ABSTRACT
BACKGROUND: Mesothelioma is a rare cancer without cure. Clinical guidelines recommend the timely provision of palliative/supportive care; however, a new study identified barriers to achieving this ambition. OBJECTIVE: The study aimed to explore palliative care needs and the role of Mesothelioma Clinical Nurse Specialists (MCNSs); and to develop resources to address study findings. METHODS: The mixed-methods study included a literature review, focus groups, interviews and surveys. RESULTS: The study highlighted the important role of the MCNSs in palliative care and the need to: address disjointed care; improve support for families; and explain the benefits of palliative care for patients/families. A co-production approach developed an animation for patients/families to demystify palliative care and explain the benefits of early-stage engagement; and an infographic targeted at community and primary care professionals. Recommendations for community nursing practice are described.
Subject(s)
Hospice and Palliative Care Nursing , Mesothelioma , Humans , Palliative Care , Mesothelioma/therapy , Focus GroupsABSTRACT
BACKGROUND: Genetically stratified therapy for malignant mesothelioma is unavailable. Mesotheliomas frequently harbour loss of the chromosome 9p21.3 locus (CDKN2A-MTAP), which is associated with shorter overall survival due to loss of the tumour suppressor p16ink4A, an endogenous suppressor of cyclin-dependent kinase (CDK)4 and CDK6. Genetic restoration of p16ink4A suppresses mesothelioma in preclinical models, underpinning the rationale for targeting CDK4 and CDK6 in p16ink4A-negative mesothelioma. We developed a multicentre, stratified, phase 2 trial to test this hypothesis. METHODS: The MiST2 study was a single-arm, open-label, phase 2 clinical trial done two UK centres. Patients older than 18 years with any histologically confirmed subtype of mesothelioma (pleural or peritoneal) with radiological progression after at least one course of platinum-based chemotherapy were molecularly screened by immunohistochemistry for p16ink4A. Patients with p16ink4A-negative mesothelioma were eligible for inclusion in the study. Patients were required to have measurable disease by modified Response Evaluation Criteria in Solid Tumours version 1.1 for malignant mesothelioma, a predicted life expectancy of at least 12 weeks, and an Eastern Cooperative Oncology Group performance status score of 0-1. Patients received oral abemaciclib 200 mg twice daily, administered in 28-day cycles for 24 weeks. The primary endpoint was the disease control rate (patients with complete responses, partial responses, or stable disease) at 12 weeks. The null hypothesis could be rejected if at least 11 patients had disease control. The efficacy and safety populations were defined as all patients who received at least one dose of the study drug. The study is registered with ClinicalTrials.gov, NCT03654833, and is ongoing (but MiST2 is now closed). FINDINGS: Between Sept 31, 2019, and March 2, 2020, 27 eligible patients consented to molecular screening. The median follow-up was 18·4 weeks (IQR 6·7-23·9). One patient was excluded before treatment because of a serious adverse event before study drug allocation. 26 (100%) of 26 treated patients were p16ink4A deficient and received at least one dose of abemaciclib. Disease control at 12 weeks was reported in 14 (54%) of 26 patients (95% CI 36-71). Grade 3 or worse treatment-related adverse events (of any cause) occurred in eight (27%) of 26 patients (diarrhoea, dyspnoea, thrombocytopenia, vomiting, urinary tract infection, increased alanine aminotransferase, ascites, chest infection or suspected chest infection, neutropenic sepsis, alopecia, blood clot left calf, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). Grade 3 or worse treatment-related adverse events occurred in three (12%) of 26 patients (diarrhoea, thrombocytopenia, vomiting, increased alanine aminotransferase, and pulmonary embolism). Serious adverse events occurred in six (23%) of 26 patients, leading to treatment discontinuation in one (4%) patient (diarrhoea, urinary tract infection, chest infection, neutropenic sepsis, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). One patient had a serious adverse event related to abemaciclib (diarrhoea). One (4%) of 26 patients died from an adverse event (neutropenic sepsis). INTERPRETATION: This study met its primary endpoint, showing promising clinical activity of abemaciclib in patients with p16ink4A-negative mesothelioma who were previously treated with chemotherapy, and warrants its further investigation in a randomised study as a targeted stratified therapy. FUNDING: University of Leicester, Asthma UK and British Lung Foundation Partnership, and the Victor Dahdaleh Foundation.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Pulmonary Embolism , Respiratory Tract Infections , Sepsis , Thrombocytopenia , Alanine Transaminase , Aminopyridines , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles , Diarrhea/etiology , Hemoptysis/drug therapy , Hemoptysis/etiology , Humans , Mesothelioma/drug therapy , Mesothelioma/genetics , Pleural Neoplasms/drug therapy , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/etiology , Vomiting/drug therapyABSTRACT
