BMJ Open

Our medical research library holds 44 studies published in BMJ Open (2012–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 44 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: BMJ Publishing Group Ltd
• Published: 2011 to the present, England
• Language: English
• ISSN: 2044-6055 (electronic)
• Its record in the NLM Catalog

2020s

• Epidemiology, exposure patterns and survival of malignant mesothelioma in Apulia, Italy (1993-2025): a population-based retrospective registry study. L. De Maria, D. Cavone, G. Delvecchio, et al. 2026;16(10):e120874. PubMed · Publisher · Free full text

  Abstract

  Objectives: To characterise the epidemiology, asbestos-exposure patterns, spatial distribution and survival of malignant mesothelioma in Apulia, Italy.

  Design: Population-based retrospective registry study.

  Setting: Apulian Regional Mesothelioma Registry, a regional operating centre of the Italian National Mesothelioma Registry.

  Participants: All 2281 malignant mesothelioma cases recorded between 1993 and 2025.

  Interventions: None.

  Primary And Secondary Outcomes: Primary outcomes were case distribution, population-adjusted incidence, asbestos-exposure category and overall survival. Secondary outcomes included temporal trends, municipal patterns, proximity of environmentally exposed cases to the former Fibronit plant in Bari and factors independently associated with mortality.

  Results: Overall, 1689 cases (74.0%) occurred in men; mean age at diagnosis was 67.8 years and 2018 cases (88.5%) were pleural. Occupational exposure accounted for 49.8% of cases, environmental exposure for 8.9% and familial exposure for 2.4%. Taranto had the highest municipal annual incidence (7.43 per 100 000), followed by Bari (4.59). Among 112 environmentally exposed Bari cases with reconstructed residential distance, 89.3% lived within 1 km of the former Fibronit plant. Kaplan-Meier median survival was 1.0-year and 5-year survival was 10.1%. Survival improved across diagnostic periods (p<0.001). Older age, male sex and pleural site independently predicted higher mortality.

  Conclusions: Mesothelioma in Apulia reflects persistent occupational and environmental consequences of historical asbestos use. Geographical hotspots and poor survival support continued registry surveillance, remediation of contaminated sites and targeted health monitoring of formerly exposed workers and communities.

  © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

• Evaluation of imaging techniques for early detection of intrathoracic cancers in symptomatic patients in primary care: a systematic review. B. Grigore, J.L. Peters, W. Hamad, et al. 2025;15(8):e091435. Systematic review PubMed · Publisher · Free full text

  Abstract

  Objectives: Intrathoracic cancers, such as lung cancer, mesothelioma and thymoma, represent diagnostic challenges in primary care. We aimed to summarise evidence on the performance of imaging techniques that could aid the detection of intrathoracic cancers in low prevalence settings.

  Design: Systematic review and quality appraisal using Quality Assessment of Diagnostic Accuracy Studies-2 and Grading of Recommendations Assessment, Development and Evaluation.

  Data Sources: MEDLINE, Embase and Web of Science were searched with a predesigned search strategy for articles from January 2000 to January 2024.

  Eligibility Criteria: We included studies relevant for primary care, where participants were suspected of having intrathoracic cancer and reported on at least one diagnostic performance measure. We excluded studies where the cancer diagnosis was already established. Data extraction and synthesis screening were conducted independently by two reviewers. Data extraction and quality appraisal were conducted by one reviewer and checked by a second reviewer.

  Results: Out of 30 539 records identified by the database searches, 13 studies were included. There was heterogeneity in the types of cancers, populations included and reported diagnosis pathways for suspected cancers. Imaging modalities investigated included chest X-ray (three studies), computer tomography (CT, six studies), magnetic resonance imaging (two studies), positron emission tomography CT (two studies), ultrasound (two studies) and scintigraphy (one study). Chest X-ray sensitivity reported for lung cancer ranged from 33.3% to 75.9%, with specificity ranging from 83.2% to 95.5%. For CT, reported sensitivity varied from 58% for pleural malignancy to 100% for lung cancer. One study investigating an artificial intelligence tool to detect lung cancer found poor detection performance in a real-world patient cohort.

  Conclusions: We found a limited number of studies reporting on the diagnostic performance of usual imaging techniques when used in unselected primary care settings for the diagnosis of intrathoracic cancer in symptomatic patients. There is a need for more studies evaluating such techniques in the general population presenting in primary care, where the prevalence is relatively low. A better understanding of the performance could lead to better detection strategies for intrathoracic cancers in primary care. Intrathoracic cancers, such as lung cancer, mesothelioma and thymoma, represent diagnostic challenges in primary care. We aimed to summarise evidence on the performance of imaging techniques that could aid the detection of intrathoracic cancers in low prevalence settings.

  © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.

• Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol. S.W.S. Yip, L. Weinberg, J. Gooi, et al. 2024;14(5):e078125. PubMed · Publisher · Free full text

  Abstract

  Introduction: Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.

  Methods And Analysis: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.

  Ethics And Dissemination: Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.

  © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers. V. Sherborne, S. Ejegi-Memeh, A.M. Tod, et al. 2024;14(6):e075071. Systematic review PubMed · Publisher · Free full text

  Abstract

  Objectives: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.

  Design: Systematic review.

  Data Sources: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA.

  Eligibility Criteria: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002.

  Data Extraction And Synthesis: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews.

  Results: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support.

  Conclusions: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma.

  Prospero Registration Number: CRD42022302187.

  © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study. N. Mills, N. Farrar, B. Warnes, et al. 2024;14(5):e079108. PubMed · Publisher · Free full text

  Abstract

  Objectives: Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent.

  Design: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period.

  Setting: Secondary thoracic cancer care.

  Results: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment.

  Conclusions: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible.

  Trial Registration Number: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

  © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

• Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres. D. Fennell, D. Griffiths, Z. Eminton, et al. 2023;13(11):e073120. PubMed · Publisher · Free full text

  Abstract

  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.

  © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018. S. Stella, D. Consonni, E. Migliore, et al. 2023;13(8):e073480. PubMed · Publisher · Free full text

  Abstract

  Objectives: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.

  Design: Case-control study.

  Setting: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies.

  Methods: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.

  Results: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.

  Conclusions: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

  © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Pneumoconiosis combined with connective tissue disease in China: a cross-sectional study. W. Xu, R. Ma, J. Wang, et al. 2023;13(4):e068628. PubMed · Publisher · Free full text

  Abstract

  Objective: To describe the prevalence, clinical features and potential risk factors of pneumoconiosis in combination with connective tissue disease (CTD) or positive autoantibodies.

  Design: Cross-sectional study.

  Setting: A retrospective study of adults recruited in China between December 2016 and November 2021.

  Participants: A total of 931 patients with pneumoconiosis at Beijing Chao-Yang Hospital were enrolled in this study; of these, 580 patients were included in the final analysis.

