Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018

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. DesignCase-control study. SettingCases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. MethodsWe 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. ResultsThe 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. ConclusionsWe 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

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Safety of Antiplatelet Agents: Analysis of ‘Real-World’ Data from the Italian National Pharmacovigilance Network

Introduction: According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs). Methods: Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class. Results: Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of ‘life-threatening’ events and ‘death’. Conclusions: Based on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice

Pleural mesothelioma risk in the construction industry: a case–control study in Italy, 2000–2018

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

Cancer incidence in Italian contaminated sites

The incidence of cancer among residents in sites contaminated by pollutants with a possible health impact is not adequately studied. In Italy, SENTIERI Project (Epidemiological study of residents in National Priority Contaminated Sites, NPCSs) was implemented to study major health outcomes for residents in 44 NPCSs. Methods: The Italian Association of Cancer Registries (AIRTUM) records cancer incidence in 23 NPCSs. For each NPCSs, the incidence of all malignant cancers combined and 35 cancer sites (coded according to ICD-10), was analysed (1996-2005). The observed cases were compared to the expected based on age (5-year period, 18 classes), gender, calendar period (1996-2000; 2001-2005), geographical area (North-Centre and Centre-South) and cancer sites specific rates. Standardized Incidence Ratios (SIR) with 90% Confidence Intervals were computed. Results: In both genders an excess was observed for overall cancer incidence (9% in men and 7% in women) as well as for specific cancer sites (colon and rectum, liver, gallbladder, pancreas, lung, skin melanoma, bladder and Non Hodgkin lymphoma). Deficits were observed for gastric cancer in both genders, chronic lymphoid leukemia (men), malignant thyroid neoplasms, corpus uteri and connective and soft-tissue tumours and sarcomas (women). Discussion: This report is, to our knowledge, the first one on cancer risk of residents in NPCSs. The study, although not aiming to estimate the cancer burden attributable to the environment as compared to occupation or life-style, supports the credibility of an etiologic role of environmental exposures in contaminated sites. Ongoing analyses focus on the interpretation of risk factors for excesses of specific cancer types overall and in specific NPCSs in relation to the presence of carcinogenic pollutants

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects

Epidemiology of rare cancers and inequalities in oncologic outcomes

Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year survival) of all rare cancers combined and of selected rare cancers that will be in depth treated in this monographic issue. Source of the results is the RARECAREnet search tool, a database publicly available. Disparities both in incidence and survival, and consequently in prevalence of rare cancers were reported across European countries. Major differences were shown in outcome: 5-year relative survival for all rare cancers together, adjusted by age and case-mix, varied from 55% or more (Italy, Germany, Belgium and Iceland) and less than 40% (Bulgaria, Lithuania and Slovakia). Similarly, for all the analyzed rare cancers, a large survival gap was observed between the Eastern and the Nordic and Central European regions. Dramatic geographical variations were assessed for curable cancers like testicular and non epithelial ovarian cancers. Geographical difference in the annual age-adjusted incidence rates for all rare cancers together varied between >140 per 100,000 (Italy, Scotland, France, Germany, and Switzerland) and <100 (Finland, Portugal, Malta, and Poland). Prevalence, the major indicator of public health resources needs, was about 7–8 times larger than incidence. Most of rare cancers require complex surgical treatment, thus a multidisciplinary approach is essential and treatment should be provided in centres of expertise and/or in networks including expert centres. Networking is the most appropriate answer to the issues pertaining to rare cancers. Actually, in Europe, an opportunity to improve outcome and reduce disparities is provided by the creation of the European Reference Networks for rare diseases (ERNs). The Joint Action of rare cancers (JARC) is a major European initiative aimed to support the mission of the ERNs. The role of population based cancer registries still remains crucial to describe rare cancers management and outcome in the real word and to evaluate progresses made at the country and at the European level

Treatment challenges in and outside a network setting: Soft tissue sarcomas

Patients with soft tissue sarcoma (STS) experienced better outcomes when treated according to existing clinical practice guidelines either at reference institution or dedicated treatment networks. Despite increasing evidence supporting referral to sarcoma specialised units, up to half of patients are not managed according to guidelines, particularly those in the early stage of their disease requiring surgery. Also, criteria to certify expertise of institutions, such as the treatment volume, are debated and health authorities have only recently started identification of these centres and creation of treatment networks in Europe as well as in several countries. This process have important implications for both patient outcomes and innovation of existing treatment strategies through clinical research, making improvement of clinical pathways a priority for health care authorities. This article will discuss issues with management of patients with STS, such as pathological diagnosis and adherence to guidelines, and the definition of referral centres and networks will be illustrated along with existing experiences and population-based data