Lung Cancer (internet-based) Delphi (LuCiD): Setting the standard for lung cancer care in Australia and New Zealand - a modified eDelphi consensus to determine clinical quality indicators for lung cancer

Protocol Version 1.1 16 August 202

Integrated care for resected early stage lung cancer: innovations and exploring patient needs

There is no consensus as to the duration and nature of follow-up following surgical resection with curative intent of lung cancer. The integration of cancer follow-up into primary care is likely to be a key future area for quality and cost-effective cancer care. Evidence from other solid cancer types demonstrates that such follow-up has no adverse outcomes, similar health-related quality of life, high patient satisfaction rates at a lower cost to the healthcare system. Core elements for successful models of shared cancer care are required: clear roles and responsibilities, timely effective communication, guidance on follow-up protocols and common treatments and rapid routes to (re)access specialist care. There is thus a need for improved communication between hospital specialists and primary care. Unmet needs for patients with early stage lung cancer are likely to include psychological symptoms and carer stress; the importance of smoking cessation may frequently be overlooked or underappreciated in the current hospital-based follow-up system. There is therefore a need for quality randomised controlled trials of patients with resected early stage lung cancer to establish optimal protocols for primary care-based follow-up and to more adequately address patients' and carers' unmet psychosocial needs, including the crucial role of smoking cessation

Weekend admission and mortality from acute exacerbations of chronic obstructive pulmonary disease in winter

Historically, acute medical staffing numbers have been lower on weekends and in winter numbers of medical admissions rise. An analysis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) admissions to Portsmouth Hospitals over a seven-year period was undertaken to examine the effects of admission on a weekend, of winter, and with the opening of a medical admissions unit (MAU). In total, 9,915 admissions with AECOPD were identified. Weekend admissions accounted for 2,071 (20.9%) of cases, winter accounted for 3,026 (30.5%) admissions, and 522 (34.4%) deaths. Adjusted odds ratio (OR) for death on day 1 after winter weekend admission was 2.89 (95% confidence interval (CI) 1.035 to 8.076). After opening the MAU, the OR for death day 1 after weekend winter admission fell from 3.63 (95% CI 1.15 to 11.5) to 1.65 (95% CI 0.14 to 19.01). AECOPD patients have an increased risk of death after admission over a weekend in winter and this effect was reduced by opening a MAU. These findings have implications for the planning of acute care provision in different seasons. © Royal College of Physicians, 2011. All rights reserved

Advance care planning uptake among patients with severe lung disease: A randomised patient preference trial of a nurse-led, facilitated advance care planning intervention

Objective Advance care planning (ACP) clarifies goals for future care if a patient becomes unable to communicate their own preferences. However, ACP uptake is low, with discussions often occurring late. This study assessed whether a systematic nurse-led ACP intervention increases ACP in patients with advanced respiratory disease. Design A multicentre open-label randomised controlled trial with preference arm. Setting Metropolitan teaching hospital and a rural healthcare network. Participants 149 participants with respiratory malignancy, chronic obstructive pulmonary disease or interstitial lung disease. Intervention Nurse facilitators offered facilitated ACP discussions, prompted further discussions with doctors and loved ones, and assisted participants to appoint a substitute medical decision-maker (SDM) and complete an advance directive (AD). Outcome measures The primary measure was formal (AD or SDM) or informal (discussion with doctor) ACP uptake assessed by self-report (6 months) and medical notes audit. Secondary measures were the factors predicting baseline readiness to undertake ACP, and factors predicting postintervention ACP uptake in the intervention arm. Results At 6 months, formal ACP uptake was significantly higher (p<0.001) in the intervention arm (54/106, 51%), compared with usual care (6/43, 14%). ACP discussions with doctors were also significantly higher (p<0.005) in the intervention arm (76/106, 72%) compared with usual care (20/43, 47%). Those with a strong preference for the intervention were more likely to complete formal ACP documents than those randomly allocated. Increased symptom burden and preference for the intervention predicted later ACP uptake. Social support was positively associated with ACP discussion with loved ones, but negatively associated with discussion with doctors. Conclusions Nurse-led facilitated ACP is acceptable to patients with advanced respiratory disease and effective in increasing ACP discussions and completion of formal documents. Awareness of symptom burden, readiness to engage in ACP and relevant psychosocial factors may facilitate effective tailoring of ACP interventions and achieve greater uptake. Trial registration number ACTRN12614000255684. © Published by the BMJ Publishing Group Limite