  Main Outcome Measures: Pneumoconiosis combined with CTD or positive autoantibodies was a major adverse outcome.

  Results: In total, 13.8% (80/580) of the patients had combined pneumoconiosis with CTD, among whom the prevalence of CTD was 18.3% (46/251) in asbestosis and 11.4% (34/298) in silicosis/coal mine workers' pneumoconiosis. In comparison to the general Chinese adult population, the relative risk of various CTD in pneumoconiosis, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren's syndrome, idiopathic inflammatory myopathy and antineutrophil cytoplasmic antibodies-associated vasculitis, were 11.85, 12.12, 127.40, 4.23, 9.94 and 644.66, respectively. Multivariate analysis revealed that female sex (OR 2.55, 95% CI 1.56 to 4.17) and a later stage of pneumoconiosis (OR 2.04, 95% CI 1.24 to 3.34) were the independent risk factors for CTD in patients with pneumoconiosis (all p<0.050).

  Conclusion: CTD is highly prevalent in patients with pneumoconiosis, especially in patients of asbestosis, and silicosis/coal mine workers' pneumoconiosis. Female sex and later stages of pneumoconiosis are associated with an increased risk of combined with CTD.

  © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study. T. Hirata, T. Kawaguchi, K. Azuma, et al. 2023;13(11):e073724. PubMed · Publisher · Free full text

  Abstract

  Introduction: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs.

  Methods And Analysis: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point.

  Ethics And Dissemination: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021.

  Registration Details: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023.

  Trial Registration Number: UMIN000046418.

  © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance. K. Ferguson, M. Neilson, R. Mercer, et al. 2023;13(8):e067780. PubMed · Publisher · Free full text

  Abstract

  Objectives: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI).

  Design: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size.

  Setting: 4 UK pleural disease centres (February 2019-January 2020).

  Participants: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up.

  Outcome Measures: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression.

  Results: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)).

  Conclusions: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500.

  Trial Registration Number: ISRCTN12840870.

  © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Development and validation of a nomogram for predicting the risk of mental health problems of factory workers and miners. Y. Lu, Q. Liu, H. Yan, et al. 2022;12(7):e057102. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Objective: A nomogram for predicting the risk of mental health problems was established in a population of factory workers and miners, in order to quickly calculate the probability of a worker suffering from mental health problems.

  Methods: A cross-sectional survey of 7500 factory workers and miners in Urumqi was conducted by means of an electronic questionnaire using cluster sampling method. Participants were randomly assigned to the training group (70%) and the validation group (30%). Questionnaire-based survey was conducted to collect information. A least absolute shrinkage and selection operator (LASSO) regression model was used to screen the predictors related to the risk of mental health problems of the training group. Multivariate logistic regression analysis was applied to construct the prediction model. Calibration plots and receiver operating characteristic-derived area under the curve (AUC) were used for model validation. Decision curve analysis was applied to calculate the net benefit of the screening model.

  Results: A total of 7118 participants met the inclusion criteria and the data were randomly divided into a training group (n=4955) and a validation group (n=2163) in a ratio of 3:1. A total of 23 characteristics were included in this study and LASSO regression selected 12 characteristics such as education, professional title, age, Chinese Maslach Burnout Inventory, effort-reward imbalance, asbestos dust, hypertension, diabetes, working hours per day, working years, marital status and work schedule as predictors for the construction of the nomogram. In the validation group, the Brier score was 0.176, the calibration slope was 0.970 and the calibration curve of nomogram showed a good fit. The AUC of training group and verification group were 0.785 and 0.784, respectively.

  Conclusion: The nomogram combining these 12 characteristics can be used to predict the risk of suffering mental health problems, providing a useful tool for quickly and accurately screening the risk of mental health problems.

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper. S. Smith, M. Brand, S. Harden, et al. 2022;12(8):e060907. PubMed · Publisher · Free full text

  Abstract

  Introduction: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand.

  Methods And Analysis: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight.

  Ethics And Dissemination: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Intraperitoneal paclitaxel for patients with primary malignant peritoneal mesothelioma: a phase I/II dose escalation and safety study-INTERACT MESO. J.P. van Kooten, M.V. Dietz, N.A.D. Guchelaar, et al. 2022;12(6):e062907. PubMed · Publisher · Free full text

  Abstract

  Introduction: Malignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.

  Methods And Analysis: The INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.

  Ethics And Dissemination: The Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.

  Trial Registration Number: NL9718. EudraCT: 2021-003637-11.

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis. T. Fu, J.X. Liu, J. Xie, et al. 2022;12(11):e063682. Meta-analysis · Systematic review PubMed · Publisher · Free full text

  Abstract

  Objectives: Accumulating evidence suggested that the laminin γ2 (LAMC2) expression level was upregulated in various cancers. However, the potential prognostic value of LAMC2 in cancers remains unclear. We conducted a meta-analysis to clarify the association of LAMC2 expression with prognosis.

  Design: We searched Embase, Web of Science and PubMed (up to 25 November 2021) to collect all eligible studies, and meta-analysis was performed to interpret the association of LAMC2 expression with clinicopathological parameters, overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS).

  Eligibility Criteria For Including Studies: We included studies that investigate the relationship between LAMC2 and prognosis of cancers, patients were divided into two groups, and associations of LAMC2 expression with clinicopathological features were described.

  Results: Seven studies were finally included. We found that increased LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p<0.001), tumour-node-metastasis stages (log OR: 0.95, 95% CI 0.39 to 1.50, p<0.001) and tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p<0.001), but not with age (log OR -0.05, 95% CI -0.37 to 0.27, p=0.75) or gender (log OR -0.07, 95% CI -0.52 to 0.38, p=0.75). In addition, higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS (HR 1.85, 95% CI 1.31 to 2.40, p<0.001). A similar result was found in The Cancer Genome Atlas database. High LAMC2 expression was significantly associated with OS in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, neck squamous cell carcinoma and brain lower grade glioma.

  Conclusion: Our results suggested that higher LAMC2 expression was correlated with worse survival, lymph node metastasis, tumour-node-metastasis stages and tumour status. This study was subject to inherent limitations, but the results presented here provide insights regarding the potential use of LAMC2 as a biomarker for human cancer.

  Study Registration: researchregistry.com (researchregistry1319).

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Protocol for a prospective observational cohort study collecting data on demographics, symptoms and biomarkers in people with mesothelioma (ASSESS-meso). R.J.H. Conway, J. Symonds, D. Walton, et al. 2022;12(11):e060850. PubMed · Publisher · Free full text

  Abstract

  Introduction: Mesothelioma is a heterogeneous disease that can be challenging to monitor and prognosticate. ASSESS-meso is a multicentre, prospective, longitudinal observational cohort study of patients with mesothelioma. The primary aim is to describe different clinical phenotypes and investigate predictive and prognostic factors, including biomarkers from blood and pleural fluid. The secondary aim is to provide a resource for future trials and substudies.

