Search

Background: Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. Aims: To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. Design: A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). Setting/Participants: People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. Results: 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. Conclusion: The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.

Background: Paracentesis is commonly undertaken in patients with cancer-related ascites. Aim: To systematically investigate the symptomatic benefits and harms experienced by patients with cancer undergoing paracentesis using real-world data in the palliative care setting. Design: Prospective, multisite, observational, consecutive cohort study. Benefits and harms of paracentesis were assessed between 01/07/2018 and 31/02/2021 as part of routine clinical assessments by treating clinicians at four timepoints: (T0) before paracentesis; (T1) once drainage ceased; (T2) 24 h after T1 and (T3) 28 days after T1 or next paracentesis, if sooner. Setting/participants: Data were collected from 11 participating sites across five countries (Australia, England, Hong Kong, Malaysia and New Zealand) on 111 patients undergoing paracentesis via a temporary (73%) or indwelling (21%) catheter: 51% male, median age 69 years, Australia-modified Karnofsky Performance Score 50. Results: At T1 ( n = 100), symptoms had improved for most patients (81%), specifically abdominal distension (61%), abdominal pain (49%) and nausea (27%), with two-thirds experiencing improvement in ⩾2 symptoms. In the remaining patients, symptoms were unchanged (7%) or worse (12%). At least one harm occurred in 32% of patients, the most common being an ascitic leak ( n = 14). By T3, 89% of patients had experienced some benefit and 36% some harm, including four patients who experienced serious harm, one of which was a fatal bowel perforation. Conclusion: Most patients obtained rapid benefits from paracentesis. Harms were less frequent and generally mild, but occasionally serious and fatal. Our findings help inform clinician-patient discussions about the potential outcomes of paracentesis in this frail population.

Background Palliative care is recommended to help meet the needs of patients with progressive non-cancer conditions, such as long-term neurological conditions. However, few trials have tested palliative care in this population. Objectives To determine the effectiveness and cost-effectiveness of short-term integrated palliative care in improving symptoms, improving patient- and caregiver-reported outcomes and reducing hospital use for people severely affected by long-term neurological conditions. Design Pragmatic, randomised controlled, multicentre, fast-track trial, with an embedded qualitative component and surveys. Setting Seven UK centres (South London, Nottingham, Liverpool, Cardiff, Brighton, Ashford and Sheffield) with multiprofessional palliative care teams and neurology services. Participants People living with multiple sclerosis, idiopathic Parkinson’s disease, motor neurone disease, multiple system atrophy or progressive supranuclear palsy, with unresolved symptoms and/or complex psychosocial needs. The qualitative study involved patients, caregivers and health-care staff. Interventions Participants were randomised to receive short-term integrated palliative care, delivered by multiprofessional teams, immediately or after a 12-week wait (standard care group). Main outcome measures The primary outcome was a combined score of eight symptoms measured by the Integrated Palliative care Outcome Scale for Neurological conditions 8 symptom subscale (IPOS Neuro-S8) at 12 weeks. Secondary outcomes included patients’ other physical and psychological symptoms, quality of life (EuroQol-5 Dimensions, five-level version), care satisfaction, caregiver burden, service use and cost, and harms. Data were analysed using multiple imputation, generalised linear mixed models, incremental cost-effectiveness ratios (threshold was the National Institute for Health and Care Excellence £20,000 per quality-adjusted life-year) and cost-effectiveness planes. Qualitative data were analysed thematically. Results We recruited 350 patients and 229 caregivers. There were no significant between-group differences for primary or secondary outcomes. Patients receiving short-term integrated palliative care had a significant improvement, from baseline to 12 weeks, on the primary outcome IPOS Neuro-S8 (–0.78, 95% confidence interval –1.29 to –0.26) and the secondary outcome of 24 physical symptoms (–1.95, 99.55% confidence interval –3.60 to –0.30). This was not seen in the control group, in which conversely, care satisfaction significantly reduced from baseline to 12 weeks (–2.89, 99.55% confidence interval –5.19 to –0.59). Incremental cost-effectiveness ratios were smaller than the set threshold (EuroQol-5 Dimensions index score –£23,545; IPOS Neuro-S8 –£1519), indicating that the intervention provided cost savings plus better outcomes. Deaths, survival and hospitalisations were similar between the two groups. Qualitative data suggested that the impact of the intervention encompassed three themes: (1) adapting to losses and building resilience, (2) attending to function, deficits and maintaining stability, and (3) enabling caregivers to care. Conclusions Our results indicate that short-term integrated palliative care provides improvements in patient-reported physical symptoms at a lower cost and without harmful effects when compared with standard care. Limitations Outcome measures may not have been sensitive enough to capture the multidimensional changes from the intervention. Our surveys found that the control/standard and intervention services were heterogeneous. Future work Refining short-term integrated palliative care and similar approaches for long-term neurological conditions, focusing on better integration of existing services, criteria for referral and research to improve symptom management. Trial registration Current Controlled Trials ISRCTN18337380. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 36. See the NIHR Journals Library website for further project information.

