[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report]. / SENTIERI: Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Quinto Rapporto.

INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings. METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs. RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system. CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.

Cancer incidence in children and young adults living in industrially contaminated sites: from the Italian experience to the development of an international surveillance system.

BACKGROUND: this paper is based upon work from COST Action ICSHNet. Children's environmental health is on the 2030 Agenda for Sustainable Development. The incidence of childhood cancer is increasing worldwide and in Europe. Yet, the aetiology of most childhood cancers, including the role of environmental carcinogens, is still largely unknown. Contaminated areas, especially of industrial origin, are of high concern due to complex mix of hazardous pollutants and their potential health impacts on human populations, notably in children. OBJECTIVES: to describe cancer risk in children and young adults (YA) residing in national priority contaminated sites (NPCSs) in Italy and to provide a suitable framework for a development of cancer surveillance in industrially contaminated sites (ICSs) in Europe. METHODS: this study is based on a collaborative work of the Italian Institute of Health (ISS) and the Italian Association of Cancer Registries (AIRTUM), in the context of the SENTIERI project (Epidemiological study of residents in National Priority Contaminated Sites). Incidence rates were standardised according to the European standard population. The number of observed cases was compared to the expected cases derived from the age-, sex-, and cancer-specific incidence rates of the national pool of AIRTUM registries for the period 2006-2013. Standardized incidence ratios (SIRs) and 90% confidence intervals (CIs) were computed. The study reports the cancer profile in all combined 28 NPCSs covered by 22 cancer registries. RESULTS: 1,050 cases of malignant tumours (MTs) were recorded among 3,161,786 person-years in people aged 0-29 years in 28 NPCSs (SIR: 1.03; 90%CI 0.98-1.09), with an age-standardised incidence rate of 317 per million. Excess risks were observed for: MT of the central nervous system in the age-group <1 year (SIR: 3.2; 90%CI 1.4-6.3); soft tissue sarcoma in the age-group 0-14 years (SIR: 1.6; 90%CI 1.1-2.3); acute myeloid leukaemia in the agegroup 0-14 years (SIR: 1.7; 90%CI 1.1-2.4); non-Hodgkin lymphoma in the age-group 20-24 years (SIR 1.5; 90%CI 1.1-2.1), and germ cell tumours of male gonads in the age-group 20-29 years (SIR: 1.33; 90%CI 1.1-1.5). A deficit of cases was observed for Hodgkin lymphomas in the age-group 20-29 years (SIR 0.8; 90%CI 0.6-1.0). DISCUSSION: this study, which is based on standardized methods and accredited information sources, supports the hypothesis that living in an NPCS increases the risk of some cancer types in children and young adults. Further work will concern groups of NPCSs characterised by common sources of contamination/key carcinogenic pollutants. In fact, in a novel project proposal we aim to monitor the cancer profile in children living in ICSs in Europe. The new project, based on the SENTIERI-AIRTUM methodology, will build on the networking activities of the COST Action on Industrially Contaminated Sites and Health Networking (ICSHNet) and childhood cancer studies coordinated by the International Agency for research on Cancer (IARC).

An estimate of the number of people in Italy living after a childhood cancer.

Cancers diagnosed in children below the age of 15 years represent 1.2% of all cancer cases, and survival after a childhood cancer has greatly improved over the past 40 years in all high income countries. This study aims to estimate the number of people living in Italy after a childhood cancer for all cancers combined and for a selection of cancer types. We computed 15-year prevalence using data from 15 Italian population-based cancer registries (covering 19% of Italian population) and estimated complete prevalence for Italy by using the CHILDPREV method, implemented in the COMPREV software. A total of 44,135 persons were alive at January 1st, 2010 after a cancer diagnosed during childhood. This number corresponds to a proportion of 73 per 100,000 Italians and to about 2% of all prevalent cases. Among them, 54% were males and 64% had survived after being diagnosed before 1995, the start of the observation period. A quarter of all childhood prevalent cases were diagnosed with brain and central nervous system tumors, a quarter with acute lymphoid leukemia, and 7% with Hodgkin lymphoma. Nearly a quarter of prevalent patients were aged 40 years and older. Information about the number of people living after a childhood cancer in Italy by cancer type and their specific health care needs may be helpful to health-care planners and clinicians in the development of guidelines aimed to reduce the burden of late effect of treatments during childhood.

Survival of cancer patients in Italy. / La sopravvivenza dei pazienti oncologici in Italia.