  Methods And Analysis: We aim to recruit 700 patients with a histological, cytological or clinicopathological diagnosis of mesothelioma, at any anatomical site (pleural, peritoneal, pericardial, etc). Longitudinal data will be collected, including clinical information, radiological investigations, blood tests and patient-reported outcome measures for breathlessness, chest pain and sweats. Preplanned analyses will use Cox proportional hazards method to evaluate factors associated with survival, linear and logistic regression models to investigate associations with symptoms, and analysis of variance modelling to explore changes in symptoms over time.

  Ethics And Dissemination: Ethical approval has been granted by the Research Ethics Committee South West-Central Bristol (17-SW-0019) and Health Research Authority (IRAS ID 220360). A study steering committee has been established and results will be published OpenAccess in peer-reviewed journals.

  Trial Registration Number: ISRCTN: 61861764.

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial. P.S. Kok, P.M. Forde, B. Hughes, et al. 2022;12(1):e057663. PubMed · Publisher · Free full text

  Abstract

  Introduction: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.

  Methods And Analysis: This multicentre open-label randomised trial will recruit 480 treatment-naïve adults with advanced pleural mesothelioma, randomised (2:1) to either 3-weekly durvalumab 1500 mg plus 3-weekly doublet chemotherapy (cisplatin 75 mg/m2 or carboplatin, Area Under the Curve,AUC 5 and pemetrexed 500 mg/m2) 4-6 cycles, followed by 4-weekly durvalumab 1500 mg until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target accrual time is 27 months, with follow-up for an additional 24 months. This provides over 85% power if the true HR for overall survival (OS) is 0.70, with two-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Randomisation is stratified by age (18-70 years vs >70), sex, histology (epithelioid vs non-epithelioid), platinum agent (cisplatin vs carboplatin) and region (USA vs Australia/New Zealand vs Other). The primary endpoint is OS. Secondary endpoints include progression-free survival, objective tumour response (by mRECIST V.1.1 and iRECIST), adverse events, health-related quality of life and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma.

  Ethics And Dissemination: The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.

  Drug Supply: AstraZeneca.

  Protocol Version: CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021.

  Trial Registration Number: ClinicalTrials.gov Identifier: NCT04334759 ACTRN 12620001199909.

  © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Hospitalisation costs of malignant mesothelioma: results from the Italian hospital discharge registry (2001-2018). P. Ferrante. 2021;11(8):e046456. PubMed · Publisher · Free full text

  Abstract

  Objectives: This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.

  Design: This is a retrospective population-based study of Italian hospitalisations treating pleura, peritoneum and pericardium mesothelioma in the period 2001-2018.

  Settings: Public and private Italian hospitals reached by the Ministry of Health (coverage close to 100%).

  Participants: 157 221 admissions with primary or contributing diagnosis of pleural, peritoneal or hearth cancer discharged from 2001 to 2018.Primary and secondary outcome measures: number, length and cost of hospitalisations with related percentages.

  Results: Each year, Italian hospitals treated a mesothelioma in 6025 admissions on average. Mean annual costs by site were €20 293 733, €3183 632 and €40 443 for pleura, peritoneum and pericardium, respectively. Pericardial mesothelioma showed the highest cost per admission (€6117), followed by peritoneal (€4549) and pleural cases (€3809). Percentage of hospitalisation costs attributable to mesothelioma was higher when it is located in pleura (53.4%) and pericardium (51.8%) with respect to peritoneum (41.2%). Overall annual hospitalisation cost, percentages of number and length of admissions showed an inverted U-shape, with maxima (of €25 850 276, 0.064% and 0.096%, respectively) reached in 2011-2013. Mean age at discharge and percentages of surgery and of urgent cases increased over time.

  Conclusions: The highest impact of mesothelioma on the National Health System was recorded 20 years after the asbestos ban (2011-2013). Hospitals should expect soon fewer but more severe patients needing more cares. To study the disease prevalence could help assistance planning of next decade.

  © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Improving mesothelioma follow-up care in the UK: a qualitative study to build a multidisciplinary pyramid of care approach. Z. Davey, C. Henshall. 2021;11(11):e048394. PubMed · Publisher · Free full text

  Abstract

  Objectives: The findings reported in this manuscript are part of a wider study that aimed to explore mesothelioma patients' experiences of follow-up care. The aim of this phase of the study was to co-produce recommendations for policy and practice and to propose a revised, patient-focused, mesothelioma follow-up care service.

  Design: The consultation phase was qualitative and consisted of three group discussions with separate stakeholder groups allowing for different priorities and needs for follow-up care to be compared. An implicit approach to consensus was adopted and data were analysed iteratively using the framework method.

  Setting: The study was conducted in three National Health Service Trusts in the South of England. Two were secondary care settings and the third was a tertiary centre.

  Participants: The consultation exercise comprised three group discussions with key stakeholders (n=35): mesothelioma specialist nurses (n=9), mesothelioma patients and carers (n=11) and local clinical commissioning group members (n=15).

  Results: Recommendations for mesothelioma follow-up care were developed using a co-production approach and highlighted the importance of continuity of care, the provision of timely information and the central role played by mesothelioma specialist nurses, supported by the wider multidisciplinary team. Recommendations were produced together with two bespoke infographics to maximise impact and facilitate patient and public engagement with the study.

  Conclusions: The recommendations developed are the first that specifically examine best practice for the follow-up care pathway for mesothelioma patients. Co-production and public engagement are crucial to priority setting develop and optimising patient-centred care. Combining the recommendations produced with a targeted dissemination strategy and well-designed, patient-focused infographics will maximise opportunities for impact at a regional and national level.

  © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study. A. Bhatt, P. Rousset, D. Baratti, et al. 2021;11(7):e046819. PubMed · Publisher · Free full text

  Abstract

  Introduction: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.

  Methods And Analysis: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.

  Ethics And Dissemination: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).

  Trial Registration Number: CTRI/2020/09/027709; Pre-results.

  © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine. S. Casjens, G. Johnen, I. Raiko, et al. 2021;11(2):e039079. PubMed · Publisher · Free full text

  Abstract

  Objectives: Calretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.

  Setting: This re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.

  Participants: The present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.

  Primary And Secondary Outcomes: Mesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.

  Results: Compared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.

  Conclusions: The newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.

  © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Recommendations for improving follow-up care for patients with mesothelioma: a qualitative study comprising documentary analysis, interviews and consultation meetings. C. Henshall, Z. Davey, H. Walthall, et al. 2021;11(1):e040679. PubMed · Publisher · Free full text

  Abstract

  Objectives: The study aim was to explore experiences of patients with pleural mesothelioma of follow-up care in three National Health Service (NHS) Trusts to develop recommendations for practice.