Objectives Healthcare systems increasingly recognise the importance of service users’ perspectives for improving care organisation and delivery. The English Cancer Patient Experience Survey (CPES) is carried out annually, however, its representativeness within cancer types is unknown. We have explored if the CPES results are representative of people with lung cancer. Materials and methods We linked cancer registry data across multiple sources to assess how CPES represents sociodemographic and clinical characteristics of the National Lung Cancer Audit population, accounting for post-sampling mortality bias. Multivariable logistic regression was used to compare people included and not included in CPES. Results Of 240,375 people diagnosed (2009–2015), 15,967 (7 %) were included in CPES. Gender and ethnicity were reasonably represented, as were sociodemographic and clinical groupings, although more received anti-cancer treatment (96 % of CPES respondents vs. 56 % of patients nationally; adjusted odds ratio = 10.3, 95 % confidence interval 9.4–11.2 for any anti-cancer treatment) with chemotherapy most over-represented, followed by surgery and then radiotherapy. CPES under-represented older, more socioeconomically deprived, and certain clinical groups, including those with worse performance status, multiple comorbidities, and diagnosis via emergency presentation. Conclusion CPES includes patients across the sociodemographic and clinical spectrum indicating its value for research and service planning. Unbalanced representation of incident lung cancer cases is a limitation that must be considered in context of using CPES findings to implement service changes. Although half the national lung cancer population who received no anti-cancer treatment do not have their experiences represented, the strength of this dataset is in providing detailed comparisons of patient experiences across different treatment groups.

Objective: Many U.S. emergency departments (EDs) lack access to stroke neurologists to support decision-making for thrombolytics and identification of thrombectomy-eligible patients. We outline a strategy to identify hospitals where telestroke might improve access and estimate potential gains in both the number of patients receiving reperfusion treatment and lives saved. Methods: We identified all EDs that provided ischemic stroke care for a Medicare beneficiary during 2018. We then excluded those with clear stroke expertise or with another ED with stroke expertise within 20 miles. At these EDs, we used annual ischemic stroke volumes and previously-derived risk ratios to quantify estimated marginal benefits (additional patients receiving reperfusion and additional lives saved) with the introduction of telestroke. Results: Among 4657 US EDs that provided stroke care in 2018, 1057 had limited stroke capabilities in their ED or within 20 miles. Of these 1057 EDs, 83.1% were in rural communities, and they cared for a median of 6 ischemic stroke patients per year. We estimate telestroke introduction to all 1057 would lead to 164 (95% CI 93-247) additional patients receiving reperfusion treatment and 90 (95% CI 2-180) additional lives saved annually (Figure). If only 263 EDs in the the top quartile of marginal benefit were targeted, this would capture over half of the estimated benefits. Conclusions: We estimate that approximately a quarter of U.S. EDs, primarily small rural EDs, would benefit most from new telestroke capacity. Our strategy may be used to improve stroke systems of care and maximize specialist access for the U.S. population.

