Key words: malignant mesothelioma, epidemiology, Cancer Registry

Transcription

1 Malignant mesothelioma in the Cancer Registry of the Friuli Venezia Giulia Region, Italy, Il mesotelioma maligno nel Registro Tumori della Regione Friuli Venezia Giulia, Gianni Vicario, Susan French, Ettore Bidoli Unit of Epidemiology and Biostatistics, National Cancer Institute, IRCCS, Aviano (PN), and Cancer Registry of Friuli Venezia Giulia, Udine, Italy Summary Aim. To evaluate the incidence of Malignant Mesothelioma (MM) in the Friuli Venezia Giulia Region, Italy. In particular, to study the incidence in the Provinces of Trieste and Gorizia, areas at high risk for asbestos exposure, characterised by an industrial district with a large shipyard. Materials and methods. Analysis of the epidemiological data collected by the General Population Cancer Registry of the Friuli Venezia Giulia Region, for cancer incidence in the period between January 1 st, 1995 and December 31 st, Average standardized incidence rates and incidence agespecific curves were calculated. A fully Bayesian modelling approach and the Monte Carlo Markov Chain method were used to compute Relative Risk estimates. Results. The area of Trieste-Gorizia showed the highest incidence rates of MM in Italy. The geographical distribution showed a difference between the Provinces of Trieste and Gorizia (high rates) and other areas, confirmed also by spatial analysis at municipality level computed using a fully Bayesian model, showing clusters of MM cases in some municipalities of the Trieste and Gorizia areas. Conclusions. Considering the high incidence rates of MM, and the need to expand the collection of information, the establishment of a Specialized MM Register in the Friuli Venezia Giulia Region is essential. Key words: malignant mesothelioma, epidemiology, Cancer Registry Riassunto Finalità. Valutare l incidenza del Mesotelioma Maligno (MM) in Friuli Venezia Giulia. In particolare, analizzare l incidenza nelle Province di Trieste e Gorizia, aree ad alto rischio per esposizione ad amianto, caratterizzate da un distretto industriale con importanti cantieri navali. Materiali e metodi. Analisi dei dati epidemiologici raccolti dal Registro Tumori di Popolazione del Friuli Venezia Giulia, nel qua- Address/Indirizzo: Dr. Gianni Vicario, Servizio di Epidemiologia, Centro di Riferimento Oncologico, IRCCS, Via Pedemontana Occ., Aviano (PN), Italia - Fax 0039/0434/ vicariog@cro.it 43

2 Eur. J. Oncol. Library, vol. 3 driennio Sono stati calcolati i tassi di incidenza standardizzati e le curve di incidenza età-specifiche. È stata condotta una analisi con approccio Bayesiano, utilizzando il metodo delle Catene di Monte Carlo, per la stima dei rischi relativi. Risultati. L area di Trieste e Gorizia è caratterizzata dai più elevati tassi di incidenza di MM in Italia. La distribuzione geografica evidenzia delle differenze tra le province di Trieste e Gorizia (alti tassi) e le altre aree, confermate anche dall analisi spaziale a livello comunale condotta usando i modelli Bayesiani, e dimostra aggregazioni di casi di MM in alcuni comuni appartenenti alle aree di Trieste e Gorizia. Conclusioni. Considerando gli alti tassi di incidenza per MM, e il bisogno di arricchire la raccolta di informazioni, si considera necessaria la strutturazione di un Registro Specializzato per la raccolta dei casi di MM in Friuli Venezia Giulia. Parole chiave: mesotelioma maligno, epidemiologia, Registro Tumori Introduction Malignant mesothelioma (MM) is a rare tumour originating from mesothelial cells, and it is found primarily in the serosas of the pleura and peritoneum. The worldwide incidence of MM is variable, mostly due to differences in methods of case registration and difficulties with diagnosis; however, notable pockets of high incidence are found in areas where shipbuilding is the primary industry. MM arising from the pleura is the most common form. Its incidence is low in women of all age groups and almost always diagnosed above age 65 years in men 1. The incidence of MM is closely associated with exposure to asbestos fibres. In cases of pleural mesothelioma, a past exposure frequency of up to 80% of cases was demonstrated in literature 1. These exposures via inhalation occur in occupational environments including asbestos mines, mills and factories, shipbuilding, railroad machinery and insulation manufacture and installation. The incidence of MM is related to the length of exposure with higher risks associated with longer length of exposure. The most important feature of MM incidence is the long duration between exposure and onset. MM mostly arises later than 20 years after initial exposure. Some studies showed death rates among asbestos insulation workers peaking at 45 years from initial exposure 2. The incidence of MM is considered a sentinel event and, given that almost all cases are associated with occupational asbestos exposure, several legislative actions have been implemented in Italy since 1991 to protect workers against exposure to major chemical, biological and physical agents, including asbestos. These actions included the establishment of a registry of cases of asbestosis and asbestos-related MM. Guidelines were developed by the National Institute of Occupational Safety and Prevention (ISPESL) to provide standard references for diagnosis and case histories. Although collaborations were developed with regional registration systems to establish specialized MM registers, registration of MM has not yet been reached at a national level 1. For this reason, epidemiological surveillance of cases is incomplete and cannot yet provide a full risk factor evaluation and the tools for prevention planning. In the Friuli Venezia Giulia Region, in northeast Italy, where an industrial district at high risk was present, a specialized MM register was not available. Thus, to evaluate the incidence of MM, for this study, we reported and analysed the epidemiological data collected by the General Population Cancer Registry of the Friuli Venezia Giulia Region (CR-FVG). 44