Symptom burden and unmet needs in MPM:exploratory analyses from the RESPECT-Meso study

© The Author(s) 2020. Objective: Malignant Pleural Mesothelioma (MPM) has a poor prognosis and high symptom burden. RESPECT-Meso was a multicenter randomized study examining the role of early specialist palliative care (SPC) on quality of life (QoL) with MPM. This is a post-hoc exploratory analysis of the symptom burden and unmet needs identified from RESPECT-Meso participants. Methods: Exploratory analysis from 174 participants using the General Health Status (GHS) measure (from the EORTC QLQ-C30 QoL questionnaire) and 87 participants using validated assessment questionnaires in those randomized to SPC. Eligibility for the study included confirmed MPM with diagnosis \u3c 6 weeks prior, performance score (PS) 0 or 1, no significant physical or psychological comorbidity. Cox proportional hazards models were derived to examine for relationships with survival. Free text was assessed using content analysis, looking for common themes and words. Results: Participants were predominantly male (79.9%), mean age 72.8 years, PS was 0 in 38%, 78% of MPM was epithelioid. At least 3 symptoms were reported in 69.8% of participants, including fatigue (81%), dyspnea (73.3%), pain (61.2%), weight loss (59.3%). Anxiety was reported by 54.7% of participants, 52.3% low mood and 48.8% anhedonia symptoms. After multivariable adjustment, only pain remained statistically significant with a hazard ratio (HR) 2.9 (95% CI 1.3-6.7; p = 0.01). For each 1 unit increase in GHS score, the HR for death was 0.987 (0.978-0.996; p = 0.006), indicating a worse reported QoL is related to shorter survival. Unmet needs were common: 25.9% wanted more information about their condition, 24.7% about their care and 21.2% about their treatment. 79.1% were concerned about the effect of their illness on family. Conclusion: There is a high symptom burden in mesothelioma despite good baseline performance status. A worse QoL is associated with a worse survival. Unmet needs are common, perhaps highlighting a need for improved communication and information sharing

Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): Rationale and protocol

Introduction Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. Methods and analysis A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival \u3e 3 months and cachexia (defined as \u3e 5% weight loss in 6 months or body mass index \u3c 20 kg/m 2 with weight loss \u3e2%). Ethics and dissemination Ethical approval has been granted. Results will be reported in peer-reviewed publications. Trial registration number Australian New Zealand Clinical Trials Registry (U1111-1240-6828). © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): Study protocol for a randomised controlled trial

Background: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. Methods: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Discussion: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Trial registration: Current controlled trials ISRCTN18955704.Date ISRCTN assigned: 31 January 2014

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma

Background: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. Methods: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. Results: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4–77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5–19.2) vs histology 11.1 (4.8–19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. Conclusions: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing

Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia

Asbestos exposure is associated with many adverse health conditions including malignant mesothelioma and lung cancer as well as production of autoantibodies. Autoantibodies may serve as biomarkers for asbestos exposure in patients with cancer, and autoimmune dysfunction has been linked to increased rates of various cancers. The aim of this study was to examine the hypothesis that autoantibodies are more frequent in asbestos-exposed individuals with either lung cancer or mesothelioma than those without these conditions. Asbestos-exposed individuals from Western Australia who had lung cancer (n = 24), malignant mesothelioma (n = 24), or no malignancy (n = 51) were tested for antinuclear autoantibodies (ANA) using indirect immunofluorescence and specific extractable nuclear autoantibodies (ENA) employing a multiplexed addressable laser bead immunoassay. Contrary to the hypothesis, data demonstrated that individuals without malignancy were more likely to be positive for ANA compared to those with cancer. However, autoantibodies to histone and Ro-60 were found to be associated with lung cancer. These results support a possible predictive value for specific autoantibodies in the early detection of lung cancer and/or in our understanding of the role of autoimmune processes in cancer. However, further studies are needed to identify specific target antigens for the antibodies

Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6