ObjectivesTo describe the current, real-world use of non-steroidal anti-inflammatory drugs for pain and the associated benefits and harms.MethodsA prospective, multicentre, consecutive cohort pharmacovigilance study conducted at 14 sites across Australia, Aotearoa/New Zealand and the UK including hospital, hospice inpatient and outpatient services. Pain scores and harms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 2 days and 14 days. Ad-hoc safety reporting continued until day 28.ResultsData were collected from 92 patients between March 2018 and October 2021. Most patients had cancer (91%) and were coprescribed opioids (90%). At 14 days, 83% of patients had benefit from non-steroidal anti-inflammatory drugs and 22% had harm. The most common harms were nausea (8%), vomiting (3%), acute kidney injury (3%) and non-gastrointestinal bleeding (3%); only 2% were severe and no patients ceased their non-steroidal anti-inflammatory drugs due to toxicity. Overall, 65% had benefit without harm and 3% had harm without benefit.ConclusionsMost patients benefited from non-steroidal anti-inflammatory drugs with only one in five patients experiencing tolerable harm. This suggests that short-term use of non-steroidal anti-inflammatory drugs in patients receiving palliative care is safer than previously thought and may be underused.

Introduction: More than 2,700 people are diagnosed with mesothelioma each year in the UK. We assessed whether the English Cancer Patient Experience Survey (CPES) respondents with mesothelioma were representative of all people diagnosed with mesothelioma in England in terms of their sociodemographic, clinical and healthcare characteristics. Method: We used national cancer registry data with individual patient record linkages to multiple sources (CPES, mortality, hospital and socioeconomic data). We included all people with a diagnosis of mesothelioma in the registry from 2009-2015 and identified the proportion of CPES respondents. Results: We identified 15,587 people diagnosed with mesothelioma, of which 1,597 (10.3%) were included in CPES. Those in CPES had similar survival to those not included. The adjusted odds of being included in CPES decreased with older age, stage at diagnosis, worsening performance status and increasing comorbidities, but was not associated with gender or socioeconomic deprivation. People with recorded non-white ethnicity were also less likely to be included in CPES. People were more likely to be included in CPES if a lung cancer nurse was present at diagnosis (odds ratio 1.22, 95% confidence interval 1.03-1.45) and were much more likely to have received anti-cancer treatment. Conclusions: CPES provides information across treatement groups, however, policy makers and healthcare providers should be aware of the under-representation of some people with mesothelioma, particularly the half who do not received treatment; feedback on their care should be sought in patient experience surveys.

ObjectivesTo describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms.MethodsThis was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks.ResultsData were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms.ConclusionsWhen used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.palliativedrugs.com. The series editors welcome feedback on the articles.

Background: A holistic needs assessment is recommended in people with cancer at key stages, including soon after diagnosis. For people with thoracic cancer, there is a lack of data obtaine...

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.medicinescomplete.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

The use of immune checkpoint inhibitors (ICIs) is growing rapidly in oncology and palliative care clinicians and other generalists will increasingly see patients who are receiving, or who have received ICI. For optimal care, it is important that clinicians have a basic understanding of the unique nature of ICI as anticancer treatments, including patterns of response, potential issues with concurrent corticosteroid use and the wide range of possible immune-related adverse effects (IrAEs). This paper, informed by a recent literature search, provides a succinct yet comprehensive overview of ICI, with a particular focus on IrAE, highlighting that some are potentially life-threatening and/or can develop a long time, sometimes years, after even a short course of an ICI.

