Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.

Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.

OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers. METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure. RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma. CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.

[Is the epidemiological surveillance of malignant mesothelioma implemented in Italy still valid and necessary?] / La sorveglianza epidemiologica del mesotelioma maligno attuata in Italia è ancora valida e necessaria?

The register of malignant mesotheliomas can still play an informative role in the context of both remediation activities and the health surveillance of former asbestos-exposed persons, and become an epidemiological surveillance system on the harmful effects of exposure to asbestos. It must, however, maintain and improve the level of quality achieved, resolve the problems that have emerged in the interaction between the local level (where cases and their exposure histories are identified, registered, assessed, and medical insurance procedures activated) and the central insurance body that also manages the national register, and become an active participant in research, including clinical research. All this is important to meet the social and welfare justice needs of individual cases.

Decade-long insights: tracking asbestos-related health impacts among formerly exposed workers in Palermo, Italy.

Background: Asbestos is a foremost occupational carcinogen globally. Despite the prohibition under Law 257/1992, Italy persists as one of the European nations most burdened by asbestos-related diseases (ARDs). This research assessed ARD cases in asbestos-exposed workers from the Province of Palermo, Italy, spanning 2010-2021. Methods: Data acquisition utilized the epidemiological dataset from the 'Service of Prevention and Safety on Work Environment' under the Prevention Department of Palermo's Local Health Authority (LHA). Results: Between 2010 and 2021, we identified 245 ARD instances, comprising 163 Asbestosis/Pleural plaques, 41 Lung Cancers, 38 Mesotheliomas, and 3 unspecified cases. Multivariate analysis indicated a notable decline in temporal exposure for mesothelioma (HR=0.933; 95% CI=0.902-0.965) and lung cancer (HR=0.93; 95% CI=0.90-0.978) relative to pleural plaques/asbestosis. Tobacco use displayed a pronounced correlation with lung cancer (smoker HR=64.520 95% CI=13,075-318.390; former smoker HR=20.917 95% CI=4,913-89.048). A significant link was observed between mesothelioma and pleural plaques/asbestosis in those employed in shipbuilding and repair (HR=0.371 95% CI=0.155-0.892). Conclusions: ARDs persist in clinical observations, even following the 1992 cessation of asbestos-related activities, emphasizing an enduring public health challenge. Enhancing prevention strategies is paramount, focusing on amplifying anamnestic and occupational data collection, thereby facilitating superior early diagnosis strategies for these maladies in the occupationally exposed cohort.

Association of mesothelioma deaths with neighborhood asbestos exposure due to a large-scale asbestos-cement plant.

A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non-occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic-regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence-specific asbestos concentration multiplied by the duration during the potential exposure period of 1957-1975 (crocidolite). We observed an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8-79.2) for all, 23.7 (95% CI 3.8-147.2) for males, and 26.0 (95% CI 2.8-237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non-occupational exposures separately, showed a dose-dependent association with neighborhood exposure and no substantial gender differences in magnitude.

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.

BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders. RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy. CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.

Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM).

INTRODUCTION: The epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to the long latency of the disease. The purposes of this study are to analyse the incidence of mesothelioma in young people and to evaluate the modalities of asbestos exposure. METHODS: Incident malignant mesothelioma (MM) cases in the period 1993-2018 were retrieved from Italian national mesothelioma registry and analysed for gender, incidence period, morphology and exposure. Age-standardised rates have been calculated and the multiple correspondence analysis has been performed. The association between age and asbestos exposure has been tested by χ2 test. RESULTS: From 1993 to 2018, 30 828 incident MM cases have been collected and 1278 (4.1%) presented diagnosis at early age (≤50 years). There is a substantial association between age at diagnosis and the type of asbestos exposure and a significantly lower frequency of cases with occupational exposure to asbestos (497 cases vs 701 expected) in young people has been documented. Paraoccupational and environmental exposure to asbestos have been found more frequent in young MM cases (85 and 93 observed cases vs 52 and 44 expected cases, respectively). CONCLUSIONS: Mesothelioma incidence surveillance at population level and the anamnestic individual research of asbestos exposure is a fundamental tool for monitoring asbestos exposure health effects, supporting the exposure risks prevention policies. Clusters of mesothelioma incident cases in young people are a significant signal of a potential non-occupational exposure to asbestos.

[The assessment of asbestos exposure of mesothelioma cases registered in Italy: which problems more than thirty years after the birth of the first regional archives]. / La valutazione dell'esposizione ad amianto dei casi di mesotelioma maligno registrati in Italia: quali problematiche a più di trent'anni dalla nascita dei primi archivi regionali.

