Cancer-related cognitive impairment and wellbeing in patients with newly diagnosed aggressive lymphoma compared to population norms and healthy controls: an exploratory study.

PURPOSE: There has been little dedicated research on cancer-related cognitive impairment in patients with aggressive lymphoma. We describe and compare patients' cognitive function with that of healthy controls and patients' wellbeing and distress with general population values. We also explore associations between patients' neuropsychological test performance and self-reported cognitive function and distress. METHODS: Secondary analysis of data from a feasibility study of 30 patients with newly diagnosed aggressive lymphoma and 72 healthy controls. Patients completed neuropsychological tests and self-report measures before and 6-8 weeks after chemotherapy. Healthy controls completed neuropsychological tests and the FACT-Cog at enrolment and 6 months later. Mixed models were used to analyze neuropsychological test and FACT-Cog scores. One-sample t-tests were used to compare patients' self-reported wellbeing and distress with population norms. Associations were explored with Kendall's Tau b. RESULTS: Patients and healthy controls were well matched on socio-demographics. Differences between neuropsychological test scores were mostly large-sized; on average, patients' scores on measures of information processing speed, executive function, and learning and memory were worse both before and after chemotherapy (all p ≤ 0.003). The same pattern was observed for impact of perceived cognitive impairment on quality-of-life (both p < 0.001). Patients' physical and emotional wellbeing scores were lower than population norms both before and after chemotherapy (all p ≤ 0.018). Associations between neuropsychological performance and other measures were mostly trivial (all p > 0.10). CONCLUSION: For many patients with aggressive lymphoma, impaired neuropsychological test performance and impact of perceived impairments on quality-of-life precede chemotherapy and are sustained after chemotherapy. Findings support the need for large-scale longitudinal studies with this population to better understand targets for interventions to address cognitive impairments.

Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists.

BACKGROUND: Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians' views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation. METHODS: A study-specific 17-question survey was emailed (01 February-12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics. RESULTS: Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation. CONCLUSION: PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians' hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.

Multidisciplinary home-based rehabilitation in inoperable lung cancer: a randomised controlled trial.

BACKGROUND: Lung cancer is associated with poor health-related quality of life (HRQoL) and high symptom burden. This trial aimed to assess the efficacy of home-based rehabilitation versus usual care in inoperable lung cancer. METHODS: A parallel-group, assessor-blinded, allocation-concealed, randomised controlled trial. Eligible participants were allocated (1:1) to usual care (UC) plus 8 weeks of aerobic and resistance exercise with behaviour change strategies and symptom support (intervention group (IG)) or UC alone. Assessments occurred at baseline, 9 weeks and 6 months. The primary outcome, change in between-group 6 min walk distance (6MWD), was analysed using intention-to-treat (ITT). Subsequent analyses involved modified ITT (mITT) and included participants with at least one follow-up outcome measure. Secondary outcomes included HRQoL and symptoms. RESULTS: Ninety-two participants were recruited. Characteristics of participants (UC=47, IG=45): mean (SD) age 64 (12) years; men 55%; disease stage n (%) III=35 (38) and IV=48 (52); radical treatment 46%. There were no significant between-group differences for the 6MWD (n=92) at 9 weeks (p=0.308) or 6 months (p=0.979). The mITT analyses of 6MWD between-group differences were again non-significant (mean difference (95% CI): 9 weeks: -25.4 m (-64.0 to 13.3), p=0.198 and 6 months: 41.3 m (-26.7 to 109.4), p=0.232). Significant 6-month differences, favouring the IG, were found for HRQoL (Functional Assessment of Cancer Therapy-Lung: 13.0 (3.9 to 22.1), p=0.005) and symptom severity (MD Anderson Symptom Inventory-Lung Cancer: -2.2 (-3.6 to -0.9), p=0.001). CONCLUSIONS: Home-based rehabilitation did not improve functional exercise capacity but there were improvements in patient-reported exploratory secondary outcomes measures observed at 6 months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12614001268639).

The trajectory of patients who die from metastatic prostate cancer: a population-based study.