Importance Palliative care has shown benefits in reducing symptom intensity and quality of life in patients with advanced cancer. However, high-quality evidence to support palliative care policy and service developments for patients with long-term neurological conditions (LTNCs) is lacking. Objective To determine the effectiveness of a short-term integrated palliative care (SIPC) intervention for people with LTNCs. Design, Setting, and Participants Multicenter, phase 3, randomized clinical trial conducted from April 1, 2015, to November 30, 2017, with a last follow-up date of May 31, 2018, in 7 UK hospitals with both neurology and palliative care services. A total of 535 patients with LTNC were assessed for eligibility and 350 were randomized. Inclusion criteria were patients 18 years or older with any advanced stage of multiple sclerosis, motor neuron disease, idiopathic Parkinson disease multiple system atrophy, or progressive supranuclear palsy. Data were analyzed from November 2018 to March 2019. Interventions Patients were randomized 1:1 using minimization method to receive SIPC (intervention, n = 176) or standard care (control, n = 174). Main Outcomes and Measures Primary outcome was change in 8 key palliative care symptoms from baseline to 12-weeks, measured by the Integrated Palliative care Outcome Scale for neurological conditions. Secondary outcomes included change in the burden of other symptoms, health-related quality of life, caregiver burden, and costs. Data were collected and analyzed blindly by intention to treat. Results A total of 350 patients (mean [SD] age 67 [12] years; years since diagnosis, 12 [range, 0-56]; 51% men; 49% requiring considerable assistance) with an advanced stage of LTNC were recruited, along with informal caregivers (n = 229). There were no between-group differences in primary outcome (effect size, −0.16; 95% CI, −0.37 to 0.05), any other patient-reported outcomes, adverse events, or survival. Although there was more symptom reduction in the SIPC group in relation to mean change in primary outcome, the difference between the groups was not statistically significant (−0.78; 95% CI, −1.29 to −0.26 vs −0.28; 95% CI, −0.82 to 0.26;P = .14). There was a decrease in mean health and social care costs from baseline to 12 weeks −$1367 (95% CI, −$2450 to −$282) in the SIPC group and −653 (95% CI, −$1839 to −$532) in the control group, but this difference was not statistically significant (P = .12). SIPC was perceived by patients and caregivers as building resilience, attending to function and deficits, and enabling caregivers. Conclusions and Relevance In this study, SIPC was not statistically significantly different from standard care for the patient-reported outcomes. However, SIPC was associated with lower cost, and in qualitative analysis was well-received by patients and caregivers, and there were no safety concerns. Further research is warranted. Trial Registration isrctn.org Identifier:ISRCTN18337380

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using &chi, 2 test for linear-by-linear association, or &chi, 2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p &lt, 0.001), low skeletal muscle density (p &lt, 0.05), and timed up and go test failure (p &lt, 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p &lt, 0.05) and hand grip strength test failure (p &lt, 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p &lt, 0.05), low visceral obesity (p &lt, 0.01), and low skeletal muscle density (p &lt, 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer.

Globally, the number of people affected by coronavirus disease 2019 (COVID-19) is rapidly increasing. In most (>80%), the illness is relatively mild and can be self-managed out of hospital. However, in about 20% the illness causes respiratory compromise severe enough to require hospital admission [1]. Patients with severe and critical disease need full active treatment. This may include oxygen for hypoxaemia and ventilatory support, along with optimal management of complications, e.g. super-imposed bacterial infection, and any underlying co-morbidities, e.g. chronic obstructive pulmonary disease, congestive heart failure. To date, no antiviral agent has shown to be effective in treating the disease [2]. Thank you to all the patients and members of the public at the European Lung Foundation and Cicely Saunders Institute as well as Howard Almond (Action for Pulmonary Fibrosis) and Sarah Dix for their valuable contributions to drafting of the information leaflets.