BACKGROUND: No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients. METHODS: This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450. FINDINGS: Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2-16·8). Median progression-free survival was 3·0 months (95% CI 2·8-4·1) in the nivolumab group versus 1·8 months (1·4-2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53-0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5-12·1) in the nivolumab group versus 6·9 months (5·0-8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52-0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group. INTERPRETATION: Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy. FUNDING: Stand up to Cancer-Cancer Research UK and Bristol Myers Squibb.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Mesothelioma, Malignant/drug therapy , Nivolumab/therapeutic use , Aged , B7-H1 Antigen/metabolism , Double-Blind Method , Female , Humans , Male , Mesothelioma, Malignant/mortality , Mesothelioma, Malignant/pathology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Pleural Neoplasms/drug therapy , Pleural Neoplasms/mortality , Pleural Neoplasms/pathology , Progression-Free Survival , Recurrence , Survival RateABSTRACT
BACKGROUND: People with mesothelioma and their families have palliative care needs throughout the relatively short trajectory of their illness. AIM: To describe the palliative care needs and experiences of people with mesothelioma and their family carers. DESIGN: Integrative systematic review with narrative synthesis (PROSPERO: CRD42020190115). DATA SOURCES: MEDLINE, CINAHL, PsycINFO and the Cochrane Library were searched for articles published between 01 January 2000 and 10 May 2020. Articles were included if they presented empirical studies or comprehensive reviews including information about the palliative care needs and experiences of people with mesothelioma and their family carers. RESULTS: The search yielded 508 articles, 14 were included in the analysis. A cross cutting theme of 'uncertainty' was identified encompassing five themes: (1) organisation and co-ordination of services, (2) communication and information needs, (3) management of care needs and high symptom burden, (4) consideration of the impact of seeking compensation and (5) family carer needs. Our findings demonstrate that people with mesothelioma want a co-ordinated, team-based approach to palliative care with a named point of contact. Whilst carers value and benefit from early referral to specialist palliative care, this does not necessarily reflect the outcomes and views of patients. CONCLUSION: The evidence base around the palliative care needs and experiences of people with mesothelioma and their carers needs to be strengthened. The results of this review support the need to develop a greater understanding about the role non-specialist palliative care clinicians' play in providing generalist palliative care for people with mesothelioma and their carers.
Subject(s)
Hospice and Palliative Care Nursing , Mesothelioma, Malignant , Mesothelioma , Caregivers , Humans , Mesothelioma/therapy , Palliative CareABSTRACT
The UK has the highest incidence of mesothelioma in the world, but services vary across the country partly due to uneven geographical distribution of cases. The Mesothelioma UK-funded national organisational audit has highlighted challenges in accessing diagnostic procedures such as thoracoscopy, as well as identifying examples of best practice, including access to clinical trials and specialist therapeutic procedures. To ensure equitable and optimal patient care, cancer alliances should have established referral pathways to specialist multidisciplinary team (MDT) services for discussion of all mesothelioma patients.
Subject(s)
Medical Oncology/standards , Mesothelioma/therapy , Standard of Care , Humans , United KingdomABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers. METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models. RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving. CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.
Subject(s)
Caregivers , Mesothelioma, Malignant , Quality of Life , Humans , Male , Female , Caregivers/psychology , Middle Aged , Mesothelioma, Malignant/psychology , Aged , United Kingdom , Qualitative Research , Australia , Pleural Neoplasms/psychology , Interviews as Topic , Adult , Aged, 80 and over , Lung Neoplasms/psychologyABSTRACT
PURPOSE: Clinical research trials are needed to enhance the medical care and treatment for lung cancer, which remains the leading cause of cancer-related deaths worldwide. While clinical trials allow for the development of novel therapies to treat cancer, the recruitment of lung cancer patients to trials is low. This review aimed to identify and synthesise the available literature concerning barriers and facilitators affecting lung cancer patients' decisions to enrol in clinical trials to guide future cancer research efforts. METHODS: Four databases were systematically searched: Academic Search Complete, CINHAL, PubMed, and PsycINFO in August 2023. A supplemental grey literature search was also conducted alongside this. Articles were quality appraised using CASP and JMI checklists, and results were narratively synthesised. RESULTS: Eighteen articles of varied design met the inclusion criteria, and results were mapped onto the Capability, Opportunity, and Motivation Behaviour (COM-B) Model to help structure and conceptualise review findings. Evidence suggests that the decision to enrol in a trial is multifaceted and informed by: when and how study information is presented, travel and trial eligibility, and altruistic hopes and fears. CONCLUSIONS: There is need to address the many different concerns that lung cancer patients have about participating in a clinical trial through the supply of accessible and timely trial information, and via the reduction of travel, expansion of study eligibility criteria, and recognition of a person's altruistic wishes, hopes, fears, and family-oriented concerns. Future research should aim to work alongside lung cancer patients, clinicians, and other stakeholders to increase research accessibility.