More than 30 years have passed since the beginning of the epidemiological surveillance of mesothelioma (MM). The Italian National Mesothelioma Register (ReNaM), part of the research department of the National Institute for insurance against industrial injuries (INAIL), has published 7 reports with the description of the cas-es concerning the assessment of diagnoses and exposures to asbestos suffered mainly during working activities but also environmental, in the family premises and during personal activities.Today we are witnessing a reduction in the commitment by some regions which negatively affects those who develop the pathology. Reading the ReNaM reports it emerges, among others, the problem of the delay in reporting new cases which limits the collection of information directly from patients. This contribution, discussing various topics, invites to develop a debate that should allow to update and resolve the critical aspects that arise after decades of activity regarding, in particular, the asbestos exposure assessment. It is the primary interest of the authors to give continuity and improve the ReNaM which remains the most prestigious MM register among those active in other countries.

[Malignant mesothelioma in two married couples exposed to asbestos]. / Mesotelioma maligno in due coppie di coniugi esposte ad amianto.

BACKGROUND: the relationship between past asbestos exposure and the onset of malignant mesothelioma (MM) is well established. However, defining the exposure is not always easy, as it occurs decades before the onset of the disease. OBJECTIVES: this report describes four cases of MM diagnosed in two different married couples, both exposed to asbestos fibers: husbands at work and wives for cohabiting and washing their work overalls. DESIGN: case report. METHODS: the information was collected through interviews using a semi-structured questionnaire and analyzed by occupational hygienists during the activity of epidemiological surveillance of this disease. The results of the mineral content of asbestos fibers performed on lung parenchymal from one of the female cases are available. RESULTS: these two cases show a longer latency in the lesser exposed confirming what an occupational epidemiological study has recently highlighted. CONCLUSIONS: whenever good quality information collected during interviews are available, skilled occupational hygienists are able to reconstruct past exposures in quali-quantitative terms.

Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.

INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993. MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed. RESULTS: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001). CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.

Projection of future numbers of mesothelioma cases in the US and the increasing prevalence of background cases: an update based on SEER data for 1975 through 2018.

Historically, mesothelioma, which is almost exclusively a cancer of the pleura or peritoneum, has been referred to as a sentinel disease for asbestos exposure meaning that the disease is an epidemiologic marker for asbestos. This description of mesothelioma often has been misinterpreted to mean that the only risk factor for mesothelioma is asbestos. In addition to a few risk factors other than asbestos, in the US, background mesotheliomas, i.e. mesothelioma cases that are a consequence of spontaneous tumor formation, are the most prevalent number of cases after asbestos-associated cases.1 My analysis of SEER data for 1973 through 2005 published in 2009 projected that around 2040 virtually all mesothelioma cases in the US will be background cases. The update here, which is based on the most current SEER data, 1975 through 2018, and the same methods used in 2009 shows that the pattern of mesothelioma incidence is unchanged. Further, in general agreement with the analysis published in 2009, after 2040 virtually all mesothelioma cases, currently estimated to be approximately 1600 per year, will be background cases.

Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).

BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates. OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship. METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42). CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.

BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases. METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.

BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021. METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos. RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure. CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.

A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma.

Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.

Integrating data from multidisciplinary Management of Malignant Pleural Mesothelioma: a cohort study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis. METHODS: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance. RESULTS: The median overall survival (OS) was 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine. CONCLUSION: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.

Incidence, mortality and survival in malignant pleural mesothelioma before and after asbestos in Denmark, Finland, Norway and Sweden.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal cancer, which is largely caused by exposure to asbestos. Reliable information about the incidence of MPM prior the influence of asbestos is lacking. The nationwide regional incidence trends for MPM remain poorly characterized. We use nationwide MPM data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to assess incidence, mortality and survival trends for MPM in these countries. METHODS: We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1958 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization. RESULTS: The lowest incidence that we recorded for MPM was 0.02/100,000 for NO women and 0.05/100,000 for FI men in 1953-57, marking the incidence before the influence of asbestos. The highest rate of 1.9/100,000 was recorded for DK in 1997. Female incidence was much lower than male incidence. In each country, the male incidence trend for MPM culminated, first in SE around 1990. The regional incidence trends matched with earlier asbestos-related industrial activity, shipbuilding in FI and SE, cement manufacturing and shipbuilding in DK and seafaring in NO. Relative 1-year survival increased from about 20 to 50% but 5-year survival remained at or below 10%. CONCLUSION: In the Nordic countries, the male incidence trends for MPM climaxed and started to decrease, indicating that the prevention of exposure was beneficial. Survival in MPM has improved for both sexes but long-term survival remains dismal.

Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.

BACKGROUND: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy. MATERIAL AND METHODS: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated. RESULTS: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months. DISCUSSION: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.