Background: Breathlessness management appears to differ between clinical specialties, but data are limited. Aims and Objectives: To explore breathlessness management by respiratory medicine (RM) and palliative care (PC) doctors, and the influence of guidelines. Methods: European RM and PC doctors were invited to complete an online survey that included 3 case vignettes: advanced COPD; fibrotic ILD; lung cancer (LC). Respondents indicated preferred management on Likert scales. We compared RM and PC responses, and if management varied with knowledge of guidelines. Results: 348 RM and 102 PC provided complete responses. PC doctors prioritised drug treatment regardless of diagnosis, but RM doctors prioritised drug treatment for breathlessness in LC, preferring physical activity and rehabilitation in other settings. Thus, more PC than RM doctors often or always use opioids in COPD (92% vs. 39%), ILD (83% vs. 36%) and LC (95% vs. 76%) (p Conclusions: Breathlessness management varies between specialties, and is influenced by knowledge of guidelines. There is a need for international interdisciplinary practice guidelines for the management of breathlessness in advanced respiratory disease. Funding: EU Horizon2020 grant #825319

OBJECTIVE: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables.METHODS: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance, and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used.RESULTS: Data from 675 patients with stage III/IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age (β = 0.05; CI[0.023; 0.074]), and patients from Italy (β = 1.57 CI[0.760; 2.388]) and Denmark (β = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries.CONCLUSIONS: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.

ObjectivesFacilitated advance care planning (ACP) helps family carers’ to be aware of patient preferences. It can improve family carers’ involvement in decision making and their overall experiences at the end of life, as well as, reduce psychological stress. We investigated the effects of the ACTION Respecting Choices (RC) ACP intervention on the family carers’ involvement in decision making in the last 3 months of the patients’ life and on the family carers’ psychological distress after 3 months of bereavement.MethodsOver six European countries, a sample of 162 bereaved family carers returned a bereavement questionnaire. Involvement in decision making was measured with a single item of the Views of Informal Carers–Evaluation of Services Short Form questionnaire. Psychological distress was measured with the Impact of Event Scale (IES).ResultsNo significant effect was found on family carers involvement in decision making in the last 3 months of the patients’ life (95% CI 0.449 to 4.097). However, the probability of involvement in decision making was slightly higher in the intervention arm of the study (89.6% vs 86.7%; OR=1.357). Overall, no statistical difference was found between intervention and control group regarding the IES (M=34.1 (1.7) vs 31.8 (1.5); (95% CI −2.2 to 6.8)).ConclusionThe ACTION RC ACP intervention showed no significant effect on family carers’ involvement in decision making or on subsequent psychological distress. More research is needed about (1) how family carers can be actively involved in ACP-conversations and (2) how to prepare family carers on their role in decision making.Trial registration numberInternational Standard Randomised Controlled Trial Number ISRCTN17231.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

Background Previous studies showed that family carers (FCs) who engaged in formal ACP had fewer adverse outcomes in wellbeing compared with FCs who did not. The ACTION trial is the first multicentre randomized controlled trial of ACP in six European countries. This study will report on the effect of ACP on the wellbeing of bereaved FCs. Methods 451 questionnaires were sent to bereaved FCs 3 months after the patient participating in the trial had died; 163 were returned (response rate: 36.1%; N control= 93, N intervention= 70). Wellbeing was measured with the Hospital Anxiety and Depression Scale (HADS) and Impact Event Scale (IES). Results No significant differences were found in wellbeing of FCs between groups. The mean scores for the HADS show no significant differences between groups for anxiety (mean score control 7,09 vs. mean score intervention 8,29) and depression (mean score control 6,72 vs. mean score intervention 7,17). No significant differences are found between groups in the mean scores for the IES. Intrusion had a mean score of 21,27 for control vs. 21,38 for intervention; Avoidance had a mean score of 10,34 for control vs. 12,72 for intervention. Conclusion Despite previous evidence about improved outcomes for wellbeing in FCs in ACP programs, our ACP intervention did not show differences between groups. Possibly the non-response or cultural discrepancies between the different countries have a part in this. More research is needed to explain what mechanisms are present. This study is supported by a grant from the FWO (nr. G034717N).