Subject(s)
Clinical Trials as Topic , Lung Neoplasms , Patient Selection , Humans , Lung Neoplasms/therapy , Lung Neoplasms/psychology , Decision Making , Patient Participation , MotivationABSTRACT
Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.
Subject(s)
Mesothelioma , Pleura , Pleural Neoplasms , Humans , Pleural Neoplasms/therapy , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Mesothelioma/drug therapy , Mesothelioma/therapy , Mesothelioma/pathology , Pleura/pathology , Pleura/diagnostic imaging , Mesothelioma, Malignant/drug therapy , Mesothelioma, Malignant/therapy , Antineoplastic Agents/therapeutic use , Pleural Effusion, Malignant/therapyABSTRACT
Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.
Subject(s)
Antibodies, Monoclonal, Humanized , B7-H1 Antigen , Bevacizumab , Gastrointestinal Microbiome , Immune Checkpoint Inhibitors , Humans , Gastrointestinal Microbiome/drug effects , Bevacizumab/therapeutic use , Bevacizumab/pharmacology , Male , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Middle Aged , Aged , Mesothelioma, Malignant/drug therapy , Vascular Endothelial Growth Factor A/metabolism , Mesothelioma/immunology , Mesothelioma/drug therapy , Mesothelioma/microbiology , Mesothelioma/pathology , Tumor Microenvironment/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/microbiology , Treatment OutcomeSubject(s)
Mesothelioma/surgery , Pleural Neoplasms/surgery , Societies, Medical , Thoracic Surgical Procedures , Diagnosis, Differential , Humans , Mesothelioma/diagnosis , Mesothelioma/mortality , Mesothelioma/therapy , Neoplasm Staging , Pleural Neoplasms/diagnosis , Pleural Neoplasms/mortality , Pleural Neoplasms/therapy , Prognosis , Survival Analysis , Thoracic Surgical Procedures/methods , Treatment Outcome , United KingdomABSTRACT
BACKGROUND: Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primary endpoint with 15% of patients having durable responses exceeding 1 year. Therefore, there is a need to evaluate PARP inhibitors in relapsed mesothelioma patients, where options are limited. Niraparib is the PARP inhibitor used in NERO. METHODS: NERO is a multicentre, two-arm, open-label UK randomised phase II trial designed to evaluate the efficacy of PARP inhibition in relapsed mesothelioma. 84 patients are being recruited. NERO is not restricted by line of therapy; however, eligible participants must have been treated with an approved platinum based systemic therapy. Participants will be randomised 2:1, stratified according to histology and response to prior platinum-based chemotherapy, to receive either active symptom control (ASC) and niraparib or ASC alone, for up to 24 weeks. Participants will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Participants randomised to niraparib will receive 200 or 300 mg daily in a 3-weekly cycle. The primary endpoint is progression-free survival, where progression is determined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or RECIST 1.1; investigator reported progression; or death from any cause, whichever comes first. Secondary endpoints include overall survival, best overall response, 12-week and 24 week disease control, duration of response, treatment compliance and safety/tolerability. If NERO shows niraparib to be safe and biologically effective, it may lead to future late phase randomised controlled trials in relapsed mesothelioma. ETHICS AND DISSEMINATION: The study received ethical approval from London-Hampstead Research Ethics Committee on 06-May-2022 (22/LO/0281). Data from all centres will be analysed together and published as soon as possible. TRIAL REGISTRATION NUMBER: ISCRTN16171129; NCT05455424.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Humans , Mesothelioma, Malignant/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Secondary Care Centers , Mesothelioma/drug therapy , Mesothelioma/pathology , United Kingdom , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as TopicABSTRACT
AIM: Lung cancer is a common malignancy that occurs worldwide and generally has a poor prognosis. Its diagnosis presents significant physical and emotional challenges for patients and their family, friends and caregivers (FFCs). This study aimed to gain insights into patients' and FFCs' perspectives regarding lung cancer and its treatment, as well as physicians' perceptions of patients' thoughts about their illness. PATIENTS & METHODS: An international online survey was conducted, assessing 113 patients diagnosed with non-small-cell lung cancer, 70 corresponding FFCs and 188 treating physicians. Data were collected using an interactive internet-based tool, in order to establish respondents' priorities. RESULTS: Interesting differences between patients', FFCs' and physicians' perspectives on lung cancer were revealed. For all respondents, the primary feeling about lung cancer was described as "sadness". Patients were more likely to express a determination to be positive, whereas fear was a common response for FFCs and was a perspective also reported by physicians. Physicians' views on how they had communicated disease information were more positive than those of the patients, with many patients detecting physician hesitancy to communicate negative news. CONCLUSION: This study provides important insights into the self-reported thoughts and feelings of patients with lung cancer, their personal networks of FFCs and the physicians who care for them.
