Standards of care in mesothelioma treatment

Summary: 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

Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272

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

A systematic review of the barriers and facilitators impacting patient enrolment in clinical trials for lung cancer

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

The Experience of Living with Mesothelioma: A Meta-ethnographic Review and Synthesis of the Qualitative Literature.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.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 synthesises 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 analysed using a meta-ethnographic 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-behavioural 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 which 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

'What matters to me': an international online survey of people treating, affected by and living with lung cancer

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

Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): a randomised, phase 2 trial

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)