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

ObjectivesInternational guidelines recommend that rehabilitation be offered to people with thoracic cancer to improve symptoms, function and quality of life. When rehabilitation interventions require a change in behaviour, the use of theory and behaviour change techniques (BCTs) enhance participation. Our objective was to systematically identify BCTs and examine their use in relation to the Capability, Opportunity, Motivation-Behaviour model and known enablers and barriers to engagement in this population.MethodBibliographic databases and grey literature were searched for controlled trials of rehabilitation interventions for adults with lung cancer or mesothelioma, with no limits on language or date. Data on the application of behavioural change theory and BCTs were extracted, categorized using the BCT Taxonomy (v1) and described according to the ‘Capability, Opportunity, Motivation-Behaviour’ model.ResultsTwenty-seven studies of exercise (n=15) and symptom self-management (n=12) interventions were identified. Four studies reported use of behavioural change theory, one study used symptom theory. Across studies, a mean (range) of 7 (1-18) BCTs were used, representing 26 of 93 possible BCTs included in the taxonomy. Most frequent enabling BCTs were ‘instructions on how to perform behaviours’ (74%), ‘behavioural practice’ (74%) and ‘action planning’ (70%). BCTs to address barriers were less frequent and included ‘information about health consequences’ (22%), and ‘verbal persuasion about capability’ (7%) to change perceptions about benefits, burden and harms.ConclusionThe application of behavioural change tools appears sub-optimal in this group of patients. Explicit use of BCTs targeting behavioural components upon which outcomes depend may improve the uptake and effectiveness of rehabilitation interventions.

Background A body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression. Methods An international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0–4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade. Results One thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in −2 log likelihood (P < 0.001) and persisted after adjustment for age, sex, and cancer type and stage (P < 0.001). Median survival decreased across the weight loss grades ranging from 407 days (95% CI 312–502)—weight loss grade 0 to 119 days (95% CI 93–145)—weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%). Conclusions The WLGS is related to survival, cachexia domains, and the likelihood of progression. Adding certain cachexia domains to the WLGS improves prognostic accuracy.

Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing.Patients with lung cancer offered platinum-based chemotherapy over 1 year were identified and, if eligible, invited to take part in a prospective feasibility study. Questionnaires examined acceptability of the DEXA scan and of a future study that randomized between traditional dosing and one adjusted according to body composition. Dose-limiting toxicity (DLT) and a lack of neutropenia explored potential over- and under-dosing, respectively.Of the 173 patients offered chemotherapy, 123 (71%) were ineligible, mostly because of failing entry criteria (84, 49%). Of the 50 approached, 18 (36%) participated, most receiving carboplatin, with 17 providing data. All found a DEXA scan acceptable; other assessments were fully completed, except nadir and pre-chemotherapy blood counts. Most (94%) were prepared to take part in a future study, although the additional hospital visits for a nadir blood count were unpopular with some. Five (29%) patients experienced six episodes of DLT which resulted in discontinuation (3), dose reduction (2) or change to a less toxic regimen (1). Nine (60%) patients experienced either no (2) or inconsistent (7) neutropenia.A randomized trial appears acceptable and feasible in patients receiving carboplatin. Adjustment of our entry criteria and avoiding a hospital visit for a nadir blood count should aid recruitment.

Background: Breathlessness is common in patients with thoracic cancer but difficult to manage. The Incremental Shuttle Walking Test (ISWT) can help assess new treatments, but its repeatability has not been described in this group. Aim: To examine within and between day repeatability of the ISWT in this setting. Methods: Patients with incurable thoracic cancer were recruited from outpatient clinics at a University Hospital. Two ISWTs were completed one hour apart on two consecutive days, with the first test for familiarization purposes only. Repeatability of distance walked was examined using Bland and Altman plots and assessed as the single determination (within subject) standard deviation of the difference between tests and its 95% range. Results: Forty-one patients participated and completed all tests. Mean (SD) distance walked was 333 (134), 349 (129) and 353 (130) m over the three tests, with the mean difference significantly different from zero between days (16 m, 95% CI 8–24 m, P = 0.043) but not within days (5 m, 95% CI –2 to 12 m, P = 0.47). Within and between day single determination SD and 95% ranges were 30 (−31 to 91) m and 36 (−37 to 109) m respectively. Conclusions: These data help inform the design of studies making use of the ISWT and the interpretation of their findings.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.palliativedrugs.com. The series editors welcome feedback on the articles.

