Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study.

BACKGROUND: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. METHODS: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000-07 and the corresponding time trends during 1995-2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000-07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern. FINDINGS: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000-07. The overall incidence rose annually by 0.5% (99·8% CI 0·3-0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999-2001 to 2007-09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes. INTERPRETATION: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied. FUNDING: The European Commission (Chafea).

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.

Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a population-based study.

BACKGROUND: Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. METHODS: We analysed survival data for 157,499 children (age 0-14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. FINDINGS: We analysed 59,579 cases. For all cancers combined for children diagnosed in 2000-07, 1-year survival was 90.6% (95% CI 90.2-90.9), 3-year survival was 81.0 % (95% CI 80.5-81.4), and 5-year survival was 77.9% (95% CI 77.4-78.3). For all cancers combined, 5-year survival rose from 76.1% (74.4-77.7) for 1999-2001, to 79.1% (77.3-80.7) for 2005-07 (hazard ratio 0.973, 95% CI 0.965-0.982, p<0.0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65.2% (95% CI 63.1-67.3) in 1999-2001, to 70.2% (67.9-72.3) in 2005-07. Europe-wide average yearly change in mortality (hazard ratio) was 0.939 (95% CI 0.919-0.960) for acute lymphoid leukaemia, 0.959 (0.933-0.986) for acute myeloid leukaemia, and 0.940 (0.897-0.984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005-07). INTERPRETATION: Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.

Air pollution and multiple acute respiratory outcomes.

Short-term effects of air pollutants on respiratory mortality and morbidity have been consistently reported but usually studied separately. To more completely assess air pollution effects, we studied hospitalisations for respiratory diseases together with out-of-hospital respiratory deaths. A time-stratified case-crossover study was carried out in six Italian cities from 2001 to 2005. Daily particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10)) and nitrogen dioxide (NO2) associations with hospitalisations for respiratory diseases (n = 100 690), chronic obstructive pulmonary disease (COPD) (n = 38 577), lower respiratory tract infections (LRTI) among COPD patients (n = 9886) and out-of-hospital respiratory deaths (n = 5490) were estimated for residents aged ≥35 years. For an increase of 10 µg·m(-3) in PM10, we found an immediate 0.59% (lag 0-1 days) increase in hospitalisations for respiratory diseases and a 0.67% increase for COPD; the 1.91% increase in LRTI hospitalisations lasted longer (lag 0-3 days) and the 3.95% increase in respiratory mortality lasted 6 days. Effects of NO2 were stronger and lasted longer (lag 0-5 days). Age, sex and previous ischaemic heart disease acted as effect modifiers for different outcomes. Analysing multiple rather than single respiratory events shows stronger air pollution effects. The temporal relationship between the pollutant increases and hospitalisations or mortality for respiratory diseases differs.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Particulate air pollution and hospital admissions for cardiac diseases in potentially sensitive subgroups.

BACKGROUND: Although numerous studies have provided evidence of an association between ambient air pollution and acute cardiac morbidity, little is known regarding susceptibility factors. METHODS: We conducted a time-stratified case-crossover study in 9 Italian cities between 2001 and 2005 to estimate the short-term association between airborne particles with aerodynamic diameter <10 µm (PM10) and cardiac hospital admissions, and to identify susceptible groups. We estimated associations between daily PM10 and all cardiac diseases, acute coronary syndrome, arrhythmias and conduction disorders, and heart failure for 167,895 hospitalized subjects ≥ 65 years of age. Effect modification was assessed for age, sex, and a priori-defined hospital diagnoses (mainly cardiovascular and respiratory conditions) from the previous 2 years as susceptibility factors. RESULTS: The increased risk of cardiac admissions was 1.0% (95% confidence interval [CI] = 0.7% to 1.4%) per 10 µg/m PM10 at lag 0. The effect was slightly higher for heart failure (lag 0, 1.4% [0.7% to 2.0%]) and acute coronary syndrome (lag 0-1, 1.1% [0.4% to 1.9%]) than for arrhythmias (lag 0, 1.0% [0.2% to 1.8%]). Women were at higher risk of heart failure (2.0% [1.2% to 2.8%]; test for interaction, P = 0.022), whereas men were at higher risk of arrhythmias (1.9% [0.8% to 3.0%]; test for interaction, P = 0.020). Subjects aged 75-84 years were at higher risk of admissions for coronary events (2.6% [1.5% to 3.8%]; test for interaction, P = 0.001). None of the identified chronic conditions was a clear marker of susceptibility. CONCLUSIONS: An important effect of PM10 on hospitalizations for cardiac diseases was found in Italian cities. Sex and older age were susceptibility factors.