3 G. Vicario, S. French, E. Bidoli: Epidemiology of malignant mesothelioma Materials and methods The CR-FVG was set up in 1998 as part of the worldwide cancer registry network coordinated by the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC). It covered the entire regional population (1,186,617 inhabitants), registering cancer incidence from FVG had, and still has, an ageing population (22% over 65), living especially in urban areas or in small towns. The percentages of employment categories were: 5% agriculture, 40% industry, and 55% trade and services. An epidemiological data base, containing individuals health information beginning from the 1980s, was the source of cancer case series. The information collected by CR-FVG included demographic/personal identifiers (including an unique personal ID number used across all sources of information), hospital discharge reports, pathology reports and death certificates. Data was deemed complete for the cancer incidence period between January 1 st, 1995 and December 31 st, Tumour information included: date of diagnosis, source of diagnosis, topography, and morphology according to the International Classification of Diseases for Oncology (ICD-O). For the purposes of this analysis, cases were selected by means of ICD-O, using the following morphological codes: Malignant Mesothelioma (ICD-O M 9050/3), Malignant Fibrous Mesothelioma (ICD-O M 9051/3), Malignant Epithelioid Mesothelioma (ICD-O M 9052/3) and Malignant Biphasic Type Mesothelioma (ICD-O M 9053/3). Average standardized incidence rates and incidence age-specific curves were calculated. A fully Bayesian modelling approach and the Monte Carlo Markov Chain method were used to compute Relative Risk estimates 4. Results For the four-year period , 32,000 malignant incidence cases were recorded. The Average Standardized Ratio (ASR, world standard population) per 100,000 for all cancer sites (except ICD-IX 173) was 397 and for males and females, respectively, the highest incidence rates in Italy. In the same time period, the ASR per 100,000 for MM was 3.6 in males and 0.5 in females (189 cases). The quality indicators of registration were good: the percentage of cases with Morphological Verification (MV) was 98.7 in males and 96.8 in females. No cases were registered on the base of Death Certificate Only (DCO). Within the Italian areas covered by cancer registration, the FVG Region ranked second, after Genoa, in MM incidence 5 (Table 1). When considering the area of Trieste-Gorizia alone, incidence rates resulted the highest in Italy (Table 2). Indeed, the geographical distribution showed a difference between the provinces of Trieste and Gorizia (high rates) and other areas, confirmed also by spatial analysis at municipality level, computed using a fully Bayesian model, showing clusters of MM cases in some municipalities of the Trieste and Gorizia areas (fig. 1). In males, the age specific rates were characterized as a curve with two peaks: the first at age 45 years, likely due to a short but strong asbestos exposure; the second at age years. This phenomenon was stronger considering the age curve in Trieste (not present in the Gorizia curve) (fig. 2). Explanations of this different pattern of incidence still need further investigation. Survival was very low. In fact, at three years after diagnosis of mesothelioma, only 12% of subjects were still alive (Table 3). Due to the short period of case registration, reporting of trends was not yet possible. 45

