic we recognised that our core key stakeholders were integral to our response. When compared to the previous 12 months, our recruitment numbers dropped markedly in early phases of the response but recovered over time, as we accommodated internal and external impacts. Conclusion(s): Our experience of agility as a necessity, adapting to support patients, and managing both clinical research activity and sponsors during the height of the pandemic response is presented here in order to inform future disaster response planning by clinical trial organisations.Copyright © 2021 John Wiley & Sons Australia, Ltd

Introduction Sars-CoV-2 is a novel coronavirus responsible for COVID-19 officially declared pandemic in March 2020. Health systems worldwide responded with swift changes to increase workflow capacity while protecting the vulnerable, including those with cancer. This led to unprecedented and rapid restructuring of health service provision. Published data from the 2003 SARS pandemic focuses on medical and nursing staff, overlooking other departmental employees such as administration officers or food service workers. Our protocol aims to document directives and adjustments communicated to staff in two cancer care departments and correlate this with measures of distress and perceived preparedness across the spectrum of all staff involved in cancer care. Methods and analysis We use a semiqualitative approach comprising weekly diarising of events and simultaneous staff surveys. Principal investigators will document changes at a metropolitan quaternary cancer centre and a regional cancer centre. Communications, directives and changes will be diarised in real time in four executional domains. Simultaneously, prospective voluntary self-administered online surveys will be conducted at regular intervals by staff. The survey assesses the perceived institutional preparedness and personal well-being, with a combination of Likert scaled and open response questions. A semiquantitative self-assessment of distress adapted from National Comprehensive Cancer Network distress thermometer is incorporated. Additionally, open-text personal reflections on themes including difficult decisions will be invited. Survey participants will be drawn from various work areas of the cancer care departments: administrative staff, health professionals, for example, allied health, ancillary workers, nursing and medical. Ethics and dissemination The study has been reviewed and approved by the Human Research Ethics Committee (LNR/2020/QRBW/62982). Published literature on domains of distress neglects catego

IntroductionGrades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsiesMethods and analysisThis study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library pr

BACKGROUND: Temozolomide 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. METHODS: VERTU 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. RESULTS: A 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. CONCLUSION: The 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.

Abstract 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

Medical encounters - while often viewed as centred on conveying clinical knowledge - are also sites of emotion and for exerting emotional labour by healthcare professionals. The temptation to view these encounters as largely 'technical' - an exchange of knowledge or information - can marginalise the complex emotions often experienced by healthcare professionals, and negates the critical work done in these encounters. Drawing on in-depth interviews with 22 Australian medical oncologists, this article explores the experience and meaning of (their) emotions in medical encounters, and the manner in which emotional labour is performed by medical oncologists. Emotions, as it emerges, are central to the 'management' of encounters, ensuring professional sustainability and in 'achieving' clinical outcomes. Here, we broaden understandings of emotionality in oncological work, focusing on emotions as central to the production and enactment of professionalism, relationships and identities across professional careers. We illustrate how the performance of emotional labour reflects a dialectic between notions of 'professionalism' and 'feelings' - which in practice are co-existing and intermingling dimensions of oncology relations - manifested in the practice of 'bounded caring'.

Men are increasingly participating, and acknowledging their roles, as informal carers. Yet, there has been comparatively little exploration of their experiences therein, especially within the context of cancer care. Here, drawing on semi-structured qualitative interviews with 16 Australian male carers for a relative with cancer, and using constructivist grounded theory, we explore their experiences of informal caring. Our analysis highlights a series of tensions, including the following: the meanings and practicalities of care provision including notions of reciprocity, duty, autonomy, and interdependence; the discomforts of dependency and vulnerability; and the complicated moralities that inflect “caring well.” Given the shifting dynamics around informal care, we argue for increased attention to the affective tensions that arise at the nexus of moralities and masculinities in informal caring relations, especially as they are articulated in the context of illness, affliction, and dependency.

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dos

OBJECTIVES: To 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. DESIGN: This 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. RESULTS: Four 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. CONCLUSIONS: The findings reveal: how culture is often misconstrued as manageable in isolation; the importance of a renewed emphasis on culture as interpersonal and institutional 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.

BACKGROUND: Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM. METHODS: M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m2) on days 1-5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve. RESULTS: There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%. CONCLUSIONS: Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).