Susceptibility factors to ozone-related mortality: a population-based case-crossover analysis.

RATIONALE: Acute effects of ozone on mortality have been extensively documented in clinical and epidemiological research. However, only a few studies have focused on subgroups of the population especially vulnerable to these effects. OBJECTIVES: To estimate the association between exposure to ozone and cause-specific mortality, and to evaluate whether individual sociodemographic characteristics or chronic conditions confer greater susceptibility to the adverse effects of ozone. METHODS: A case-crossover analysis was conducted in 10 Italian cities. Data on mortality were collected for the period 2001 to 2005 (April-September) for 127,860 deceased subjects. Information was retrieved on cause of death, sociodemographic characteristics, chronic conditions from previous hospital admissions, and location of death. Daily ozone concentrations were collected from background fixed monitors. MEASUREMENTS AND MAIN RESULTS: We estimated a 1.5% (95% confidence interval [CI], 0.9-2.1) increase in total mortality for a 10 microg/m(3) increase in ozone (8-h, lag 0-5). The effect lasted several days for total, cardiac and respiratory mortality (lag 0-5), and it was delayed for cerebrovascular deaths (lag 3-5). In the subgroup analysis, the effect was more pronounced in people older than 85 years of age (3.5%; 95% CI, 2.4-4.6) than in 35- to 64-year-old subjects (0.8%; 95% CI, -0.8 to 2.5), in women (2.2%; 95% CI, 1.4-3.1) than in men (0.8%; 95% CI, -0.1 to 1.8), and for out-of-hospital deaths (2.1%; 95% CI, 1.0-3.2), especially among patients with diabetes (5.5%; 95% CI, 1.4-9.8). CONCLUSIONS: A greater vulnerability of elderly people and women was indicated; subjects who died at home and had diabetes emerged as especially affected.

A direct method for the identification of patterns of care using administrative databases: the case of breast cancer.

OBJECTIVES: To identify and provide lists of procedures and drugs related to diagnosis and treatment of breast cancer. These lists can be used for the estimation of the cost of illness. METHODS: The method consists of identifying lists of procedures/interventions/drugs related to the tumour of interest, drawn by a panel of expert clinicians and oncologists on the basis of clinical guidelines and current practice. The lists are applied to data referring to breast cancer female patients, collected by population-based Cancer Registries and linked at individual level with information on health care treatments. A comparison with lists obtained via the matched control method is implemented. RESULTS: The distribution of administered procedures and drug prescriptions is coherent with the patient clinical pathway: surgery is the main cause of hospitalization in the first year since diagnosis, diagnostic and monitoring interventions are more frequent in the following years (recurrences detection), and at end-of-life (palliative care). Most outpatient services are due to diagnosis and monitoring, one third of services in the first year since diagnosis is radiotherapy and chemotherapy. Drugs prescribed to patients and sold in pharmacy include hormonal drugs as first course treatment and analgesics as palliative care. CONCLUSIONS: This direct method represents a valid alternative to the matched control method in describing patterns of care and costs related to the entire disease pathway. It is particularly suitable in case of cancer sites with complex patterns of care, such as breast cancer. The lists of codes developed here are based on international classification systems and can be easily applicable to other countries.