Subject(s)
Attitude of Health Personnel , Carcinoma, Non-Small-Cell Lung/psychology , Caregivers/psychology , Lung Neoplasms/psychology , Adult , Aged , Carcinoma, Non-Small-Cell Lung/therapy , Data Collection , Emotions , Fear , Female , Health Surveys/methods , Humans , Lung Neoplasms/therapy , Male , Middle Aged , Online Systems , Physician-Patient Relations , Self Report , Surveys and Questionnaires , Truth DisclosureABSTRACT
BACKGROUND: The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. METHODS: MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. FINDINGS: Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. INTERPRETATION: In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. FUNDING: Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.
Subject(s)
Mesothelioma/surgery , Pleural Neoplasms/surgery , Pneumonectomy , Adult , Aged , Combined Modality Therapy , Disease-Free Survival , Feasibility Studies , Female , Humans , Male , Mesothelioma/radiotherapy , Middle Aged , Pleural Neoplasms/radiotherapy , Treatment OutcomeABSTRACT
Objectives: Mesothelioma is a rare, progressive cancer with a short trajectory from diagnosis to the end of life. This study explores the experiences of palliative and end of life care for patients with mesothelioma from the perspective of bereaved family caregivers. Methods: A qualitative, descriptive approach was adopted comprising face-to-face, semi-structured interviews with bereaved caregivers of patients with mesothelioma in the UK. An inductive, thematic analysis was conducted using the 'Framework' approach. Results: Nine bereaved caregivers participated. Four themes emerged: understanding what lies ahead; carer support; care co-ordination; managing after death: practicalities, inquests and abandonment. Caregivers need to understand what lies ahead in order to emotionally and practically prepare themselves for supporting the patient at the end of life. Information and support needs of caregivers were often distinct from those of patients, including the importance of information about the coroner's involvement. The importance of care co-ordination was emphasised, with caregivers valuing on-going relationships and a named individual taking responsibility for co-ordinating the patients care. Feelings of abandonment arose when there was no contact with healthcare professionals following the death of the patient. Conclusions: Greater opportunity for open, one-to-one communication between family caregivers and healthcare professionals is vital to enable the caregiver to prepare for what lies ahead at the end of life and prevent feelings of abandonment after the death of the patient. Improved care co-ordination and partnership working are essential for supporting both patient and caregiver at the end of life.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Terminal Care , Caregivers/psychology , Death , Humans , Palliative Care/psychology , Qualitative Research , Terminal Care/psychology , United KingdomABSTRACT
OBJECTIVES: Malignant mesothelioma is an aggressive malignancy of mesothelial surfaces, most commonly those of the pleura. The aim of this study was to understand, using a national questionnaire, the gendered care experiences of patients with malignant pleural mesothelioma (MPM).Patients were asked about their experience of the diagnostic process, about information clarity, health care professionals' knowledge, general practitioner support and overall satisfaction with care received. SETTING: Recruitment of patients was carried out in three UK countries (England, Wales and Scotland) via mesothelioma clinical nurse specialists. PARTICIPANTS: In total, 503 patients completed the questionnaire. 460 had MPM, the remainder had other types of mesothelioma. In accord with the study protocol, only the MPM patients were included in this study.Primary and secondary measures were: (1) time from symptom to diagnosis, (2) satisfaction with the diagnosis and treatment, and (3) quality of life and well-being. RESULTS: There were gender differences in time from symptom to diagnosis. The time from symptom to diagnosis was significantly longer for women than men (median=152 days vs men=92 days, p=0.01). Lack of a verified source of exposure to asbestos was a hindrance to private treatment access for women (95% of those that access private treatment are men). Patients were five times more likely to be satisfied if they thought that the doctors knew enough about their condition (OR=4.4, p=0.001) and nearly three times more likely to be satisfied if information was presented in a sensitive way (OR=2.8,p=0.01). CONCLUSIONS: This study has several implications for clinical practice. Our findings suggest that the diagnostic time in women might be reduced by reviewing diagnostic processes including occupational history taking, and by revising the occupational risk of mesothelioma categorisation.
