Epidemiology of Adult Pleural Disease in the United States.

BACKGROUND: Comprehensive US epidemiologic data for adult pleural disease are not available. RESEARCH QUESTION: What are the epidemiologic measures related to adult pleural disease in the United States? STUDY DESIGN AND METHODS: Retrospective cohort study using Healthcare Utilization Project databases (2007-2016). Adults (≥ 18 years of age) with malignant pleural mesothelioma, malignant pleural effusion, nonmalignant pleural effusion, empyema, primary and secondary spontaneous pneumothorax, iatrogenic pneumothorax, and pleural TB were studied. RESULTS: In 2016, ED treat-and-discharge (T&D) visits totaled 42,215, accounting for charges of $286.7 million. In 2016, a total of 361,270 hospitalizations occurred, resulting in national costs of $10.1 billion. A total of 64,174 readmissions contributed $1.16 billion in additional national costs. Nonmalignant pleural effusion constituted 85.5% of ED T&D visits, 63.5% of hospitalizations, and 66.3% of 30-day readmissions. Contemporary sex distribution (male to female ratio) in primary spontaneous pneumothorax (2.1:1) differs from older estimates (6.2:1). Decadal analyses of annual hospitalization rates/100,000 adult population (2007 vs 2016) showed a significant (P < .001) decrease for malignant pleural mesothelioma (1.3 vs 1.09, respectively), malignant pleural effusion (33.4 vs 31.9, respectively), iatrogenic pneumothorax (17.9 vs 13.9, respectively), and pleural TB (0.20 vs 0.09, respectively) and an increase for empyema (8.1 vs 11.1, respectively) and nonmalignant pleural effusion (78.1 vs 100.1, respectively). Empyema hospitalizations have high costs per case ($38,591) and length of stay (13.8 days). The mean proportion of readmissions attributed to a pleural cause varied widely: malignant pleural mesothelioma, 49%; malignant pleural effusion, 45%; nonmalignant pleural effusion, 31%; empyema, 27%; primary spontaneous pneumothorax, 27%; secondary spontaneous pneumothorax, 27%; and iatrogenic pneumothorax, 20%. Secondary spontaneous pneumothorax had the shortest time to readmission in 2016 (10.3 days, 95% CI, 8.8-11.8 days). INTERPRETATION: Significant epidemiologic trends and changes in various pleural diseases were observed. The analysis identifies multiple opportunities for improvement in management of pleural diseases.

CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.

BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK. TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.

The economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure.

OBJECTIVES: To estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada. METHODS: We estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs. RESULTS: There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively. CONCLUSIONS: The economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation.

MesobanK UK: an international mesothelioma bioresource.

Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos-related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750-patient tissue microarray and prospectively collected tissue, blood and pleural fluid from 300 patients with mesothelioma. Twenty-six new cell lines have also been developed. MesobanK meets all appropriate ethical and regulatory procedures and has recently opened to requests for tissue and data.

[Health expenditures for cases of pleural mesothelioma]. / Quanto costa in prestazioni sanitare un paziente con mesothelioma della pleura?.

Through the study of 65 cases of probable pleural mesothelioma currently under discussion in 4 criminal trials in the Lombardy Region, who died between 2002 and 2015, this study aimed to provide economical information regarding the health expenditures sustained by the Regional Health Service (RHS) for providing hospitalization, outpatient services and drugs to such patients. Health information regarding the services provided for the cases under study were electronically retrieved from the RHS information system. For each pleural mesothelioma case the costs (on average) were about 67,000 euros, 37,000 of which were spent after the date of diagnosis. Drugs formed the largest part of health expenditure (about 37,000 euros per person). Per capita expenditures showed a peak near (before and after) the date of diagnosis, rising when approaching the date of death and with increasing age of the patient, and did not vary with survival time. This information, reported for the first time in detail in this paper, will be useful for out-of-court agreements and for setting up reimbursement schemes, and describe per capita expenditures which are higher than estimations proposed in recent criminal trials in Italy and to those reported in the international literature.

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

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

Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.

BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. FUNDING: BUPA Foundation.

Estimating the social cost of respiratory cancer cases attributable to occupational exposures in France.

PURPOSE: The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010. METHODS: According to the attributable fraction method and based on available epidemiological data from the literature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost-of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres. RESULTS: The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92%) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66% of total costs. CONCLUSION: Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valuable information for policy-makers responsible for defining public health priorities.

Post-occupational health surveillance of asbestos workers.