The Economic Impact of Rectal Cancer: A Population-Based Study in Italy

Costs of cancer care are increasing worldwide, and sustainability of cancer burden is critical. In this study, the economic impact of rectal cancer on the Italian healthcare system, measured as public healthcare expenditure related to investigation and treatment of rectal cancer patients is estimated. A cross-sectional cohort of 9358 rectal cancer patients is linked, on an individual basis, to claims associated to rectal cancer diagnosis and treatments. Costs refer mainly to years 2010-2011 and are estimated by phase of care, as healthcare needs vary along the care pathway: diagnostic procedures are mainly provided in the first year, surveillance procedures are addressed to chronically ill patients, and end-of-life procedures are given in the terminal status. Clinical approaches and corresponding costs are specific by cancer type and vary by phase of care, stage at diagnosis, and age. Surgery is undertaken by the great majority of patients. Thus, hospitalization is the main cost driver. The evidence produced can be used to improve planning and allocation of healthcare resources. In particular, early diagnosis of rectal cancer is a gain in healthcare budget. Policies raising spreading of and adherence to screening plans, above all when addressed to people living in Southern Italy, should be strongly encouraged.

Particulate matter and out-of-hospital coronary deaths in eight Italian cities.

OBJECTIVES: We evaluated the association between PM(10) concentration and out-of-hospital coronary deaths in eight Italian cities during 1997-2004. METHODS: 16 989 subjects aged >35 years who died out-of-hospital from coronary causes were studied and hospital admissions in the previous 2 years identified. We studied the effect of the mean of current and previous day PM(10) values (lag 0-1). A city-specific case-crossover analysis was applied using a time-stratified approach considering as confounders weather, holidays, influenza epidemics, and summer decrease in population. The pooled percentage increase (95% CI) in mortality per 10 microg/m(3) increase in PM(10) was estimated. RESULTS: A statistically significant increase in out-of-hospital coronary deaths was related to a 10 microg/m(3) increase in PM(10): 1.46% (95% CI 0.50 to 2.43). Although no statistically significant effect modification by age was found, the effect was stronger among subjects aged >65 years (1.60%, 0.59 to 2.63), particularly those aged 65-74 (3.01%, 0.74 to 5.34). People in the lowest socio-economic category (3.34%, 1.28 to 5.45) had a stronger effect than those in the highest category. No clear effect modification was seen for gender, season or any specific comorbidity. An indication of negative effect modification was seen for previous admission for cardiac dysrhythmias. Subjects without hospital admissions in the previous 2 years were slightly more affected by PM(10) effects (1.91%, 0.28 to 3.47) than those with at least one previous hospital admission (1.44%, 0.09 to 2.82). CONCLUSIONS: Our results show that short term exposure to PM(10) is associated with coronary mortality especially among the elderly and socio-economically disadvantaged. No clear effect modification by previous hospitalisations was detected except for cardiac dysrhythmias, possibly due to protective treatment.

Incidence and Survival of Patients With Conjunctival Melanoma in Europe.

Importance: Conjunctival melanoma (CM) is a rare ocular tumor. Estimates of incidence and survival of patients with CM are important to researchers and policy makers. Objective: To estimate incidence and survival of patients with CM in Europe. Design, Setting, and Participants: This population-based cohort study used data from 41 European cancer registries adhering to the RARECAREnet project. All individuals diagnosed as having malignant CM from January 1995 to December 2007 coded according to the International Classification of Diseases for Oncology, Third Edition codes C69.0 (conjunctiva) and 8720-8780 (melanoma) were included. Analysis began March 2019. Main Outcomes and Measures: Trend estimates for incidence and for 5-year relative survival (the ratio of the measured survival of patients to the expected survival in the general population for the same country, age, sex, and calendar year). Crude, age-standardized, and bayesian incidence rates were calculated. Five-year relative survival was calculated by the Ederer II method with the cohort and period approach. Results: A total of 724 patients 15 years or older (512 [70.7%] were 55 years or older; 366 [50.6%] were female) were analyzed with an overall crude incidence of CM (per 1 000 000 person/y) of 0.46 (95% CI, 0.42-0.49). Crude incidence was similar in men and women (0.48; 95% CI, 0.44-0.54 and 0.46; 95% CI, 0.41-0.51, respectively) and increased with age. Age-standardized incidence increased over time only in men and was the highest in Norway and the Netherlands (more than 0.70). Only 1 case in 14 years was estimated to occur in Iceland vs about 20 cases per year in large countries such as France and Germany. Percentage of 5-year survival (83.5 overall; 95% CI, 78.6-87.3) was not different between adult and elderly patients but showed large geographical disparities across European regions (range, 66-89) and improved markedly in male patients (from 76 in 1995-1998 to 86 in 2003-2007, with a difference of 10.2 [95% CI, 1.3-19.2]; P < .05) becoming similar to that of women in the last period. Conclusions and Relevance: Although these data are only available through 2007 and based on registries not uniformly covering the European population, the study provides the first Europe-wide estimates of the incidence and relative survival of patients with CM using population-based data. Geographical differences in survival indicate room for outcome improvement in Southern, Northern, and Eastern European countries.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to <6 months for those with liver, pancreas, brain, gallbladder and lung cancers. It was 7.7 years for patients with prostate cancer at age 65-74 years and >5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life.