OBJECTIVES: Population-based survival statistics are fundamental to assess the efficacy of services offered to improve cancer patients' prognosis. This study aims to update cancer survival estimates for the Italian population, as well as provide new measures, such as the crude probability of death, which takes into account the possibility of dying from causes other than cancer, and the change in life expectancy after a cancer diagnosis, to properly address various questions. RESULTS: The study includes 1,932,450 cancer cases detected by the Network of Italian Cancer Registries (AIRTUM) from 1994 to 2011 and provides estimates for 38 cancer sites and for allsites cancer. For most common cancers diagnosed from 2005 to 2009, age-standardized 5-year net survival was: colon-rectum - males 65%, females 65%; lung - males 15%, females 19%; breast 87%; prostate 91%. For cancer sites such as stomach, colon, rectum, lung, skin melanoma, breast, cervix, prostate, and kidney, 5-year net survival is consistent between Central and Northern Italy, while it is a few percentage points lower in Southern Italy. Funnel plots expose these differences more in detail by showing the survival estimates in 13 Italian regions. For all sites but skin, 5- and 10-year net survival increased by about 10 percentage points in men and 7 points in women from 1994 to 2011. DISCUSSION: Specific articles deal with results on solid and haematological malignancies, international comparisons and analysis of time trends of incidence, mortality, and survival in combination for key cancer sites, aiming to interpret overall progress in the control of cancer in Italy.

Adolescents with Cancer in Italy: Improving Access to National Cooperative Pediatric Oncology Group (AIEOP) Centers.

This analysis compared the numbers of patients treated at Italian pediatric oncology group (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]) centers with the numbers of cases predicted according to the population-based registry. It considered 32,431 patients registered in the AIEOP database (1989-2012). The ratio of observed (O) to expected (E) cases was 0.79 for children (0-14 years old) and 0.15 for adolescents (15-19 years old). The proportion of adolescents increased significantly over the years, however, from 0.05 in the earliest period to 0.10, 0.18, and then 0.28 in the latest period of observation, suggesting a greater efficacy of local/national programs dedicated to adolescents.

[The contribution of the Italian association of cancer registries (AIRTUM)]. / Il contributo dell'Associazione italiana dei registri tumori (AIRTUM).

The study of cluster requires the ability to identify, with accuracy and completeness, the health events of interest and their geographical location and time of occurrence. For rare and complex diseases, such as childhood cancers, it is possible to observe a significant health migration from the place of residence, which makes the detection even more complex. The best tool to identify these rare diseases is represented by cancer registries (CRs). In fact, CRs collect, through many sources, information related to tumours that arise in the population resident in their areas of activity. The number of the sources of information has increased thanks to the computerization of health services. The availability of multiple sources of information increases the completeness of data collection overcoming the limits of a single source, and makes it possible to describe the diagnostic-therapeutic course and the outcome of the cases. Among all data sources, for childhood cancers the model 1.01, which summarize the clinical information of the cases treated in one of the Italian Association of paediatric haematology and oncology (AIEOP) centres, is relevant. Moreover, CRs produce reliable and comparable data due to the use of international rules and classifications for the definition of the topography and morphology of cancer, for the date of diagnosis, and for quality checks. In Italy, the Italian association of cancer registries (AIRTUM) coordinates the activities of 45 population CRs, both general and specialized (by age or tumour type). AIRTUM involves a population of over 6.7 million citizens under the age of 20 years, approximately 60% of the total resident population. AIRTUM plays a role of coordination, support, and harmonization for Italian CRs through training, accreditation, and a shared database, it promotes and participates in national and international collaboration involving scientific societies (AIEOP, Italian Association of medical oncology - AIOM, Italian Federation of volunteer-based cancer organisations - FAVO) and institutions (Italian national Institute of health, Italian national cancer institute of Milan) and performs analysis on key epidemiological indicators (incidence, mortality, survival, and prevalence). The AIRTUM database contains 19,650 cancer cases in child/ adolescent patients diagnosed from 1967 to 2011. The epidemiology of childhood cancers has been the subject of two AIRTUM monographs published in 2008 and in 2013 in collaboration with AIEOP; the latter includes specific contributions on polluted sites, on the psychological side, and on the experience of the parents of young cancer patients. The collaboration between different professionals, needs, and knowledge is the policy followed by AIRTUM to build up a complete picture of cancer epidemiology, even of childhood cancer, in Italy.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

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.

[A comparative analysis between regional mesothelioma registries and cancer registries: results of the ReNaM-AIRTUM project]. / Confronto fra registri specializzati e registri tumori di popolazione: i risultati del progetto ReNaM-AIRTUM.