© 2019 Royal Australasian College of Physicians The antibiotic optimisation imperative is now ubiquitous, with national policy frameworks in Organisation for Economic Co-operation and Development (OECD) countries incorporating the requirement for antimicrobial stewardship within healthcare services. Yet in practice, the optimisation agenda often raises complex ethical- and practice-based dilemmas. Antibiotic use at the end of life is multidimensional. It includes balancing complex issues, such as accuracy of prognostic estimates, benevolence to the individual versus the broader public health, personalised value judgement of time and quality of life and the right to treatment versus the right to die. It also occurs in an emotional context where the clinician and patient (and their family) collectively confront mortality. This provides a scenario where amplification of the already strong social and behavioural forces that drive overuse of antibiotics in many other clinical settings may occur. It therefore offers an important case for illustrating how antibiotic optimisation may be limited by social, value-based and ethical dilemmas.

© 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group. The impact of a cancer diagnosis flows beyond the person, fundamentally shaping relationships with partners, family and friends. Living with cancer can change people’s needs considerably, often requiring additional care from loved ones, potentially disrupting existing relational expectations, capacities and dynamics. A relational ontological approach is needed to better understand how women’s cancer experiences are inter-subjectively shaped within relationships and by prevailing social scripts. Drawing on interviews with 81 women with cancer, we explore women’s accounts of living with cancer and their experience of ‘care’ within close relationships with others. The interviews revealed how women respond to their illness as an experience in relation to their (male) partners; how they navigate patterns of care in their lives; and how social scripts of gender, care and emotionality shape their experiences. This adds to the sociology of care, and the understanding of care as situated within gendered, relational and social expectations around illness, coping and caring.

Background: The end of life represents a therapeutic context that acutely raises cultural and linguistic specificities, yet there is very little evidence illustrating the importance of such dynamics in shaping choices, trajectories and care practices. Culture and language interplay to offer considerable potential challenges to both patient and provider, with further work needed to explore patient and caregiver perspectives across cultures and linguistic groups, and provider perspectives. The objective of this study was to develop a critical, evidence-based understanding of the experiences of people from Culturally and Linguistically Diverse (CALD) backgrounds, and their caregivers, in a palliative care setting. Methods: A qualitative study, using semi-structured interviews to explore key experiences and perspectives of CALD patients and caregivers currently undergoing treatment under oncology or palliative care specialists in two Australian hospitals. Interviews were digitally audio recorded and transcribed in full. A thematic analysis was conducted utilising the framework approach. Results: Sixteen patients and fourteen caregivers from a range of CALD backgrounds participated in semi-structured interviews. The research identified four prevalent themes among participants: (1) Terminology in the transition to palliative care; (2) Communication, culture and pain management; (3) (Not) Talking about death and dying; and, (4) Religious faith as a coping strategy: challenging the terminal diagnosis. Conclusions: CALD patients and caregivers' experiences are multifaceted, particularly in negotiating linguistic difficulties, beliefs about treatment, and issues related to death and dying. Greater attention is needed to develop effective communication skills, recognise CALD patients' particular cultural, linguistic and spiritual values and needs, and acknowledge the unique nature of each doctor-patient interaction.

Aim: A viable and sustainable medical oncology profession is integral for meeting the increasing demand for quality cancer care. The aim of this study was to explore the workforce-related experiences, perceptions and career expectations of early-career medical oncologists in Australia. Methods: A mixed-methods design, including a survey (n = 170) and nested qualitative semistructured interviews (n = 14) with early-career medical oncologists. Recruitment was through the Medical Oncology Group of Australia. Qualitative data were thematically analyzed and for the survey results, logistic regression modeling was conducted. Results: Early-career medical oncologists experienced uncertainty regarding their future employment opportunities. The competitive job market has made them cautious about securing a preferred job leading to a perceived need to improve their qualifications through higher degree training and research activities. The following themes and trends were identified from the qualitative and quantitative analyses: age, career stage and associated early-career uncertainty; locale, professional competition and training preferences; participation in research and evolving professional expectations; and workload and career development opportunities as linked to career uncertainty. Conclusion: Perceived diminished employment opportunities in the medical oncology profession, and shifting expectations to be “more qualified,” have increased uncertainty among junior medical oncologists in terms of their future career prospects. Structural factors relating to adequate funding of medical oncology positions may facilitate or inhibit progressive change in the workforce and its sustainability. Workforce planning and strategies informed by findings from this study will be necessary in ensuring that both the needs of cancer patients and of medical oncologists are met.