  Design: The study design was qualitative and comprised three interlinked phases: a documentary analysis, interviews and consultation meetings. Altheide and Johnson's Analytic Realism theoretical framework guided the thematic data analysis process.

  Setting: The study was conducted in three NHS Trusts in South England. Two were secondary care settings and the third was a tertiary centre.

  Participants: The secondary care trusts saw 15-20 patients with new mesothelioma per year and the tertiary centre 30-40. The tertiary centre had a designated mesothelioma team. Twenty-one patients met the inclusion criteria: >18 years, mesothelioma diagnosis and in follow-up care. Non-English speaking participants, those unable to provide written informed consent or those whom the clinical team felt would find participation too distressing were excluded. All participants were white, 71% were 70-79 years old and 71% were men. Three consultation meetings were conducted with key stakeholders including mesothelioma nurse specialists, patients with mesothelioma, carers and local clinical commissioning group members.

  Main Outcome Measures: Specific outcomes were to gain a detailed understanding of mesothelioma follow-up care pathways and processes and to develop coproduced recommendations for practice.

  Results: Mesothelioma pathways were not always distinct from lung cancer care pathways. All trusts provided follow-up information and resources but there was varied information on how to access local support groups, research or clinical trial participation. Five themes were developed relating to people; processes; places; purpose and perception of care. Coproduced recommendations for improving mesothelioma follow-up pathways were developed following the consultation meetings.

  Conclusions: This study has developed recommendations which identify the need for patients with pleural mesothelioma to access consistent, specialist, streamlined mesothelioma care, centred around specialist mesothelioma nurses and respiratory consultants, with input from the wider multidisciplinary team.

  © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Association of occupational dust exposure with combined chronic obstructive pulmonary disease and pneumoconiosis: a cross-sectional study in China. Y. Fan, W. Xu, Y. Wang, et al. 2020;10(9):e038874. PubMed · Publisher · Free full text

  Abstract

  Objectives: Occupational dust exposure may induce various lung diseases, including pneumoconiosis and chronic obstructive pulmonary disease (COPD). The features of combined COPD and pneumoconiosis have not been well described, and this may hamper the management. This study aimed to describe the prevalence and characteristics as well as the risk factors of the combined diseases.

  Design: A cross-sectional study.

  Setting And Participants: 758 patients with pneumoconiosis were recruited at a single-medical centre. Of these, 675 patients with pneumoconiosis, including asbestosis, silicosis, coal workers' pneumoconiosis and other pneumoconiosis, was eligible for analysis.

  Primary Outcome Measures: COPD was diagnosed based on clinical features and/or history of exposure to risk factors and post bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. Clinical data were collected from predesigned medical reports. The patients underwent both chest radiograph and high-resolution CT scans. Risk factors for combined COPD and pneumoconiosis were analysed using regression analysis.

  Results: COPD prevalence overall was 32.7% (221/675) and was the highest in silicosis (84/221) and coal workers' pneumoconiosis (100/221). COPD prevalence increased with smoking pack-years, dust exposure duration and pneumoconiosis stage. Patients with combined diseases had lower body mass index, higher smoking index and worse pulmonary function. Risk factors for combined diseases included heavy smoking, silica or coal exposure and advanced pneumoconiosis. The interaction between dust exposure and smoking in COPD was also identified. The risk of combined COPD significantly increased with heavy smoking and silica or coal exposure (OR 5.49, 95% CI 3.04 to 9.93, p<0.001).

  Conclusions: COPD is highly prevalent in patients with pneumoconiosis, especially patients with silicosis and coal workers' pneumoconiosis. Occupational dust exposure as well as heavy smoking is associated with an increased risk of combined COPD and pneumoconiosis, which demands an effective preventive intervention.

  © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• 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. E. Lim, L. Darlison, J. Edwards, et al. 2020;10(9):e038892. PubMed · Publisher · Free full text

  Abstract

  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.

  © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

• Relative burden of lung and pleural cancers from exposure to asbestos: a cross-sectional analysis of occupational mortality in England and Wales. E.C. Harris, S. D'Angelo, A. Darnton, et al. 2020;10(4):e036319. PubMed · Publisher · Free full text

  Abstract

  Objectives: To explore the extent to which asbestos-exposed jobs vary in the ratio of excess mortality from lung cancer to deaths from pleural cancer.

  Design: Using data on underlying cause of death and last full-time occupation for 3 688 916 deaths among men aged 20-74 years in England and Wales during 1979-2010, we calculated proportional mortality ratios (PMRs), standardised for age and social class, with all occupations combined as reference. For each of 22 asbestos-exposed job groups with significantly elevated PMRs for pleural cancer, we calculated excess mortality from lung cancer (observed minus expected deaths) and its ratio to number of deaths from pleural cancer. To reduce confounding effects of smoking, we adjusted expected deaths from lung cancer in each job group, according to a formula based on its PMR for chronic obstructive pulmonary disease.

  Setting: England and Wales.

  Participants: 3 688 916 men who died aged 20-74 years during 1979-2010.

  Outcome Measures: Ratios of excess mortality from lung cancer to deaths from pleural cancer by job group.

  Results: Adjusted PMRs for lung cancer were elevated in all but 4 of the 22 asbestos-exposed job groups, but the ratio of excess lung cancer to deaths from pleural cancer varied widely between job groups, being significantly greater than the overall ratio in six, and significantly less in seven. Analysis for 2001-2010, when (because of changes in coding) ascertainment of pleural tumours was more reliable, showed similar variation between job groups, and indicated an overall ratio of 0.28.

  Conclusions: Excess lung cancer in asbestos-exposed jobs is not in a simple proportion to deaths from pleural cancer, and the ratio may vary importantly according to intensity of exposure to different types of asbestos and concomitant smoking habits. The current burden of lung cancer from occupational exposure to asbestos in Britain may not be so high as previously thought.

  © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

2010s

• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial. N.L. de Boer, J.P. van Kooten, J.W.A. Burger, et al. 2019;9(5):e026779. PubMed · Publisher · Free full text

  Abstract

  Introduction: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

  Methods And Analysis: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.

  Intervention: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

  Ethics And Dissemination: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

  Trial Registration Number: NTR7060. EudraCT: 2017-000897-12; Pre-Results.

  © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Are the knowledge of non-malignant asbestos-related diseases and lung function impairment differentially associated with psychological well-being? A cross-sectional study in formerly asbestos-exposed workers in Germany. J. Lang, M.K. Felten, T. Kraus. 2019;9(10):e030094. PubMed · Publisher · Free full text

  Abstract

  Objectives: The knowledge of past asbestos exposure may lead to chronic psychological strain. In addition, the information about an increased cancer risk can place a psychological burden on individuals triggering mental health symptoms of depression or anxiety. This applies in particular to individuals with non-malignant asbestos-related disease (ARD) such as lung fibrosis and pleural thickening with or without lung function impairment. ARDs with or without lung function impairment may develop even years after exposure cessation. Therefore, the aim of the present study was to test for our cohort whether non-malignant ARD and lung function impairment have differential effects on mental health and psychological strain.