OBJECTIVES: to assess the agreement on row data and incidence rates between regional mesothelioma registries (CORs) and population cancer registries (CRs) in Italy, and to contribute in harmonizing the procedures used in identifying the date of incidence and the morphology of mesothelioma cases. SETTING E PARTICIPANTS: the mesothelioma cases registered by 19 CRs and by 9 out of 19 CORs were included in the study. Some CORs were not able to participate in the study, because there were no active CRs in their areas. MAIN OUTCOME MEASURES: agreement on cases defined as mesotheliomas by the two types of registries; Cohen's k was used for the evaluation of the agreement on morphology on specific mesothelioma (ICD-O-3 90513-90533) and mesothelioma not otherwise specified (NOS) (ICD-O-3 90503); instead, Odds Ratio was calculated to evaluate the direction of the discrepancy. Difference among incidence rates were calculated using data collected by the two types of registries. It was also made a comparison between dates of incidence. RESULTS: the comparison among the registered data by the two different types of registry showed a high concordance (>80%), especially in the areas where there is a continuous exchange of data. Only in a few areas a lower concordance was observed. The agreement between specific and non-specific morphology showed a fairly wide range and lower values than the calculation of the positive agreement. CORs used the specific morphology (ICD-O-3 90503-90533) with higher frequency compared to CRs. The CRs incidence standardized rates are higher when only cases defined as «certain ¼ by ReNaM are considered; on the opposite the CORs rates are higher when all cases defined as «certain, probable and possible¼ are considered. CONCLUSIONS: the study permitted to compare and bring out the different procedures used in identifying the date of incidence of cases and morphology definition. This represents a first step of a cooperative discussion process among the involved registries: the working group hope it will end with the implementation of shared guidelines.

[Risk profiling in cancer surveillance in contaminated sites: an example from the ISS-AIRTUM collaborative study]. / Sintesi del profilo di incidenza di tumore nei SIN: un esempio dallo studio collaborativo ISS-AIRTUM.

Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.

[SENTIERI Project: materials and methods]. / Materiali e metodi del Progetto SENTIERI.

The Report considers three health outcomes - mortality, cancer incidence and hospital discharges - studied using homogenous methods and using data from official sources, namely the National Institute of Statistics (Istat), Italian Network of Cancer Registries (AIRTUM) and the Health Ministry. The timeframes of observation are: 2003-2010 for mortality, 1996-2005 for cancer incidence and 2005-2010 for hospital discharges. The causes of death are those examined by the SENTIERI Project. Hospital discharges are analysed with reference to the main diagnosis. The study of cancer incidence applies to the sites selected by AIRTUM. Statistical parameters (SMR, Standardized Mortality Ratio; SIR, Standardized Incidence Ratio; SHR, Standardized Hospitalization Ratio) were computed with a 90% confidence interval; the estimators were adjusted for age and socioeconomic status.

[SENTIERI Project: results]. / Risultati del Progetto SENTIERI.

Of the 18 National Priority Contaminated Sites (NPCSs) analysed in this Report, some have a single source of environmental contamination (such as fluoro-edenite in Biancavilla). In most cases, however, we are looking at multiple heterogeneous sources of contamination. In this respect, the a priori causal evaluation of the association between diseases and environmental exposures in NPCSs, based on epidemiological evidence, can help trace the health impact back to specific types of environmental exposure. There are several cases in which the project's findings have been consistent with a priori evidence: stomach cancer (both genders, excess cancer incidence) in the Fidenza NPCS; stomach cancer (women, excess mortality, cancer incidence and hospital discharges) in the Laguna di Grado e Marano NPCS; excess hospitalisation from respiratory diseases in Brescia-Caffaro, Milazzo and Terni Papigno NPCSs; excesses for non-Hodgkin lymphomas and melanoma (incidence and hospitalisation in men and women) and breast cancer (incidence and hospital discharges, women) in Brescia-Caffaro NPCS. In preorder to properly evaluate the population's health profile, we must also observe whether results remain consistent for all three health outcomes or in both genders. The first is the case of excess mortality, cancer incidence and hospital discharges for bladder cancer (men) in Porto Torres and diseases of the urinary tract in the Basso bacino del fiume Chienti NPCS). Gender consistency is observed, for instance, for all cancer in Bolzano, Porto Torres, Venice, Litorale Domizio Flegreo, Priolo, and Taranto, for all causes in Taranto, Litorale Domizio Flegreo and Trieste. The health impact in the various NPCSs needs to be considered carefully and used as a springboard for further analytical research that could confirm and explain causal links to specific environmental exposures. The observations can, however, already be considered as a basis for mandatory primary prevention measures.