BACKGROUND: Italian law requires an extensive health surveillance of workers after cessation of their employment status in the case of occupational exposure to carcinogens, including asbestos. Nonetheless, Italian law does not specify the timeframe of these clinical checks, nor who has financial and organizational responsibility for this surveillance. A literature search confirmed a lack of consensus around the objectives and methods to follow up workers with past occupational exposure to asbestos. OBJECTIVES: To develop an updated evidence-based methodology for an appropriate health surveillance programme. METHODS: We present an overview of the field experience developed by the Veneto Region from 2000 to 2011, and new studies that could contribute to establishing a national policy for the medical surveillance of workers with past asbestos exposure. RESULTS: There were three specific topics: (1) definition of a reliable method to identify asbestos workers (through multiple sources and procedures that meet current confidentiality regulations); (2) detection of asbestos fibres in biological media (to support the etiological diagnosis of asbestos-related diseases); (3) creation of a national protocol of health surveillance (through the assessment of policies developed by other Regions in this field, and recruiting from these regions a cohort of past-exposed workers: the epidemiological study should offer relevant suggestions for specific surveillance approaches, based on either estimated cumulative asbestos exposure or detection of x-ray patterns of pleural plaques and/or asbestosis). CONCLUSIONS: These studies will support the Regions in setting up health care policies directed at workers with past asbestos exposure.

Compensation of pleural mesothelioma in France: data from the French National Mesothelioma Surveillance Programme.

BACKGROUND: The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France. METHODS: The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed. RESULTS: Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease. CONCLUSIONS: Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France.

[The effectiveness of compensation system for mesotheliomas due to occupational exposure to asbestos and determinants for requests and awards: an evaluation based on record-linkage between the Veneto Mesothelioma Register and the claims and compensations recorded by the National Insurance Institute (INAIL)]. / I fattori che influenzano in Italia la domanda e il riconoscimento dei mesoteliomi di origine professionale: analisi basata su record-linkage tra dati del registro regionale del Veneto e INAIL.

AIM: To determine the rate of requests for compensation and of compensations awarded for mesothelioma cases due to occupational exposure to asbestos; to identify factors that may influence the outcome; to provide an appreciation of the amount of compensation. DESIGN AND MAIN OUTCOME MEASURES: Record-linkage study at individual level between the new cases of mesothelioma occurred among the residents of the Veneto Region (Northern Italy) between 1999- 2007 and the file of the Insurance Institute, with individual data on all claims and compensations. Adjusted logistic regression models were used to estimated the association between submitting claims and obtaining an award and socio-demographic and other characteristics. RESULTS: 349 on 499 mesotheliomas considered to be due to occupational exposure to asbestos submitted a claim (70% of those of occupational origin) and 72%of claims were accepted. The welfare system covers only 35%of mesothelioma occurred. The probability of submitting and obtaining a claim was associated with gender, cancer site, age at diagnosis, vital status, and residence or local office in charge of the evaluation. A strong discrimination against women is observed. If exposure to asbestos at work was due to a direct manipulation of asbestos, claims were more easily accepted.As a consequence,mesothelioma occurred among construction workers, the occupational activity at the origin of the largest number of occurring mesotheliomas, are more frequently rejected.When submitted by a relative, the lag between a request for compensation and the decision is on average of about two years. CONCLUSION: This is the first study in Italy using a record-linkage method and was made possible thanks to a population based mesothelioma Register and the availability of memorized information of the Insurance Institute.The welfare system shown clear limitations and there is the need for more appropriate strategies.

Cost-effectiveness of pemetrexed plus cisplatin: malignant pleural mesothelioma treatment in UK clinical practice.

OBJECTIVES: Findings from the largest randomized phase III trial in patients with unresectable malignant pleural mesothelioma (EMPHACIS study; n = 448) were used to examine the cost-effectiveness of pemetrexed plus cisplatin therapy versus cisplatin monotherapy in patients with the disease. The cost-effectiveness of pemetrexed/cisplatin versus alternative treatments was also examined. METHODS: Two cost-effectiveness analyses were designed to model best survival outcome over time for a number of patient cohorts. First, trial-based patient-level data were utilized and resource use was costed for the study arm and comparator. A second cost-effectiveness analysis then compared the mean costs and outcomes associated with pemetrexed/cisplatin with the most commonly used (unlicensed) regimens in the United Kingdom-mitomycin-C, vinblastine, and cisplatin (MVP); vinorelbine; and active symptom control-using trial-based data and data extrapolated from a review of the literature. RESULTS: The total pemetrexed/cisplatin cost per patient varied between pound8779 and pound9020 for all cohorts studied in model 1. Average life-years gained per patient were between 0.20 and 0.28. Quality-adjusted life-years, based on mean and median survival, ranged from 0.13 to 0.31. Incremental cost per life-year gained and quality-adjusted life-year ratios, using both mean and median survival, ranged from pound20,475 to pound68,598. The second cost-effectiveness analysis resulted in ratios ranging from pound14,595 to pound32,066. CONCLUSIONS: Pemetrexed/cisplatin demonstrated acceptable cost-effectiveness when compared with cisplatin monotherapy and alternative treatments commonly used in UK clinical practice.