Limited drug treatments exist to relieve severe breathlessness in advanced disease. Antidepressants warrant consideration due to potential effects. However, trials are challenging. We aim to test the feasibility of a larger randomised mirtazapine trial, focusing on best settings and methods for recruitment. The BETter TreatmEnts for Refractory Breathlessness (BETTER-B feasibility) trial was a randomised, double-blind, placebo-controlled mixed-methods feasibility trial in London, Nottingham, Hull/York in adults with advanced diseases and modified Medical Research Council breathlessness scale (mMRC) scores of 3/4. We screened 409 patients, randomising 64 participants (30 mirtazapine, 34 placebo), averaging 1.8 patients per centre pcm. Existing antidepressant use was the main reason for ineligibility. 63% needed help completing questionnaires. Missing data were low. Participants (47 men) had a mean age of 72 (range 51–90) years. Primary diagnoses: chronic obstructive pulmonary disease (COPD) (40, 67%), interstitial lung disease (ILD) (19, 32%), cancer (1), heart failure (4). Several had multimorbidity. A 6.4:1 (16%) screen to recruit conversion suggests recruiting people with stage 3/4 mMRC breathlessness is possible. We consider screen to recruit ratios for different settings and diagnoses. Cancer patients were difficult to recruit. Achieving recruitment requires dedicated research teams. Six participants per arm stopped treatment prematurely; 4 mirtazapine, 5 placebo experienced serious adverse events (SAE); 1 (placebo) suspected as medication related. One participant per arm died, both unrelated to intervention. Qualitative data suggests feasibility and acceptability. A randomised double-blind phase III trial of mirtazapine is feasible and acceptable in patients with COPD/ILD, with low toxicity, and is warranted.

Background The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. Materials and Methods A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician-predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C-reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. Results Data were available on 478 patients, and the median survival was 4.27 (1.86–7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG-PS, mGPS, WCC, NC (all p < .001), dyspnea, global health (both p ≤ .001), cognitive impairment, anorexia, LDH (all p < .01), and weight loss (p < .05). On multivariate analysis ECOG-PS, mGPS, and NC were independent predictors of survival at 1 and 3 months (all p < .01). Conclusion The simple combination of ECOG-PS and mGPS is an important novel prognostic framework which can alert clinicians to patients with good performance status who are at increased risk of having a higher symptom burden and dying at 3 months. From the recent literature it is likely that this framework will also be useful in referral for early palliative care with 6–24 months survival. Implications for Practice This large cohort study examined all validated prognostic factors in a head-to-head comparison and demonstrated the superior prognostic value of the Eastern Cooperative Oncology Group performance status (ECOG-PS)/modified Glasgow Prognostic Score (mGPS) combination over other prognostic factors. This combination is simple, accurate, and also relates to quality of life. It may be useful in identifying patients who may benefit from early referral to palliative care. It is proposed ECOG-PS/mGPS as the new prognostic domain in patients with advanced cancer.

ObjectivesPatient-relevant measures of functional status are required in chronic obstructive pulmonary disease (COPD) and lung cancer in clinical practice and research. We explored the relationship between the Australia-modified Karnofsky Performance Scale (AKPS) and measures of functional capacity and physical activity in these patient groups.MethodsPooled clinical trial data were analysed to explore the relationship between AKPS and average daily steps (ADS), 6 min walk distance (6MWD), and body mass index, airflow obstruction, dyspnoea and exercise score (COPD group). Receiver operator characteristic curves were produced to compare sensitivity and specificity of cut-offs (no dependency >70, high dependency ResultsSeven clinical trials included people with COPD (n=79) and lung cancer (n=150). To detect an AKPS of >70, the optimal ADS cut-points were COPD, 3342 steps (AUC 0.88, 95% CI 0.79 to 0.97, sensitivity 82%, specificity 76%), and lung cancer, 3380 steps (AUC 0.72, 95% CI 0.64 to 0.81, sensitivity 61%, specificity 74%), and for 6MWD (COPD only) 242 m (AUC 0.72, 95% CI 0.63 to 0.81, sensitivity 73%, specificity 34%).ConclusionsAn AKPS score is strongly related to ADS in people with COPD and lung cancer. The AKPS may be useful in clinical practice and research to indicate levels of physical activity where ADS and 6 min walk test are not possible. Longitudinal data are needed to confirm these findings.