Real-World Treatment Patterns and Healthcare Resource Use for Ulcerative Colitis and Crohn's Disease in Italy.

INTRODUCTION: Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy. METHODS: This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed. RESULTS: At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period 2013-2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678 euro (€), for UC and €6925 for CD. CONCLUSION: This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers.

Data from clinical practice can be used to guide healthcare decisions and optimise treatment for patients with ulcerative colitis and Crohn's disease. This study used anonymised patient information from almost four million individuals across Italy to describe the epidemiology, patient characteristics, treatment patterns and healthcare costs of patients with ulcerative colitis and Crohn's disease. Adults with an Italian National Health System code in their records associated with the diagnosis of ulcerative colitis or Crohn's disease were included. Baseline characteristics were balanced between groups and rates of perceived incidence were numerically similar to the results reported in similar Italian studies. This study found that patients with ulcerative colitis and Crohn's disease were most often prescribed conventional treatments, and biological treatments were least-commonly prescribed. More than half of patients with ulcerative colitis and nearly half of those with Crohn's disease were persistent with first (index) treatment of mesalazine and topical corticosteroids and with biologic index treatment during the follow-up period. Switch occurred in up to approximately a quarter of patients with ulcerative colitis and Crohn's disease. The main factors that predicted switch were index biologic for ulcerative colitis and baseline comorbidities for Crohn's disease. The average direct cost per patient in 1 year was 7678 euro (€) for ulcerative colitis and €6925 for Crohn's disease. The results of this analysis may help to optimise therapy for patients with ulcerative colitis and Crohn's disease, and to inform decision-makers in healthcare systems on which treatment options provide value for money and benefit patients.

Long-Term Effectiveness of Galcanezumab in the Prevention of Migraine: An Italian Retrospective Analysis (REALITY).

BACKGROUND: Galcanezumab is approved in the European Union (EU) as migraine prophylaxis in adults with at least four migraine days per month. The aim of this retrospective observational study was to evaluate the long-term effectiveness of galcanezumab on migraine-related burdens and its impact on the use of healthcare resources for migraine prophylaxis in an Italian setting. METHODS: This retrospective study was conducted in patients with migraine who initiated treatment with galcanezumab for migraine prevention between September 2019 and December 2020. Patient data for monthly migraine days (MMDs) and MMDs with acute medication intake were obtained by medical chart reviews. Information on patient-reported outcomes (using the Migraine Disability Assessment [MIDAS] questionnaire and Headache Impact Test 6 [HIT-6] questionnaire) and on the use of healthcare resources were also collected. The time points of interest were 1, 3, 6, 9, 12 months after the initiation of galcanezumab, and the most recent time point available during follow-up. RESULTS: A total of 207 patients were enrolled in the study. Starting from month 3 after treatment initiation, more than half of the patients presented at least a 50% reduction in MMDs, and approximately one-third of non-responders at month 3 became responders at month 6. From month 3 to month 12, MMDs decreased on average by 10 days. Headache impact and disability, as well as migraine-associated health resource utilization decreased significantly during the treatment period. A positive significant association among the three dimensions of clinical burden (MMDs, MIDAS and days of acute medication intake) was also observed. CONCLUSION: The results of this Italian real-world study confirmed that galcanezumab has a rapid onset of effect and provides a long-term response among patients over different migraine-related burdens. The use of healthcare resources was also remarkably reduced.

Description of characteristics, management of care and healthcare direct costs of patients with HR+/HER2- early breast cancer in Italy: a real-world study involving administrative and pathological anatomy databases.

BACKGROUND: Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice. METHODS: This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015-12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed. RESULTS: Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0-50.6). Local relapse occurred in approximately 9.1-9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse. CONCLUSIONS: One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence.

Galcanezumab in the Treatment of Migraine: A Narrative Review of Real-World Studies.