OBJECTIVES: To describe health service use, symptom and survival characteristics in metastatic prostate cancer (mPCa) in order to outline usual care practices and identify future opportunities to improve the quality of care in this patient group. PATIENTS AND METHODS: This population cohort study, conducted in Victoria, Australia, used 10 years (2000-2010) of linked hospital discharge, emergency visit, and death registration data, to track patients from their first inpatient admission with mPCa until death. Descriptive statistics on inpatient health service use, symptoms, procedures, survival, and place of death are presented. RESULTS: In all, 4436 patients survived a median (interquartile range [IQR]) of 4 (1, 12) months from their first multiday admission with mPCa. They had a median (IQR) of 3 (1, 9) admissions, 1 (0, 2) emergency department presentation, and 35 (18, 63) days admitted to hospital. Lower urinary tract symptoms were common (50%), and 21% underwent lower urinary tract procedures, whilst 48% had blood product transfusions. In the last month of life, 3685 (83%) had at least one indicator of aggressive end-of-life care, including 48% with more than one acute hospital admission, and 55% staying ≥14 days. Hospital-based palliative care was accessed by 2657 (60%), occurring a median (IQR) of 30 (11, 74) days before death. In all, 23% died in the community, whilst 77% died in hospital, of whom 55% died in an acute hospital bed. CONCLUSION: Half of all decedents first admitted for a multiday stay with mPCa survived <4 months thereafter. They had a marked symptom burden, underwent multiple procedures and had multiple admissions. In all, 40% of patients did not receive any hospital-based palliative care. Several opportunities exist to improve the timely transition to palliative care services with mPCa. These data form a benchmark against which future improvements to palliative care integration may be measured.

Uncertainty and sense-of-self as targets for intervention for cancer-related fatigue.

Cancer-related fatigue (CRF) can be a devastating consequence of cancer and cancer treatments, negatively impacting 50%-90% of cancer patients regardless of age, sex or diagnosis. Limited evidence and research exist to inform effective patient-centred interventions. To target symptom management, there must first be a broader understanding of the symptoms and the lived experience of the persons experiencing CRF and those caring for them, from a supportive as well as a healthcare perspective. This study set out to consider whether components of the language used or descriptors reported by patients, family members, and/or healthcare professionals may provide new insights for potential targets for intervention development. Descriptors from 84 responses (n = 84) from cancer survivors, family members and healthcare professionals were analysed for content. The descriptors reiterate the physical, emotional and functional consequences of CRF, but also reflect two new potential targets for intervention to mitigate the impacts of CRF: uncertainty and sense-of-self.

Socio-demographic and disease related characteristics associated with unplanned emergency department visits by cancer patients: a retrospective cohort study.

BACKGROUND: Emergency department (ED) presentations made by patients having cancer treatment are associated with worth outcomes. This study aimed to explore the socio-demographic and disease related characteristics associated with ED presentation, frequent ED presentations, and place of discharge for cancer patients receiving systemic cancer therapies in the ambulatory setting. METHODS: This was a single site, retrospective observational cohort design. Hospital data for patients treated in the Day Oncology Unit of a large public tertiary hospital in Melbourne, Australia between December 2014 and November 2017 were extracted from clinical databases and retrospectively matched to ED attendance records. Andersen's Behavioral Model of Health Service Utilisation provided the conceptual framework for exploring associations between socio-demographic and disease characteristics and ED use. RESULTS: A total of 2638 individuals were treated in the Day Oncology Unit over the study dates. Of these, 1182 (45%) made an unplanned ED presentation within 28 days of receiving systemic cancer therapy. One hundred and twenty-two (12%) patients attended the ED on two or more occasions within 28 days; while 112 (10%) patients attended the ED four or more times (within 28 days of receiving systemic cancer therapy) within any given 12 month period. Being born outside of Australia was independently related to making an unplanned ED presentation within 28 days of receiving anti-cancer therapy (p < .01) as was being diagnosed with head and neck (p = .03), upper gastrointestinal (p < .001), colorectal (p < .001), lung (p < .001), skin (p < .001) or breast cancer (p = .01). CONCLUSIONS: This study identified a subgroup of cancer patients for whom an ED presentation is more likely. Better understanding of socio-demographic and disease related characteristics associated with the risk of an ED presentation may help inform targeted follow up of patients, to mitigate potentially avoidable ED presentation and optimize outcomes of care.