4 Eur. J. Oncol. Library, vol. 3 Table 1 - Malignant mesothelioma: Average Standardized Rates (ASR) per 100,000 in Italian areas covered by cancer registration ( ) Cancer Registry Males Females Genoa Friuli Venezia Giulia North-East a Turin Naples Italy total Ferrara Venice Biella Parma Varese Ragusa Macerata Romagna Modena Florence-Prato Umbria Sassari Latina a Cancer Registry of Bolzano, Trento and Friuli Venezia Giulia Table 2 - Malignant mesothelioma: Average Standardized Rates (ASR) per 100,000 in Friuli Venezia Giulia Local Health Units ( ) Local Health Unit Males Females Trieste Gorizia Gemona-Tolmezzo Udine Palmanova-Latisana Pordenone Discussion The highest MM incidence rates were found in the Monfalcone-Trieste area, in the FVG Region: an industrial district with a large shipyard, operative since 1907, which is now becoming the most important shipbuilding installation in the Mediterranean region. According to previous studies 6, 7 MM cases in the Monfalcone-Trieste area were, above all, attributable to asbestos exposure that had occurred in the shipyards. The sporadic MM incidence cases in the other FVG areas were probably due to asbestos exposure that had occurred during other working situations, for instance in construction work. Investigating the relevance of nonasbestos-related mesothelioma, especially for the sporadic cases, would also have been of great interest; unfortunately, CR-FVG did not collect data on occupational history. Considering, however, the high incidence rates of MM, and 46

5 G. Vicario, S. French, E. Bidoli: Epidemiology of malignant mesothelioma Fig. 1. Spatial distribution at municipality level of Relative Risk (RR) for Malignant Mesothelioma in Friuli Venezia Giulia Region, Italy, Fig. 2. Age specific incidence rates for Malignant Mesothelioma in males in Gorizia and Trieste areas, Friuli Venezia Giulia, the need to broaden the collection of information, the establishment of a specialized MM register in the FVG region is a necessity. In point of fact, compared to a specialized mesothelioma registry, a general cancer registry is less timely in registering cases, it does not collect additional information, such as patient occupation, nor does it use a specific protocol to identify cases of mesothelioma (for example, a local panel of pathologists review- 47

6 Eur. J. Oncol. Library, vol. 3 Table 3 - Observed and relative survival for malignant mesothelioma in Friuli Venezia Giulia, Males Females Observed Relative Observed Relative (%) (%) (%) (%) 1 year years years ing histological findings). Nonetheless, the information collected by a general cancer registry was very useful in defining the epidemiological environment, in identifying areas at risk, and in surveying trends in incidence. Conclusions FVG is presently planning the establishment of a specialized mesothelioma registry, following the national guidelines elaborated by ISPESL. The CR-FVG and the specialized mesothelioma registry will collaborate in exchanging information and in developing epidemiological studies of malignant mesothelioma in FVG, in order to guide efforts to control asbestos exposure and aid in the development of risk reduction strategies, to prevent new cases of MM in the potentially exposed population. Acknowledgement The authors wish to thank Dr P. Romor for the development of cancer registry software, Mrs T. Angelin, G. Bessega, L. Zaina, O. Forgiarini for data collection, and Mrs L. Mei for editorial assistance. References 1. National Institute of Occupational Safety and Prevention (NIOSP). The National Mesothelioma Registry. First Report, Schottenfeld D, Fraumeni JF Jr. Cancer epidemiology and prevention, 2 nd ed. New York: Oxford University Press, ARS (Agenzia Regionale della Sanità) Regione Friuli Venezia Giulia. Registro Tumori Regionale. Dati di incidenza Trieste: Artigraficheriva srl, Bernardinelli L, Montomoli C. Empirical Bayes versus fully Bayesian analysis of geographical variation in disease risk. Stat Med 1992; 11: Zanetti R, Gafà L, Pannelli F, et al. Il cancro in Italia. Roma: Il Pensiero Scientifico Editore, Bianchi C, Brollo A, Ramani L, et al. Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases. Ind Health 2001; 39: Bianchi C, Brollo A, Ramani L. Asbestos exposure in a shipyard area, Northeastern Italy. Ind Health 2000; 38: