Causes of death in women with breast cancer: a risks and rates study on a population-based cohort.

Introduction: The increasing survival of patients with breast cancer has prompted the assessment of mortality due to all causes of death in these patients. We estimated the absolute risks of death from different causes, useful for health-care planning and clinical prediction, as well as cause-specific hazards, useful for hypothesis generation on etiology and risk factors. Materials and methods: Using data from population-based cancer registries we performed a retrospective study on a cohort of women diagnosed with primary breast cancer. We carried out a competing-cause analysis computing cumulative incidence functions (CIFs) and cause-specific hazards (CSHs) in the whole cohort, separately by age, stage and registry area. Results: The study cohort comprised 12,742 women followed up for six years. Breast cancer showed the highest CIF, 13.71%, and cardiovascular disease was the second leading cause of death with a CIF of 3.60%. The contribution of breast cancer deaths to the CIF for all causes varied widely by age class: 89.25% in women diagnosed at age <50 years, 72.94% in women diagnosed at age 50-69 and 48.25% in women diagnosed at age ≥70. Greater CIF variations were observed according to stage: the contribution of causes other than breast cancer to CIF for all causes was 73.4% in women with stage I disease, 42.9% in stage II-III and only 13.2% in stage IV. CSH computation revealed temporal variations: in women diagnosed at age ≥70 the CSH for breast cancer was equaled by that for cardiovascular disease and "other diseases" in the sixth year following diagnosis, and an early peak for breast cancer was identified in the first year following diagnosis. Among women aged 50-69 we identified an early peak for breast cancer followed by a further peak near the second year of follow-up. Comparison by geographic area highlighted conspicuous variations: the highest CIF for cardiovascular disease was more than 70% higher than the lowest, while for breast cancer the highest CIF doubled the lowest. Conclusion: The integrated interpretation of absolute risks and hazards suggests the need for multidisciplinary surveillance and prevention using community-based, holistic and well-coordinated survivorship care models.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Molecular Subtypes, Metastatic Pattern and Patient Age in Breast Cancer: An Analysis of Italian Network of Cancer Registries (AIRTUM) Data.

Breast cancer stage at diagnosis, patient age and molecular tumor subtype influence disease progression. The aim of this study was to analyze the relationships between these factors and survival in breast cancer patients among the Italian population using data from the AIRTUM national database. We enrolled women with primary breast cancer from 17 population-based cancer registries. Patients were subdivided into older (>69 years), middle (50-69 years) and younger age groups (<50 years) and their primary tumors categorized into four molecular subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. There were 8831 patients diagnosed between 2010 and 2012 included. The most represented age group was 50-69 years (41.7%). In 5735 cases the molecular subtype was identified: HER2-/HR+ was the most frequent (66.2%) and HER2+/HR- the least (6.2%). Of the 390 women with metastases at diagnosis, 38% had simultaneous involvement of multiple sites, independent of age and molecular profile. In women with a single metastatic site, bone (20% of cases), liver (11%), lung (7%) and brain (3%) were the most frequent. In the studied age groups with different receptor expression profiles, the tumor metastasized to target organs with differing frequencies, affecting survival. Five-year survival was lowest in women with triple-negative (HER2-/HR-) tumors and women with brain metastases at diagnosis.

BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees.

OBJECTIVE: As prostate cancer (PrC) shows a BRCA mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the BRCA mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among BRCA1 and BRCA2 carriers. METHODS: Following the Modena criteria for the BRCA test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ2) test and Kaplan-Meier methods, respectively. RESULTS: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for BRCA and one for CHEK2 genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the BRCA2 gene fell in the prostate cancer cluster region (PCCR) at the 3´ terminal of the 7914 codon. CONCLUSIONS: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in BRCA2 carriers.

Impact of Rhabdomyosarcoma Treatment Modalities by Age in a Population-Based Setting.

Purpose: Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study describes treatment for RMS in patients more than 10 years old and examines to what extent treatment contributes to explain the different age-related survival observed and to what extent treatment centers impact treatment appropriateness. Methods: A retrospective population-based study was developed considering 104 RMS cases (excluding the pleomorphic subtype) diagnosed in Italy between 2000 and 2015. Patients were grouped by age (10-19 vs. 20-60 years old) and scored according to whether or not their chemotherapy was consistent with the schemes used in pediatric protocols (score 1 = chemotherapy in line with pediatric protocols). Treatment centers were grouped according to whether or not they have a pediatric-dedicated unit affiliated to the national pediatric oncology network (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]). Results: Older patients were more likely to have tumors at unfavorable sites (p = 0.045). A treatment score of 1 was assigned to 85% of younger patients, but only to 32% of older patients (p < 0.001). Furthermore, the proportion of score 1 was higher in younger patients treated in centers with an AIEOP Unit. A multivariate model confirmed age as a significant prognostic factor (Hazard rate ratio [HR] = 2.06; p = 0.04) and showed a significant impact of treatment on survival (HR = 2.13; p = 0.03). Conclusions: Adult RMS patients are still relatively unlikely to be treated with pediatric protocols and in centers with a pediatric oncology expertise. This may explain the survival gap between older and younger patients.

Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions. METHODS: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department. RESULTS: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department. CONCLUSIONS: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services. KEY POINTS: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions. WHAT THIS STUDY ADDS: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

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

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

The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998-2012.

AIMS: In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS: Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS: In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S): Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.

Socioeconomic deprivation worsens the outcomes of Italian women with hormone receptor-positive breast cancer and decreases the possibility of receiving standard care.

BACKGROUND: Socioeconomic factors influence access to cancer care and survival. This study investigated the role of socioeconomic status on the risk of breast cancer recurrence and on the delivery of appropriate cancer care (sentinel lymph node biopsy and breast-conserving surgery plus radiotherapy), by patients' age and hormone receptor status. METHODS: 3,462 breast cancer cases diagnosed in 2003-2005 were selected from 7 Italian cancer registries and assigned to a socioeconomic tertile on the basis of the deprivation index of their census tract. Multivariable models were applied to assess the delivery of sentinel lymph node biopsy and of breast-conserving surgery plus radiotherapy within socioeconomic tertiles. RESULTS: In the 1,893 women younger than 65 years, the 5-year risk of recurrence was higher in the most deprived group than in the least deprived, but this difference was not significant (16.4% vs. 12.9%, log-rank p=0.08); no difference was seen in women ≥65 years. Among the 2,024 women with hormone receptor-positive cancer, the 5-year risk was significantly higher in the most deprived group than in the least deprived one (13.0% vs. 8.9%, p=0.04); no difference was seen in cases of hormone receptor-negative cancer. The most deprived women were less likely than the least deprived women to receive sentinel lymph node biopsy (adjusted odds ratio (ORa), 0.69; 95% CI, 0.56-0.86) and to undergo breast-conserving surgery plus radiotherapy (ORa=0.66; 95% CI, 0.51-0.86). Conclusions: Socioeconomic inequalities affect the risk of recurrence, among patients with hormone receptor-positive cancer, and the opportunity to receive standard care.

Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.

BACKGROUND: The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. METHODS: The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. RESULTS: Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. CONCLUSIONS: Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+.

Increased Incidence of Breast Cancer in Postmenopausal Women with High Body Mass Index at the Modena Screening Program.

PURPOSE: We conducted a study to evaluate the relationship between body mass index (BMI) and the risk of breast cancer (BC) and outcome in a population of 14,684 women aged 55 to 69 years eligible to participate in the Mammography Screening Program (MSP) in the Province of Modena, Italy. METHODS: The study population was drawn from women who underwent mammography screening between 2004 and 2006 in the Province of Modena. Women were subdivided into obese, overweight, and normal-weight categories according to BMI and followed until July 31, 2010, to evaluate the BC incidence. The clinicopathological characteristics of BC were also evaluated in different groups of patients classified according to BMI. After BC diagnosis, patients were followed for a median period of 65 (range, 2-104) months. Second events (recurrences and second tumors) were recorded, and the 5-year event-free survival (EFS) was calculated. RESULTS: After a period of 73 months, 366 cases of BC were diagnosed. Compared with normal-weight women, obese women had a significantly higher incidence of BC (relative risk [RR], 1.32; p=0.040) (RR=1), larger tumors (27% of tumors were larger than T2 size), and more nodal involvement (38.5% of tumors were node-positive). Furthermore, a significantly higher rate of total events was seen in obese women compared with overweight and normal-weight patients, respectively (17.9% vs. 11.4% vs. 10.8%, p=0.032). The 5-year EFS was 89.0%, 89.0%, and 80.0% for normal-weight, overweight, and obese patients, respectively. CONCLUSION: We observed a significantly higher risk of BC in obese women among those eligible to participate in the MSP in the Province of Modena. Finally, obese women had more second events and poorer EFS compared to nono bese women.

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.

Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study.

Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15-20% of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena--(Northern Italy) within the 2002-2006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7% (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p < 0.003), in high-grade tumors (p < 0.008), in right-sided neoplasms (p < 0.005), and in patients with a better prognosis, though the difference was not statistically significant (11/59 patients -18.6% vs 4/59 patients -6.7%; OR 0.36 CI 95% 0.11-1.15; p = 0.08). However, in multivariate analysis, MSI status becomes the strongest independent factor associated with relapse (OR 0.21, CI 95% 0.06-0.81; p = 0.023), together with mucinous histological type (OR 0.40, CI 90% 0.18-0.92). MSI is a relevant prognostic factor in stage pT3N0M0 colon cancer suitable to discriminate those patients with a high risk of relapse.

[Evaluation of the cancer co-pay fee exemption data source (048 code) to estimate cancer incidence]. / Valutazione del flusso delle esenzioni ticket per neoplasia (codice 048) per stimare l'incidenza dei tumori.

OBJECTIVES: to assess whether the data source of cancer exemption ticket (code 048) correctly estimate the cancer incidence produced by Cancer registries (CR). DESIGN: comparison between incidence estimates produced by cancer exemptions ticket and cases registered by CR. SETTING AND PARTICIPANTS: six CRs provided incidence data for one year in the five-year period from 2007 to 2011 and for the previous five years, the exemptions provided for the same year and for the previous five years. MAIN OUTCOME MEASURES: incidence distribution by gender, age and tumour site, exemptions 048/incident cancers ratio, and trend estimates. RESULTS: out of 14,586 patients with 048 exemption, a first group was present in the CR database in the same reference year (No. 8,015) and a second group in the previous 6 months (No. 1,696). Of the remaining 4,875, only 2,771 were prevalent cases and 2,104 were manually re-valued: 514 non-cancer; 710 non-malignant/noninfiltrating tumours, 250 non-residents, 532 unknown, and 98 lost at CR. The exemption/ tumours ratio was 32%in males and 37% in females. Out of 27,632 cancer patients in CR, only 29% had a 048 exemption. Among linked cases, there is a case-mix problem: the exemptions overestimated the weight of some cancer sites (breast, prostate), but underestimate the weight of other sites (stomach, liver, lung) and the burden of tumours in the elderly.The trend estimated from the exemptions underestimates the true incidence of tumours and presents fluctuations, because of local administrative and organisational issues. CONCLUSIONS: the 048 codes are an accessory source for CRs, but when used as single flow they are not able to estimate the true incidence of tumours and, therefore, do not provide useful information on cancer trends.