  Design: Cross-sectional study.

  Participants And Setting: Overall, 612 male participants (mean age=66.2 years, SD=9.5) attending a surveillance programme for ARDs received routine examinations including lung function testing (24% refused to fill in the psychological questionnaire) at a German university hospital study centre from August 2008 to August 2013.

  Outcome Measures: Using multiple hierarchical regression analysis, ARD diagnosis and lung function impairment were used to predict psychological health as measured with validated questionnaires for depression and anxiety. Psychological strain was operationalised by intrusive thoughts and specific fear of cancer.

  Results: The strongest predictor for mental health was obstructive functional impairment (eg, anxiety: β=0.22, p<0.001). Psychological strain was predicted by the presence of a non-malignant ARD (eg, intrusive thoughts: β=0.17, p=0.003).

  Conclusions: The presence of mental health symptoms is associated with ventilation disturbances, whereas the knowledge of an already initiated morphological change-caused by asbestos exposure-is primarily associated with psychological strain. Specifically, the affected individuals are more prone to intrusive thoughts and specific fear of asbestos-related cancer. As an implication, physicians should be sensitised about possible consequences of risk communication and functional impairment to counteract excessive fear or anxiety.

  © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Bibliometric analysis of gaps in research on asbestos-related diseases: declining emphasis on public health over 26 years. R.T. Lin, M.J. Soeberg, L.C. Chien, et al. 2018;8(7):e022806. PubMed · Publisher · Free full text

  Abstract

  Objectives: The global burden of asbestos-related diseases (ARDs) is significant, and most of the world's population live in countries where asbestos use continues. We examined the gaps between ARD research and suggestions of WHO and the International Labour Organization on prevention.

  Methods: From the Web of Science, we collected data on all articles published during 1991-2016 and identified a subset of ARD-related articles. We classified articles into three research areas-laboratory, clinical and public health-and examined their time trends. For all and the top 11 countries publishing ARD-related articles, we calculated the proportions of all ARD-related articles that were in each of the three areas, the average rates of ARD-related articles over all articles, and the average annual per cent changes of rates.

  Results: ARD-related articles (n=14 284) accounted for 1.3‰ of all articles in 1991, but this had declined to 0.8‰ by 2016. Among the three research areas, the clinical area accounted for the largest proportion (65.0%), followed by laboratory (26.5%) and public health (24.9%). The public health area declined faster than the other areas, at -5.7% per year. Discrepancies were also observed among the top 11 countries regarding emphasis on public health research, with Finland and Italy having higher, and China and the Netherlands lower, emphases.

  Conclusions: There is declining emphasis on the public health area in the ARD-related literature. Under the ongoing global situation of ARD, primary prevention will remain key for some time, warranting efforts to rectify the current trend in ARD-related research.

  © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan. L.J. Lee, C.K. Lin, C.H. Pan, et al. 2018;8(12):e021063. PubMed · Publisher · Free full text

  Abstract

  Objective: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.

  Methods: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.

  Results: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.

  Conclusions: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.

  © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study. S. Casjens, D.G. Weber, G. Johnen, et al. 2017;7(10):e017104. PubMed · Publisher · Free full text

  Abstract

  Objectives: Mesothelin and calretinin are blood-based markers for malignant mesothelioma. The objective of this study was to analyse the markers in plasma samples from cancer-free men and to identify factors influencing their concentrations to minimise false-positive test results when using these markers for the early detection of malignant mesothelioma.

  Setting: The present analyses used data and archived blood samples of the population-based Heinz Nixdorf Recall Study among elderly people collected from 2011 to 2014.

  Participants: A total of 569 men (median age 70 years) without a malignant disease at the time of blood sampling were selected for these analyses.

  Primary And Secondary Outcome: Mesothelin and calretinin concentration in plasma samples.

  Results: We observed 24 mesothelin concentrations ≥1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%) and 34 calretinin concentrations ≥1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to 95.7%). Only five men had both markers above these cut-offs. Renal dysfunction and hypertension were major predictors of elevated mesothelin in addition to age. Regarding calretinin, the effect of renal dysfunction was slightly weaker and hypertension was not associated with increased concentrations. However, a diagnosis of cancer after blood collection and bronchial asthma were associated with positive calretinin results.

  Conclusions: The combined determination of mesothelin and calretinin results in only few false-positive marker tests. Both markers are mainly influenced by renal dysfunction. The determination of cystatin C concentrations may be informative when interpreting the test results.

  © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

• Investments in cancer research awarded to UK institutions and the global burden of cancer 2000-2013: a systematic analysis. M. Maruthappu, M.G. Head, C.D. Zhou, et al. 2017;7(4):e013936. PubMed · Publisher · Free full text

  Abstract

  Objectives: To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs).

  Design: Systematic analysis of all open-access data.

  Setting And Participants: Public and philanthropic funding to all UK cancer research institutions, 2000-2013.

  Main Outcome Measures: Number and financial value of cancer research investments reported in 2013 UK pounds (UK£). Mortality, DALYs and YLDs data were acquired from the Global Burden of Disease Study. A compound metric was adapted to estimate research investment relative to disease burden as measured by mortality, DALYs and YLDs.

  Results: We identified 4299 funded studies with a total research investment of £2.4 billion. The highest fundings by anatomical sites were haematological, breast, prostate, colorectal and ovarian cancers. Relative to disease burden as determined by a compound metric combining mortality, DALYs and YLDs, gender-specific cancers were found to be highest funded-the five sites that received the most funding were prostate, ovarian, breast, mesothelioma and testicular cancer; the least well-funded sites were liver, thyroid, lung, upper gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of award numbers and 62.2% of all funding. The top five areas of primary research focus by funding were pathogenesis, drug therapy, diagnostic, screening and monitoring, women's health and immunology. The largest individual funder was the Medical Research Council. In combination, the five lowest funded site-specific cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of worldwide cancer mortality, DALYs and YLDs.

  Conclusions: Research funding for cancer is not allocated according to relative disease burden. These findings are in line with earlier published studies. Funding agencies and industry should openly document their research investments to improve better targeting of research investment.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

• Radiographic features of importance in the National Institute for Occupational Safety and Health-administered Coal Workers' Health Surveillance Program: characterising the use of the 'other symbols'. C.N. Halldin, J.M. Hale, D.J. Blackley, et al. 2017;7(8):e015876. PubMed · Publisher · Free full text

  Abstract

  Objective: The National Institute for Occupation Safety and Health-administered Coal Workers' Health Surveillance Program (CWHSP) provides radiographic pneumoconiosis screening for US coal miners. Radiographs are classified by readers according to International Labour Office criteria. In addition to pneumoconiotic parenchymal and pleural lung abnormalities, readers document radiographic features of importance (other symbols). Other symbols are not meant to imply a diagnosis or interpretation but are relevant as they provide information beyond a pneumoconiosis classification for features related to dust exposure and other aetiologies. Our objective was to summarise other symbol data from 48 years of CWHSP participants.