Development of a hospital-based patient-reported outcome framework for lung cancer patients: a study protocol.

BACKGROUND: Patient-reported outcome (PRO) data is central to the delivery of quality health care. Establishing sustainable, reliable and cost-efficient methods for routine collection and integration of PRO data into health information systems is challenging. This protocol paper describes the design and structure of a study to develop and pilot test a PRO framework to systematically and longitudinally collect PRO data from a cohort of lung cancer patients at a comprehensive cancer centre in Australia. METHODS: Best-practice guidelines for developing registries aimed at collecting PROs informed the development of this PRO framework. Framework components included: achieving consensus on determining the purpose of the framework, the PRO measures to be included, the data collection time points and collection methods (electronic and paper), establishing processes to safeguard the quality of the data collected and to link the PRO framework to an existing hospital-based lung cancer clinical registry. Lung cancer patients will be invited to give feedback on the PRO measures (PROMs) chosen and the data collection time points and methods. Implementation of the framework will be piloted for 12 months. Then a mixed-methods approach used to explore patient and multidisciplinary perspectives on the feasibility of implementing the framework and linking it to the lung cancer clinical registry, its clinical utility, perceptions of data collection burden, and preliminary assessment of resource costs to integrate, implement and sustain the PRO framework. The PRO data set will include: a quality of life questionnaire (EORTC-QLQ-C30) and the EORTC lung cancer specific module (QLQC-LC-13). These will be collected pre-treatment (baseline), 2, 6 and 12 months post-baseline. Also, four social isolation questions (PROMIS) will be collected at baseline. DISCUSSION: Identifying and deciding on the overall purpose, clinical utility of data and which PROs to collect from patients requires careful consideration. Our study will explore how PRO data collection processes that link to a clinical data set can be developed and integrated; how PRO systems that are easy for patients to complete and professionals to use in practice can be achieved, and will provide indicative costs of developing and integrating a longitudinal PRO framework into routine hospital data collection systems. TRIAL REGISTRATION: This study is not a clinical trial and is therefore not registered in any trial registry. However, it has received human research ethics approval (LNR/16/PMCC/45).

Identifying essential information to support patient decision-making regarding participation in cancer clinical trials: A Delphi study.

PURPOSES: This research set out to contribute to ongoing efforts to improve the quality of informed consent information provided to patients by specifically focusing on establishing consensus with regard to essential information to enhance the informed consent process. DESIGN AND METHODS: A Delphi consensus method was used to conduct three rounds of online surveys. Five groups of experts directly or indirectly involved in the informed consent process were invited to participate: patients, family members/friends, physicians, other health professionals and other key informants, including ethicists, contract research staff and pharmaceutical company staff. FINDINGS: Of 156 eligible participants, 101 participants (64.7%) completed all three rounds. In round 1, 994 information items were reported and generated into 74 statements. These were grouped under eight headings essential to the informed consent process. In rounds 2 and 3, the list was reduced to 15 statements representing consensus on essential information to be included in a summarised patient information document to support decision-making regarding trial participation. Risks and discomforts, participation requirements and trial governance were identified as important considerations. CONCLUSIONS: The 15 essential statements identified in this study could be used as components of a summarised information sheet given to potential cancer clinical trial participants, as an adjunct to the informed consent process. A robust evaluation of the impact of these statements on the quality of the informed consent process is needed.

Benefits of home-based multidisciplinary exercise and supportive care in inoperable non-small cell lung cancer - protocol for a phase II randomised controlled trial.