OBJECTIVES: Randomized controlled trials (RCTs) have established the efficacy of galcanezumab, an antibody binding calcitonin gene-related peptide (CGRP) ligand, in the preventive treatment of migraine. The objective was to summarize real-world data evaluating galcanezumab in the preventive treatment of migraine, to complement RCT results with evidence observed in clinical practice. METHODS: A literature search was conducted to identify real-world studies evaluating galcanezumab in the treatment for patients with migraine. RESULTS: Twenty-five studies were identified; some only evaluated galcanezumab, and others used pooled data from multiple anti-CGRP antibodies. The studies recruited diverse patient populations, including patients who had failed multiple prior preventive therapies. Treatment was associated with significant reductions from baseline in monthly migraine days and monthly headache days by 4.3 to 12.9 and 3.1 to 13.9, respectively. These values were numerically greater than those reported in most galcanezumab RCTs. Significant decreases from baseline were evident within the first month of treatment, and efficacy was maintained throughout the follow-up periods, ranging from 3 to 12 months. Galcanezumab was also associated with improvements in other efficacy end points, including decreased headache pain intensity, reduction in analgesic use, and improvements in daily functioning and quality of life. Functionality scores, as assessed by the Migraine Disability Assessment Scale questionnaire, decreased by 27 to 75 points from baseline at 3 to 12 months. Galcanezumab was associated with a low discontinuation rate and higher rates of persistence compared with standard migraine preventive treatments. CONCLUSIONS: The results provide complementary data that galcanezumab is effective across the diverse patient populations observed in routine clinical practice.

Ixekizumab is effective in the long-term management in moderate-to-severe plaque psoriasis: results from an Italian retrospective cohort study (the LOTIXE study).

PURPOSE: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy. MATERIALS AND METHODS: A retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data. RESULTS: A total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term. CONCLUSION: This 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis.

Cancer prevalence in Italy: an analysis of geographic variability.

PURPOSE: Statistics on cancer prevalence are scanty. The objectives of this study were to describe the cancer prevalence in Italy and to explore determinants of geographic heterogeneity. METHODS: The study included data from 23 population-based cancer registries, including one-third of the Italian population. Five-year cancer prevalence was observed, and complete prevalence (i.e., all patients living after a cancer diagnosis) was estimated through sex-, age-, cancer site-, and observation period length-specific completeness indices by means of regression models. RESULTS: In 2006, 3.8 % of men and 4.6 % of women in Italy were alive after a cancer diagnosis, with a 5-year prevalence of 1.9 % and 1.7 % in men and women, respectively. A relevant geographic variability emerged for all major cancer sites. When compared to national pooled estimates, crude cancer prevalence proportions were 10 % higher in the north and 30 % lower in the south of Italy. However, these variations were consistently reduced after age adjustment and, in both sexes, largely overlapped those of incidence rates, with correlations >0.90 between variations of prevalence and incidence for all cancer sites and areas. CONCLUSIONS: Magnitude of the cancer prevalence and the geographic heterogeneity herein outlined in Italy will help in meeting the needs of specific population of survivor patients.

[Suicide mortality among cancer patients]. / Decessi per suicidio in pazienti con tumore.

OBJECTIVE: to evaluate the excess risk in the deaths due to suicide in a huge case-series of cancer patients and in particular in a group with recent diagnosis. DESIGN: observational cohort. SETTING AND PARTICIPANTS: population-based study based on 136,105 patients of the cancer registry of Tuscany Region, incident during 1985-2005, 42,321 of whom diagnosed during 2000-2005. MAIN OUTCOME MEASURES: standardised mortality ratio (SMR) of suicide by sex, age, prognosis, time since diagnosis and period of incidence. RESULTS: deaths due to suicide were 0.2% of all the deaths observed in the cohort of patients. Overall cases, 1985-2005, showed a SMR of 1.47 (p<0.05), it was higher than expected for men (SMR =1.50), for subjects older that 54 years, especially for cancers with poor prognosis (SMR=2.27), particularly during the first year after diagnosis (SMR=2.87) but also in the following years. Cases diagnosed in 2000-2005 had a SMR=1.19 (n.s.), confirmed the high risk for the age 55-64 years (SMR=2.27), for cancers with worse prognosis (SMR=3.23) and during the first year after diagnosis (SMR=2.64). Trend analysis showed that the excess in the risk of suicide death among cancer patients decreased over time (p=0.042). CONCLUSION: although suicide is not one of the major cause of death among cancer patients, we confirmed that those patients had a higher risk than the general population. SMR higher than expected were documented for the age 55-64 years, for cancers with poor prognosis and during the first year after diagnosis. Trend analysis shows that excess in the risk of suicide death among cancer patients is decreasing over time. This may be due, among other possible explanations, to the relevant development of the palliative care system in the area based both on hospices and on home care. Although suicide deaths are rather rare, their prevention among cancer patients is still a priority, due to its likely depressive etiology and to the effects on the family and on the health system.