Subject(s)
Mesothelioma, Malignant , Cross-Sectional Studies , Female , Humans , Male , Quality of Life , Surveys and Questionnaires , United KingdomABSTRACT
OBJECTIVE: Mesothelioma is a life limiting cancer caused by previous exposure to asbestos. Due to the continued use of asbestos products internationally, the condition presents an increasing risk to global health with case numbers peaking in industrially developed nations. With the cancer reducing patient well-being, this study aimed to synthesizes the qualitative findings of studies exploring the experiences of patients living with mesothelioma to generate new conceptual insights and guide therapeutic care. METHOD: Thirteen databases were systematically searched: Academic Search Premier, BioMed Central, British Nursing Database, CINAHL Plus, Cochrane Library, Europe PubMed Central, MEDLINE, PsycARTICLES, PsycINFO, Science Direct, Scopus, Social Care Online, and Web of Science, between August and September 2020. Included articles were subject to quality appraisal using CASP checklists, and their respective findings analyzed using a metaethnographic form of qualitative data synthesis. RESULTS: Twenty-two articles met the inclusion criteria, and the data synthesis produced three themes: (1) "complex trauma"; (2) "psycho-behavioral coping strategies"; and (3) "external sources of support." Combined, these themes form a novel conceptual framework and awareness of the patient experience that presents the lived trauma of disease alongside a patients coping processes and support pathways. CONCLUSION: Robust therapeutic support is needed to address the psychosocial and existential burden shouldered by people with mesothelioma. Therapies that promote sentiments of acceptance, hope, and benefit finding are proposed alongside initiatives that foster patient empowerment and meaning, and further promote patient choice in deciding end-of-life care. Recommendations for future research are also made. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Subject(s)
Adaptation, Psychological , Mesothelioma , Europe , Humans , Mesothelioma/ethnology , Mesothelioma/psychology , Mesothelioma/therapyABSTRACT
PURPOSE: The covid-19 global pandemic has impacted on nurses who have rapidly adapted to new ways of working, and experienced negative impacts due to over-stretched services. Two surveys captured the experiences of lung cancer and mesothelioma specialist nurses in the United Kingdom (UK) in 2020, but the impact of later stages of the pandemic was unknown. This study aimed to explore the impact of covid-19 on lung Cancer and mesothelioma nurses since January 2021, the second wave of the pandemic. METHODS: An online cross-sectional survey with both open and closed questions explored the impact of covid-19 on ways of working and workload, quality of care, and health and wellbeing. The survey was open to UK based lung cancer and mesothelioma advanced or specialist nurses. RESULTS: 85 nurses responded to the survey. The majority were Clinical Nurse Specialists, based in England. Respondents reported changes in ways of working due to redeployment, staff shortages, and home working. Widespread adoption of virtual working practices led to concerns of negative impacts. Perceived excessive workload impacted on care with two-thirds of the sample (57, 67%) reporting they had been unable to provide the same quality of care to patients. Impacts on nurses' health and wellbeing were reported with two-thirds of the sample (56, 66%) reporting a deterioration in emotional wellbeing and mental health. Coping mechanisms employed included online team support to share experiences and increased uptake of exercise; however, impacts on lifestyle and access to coping mechanisms varied. CONCLUSION: Nurses have stepped up to the challenges of the pandemic with teamwork and innovation, but pressure arising from the pandemic and high workloads led to negative impacts on wellbeing. The authors have provided recommendations to improve patient care and support the wellbeing of nurses, which will be key to a resilient workforce living with covid-19. Whilst this study focussed on lung cancer and mesothelioma specialists, the findings have wider implications for other cancer specialties.