[EpiAir health data]. / I dati sanitari nel Progetto EpiAir.

INTRODUCTION: the EpiAir (Air pollution and health: epidemiological surveillance and prevention) Project has been conducted in 10 Italian cities. In this paper we describe the health data used to detect adverse health effects associated with air pollution exposure (mortality and hospital discharge databases) and to identify comorbidities (based on hospital discharge databases) as susceptibility factors to the effects of air pollution. MATERIAL AND METHODS: for each city, we performed descriptive analyses of mortality data included in the study.We considered subjects aged 35+ years old, resident and deceased within the cities in the study period (2001-2005) for non-accidental causes. For each deceased subject, information were collected on hospital discharge diagnoses in the previous 2-year period. Urgent hospital admissions of subjects resident in nine cities and hospitalized within the city for specific diseases (including cardiac, cerebrovascular and respiratory conditions) were also included as endpoints. Annual mean raw death and hospitalization rates were calculated for each city. RESULTS: 276,205 deaths and 701,902 urgent hospital admissions have been included in the study. Annual mean crude death rates for non accidental causes in the population aged +35 yrs resident and deceased in the municipalities ranged from 12.1 and 15.7 per 1,000 residents.The percentage of deceased subjects with at least one of the selected comorbidities ranged from 32 to 48%. Annual mean crude urgent hospitalization rates in the resident population ranged from 5.5 to 11.7 per 1,000 residents for cardiac diseases; 1.7 to 3.7 per 1,000 residents for cerebrovascular diseases and 3.3 to 10.7 per 1,000 residents for respiratory diseases. Several factors can explain the between-cities differences observed, especially in the hospitalization rates, including availability and variability in the health care services utilization. CONCLUSION: an epidemiological surveillance system based on health databases has to take into account the observed differences.

[Air pollution and urgent hospital admissions in nine Italian cities. Results of the EpiAir Project]. / Inquinamento atmosferico e ricoveri ospedalieri urgenti in nine città italiane. Risultati del Progetto EpiAir.

INTRODUCTION: the relationship between air pollution and hospital admissions has been well studied. In this study, the results of the Italian EpiAir Project are reported on the effect of air pollution on hospital admissions in 9 Italian cities during 2001-2005. The association between particulate matter (PM10) and gases (NO2 and O3) and hospital admissions for cardiac, cerebrovascular, respiratory conditions, pulmonary embolism and diabetes has been evaluated. MATERIAL AND METHODS: The study population consists of 701,902 hospital admissions of subjects residents in nine Italian cities and hospitalized in the city in the period 2001- 2005. We used a case-crossover approach and the statistical analysis considered the relevant temporal and meteorological factors for confounding adjustment. The results for ozone refer to the warm semester. The analysis of the association between air pollution and admissions was conducted for each city, and the city-specific estimates were meta-analyzed to obtain pooled results. RESULTS: we found an immediate effect of PM10 and NO2 (lag 0) for cardiac diseases as a group and for specific conditions (coronary syndrome and heart failure). No effect of ozone was observed. For cerebrovascular diseases we did not observe a positive effect of the three pollutants. An effect of NO2 on pulmonary embolism was detected. The association between air pollutants and hospitalization for respiratory diseases (respiratory infections, COPD and asthma) showed different lags for the three pollutants: the effect of PM10 was immediate at lag 0-1 while the effects of NO2 and ozone were prolonged at lag 0-5. The strongest association was between NO2 and asthma admissions, especially in children. No effects on diabetes were found. CONCLUSIONS: the main results of the present study confirm the deleterious short term impact of air pollution on cardiovascular and respiratory morbidity in Italian cities.