BACKGROUND: Lung cancer is one of the most commonly diagnosed cancers, and is a leading cause of cancer mortality world-wide. Due to lack of early specific symptoms, the majority of patients present with advanced, inoperable disease and five-year relative survival across all stages of non-small cell lung cancer (NSCLC) is 14%. People with lung cancer also report higher levels of symptom distress than those with other forms of cancer. Several benefits for survival and patient reported outcomes are reported from physical activity and exercise in other tumour groups. We report the protocol for a study investigating the benefits of exercise, behaviour change and symptom self-management for patients with recently diagnosed, inoperable, NSCLC. METHODS: This multi-site, parallel-group, assessor-blinded randomised controlled trial, powered for superiority, aims to assess functional and patient-reported outcomes of a multi-disciplinary, home-based exercise and supportive care program for people commencing treatment. Ninety-two participants are being recruited from three tertiary-care hospitals in Melbourne, Australia. Following baseline testing, participants are randomised using concealed allocation, to receive either: a) 8 weeks of home-based exercise (comprising an individualised endurance and resistance exercise program and behaviour change coaching) and nurse-delivered symptom self-management intervention or b) usual care. The primary outcome is the between-group difference in the change in functional exercise capacity (six-minute walk distance) from baseline to post-program assessment. Secondary outcomes include: objective and self-reported physical activity levels, physical activity self-efficacy, behavioural regulation of motivation to exercise and resilience, muscle strength (quadriceps and grip), health-related quality of life, anxiety and depression and symptom interference. DISCUSSION: There is a lack of evidence regarding the benefit of exercise intervention for people with NSCLC, particularly in those with inoperable disease receiving treatment. This trial will contribute to evidence currently being generated in national and international trials by implementing and evaluating a home-based program including three components not yet combined in previous research, for people with inoperable NSCLC receiving active treatment and involving longer-term follow-up of outcomes. This trial is ongoing and currently recruiting. TRIAL REGISTRATION: This trial was prospectively registered on the Australian New Zealand Clinical Trials Registry ( ACTRN12614001268639 : (4/12/14).

The Women's wellness after cancer program: a multisite, single-blinded, randomised controlled trial protocol.

BACKGROUND: Despite advances in cancer diagnosis and treatment have significantly improved survival rates, patients post-treatment-related health needs are often not adequately addressed by current health services. The aim of the Women's Wellness after Cancer Program (WWACP), which is a digitised multimodal lifestyle intervention, is to enhance health-related quality of life in women previously treated for blood, breast and gynaecological cancers. METHODS: A single-blinded, multi-centre randomized controlled trial recruited a total of 351 women within 24 months of completion of chemotherapy (primary or adjuvant) and/or radiotherapy. Women were randomly assigned to either usual care or intervention using computer-generated permuted-block randomisation. The intervention comprises an evidence-based interactive iBook and journal, web interface, and virtual health consultations by an experienced cancer nurse trained in the delivery of the WWACP. The 12 week intervention focuses on evidence-based health education and health promotion after a cancer diagnosis. Components are drawn from the American Cancer Research Institute and the World Cancer Research Fund Guidelines (2010), incorporating promotion of physical activity, good diet, smoking cessation, reduction of alcohol intake, plus strategies for sleep and stress management. The program is based on Bandura's social cognitive theoretical framework. The primary outcome is health-related quality of life, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Secondary outcomes are menopausal symptoms as assessed by Greene Climacteric Scale; physical activity elicited with the Physical Activity Questionnaire Short Form (IPAQ-SF); sleep measured by the Pittsburgh Sleep Quality Index; habitual dietary intake monitored with the Food Frequency Questionnaire (FFQ); alcohol intake and tobacco use measured by the Australian Health Survey and anthropometric measures including height, weight and waist-to-hip ratio. All participants were assessed with these measures at baseline (at the start of the intervention), 12 weeks (at completion of the intervention), and 24 weeks (to determine the level of sustained behaviour change). Further, a simultaneous cost-effectiveness evaluation will consider if the WWACP provides value for money and will be reported separately. DISCUSSION: Women treated for blood, breast and gynaecological cancers demonstrate increasingly good survival rates. However, they experience residual health problems that are potentially modifiable through behavioural lifestyle interventions such as the WWACP. TRIAL REGISTRATION: The protocol for this study was registered with the Australian and New Zealand Clinical Trials Registry, Trial ID: ACTRN12614000800628 , July 28, 2014.