  Methods: Chest radiograph classifications obtained from CWHSP participants between July 1968 and July 2016 were analysed. Any 'other symbol' indication from any of the readings were counted. Frequencies were tabulated by individual reader and those identified by any reader.

  Results: Of the 469 922 radiographs included in this study, nearly 15% had at least one reader identify a radiographic feature of importance. The most commonly identified other symbol was cancer (excluding mesothelioma) (6.83%), followed by emphysema (1.68%). Some features were rarely identified over the 48 years of data collection such as rheumatoid pneumoconiosis (n=46), pneumothorax (n=32), mesothelioma (n=12) and rounded atelectasis (n=4).

  Conclusions: This is the largest study to date describing radiographic features of importance as part of routine chest radiographic surveillance. While these symbols are not diagnostic they can be used to describe features associated with dust exposure. One of the most commonly identified radiographic features in our population is emphysema which is associated with respirable dust exposure. These results can be compared with other dust exposed populations.

  © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

• Cancer and non-cancer mortality among French uranium cycle workers: the TRACY cohort. E. Samson, I. Piot, S. Zhivin, et al. 2016;6(4):e010316. PubMed · Publisher · Free full text

  Abstract

  Objectives: The health effects of internal contamination by radionuclides, and notably by uranium, are poorly characterised. New cohorts of uranium workers are needed to better examine these effects. This paper analyses for the first time the mortality profile of the French cohort of uranium cycle workers. It considers mortality from cancer and non-cancer causes.

  Methods: The cohort includes workers employed at least 6 months between 1958 and 2006 in French companies involved in the production of nuclear fuel. Vital status and causes of death were collected from French national registries. Workers were followed-up from 1 January 1968 to 31 December 2008. Standardised mortality ratios (SMRs) were computed based on mortality rates for the French general population.

  Results: The cohort includes 12,649 workers (88% men). The average length of follow-up is 27 years and the mean age at the end of the study is 60 years. Large mortality deficits are observed for non-cancer causes of death such as non-cancer respiratory diseases (SMR=0.51 (0.41 to 0.63)) and circulatory diseases (SMR=0.68 (0.62 to 0.74)). A mortality deficit of lower magnitude is also observed for all cancers combined (SMR (95% CI): 0.76 (0.71 to 0.81)). Pleural mesothelioma is elevated (SMR=2.04 (1.19 to 3.27)).

  Conclusions: A healthy worker effect is observed in this new cohort of workers involved in the uranium cycle. Collection of individual information on internal uranium exposure as well as other risk factors is underway, to allow for the investigation of uranium-related risks.

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• Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study. S. Tsim, C. Kelly, L. Alexander, et al. 2016;6(11):e013324. PubMed · Publisher · Free full text

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

  Methods And Analysis: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.

  Ethics And Dissemination: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.

  Trial Registration Number: ISRCTN10079972, Pre-results.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

• Principal components analysis to identify influences on research communication and engagement during an environmental disaster. C.A. Winters, C.F. Moore, S.W. Kuntz, et al. 2016;6(8):e012106. PubMed · Publisher · Free full text

  Abstract

  Objectives: To discern community attitudes towards research engagement in Libby, Montana, the only Superfund site for which a public health emergency has been declared.

  Study Design: Survey study of convenience samples of residents near the Libby, Montana Superfund site.

  Participants: Residents of the Libby, Montana area were recruited from a local retail establishment (N=120, survey 1) or a community event (N=127, survey 2).

  Measures: Two surveys were developed in consultation with a Community Advisory Panel.

  Results: Principal components of survey 1 showed four dimensions of community members' attitudes towards research engagement: (1) researcher communication and contributions to the community, (2) identity and affiliation of the researchers requesting participation, (3) potential personal barriers, including data confidentiality, painful or invasive procedures and effects on health insurance and (4) research benefits for the community, oneself or family. The score on the first factor was positively related to desire to participate in research (r=0.31, p=0.01). Scores on factors 2 and 3 were higher for those with diagnosis of asbestos-related disease (ARD) in the family (Cohen's d=0.41, 0.57). Survey 2 also found more positive attitudes towards research when a family member had ARD (Cohen's d=0.48).

  Conclusions: Principal components analysis shows different dimensions of attitudes towards research engagement. The different dimensions are related to community members' desire to be invited to participate in research, awareness of past research in the community and having been screened or diagnosed with a health condition related to the Superfund contaminant.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention. N. Bayman, D. Ardron, L. Ashcroft, et al. 2016;6(1):e010589. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Introduction: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development.

  Methods And Analysis: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year.

  Ethics And Dissemination: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018.

  Trial Registration Number: ISRCTN04240319; NCT01604005; Pre-results.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters. M. Azzopardi, R. Thomas, S. Muruganandan, et al. 2016;6(7):e011480. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Introduction: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.

  Methods And Analysis: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.

  Ethics And Dissemination: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.

  Trial Registration Number: ACTRN12615000963527; Pre-results.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• What is the role of a specialist regional mesothelioma multidisciplinary team meeting? A service evaluation of one tertiary referral centre in the UK. A.C. Bibby, K. Williams, S. Smith, et al. 2016;6(9):e012092. PubMed · Publisher · Free full text

  Abstract

  Background: Multidisciplinary team meetings are standard care for cancer in the UK and Europe. Professional bodies recommend that mesothelioma cases should be discussed at specialist multidisciplinary team meetings. However, no evidence exists exploring the role of the specialist mesothelioma multidisciplinary team meeting.

  Objectives: To evaluate the clinical activity of 1 specialist mesothelioma multidisciplinary team meeting and to determine how often a definitive diagnosis was made, whether the core requirements of the meeting were met and whether there was any associated benefit or detriment.

  Design And Setting: A service evaluation using routinely collected data from 1 specialist mesothelioma multidisciplinary team meeting in a tertiary referral hospital in the South-West of England.

  Participants: All cases discussed between 1/1/2014 and 31/12/2015.

  Outcome Measures: The primary outcome measure was whether a definitive diagnosis was made. Secondary outcomes included whether treatment advice was offered, information on clinical trials provided or further investigations suggested. Additional benefits of the multidisciplinary team meeting and time taken from referral to outcome were also collected.