[Environmental indicators in ten Italian cities (2001-2005): the air quality data for epidemiological surveillance]. / Indicatori ambientali in dieci città italiane (2001-2005): i dati di qualità dell'aria per la sorveglianza epidemiologica.

OBJECTIVE: to produce environmental indicators suitable for an epidemiological surveillance in 10 Italian cities part of the EpiAir Project (2001-2005). METHODS: the environmental parameters that correlate to relevant health effects are the particles with diameters less than or equal to 10 micrometers (PM10), the nitrogen dioxide (NO2) and the ozone (O3). The necessary meteorological data are: temperature, relative humidity, barometric pressure and apparent temperature.We have identified some criteria to select monitoring stations and have taken standard methods of calculation to produce environmental indicators starting from the daily data available after closely evaluating the completeness of the existing data. Furthermore, we have checked the homogeneity of the selected data to ensure that it represents the population's exposure. RESULTS: close examination of descriptive statistics shows a critical situation of the considered pollutants. The analysis of the yearly state underlines for PM10 values higher than 40 microg/m3 in the area of Mestre-Venice and in Milan, Turin, Bologna e Taranto. For NO2, values are consistently above 40 microg/m3 in Milan, Turin, Bologna, Florence, Rome and Palermo. For ozone, the concentrations were stable, with the exception of Summer 2003 when we recorded, on average, an increase of 13% compared to the mean value estimated for the ten cities during the study period, especially in Mestre-Venice, Turin and Palermo. CONCLUSIONS: it is important to ensure the consistency of the methods and instruments in environmental monitoring. To evaluate health effects and perform interventions over the longterm, it is therefore fundamental that the data be homogenous, especially during the periodic reorganizations and rationalizations of air quality management. It is also necessary to include daily meteorological data that influence pollutant dispersion and population health status.

[Air pollution and mortality in ten Italian cities. Results of the EpiAir Project]. / Inquinamento atmosferico e mortalità in dieci città italiane. Risultati del Progetto EpiAir.

OBJECTIVE: the relationship between air pollution and mortality has been well established in national and international scientific literature. This study reports the results of the EpiAir Project relative to the effect of air pollution on mortality in 10 Italian cities during 2001-2005. The association between particulate matter (PM10) and gases (nitrogen dioxide, NO2, and ozone, O3), and all natural mortality, as well as cardiac, cerebrovascular and respiratory mortality, is presented. Specific issues have been investigated, such as the latency of the air pollution-mortality effects and the identification of individual demographic characteristics and clinical conditions that result in greater susceptibility to the effects of particulate matter. METHODS: the study population consisted of 276,205 subjects aged 35+ years old, resident in one of the 10 Italian cities studied, which died in the city between 2001-2005. For each subject, information was collected on cause of death, location of death, demographical variables and hospital discharge diagnoses in the previous 2-year period. The statistical analysis was adjusted for the relevant temporal and meteorological factors using the case-crossover approach. The results for ozone are limited to the warm semester (April through September). An analysis of the association between air pollution and mortality was conducted for each city, and the city-specific estimates were meta-analyzed on a second level to obtain a pooled result, and reported inter-city heterogeneity. RESULTS: a short-term effect of PM10 on mortality has been detected for all the groups of causes considered, with latencies ranging from lag 0 for cerebrovascular mortality to lag 0-3 for respiratory mortality. The association between NO2 and mortality displays strong and similar effects for all death causes, with prolonged effects (lag 0-5) for all groups of causes. The results for O3 are similar to those found for NO2, with prolonged latency (lag 0-5) for all causes of death with the exception of cerebrovascular mortality, for which a delayed effect (lag 3-5) was identified. Individual susceptibility factors of the PM10-natural mortality association include age, as elderly subjects are especially vulnerable to the effects of particles. CONCLUSIONS: the main results of the study suggest that the air pollution originated by vehicular traffic is the most relevant environmental problem in Italian cities from a public health viewpoint.