Subject(s)
COVID-19 , Lung Neoplasms , Mesothelioma , Nurse Clinicians , Nurses , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Surveys and QuestionnairesABSTRACT
Background: Currently, there is no US Food and Drug Administration approved therapy for patients with pleural mesothelioma who have relapsed following platinum-doublet based chemotherapy. Vinorelbine has demonstrated useful clinical activity in mesothelioma, however its efficacy has not been formally evaluated in a randomised setting. BRCA1 expression is required for vinorelbine induced apoptosis in preclinical models. Loss of expression may therefore correlate with vinorelbine resistance. Methods: In this randomised, phase 2 trial, patients were eligible if they met the following criteria: age ≥ 18 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, histologically confirmed pleural mesothelioma, post platinum-based chemotherapy, and radiological evidence of disease progression. Consented patients were randomised 2:1 to either active symptom control with oral vinorelbine versus active symptom control (ASC) every 3 weeks until disease progression, unacceptable toxicity or withdrawal at an initial dose of 60 mg/m2 increasing to 80 mg/m2 post-cycle 1. Randomisation was stratified by histological subtype, white cell count, gender, ECOG performance status and best response during first-line therapy. The study was open label. The primary endpoint was progression-free survival (PFS), measured from randomisation to time of event (or censoring). Analyses were carried out according to intention-to-treat (ITT) principles. Recruitment and trial follow-up are complete. This trial is registered with ClinicalTrials.gov, number NCT02139904. Findings: Between June 1, 2016 and Oct 31, 2018, we performed a randomised phase 2 trial in 14 hospitals in the United Kingdom. 225 patients were screened for eligibility, of whom 154 were randomly assigned to receive either ASC + vinorelbine (n = 98) or ASC (n = 56). PFS was significantly longer for ASC+vinorelbine compared with ASC alone; 4.2 months (interquartile range (IQR) 2.2-8.0) versus 2.8 months (IQR 1.4-4.1) for ASC, giving an unadjusted hazard ratio (HR) of 0·60 (80% CI upper limit 0.7, one-sided unadjusted log rank test p = 0.002); adjusted HR 0.6 (80% CI upper limit 0.7, one-sided adjusted log rank test p < 0.001). BRCA1 did not predict resistance to ASC+vinorelbine. Neutropenia was the most common grades 3, 4 adverse events in the ASC +vinorelbine arm. Interpretation: Vinorelbine plus ASC confers clinical benefit to patients with relapsed pleural mesothelioma who have progressed following platinum-based doublet chemotherapy. Funding: This study was funded by Cancer Research UK (grant CRUK A15569).
ABSTRACT
This article describes the establishment and work of the national Mesothelioma Nurse Action Team, a nursing initiative aimed at improving the care and support of people affected by mesothelioma in the UK. The incidence of mesothelioma is increasing and survival is poor, with more patients in the UK dying from mesothelioma than from malignant melanoma or cervical cancer.
Subject(s)
Mesothelioma/nursing , Humans , Mesothelioma/epidemiology , Mesothelioma/mortality , United Kingdom/epidemiologyABSTRACT
PURPOSE: Mesothelioma is a terminal cancer caused by exposure to asbestos. As a cancer with a higher rate in men than women, women's experiences of living with mesothelioma are often underexplored. Furthermore, men's experiences are often taken for granted and therefore have remained underexplored. This paper considers men's and women's experiences across the mesothelioma pathway. METHODS: This qualitative study incorporated semi-structured interviews with 13 men and 11 women living with mesothelioma. Telephone interviews took place between July and December 2019, and were audio recorded, transcribed and anonymised. Thematic analysis was used to analyse the data. RESULTS: Three themes were developed in relation to the gendered experience of mesothelioma: familial responsibility and social perceptions; support preferences; and treatment and trials. Analysis suggests that men and women's sense of familial responsibility varied. Differences in priorities and motivations influenced approaches to seeking support, compensation and, making decisions around treatments and clinical trials. CONCLUSIONS: The current study reports on how gender can influence the experience of living with mesothelioma. The findings indicate how the patients' role in their families and society can more broadly influence their experiences, choices and preferences. Nurses caring for mesothelioma patients need high quality research on which to base their practice. Recognition and an understanding of the underlyingfactors influencing patients' decision-making will enable nurses and other professionals to support their patients better.