Management options for malignant pleural mesothelioma: clinical and cost considerations.

Malignant pleural mesothelioma (MPM) is a resistant form of lung cancer that is often related to prior asbestos exposure. While surgical resection and radiotherapy techniques have been refined in recent years, neither has been proven to significantly extend patient survival compared with untreated controls. Until the release of pemetrexed in 2004, even combination chemotherapy regimens often resulted in a response rate of <20%. A recent phase III trial documented a 41.3% response rate for cisplatin plus pemetrexed. In the future, new multimodality regimens featuring novel targeted therapies directed against molecular targets, such as the vascular endothelial growth factor, hold the greatest promise for improved outcomes in MPM. The standard radiographic assessment of response to MPM therapy remains a poor surrogate for clinically relevant endpoints such as median survival. Furthermore, it is not currently known whether aggressive multimodality treatment for MPM will improve survival or quality of life above and beyond symptomatic care. Ongoing clinical trials are comparing chemotherapy and surgery with supportive care in an effort to define the role of different therapies in MPM. MPM treatment is a costly public health issue; after efficacy is proven, additional studies are needed to measure the cost effectiveness of MPM treatment regimens.

Mesothelioma.

Mesothelioma is one of the most aggressive human malignancies. In this article the research team of Dr. Michele Carbone reviewed the most significant scientific and medical advances in understanding the pathogenesis of mesothelioma and some novel preventive and therapeutic approaches that are being developed. The public health and litigation issues, together with the economics surrounding mesothelioma research and therapy are also discussed.

Compensation of asbestos victims in France.

The alarming development of pathologies linked to asbestos led to the creation in France of two funds to indemnify the victims of asbestos-related illnesses: the FCAATA (Fund for asbestos workers who take early retirement), which compensates for their reduced life expectancy, and the FIVA (Indemnification fund for asbestos victims) which ensures full compensation for harm suffered by asbestos victims.

[Diagnosis of malignant pleural mesothelioma and asbestosis]. / Diagnostiek van maligne pleuramesothelioom en asbestose.

The incidence of malignant mesothelioma, the main consequence of exposure to asbestos, will increase considerably in the Netherlands in the coming decades. In the next 35 year, some 20,000 people will die from malignant mesothelioma. The diagnosis of malignant pleural mesothelioma in practice is based on histological examination in about 80%, on cytological examination in 15% and on other forms of examination, e.g., high resolution computer tomography (HRCT), in 6% of the cases. Using a combination of various noninvasive methods, such as anamnesis, physical and röntgenologic examination, HRCT and spirometry, the diagnosis of asbestosis is made erroneously in 5% of the patients examined. With regard to allowance of financial compensation to patients with pleural mesothelioma and asbestosis, a part is played by the fact that views differ internationally concerning the criteria on which the diagnosis should be based. For mesothelioma cytologic and histologic examination are the most important. For asbestosis, the Health Council considers HRCT as crucial, if necessary supplemented by histological examination, plus a history of exposure to asbestos and pulmonary dysfunction. In mesothelioma cytological and histological examination are the most important.

[Use of occupational disease benefits]. / Bruk av yrkesskadetrygd ved yrkessykdom.

Persons with pleuramesothelioma were studied to find out the share receiving occupational injury benefit from the National Insurance Scheme. This disease, caused by inhaling asbestos, was chosen because it has been estimated that between 70 and 80 per cent of persons with pleuramesothelioma fulfil the criteria for compensation. During the period 1970-93, 662 men and 104 women were recorded as having this disease. Up to June 1996, the National Insurance Administration had considered the cases of only 163 men, and no women. A further 25-30 patients may have filed claims with the local national insurance office. This implies that, overall, maximum one third of those entitled to occupational injury benefit have received it. The fraction would probably be even lower in the case of diseases where the association with occupation is less certain. It is recommended that national disease registries, such as the Cancer Registry, should report possible cases of occupational disease to the National Insurance Administration.