Aims The role of selected treatments for brain metastases (BM) is well documented; however, the prevalence of these is not. We report on the patterns of care in the management of BM in a large oncology centre. Materials and methods We retrospectively audited 236 cases of newly diagnosed BM from January 2016 to December 2017 by looking at 2 years of radiology reports and gathered data on primary site, survival, treatment received, palliative care input and brain metastases-related admissions. Results Eighty-two per cent of cases were related to lung, breast and melanoma primaries. Half of patients received a form of treatment with the other half receiving best supportive care. Of these, whole-brain radiotherapy (39%) and stereotactic radiosurgery (40%) were the most common treatment modalities. Most common reasons for admissions were headaches, seizures, weakness and confusion. Conclusion This is the first study in the UK that gives an in-depth overview of the real-world management of brain metastases. We have demonstrated the prevalence of treatment across the spectrum of brain metastases patients. Radiotherapy is the mainstay of treatment in nearly 80% of cases; however, care needs to be taken in ensuring that SRS is offered to those who are suitable.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.medicinescomplete.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

Objectives There is a need to improve the assessment of emotional functioning (EF). In the international Advance Care Planning: an Innovative Palliative Care Intervention to Improve Quality of Life in Cancer Patients - a Multi-Centre Cluster Randomized Clinical Trial (ACTION) trial involving patients with advanced cancer, EF was assessed by a customized 10-item short form (EF10). The EF10 is based on the European Organisation for Research and Treatment of Cancer (EORTC) EF item bank and has the potential for greater precision than the common EORTC Quality of Life Questionnaire Core 30 four-item scale (EF4). We assessed the relative validity (RV) of EF10 compared with EF4. Methods Patients from Belgium, Denmark, Italy, the Netherlands, Slovenia, and the United Kingdom completed EF10 and EF4, and provided data on generic quality of life, coping, self-efficacy, and personal characteristics. Based on clinical and sociodemographic variables and questionnaire responses, 53 “known groups” that were expected to differ were formed, for example, females versus males. The EF10 and EF4 were first independently compared within this known group, for example, the EF10 score of females vs the EF10 score of males. When these differences were significant, the RV was calculated for the comparison of the EF10 with the EF4. Results A total of 1028 patients (57% lung, 43% colorectal cancer) participated. Forty-five of the 53 known-groups comparisons were significantly different and were used for calculating the RV. In 41 of 45 (91%) comparisons, the RV was more than 1, meaning that EF10 had a higher RV than EF4. The mean RV of EF10 compared with that of EF4 was 1.41, indicating superior statistical power of EF10 to detect differences in EF. Conclusions Compared with EF4, EF10 shows superior power, allowing a 20% to 34% smaller sample size without reducing power, when used as a primary outcome measure.

Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments. Central nervous system mechanisms are important in respiratory sensation and control. Consequently, drugs which may modify processing and perception of afferent information in the brain may have a role. Antidepressants have been proposed; however, current evidence is limited. Of potentially suitable antidepressants, mirtazapine is an attractive option given its tolerability profile, low cost, and wide availability, along with additional potential benefits. Areas covered: The paper provides an overview of the physiology of breathlessness, with an emphasis on central mechanisms, particularly the role of fear circuits and the associated neurotransmitters. It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease. The evidence was identified by a literature search performed in PubMed through to October 2018. Expert opinion: Currently, there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease. Mirtazapine is a promising candidate to pursue, with definitive randomized controlled trials required to determine its efficacy and safety in this setting.