  Results: A definitive diagnosis was reached in 171 of 210 cases discussed (81%). Mesothelioma was diagnosed in 153/210 (73%). Treatment advice was provided for 127 of 171 diagnostic cases (74%) and further investigations suggested for all 35 non-diagnostic cases. 86/210 cases (41%) were invited to participate in a trial, of whom 43/86 (50%) subsequently enrolled. Additional benefits included the avoidance of postmortem examination if the coroner was satisfied with the multidisciplinary team decision. The overall process from referral to outcome dispatch was <2 weeks in 75% of cases.

  Conclusions: This specialist mesothelioma multidisciplinary team meeting was effective at making diagnoses and providing recommendations for further investigations or treatment. The core requirements of a specialist mesothelioma multidisciplinary team meeting were met. The process was timely, with most outcomes returned within 2 weeks of referral.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001-2009). L. Van den Borre, P. Deboosere. 2015;5(6):e007384. PubMed · Publisher · Free full text

  Abstract

  Objective: To investigate cause-specific mortality among asbestos workers and potentially exposed workers in Belgium and evaluate potential excess in mortality due to established and suspected asbestos-related diseases.

  Design: This cohort study is based on an individual record linkage between the 1991 Belgian census and cause-specific mortality information for Flanders and Brussels (2001-2009).

  Setting: Belgium (Flanders and Brussels region).

  Participants: The study population consists of 1,397,699 male workers (18-65,years) with 72,074 deaths between 1 October 2001 and 31 December 2009. Using a classification of high-risk industries, mortality patterns between 2056 asbestos workers, 385,046 potentially exposed workers and the working population have been compared.

  Outcome Measures: Standardised mortality ratios (SMRs) and 95% CIs are calculated for manual and non-manual workers.

  Results: Our findings show clear excess in asbestos-related mortality in the asbestos industry with SMRs for mesothelioma of 4071 (CI 2327 to 6611) among manual workers and of 4489 (CI 1458 to 10,476) among non-manual workers. Excess risks in asbestos-related mortality are also found in the chemical industry, the construction industry, the electrical generation and distribution industry, the basic metals manufacturing industry, the metal products manufacturing industry, the railroad industry, and the shipping industry. Oral cancer mortality is significantly higher for asbestos workers (SMR 383; CI 124 to 894), railroad workers (SMR 192; CI 112 to 308), shipping workers (SMR 172; CI 102 to 271) and construction workers (SMR 125; CI 100 to 153), indicating a possible association with occupational asbestos exposure. Workers in all four industries have elevated mortality rates for cancer of the mouth. Only construction workers experience significantly higher pharyngeal cancer mortality (SMR 151; CI 104 to 212).

  Conclusions: The study identifies vulnerable groups of Belgian asbestos workers, demonstrating the current-day health repercussions of historical asbestos use. Results support the hypothesis of a possible association between the development of oral cancer and occupational asbestos exposure.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

• Protocol for the surgical and large bore procedures in malignant pleural mesothelioma and radiotherapy trial (SMART Trial): an RCT evaluating whether prophylactic radiotherapy reduces the incidence of procedure tract metastases. A.O. Clive, P. Wilson, H. Taylor, et al. 2015;5(1):e006673. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Introduction: Patients with malignant pleural mesothelioma (MPM) may develop painful 'procedure tract metastasis' (PTM) at the site of previous pleural interventions. Prophylactic radiotherapy has been used to minimise this complication; however, three small randomised trials have shown conflicting results regarding its effectiveness. The surgical and large bore procedures in malignant pleural mesothelioma and radiotherapy trial (SMART Trial) is a suitably powered, multicentre, randomised controlled trial, designed to evaluate the efficacy of prophylactic radiotherapy within 42 days of pleural instrumentation in preventing the development of PTM in MPM.

  Methods And Analysis: 203 patients with a histocytologically proven diagnosis of MPM, who have undergone a large bore pleural intervention (thoracic surgery, large bore chest drain, indwelling pleural catheter or local anaesthetic thoracoscopy) in the previous 35 days, will be recruited from UK hospitals. Patients will be randomised (1:1) to receive immediate radiotherapy (21 Gy in 3 fractions over 3 working days within 42 days of the pleural intervention) or deferred radiotherapy (21 Gy in 3 fractions over 3 working days given if a PTM develops). Patients will be followed up for 12 months. The primary outcome measure is the rate of PTM until death or 12 months (whichever is sooner), as defined by the presence of a clinically palpable nodule of at least 1 cm diameter felt within 7 cm of the margins of the procedure site as confirmed by two assessors. Secondary outcome measures include chest pain, quality of life, analgaesic requirements, healthcare utilisation and safety (including radiotherapy toxicity).

  Ethics And Dissemination: The trial has received ethical approval from the Southampton B Research Ethics Committee (11/SC/0408). There is a Trial Steering Committee, including independent members and a patient and public representative. The trial results will be published in a peer-reviewed journal and presented at international conferences.

  Trial Registration Number: ISRCTN72767336.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

• Comparison of the ultra-low-dose Veo algorithm with the gold standard filtered back projection for detecting pulmonary asbestos-related conditions: a clinical observational study. M. Tekath, F. Dutheil, R. Bellini, et al. 2014;4(5):e004980. PubMed · Publisher · Free full text

  Abstract

  Objectives: Radiation delivered during CT is a major concern, especially for individuals undergoing repeated screening. We aimed to compare a new ultra-low-dose algorithm called Veo with the gold standard filtered back projection (FBP) for detecting pulmonary asbestos-related conditions.

  Setting: University Hospital CHU G. Montpied, Clermont-Ferrand, France

  Participants: Asbestos-exposed workers were recruited following referral to screening for asbestos-related conditions. Two acquisitions were performed on a 64-slice CT: the gold standard FBP followed by Veo reconstruction.

  Outcome Measures: Two radiologists independently assessed asbestos-related abnormalities, pulmonary nodules, radiation doses and image quality (noise).

  Results: We included 27 asbestos-exposed workers (63.3±6.5 years with 11.9±9.7 years of asbestos exposure). We observed 297 pleural plaques in 20 participants (74%). All patients (100%) had pulmonary nodules, totalling 167 nodules. Detection rates did not differ for pleural plaques (Veo 87% vs FBP 97%, NS), pleural thickening (100% for both) and pulmonary nodules (80% for both). Interstitial abnormalities were depicted less frequently with Veo than FBP. False negative and false positive did not exceed 2.7%. Compared with FBP, Veo decreased the radiation dose up to 87% (Veo 0.23±0.07 vs FBP 1.83±0.88 mSv, p<0.001). The objective image noise also decreased with Veo as much as 23% and signal-to-noise ratio increased up to 33%.

  Conclusions: A low-dose CT with Veo reconstruction substantially reduced radiation. Veo compared favourably with FBP in detecting pleural plaques, pleural thickening and pulmonary nodules. These results should be confirmed on a larger sample size before the use of Veo in clinical routine practice in asbestos-related conditions, especially regarding the low prevalence of interstitial abnormalities in this study.