The Prognostic Role of TNM Staging Compared With Tumor Volume and Number of Pleural Sites in Malignant Pleural Mesothelioma.

BACKGROUND: Age, sex, stage, histotype, and surgery are the most recognized prognostic factors for malignant pleural mesothelioma (MPM). Tumor volume (TV) was suggested as an alternative prognostic evaluation. We aimed to assess the prognostic role of Tumor, Node, Metastases (TNM) versus TV and number of pleural sites (NPS). PATIENTS AND METHODS: Information on stage, TV, and NPS was collected for 52 MPM patients (pts) at our institution from 2009 to 2012. Baseline computed tomography imaging was performed to define TNM, TV, and NPS. Pts were divided in 3 stage groups: early (I-II), III, and IV. A dedicated computer system calculated TV. Pts were divided in 2 groups according to mean baseline TV (483 cm3). NPS was defined on the basis of the NPS macroscopically involved by disease (1-3). The association between TNM, tumor size (T), TV, NPS, TV and NPS, and overall survival was assessed using Cox models adjusted for age, sex, histology, and treatment. RESULTS: Most pts were male; mean age was 62 years. We showed an association between TV, TNM, and T. Stage III (hazard ratio [HR], 4.71; P = .02) and IV (HR, 7.40; P < .01), T3 (HR, 5.07; P < .01) and T4 (HR, 5.09; P < .01), TV > 483 cm3 (HR, 3.47; P < .01) and NPS 2 (HR, 3.00; P = .08) and 3 (HR, 6.05; P < .01) were predictive of worse survival. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as a prognostic classifier. CONCLUSION: We showed that TV is related to TNM staging and T, in particular. Improved prognostic performance might be achievable using quantitative clinical staging combining TV and NPS.

Particulate matter and daily mortality: a case-crossover analysis of individual effect modifiers.

BACKGROUND: Several time-series studies have established the relationship between particulate matter (PM10) and mortality. We adopted a case-crossover design to evaluate whether individual socio-demographic characteristics and chronic or acute medical conditions modify the PM10-mortality association. METHODS: We selected all natural deaths (321,024 subjects) occurring among adult (aged 35+ years) residents of 9 Italian cities between 1997 and 2004. We had access to individual information on socio-demographic variables, location of death, and chronic conditions (hospital admissions in the preceding 2-year period). For in-hospital deaths, we collected information on treatment wards at time of death and acute medical conditions. In a case-crossover analysis we adjusted for time, population changes, and meteorological conditions. RESULTS: PM10 was associated with mortality among subjects age 65 years and older (0.75% increase per 10 microg/m3 [95% confidence interval = 0.42% to 1.09%]), with a more pronounced effect among people age 85 and older. A weaker effect was found among the most affluent people. The effect was present for both out-of-hospital and in-hospital deaths, especially among those treated in general medicine and other less specialized wards. PM10 effects were stronger among people with diabetes (1.03% [0.28% to 1.79%]) and chronic obstructive pulmonary disease (0.84% [0.17% to 1.52%]). The acute conditions with the largest effect estimates were acute impairment of pulmonary circulation (4.56% [0.75% to 8.51%]) and heart failure (1.67% [0.30% to 3.04%]). CONCLUSIONS: Several factors, including advanced age, type of hospital ward, and chronic and acute health conditions, modify the PM10-related risk of death. Altered pulmonary circulation and heart failure are important effect modifiers, suggesting that cardiac decompensation is a possible mechanism of the fatal PM10 effect.