Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.

OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks. METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death. RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death. CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020.

Background: Hematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs' accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis. Material and methods: A dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs' main categories, were noted. Results: Overall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records. Conclusions: The study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.

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.

New information flows for cancer registries: testing the use of laboratory data in the province of Reggio Emilia, Italy.

INTRODUCTION: Haematological malignancies often escape the standard information flows of cancer registries because diagnosis is not always based on bone marrow histology but, rather, on other laboratory tests. OBJECTIVE: To quantify incident haematological malignancies identified exclusively through the laboratory information system and to measure the impact of that source on the sensitivity and accuracy of registering these malignancies. METHODS: We collected data from the only provincial laboratory of Reggio Emilia on molecular biology, flow cytometry tests and bone marrow smears to detect specific markers of some chronic haematological malignancies. We carried out a record linkage between laboratory reports (period 2013-2017) of patients resident in the province of Reggio Emilia and the Cancer Registry of Reggio Emilia. RESULTS: Of the 303 patients who underwent at least one of these tests, 85 were not included in our Cancer Registry. Of these 85 patients, 42 had received a diagnosis of cancer: 34 myeloproliferative neoplasms, 3 chronic myeloid leukaemias, 3 myelodysplastic neoplasms, 1 multiple myeloma and 1 chronic lymphocytic leukaemia. We recovered 4.2% of the total number of chronic haemolymphopoietic cancers registered in the study period, accounting for 15% of myeloproliferative neoplasms. For 30% of prelinkage cases, the specificity of the morphological code improved. CONCLUSIONS: Although the laboratory information system's contribution to the completeness of Cancer Registry incident cases was modest, it is useful to add laboratory data to routine cancer registry information flows due to the increasing use of molecular characterisation and to the phenomenon of dehospitalisation.

Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.

OBJECTIVES: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres. METHODS: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied. RESULTS: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos. CONCLUSIONS: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.

The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study.

BACKGROUND: Chronic myeloid leukemia is associated with a BCR/ABL oncoprotein inhibited by imatinib mesylate, the first tyrosine kinase inhibitor. Although experimental studies have clearly demonstrated the efficacy of imatinib, up-to-date data on its effectiveness at the population level are limited. Our study aims to assess the change in disease-specific survival for chronic myeloid leukemia after introducing tyrosine kinase inhibitors in first-line treatment. METHODS: This study analyzed data from two population-based cancer registries in Italy. Disease-specific survival for chronic myeloid leukemia cases diagnosed before and after the introduction of tyrosine kinase inhibitors (February 2002) were calculated up to 10 years. Hazard ratios were calculated using Cox regression models adjusted for sex, age at diagnosis and residency. An interrupted time series analysis was also performed. RESULTS: Between 1996 and 2012, 357 new cases of chronic myeloid leukemia were diagnosed (standardized incidence rate of 1.2 per 100,000 residents), quite constant throughout the period. The interrupted time series analysis showed a gain of 40.4% in 5 years of disease-specific survival for chronic myeloid leukemia (from 47.3, 95%CI 38.5-55.5% to 80.8%, 95%CI 74.5-85.8%) after the introduction of tyrosine kinase inhibitors. The hazard ratio was 0.36 (95%CI 0.25-0.52) for cases diagnosed after tyrosine kinase inhibitor introduction, with differences per age at diagnosis: <65yo 0.17 (95%CI 0.08-0.39), >74yo 0.41 (95%CI 0.23-0.73). An improvement in survival (hazard ratio 0.66, 95%CI 0.36-1.20) was also observed in cases diagnosed before, and alive at, tyrosine kinase inhibitors introduction. CONCLUSIONS: Tyrosine kinase inhibitors increased disease-specific survival both for new and prevalent chronic myeloid leukemia cases. The effectiveness was similar to that observed in trials only in patients ages 65 years or younger.

Trends in net survival from kidney cancer in six European Latin countries: results from the SUDCAN population-based study.

Kidney cancer is a frequent malignant disease. To date, there is no evidence on the effectiveness of early detection and, in most cases, surgery represents the only standard treatment. So far, there is no standardized therapy for localized and locally advanced renal tumors; however, the recent introduction of target therapy has significantly improved the prognosis of metastatic disease. Therefore, survival differences in Europe are deemed to involve differences in diagnostic and therapeutic approaches. The aim of the SUDCAN collaborative study was to compare the net survival from kidney cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analysis, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland, and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modeling strategy. In 2000-2004, the 5-year net survival ranged between 59% (Spain) and 67% (France and Italy) in men and between 60% (Spain) and 73% (Portugal) in women. There was an increase in the age-standardized net survival between 1992 and 2004 at 1 year, as well as at 5 years, in all age groups and countries. Irrespective of the year of diagnosis, the excess mortality rate decreased with time elapsed since diagnosis. There are some differences in survival from kidney cancer between European Latin countries, but a considerable improvement was observed in most countries.

Impact of Screening Program on Incidence of Colorectal Cancer: A Cohort Study in Italy.

OBJECTIVES: Colorectal cancer (CRC) screening using the fecal occult blood test (FOBT) has been shown to be effective in reducing cause-specific mortality. However, although it detects pre-cancerous adenomas, it is uncertain whether FOBT reduces the incidence of invasive cancer. The objective is to evaluate the impact of screening with immunochemical FOBT (FIT) on CRC incidence and mortality. METHODS: An organized screening program was implemented in 2005 in the province of Reggio Emilia (Northern Italy). The program invites the resident population aged 50-69 for FIT every 2 years. Subjects who test positive are referred for colonoscopy. Incidence was studied through cancer registry. Person-times of people aged 50-74 from 1997 to 2012 were classified for exposure to screening according to age and period. Furthermore, two open cohorts-one never screened (aged 50-69 in 1997) and one invited for screening (aged 50-69 in 2005)-were followed up for 8 years. RESULTS: A total of 171,785 people have been invited, and approximately 70% have undergone FIT at least once (272,197 tests). The rate of colonoscopy participation has been about 90%, and 2896 cancers have been recorded (1237 in the screening period). The age-adjusted and sex-adjusted incidence rate ratios as compared with pre-screening were 1.60 (95% confidence interval (CI), 1.43-1.79), 0.86 (95% CI, 0.78-0.94), and 0.59 (95% CI, 0.50-0.69) for the first round, subsequent rounds, and post screening, respectively. Cumulative incidence and incidence-based mortality decreased by 10% (95% CI, 3-17%) and 27% (95% CI, 15-37%), respectively. CONCLUSIONS: FIT screening leads to a decrease in the incidence of CRC and in its mortality.