  Trial Registration Number: NCT01955018.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

• Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis. A. Cui, X.G. Jin, K. Zhai, et al. 2014;4(2):e004145. Meta-analysis · Systematic review PubMed · Publisher · Free full text

  Abstract

  Objective: Although the values of soluble mesothelin-related peptides (SMRPs), including mesothelin and megakaryocyte potentiating factor, in serum and/or pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been extensively studied, the exact diagnostic accuracy of these SMRPs remains controversial. The purpose of the present meta-analysis is to update the overall diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic accuracy of SMRPs in pleural fluid for MPM.

  Design: Systematic review and meta-analysis.

  Methods: A total of 30 articles of diagnostic studies were included in the current meta-analysis. Sensitivity, specificity and other measures of accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.

  Results: The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was also found that megakaryocyte potentiating factor in serum had a superior diagnostic accuracy compared with mesothelin for MPM.

  Conclusions: SMRPs in both serum and pleural fluid are helpful markers for diagnosing MPM with similar diagnostic accuracy. The negative results of SMRP determinations are not sufficient to exclude non-MPM, and the positive test results indicate that further invasive diagnostic steps might be necessary for the diagnosis of MPM.

• A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema. T. Kishaba, Y. Shimaoka, H. Fukuyama, et al. 2012;2(3). PubMed · Publisher · Free full text

  Abstract

  Objectives: Our purpose was to assess the clinical data, predictors of mortality and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE) patients.

  Design: Single-centre retrospective cohort study.

  Setting: Teaching hospital in Japan.

  Participants: We identified 93 CPFE patients with high-resolution computed tomographic (HRCT) through multidisciplinary discussion. Patients who had connective tissue disease, drug-associated interstitial lung disease and occupationally related interstitial lung disease, such as asbestosis and silicosis, were excluded.

  Interventions: There were no interventions.

  Methods: Medical records and HRCT scans from January 2002 through December 2007 were reviewed retrospectively at our hospital. Ninety-three patients had CPFE.

  Results: The mean age of CPFE patients was 74 years. Idiopathic pulmonary fibrosis and non-specific interstitial pneumonia were observed as distinct HRCT patterns. Forty-two patients showed finger clubbing. Mean serum Krebs von den Lungen-6 (KL-6) and per cent predicted forced vital capacity (%FVC) were 1089 IU/l, 63.86%, respectively. Twenty-two patients developed AE during observation period. Baseline KL-6 was a strong predictor of AE (OR=1.0016, p=0.009). Finger clubbing (HR=2.2620, p=0.015) and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 (HR=1.9259, p=0.048) were independent predictors of mortality in CPFE.

  Conclusions: Baseline serum KL-6 was a useful predictor of AE (cut-off =1050, receiver operator characteristic curve: 0.7720), which occurred in 24% (22/93) of the CPFE patients. Finger clubbing and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 were independent predictors of mortality.

• Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos. C.A. Winters, W.G. Hill, K. Rowse, et al. 2012;2(6). PubMed · Publisher · Free full text

  Abstract

  Objective: Describe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite.

  Design: Cross-sectional descriptive.

  Setting: Asbestos-related disease clinic in Libby, Montana USA.

  Participants: 329 individuals exposed to LAA; mostly men, married, between 50 and 69 years; two-thirds lived in the surrounding county; one-third lived elsewhere in the state and USA.

  Primary Outcome Measures: Chest radiograph (CXR), pulmonary function data and the St George Respiratory Questionnaire (SGRQ).

  Results: Exposure categories included vermiculite workers=7.6%; family/household contact of vermiculite worker=32%; and environmental exposure only=60%. Of the participants, 55% had only pleural abnormalities; 5.4% had only interstitial abnormalities; nearly 21% had both abnormalities and 18% had no lung abnormality on chest x-ray. Mean forced vital capacity (FVC) 95.3% (SD=18.7); forced expiratory volume (FEV(1)) mean 87% (SD=20.2); ratio of FEV1(1)/FVC 95.5% (SD=12.0); and diffusing capacity (DLCO) of 83% (SD=21.7) of the percent predicted. The mean total SGRQ (38.5; SD=22.1) indicated a lower quality of life than healthy persons and persons with other chronic conditions. SGRQ subscale means were Symptoms 52.1 (SD=24.9), activity 49.4 (SD=26.9) and impacts 27.5 (SD=21.9). Participants with normal CXR differed significantly from those with both interstitial and pleural abnormalities on total, activity and impacts scores. For activity alone, subjects with normal CXR differed significantly from those with pleural disease; no differences were found for those with interstitial disease. Significant findings were found for smoking history across all pulmonary measures, and for exposure status, radiographic findings, age and gender for select pulmonary parameters. Subjects with any smoking history had significantly worse average total and subscale scores on the SGRQ.

  Conclusions: Of 329 persons exposed to LAA, the majority (182) had pleural abnormalities identified on CXR. SGRQ scores for persons with abnormalities (pleural, interstitial or both) (269) differed significantly from those with a normal CXR.

• Utilisation of a thoracic oncology database to capture radiological and pathological images for evaluation of response to chemotherapy in patients with malignant pleural mesothelioma. G.B. Carey, S. Kazantsev, M. Surati, et al. 2012;2(5). PubMed · Publisher · Free full text

  Abstract

  Objective: An area of need in cancer informatics is the ability to store images in a comprehensive database as part of translational cancer research. To meet this need, we have implemented a novel tandem database infrastructure that facilitates image storage and utilisation.

  Background: We had previously implemented the Thoracic Oncology Program Database Project (TOPDP) database for our translational cancer research needs. While useful for many research endeavours, it is unable to store images, hence our need to implement an imaging database which could communicate easily with the TOPDP database.

  Methods: The Thoracic Oncology Research Program (TORP) imaging database was designed using the Research Electronic Data Capture (REDCap) platform, which was developed by Vanderbilt University. To demonstrate proof of principle and evaluate utility, we performed a retrospective investigation into tumour response for malignant pleural mesothelioma (MPM) patients treated at the University of Chicago Medical Center with either of two analogous chemotherapy regimens and consented to at least one of two UCMC IRB protocols, 9571 and 13473A.

  Results: A cohort of 22 MPM patients was identified using clinical data in the TOPDP database. After measurements were acquired, two representative CT images and 0-35 histological images per patient were successfully stored in the TORP database, along with clinical and demographic data.

  Discussion: We implemented the TORP imaging database to be used in conjunction with our comprehensive TOPDP database. While it requires an additional effort to use two databases, our database infrastructure facilitates more comprehensive translational research.

  Conclusions: The investigation described herein demonstrates the successful implementation of this novel tandem imaging database infrastructure, as well as the potential utility of investigations enabled by it. The data model presented here can be utilised as the basis for further development of other larger, more streamlined databases in the future.

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