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Lucia Mangone,1 Isabella Bisceglia,1 Maria Michiara,2 Antonino Musolino,2 Guido Mazzoleni,3 Adele Caldarella,4 Sante Minerba,5 Giuseppe Cascone,6 Francesca Bella,7 Ylenia Dinaro,7 Loredana Pau,8 Carmine Pinto9 1Epidemiology Unit, Azienda Unità Sanitaria Locale–IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy; 3Pathology Service South Tyrol Local Health Authority, Bolzano, 39100, Italy; 4Tuscany Cancer Registry, Clinical and Descriptive Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy; 5Local Health Service Taranto, Taranto, Italy; 6Cancer Registry, Provincial Health Department, Ragusa, Italy; 7Siracusa Cancer Registry, Azienda Sanitaria Provinciale Di Siracusa, Siracusa, Italy; 8Europa Donna, Italia, Milan, Italy; 9Medical Oncology Unit, Comprehensive Cancer Centre, Azienda Unità Sanitaria Locale -IRCCS Di Reggio Emilia, Reggio Emilia, ItalyCorrespondence: Isabella Bisceglia, Via Giovanni Amendola 2, Tel +39 0522/35075, Email isabella.bisceglia@ausl.re.itPurpose: Describe breast cancer in Italy by age, geographical area, stage and sites of metastases. In addition, incident and prevalent cases by region are provided.Patients and Methods: This population-based study included all female patients with histologically confirmed breast cancer diagnosed in Italy between 2013 and 2019 in the eight participating Cancer Registries. Cases were described by geographic area (north, center, south), age group (< 50, 50– 69 and 70+) and site of metastases. In addition, the study also provided an estimate of the cases of metastatic breast cancer per single region.Results: Of the total 5731 cases, the number of unknown stage cases (eliminated from our analyses) was 545 (10.5% of cases); therefore, the study was conducted on 5186 cases. Overall, 333 (6.5%) of tumors were metastatic at diagnosis but the distribution by geographical area was different: 5.1% in the north, 7.4% in the center and 7.8% in the south. Related to age, 5.6% were diagnosed before the age of 50 and 5.6% within the screening target group (50– 69 years), while in elderly women the percentage rose to 8.1%. As regards the site of the metastases, 27.1% developed metastasis to the bone, 12.4% to the liver, 8.6% to the lung and 2.6% to the brain; in 34.9%, multiple sites were already present at the beginning of the cancer. Overall, 3520 cases of incident mBC are estimated in Italia every year (520 in Lombardy in northern Italy, 350 in Lazio in the center, followed by 330 in Campania in the south), and finally they are out of 52,000 prevalent cases.Conclusion: A greater possibility of treating and living with the disease for a long time now requires careful monitoring of these tumors.Keywords: breast cancer, metastatic, incidence, Italy

Invasive breast cancer prognosis has significantly improved over time; however, there are few data about the long-term survival.We analysed the data on female breast cancer incident during 2004-2005 in the area of the Tuscan Cancer Registry, distinguishing them in five subtypes, according to ER, PgR, HER2, and Ki67 expression: luminal A, luminal B, luminal B/HER2 + , triple-negative, and HER2 + . Effects of subtypes and age on 10 years breast cancer specific survival were analysed by Kaplan-Meier and multivariate Cox analysis.The majority of breast cancer were luminal B (57%), and 45% of them were diagnosed at pathological stage I. The 10-year survival rates (p 0.001) were higher among luminal A (90.2%) and lower among HER-2 + patients (70.3%). Prognostic effect of age was statistically significant (p 0.0004): the 10-year cancer specific survival rates were higher among 40-59 years of age patients (88.5%), lower among 0-39 (75.8%). Luminal A breast cancer patients had a constant low risk throughout 10 years of follow up, while luminal B/HER2 + and triple negative tumours showed a peak 5 years after the diagnosis and then declined.Our study confirmed the prognostic effect of biological subtype also in a long term follow up study; moreover, age at diagnosis showed to influence the outcome, other than stage at diagnosis and treatment. The long term follow up showed a constant risk of death for luminal A and B tumours, whereas for non-luminal cancer a peak 5 years after the diagnosis was found.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

(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.

The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.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.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.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.

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. Methods: In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. Findings: 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia. Interpretation: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. Funding: European Commission.

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 (

(1) Background: Liver cancer in Italy is characterised by one of the highest incidence rates worldwide outside of Asia coupled with comparatively favourable survival figures. The objective of this study was to evaluate the most recent epidemiologic trends of the disease. (2) Methods: Thirteen cancer registries covering a population of about 12,740,000 (21% of the national population) made available the records of 35,574 cases registered between 2003 and 2017. Trends in age-standardised (Europe 2013) incidence rates were analysed using the results of age–drift models. Trends in survival were analysed using 1-year, 2-year, 5-year and 10-year net survival (NS) and 5|1-year and 5|2-year conditional NS. (3) Results: Over the study period, the average annual incidence rates per 100,000 persons were 29.4 (men) and 9.4 (women) for total liver cancer; 14.6 and 3.5 for hepatocellular carcinoma (HCC); 1.8 and 1.1 for intrahepatic cholangiocarcinoma (ICC); and 13.0 and 4.8 for the ‘other liver cancer types’ group. The incidence of total liver cancer and HCC decreased significantly for both sexes. For total liver cancer, the estimated average annual percent change was −1.6% among men and −2.1% among women. For HCC, the change was −1.3% among men and −2.7% among women. ICC followed an opposite trend. For men, the risk of HCC had two peaks, one in the birth cohorts of 1928 and 1933 and another, more moderate peak in the cohort of 1958. Men and women exhibited comparable improvements in both early and mid-term conditional NS from HCC. In 2013–2017, 5-year NS was 28.9% (95% CI: 27.3%; 30.6%) for men and 30.1% (95% CI: 26.9%; 33.5%) for women. The uptrend in survival from ICC was less pronounced and was weakly significant, with a 5-year NS in 2013-2017 of 13.9% (95% CI: 10.8%; 17.3%) for men and 17.4% (95% CI: 13.5%; 21.7%) for women. (4) Conclusions: The opposite incidence trends of HCC and ICC confirm a pattern observed in other populations. The generalised, albeit slow, improvement in survival from HCC indicates a trend towards earlier detection coupled with improvements in treatments.

Background: Recent studies have shown an increasing incidence of cutaneous adnexal carcinomas (CACs). Objectives: The aim of our study was to evaluate incidence and survival for cases of CACs and investigate their association with other skin neoplasms. Methods: We conducted a population-based study. Data on incident cases of CACs were obtained from the Tuscany Cancer Registry between 1985 and 2010. In order to determine whether the occurrence of squamous cell carcinoma (SCC) among patients with CAC is higher or lower than expected in the general population, the standardized incidence ratio (SIR) was calculated. Results: A total of 242 patients with CAC were observed; the age-standardized incidence rate was 3·8 cases per million person-years. From 1997 to 2010 crude incidence rates increased by 159%. Age-specific incidence was higher in men over 80 years old than in women of the same age and younger individuals. Carcinomas of sweat gland origin prevailed; the most common histotype was porocarcinoma and the most frequently affected site was the head/neck. Overall, 88% of CACs were diagnosed at a localized stage. The 5-year overall survival and disease-specific survival rates were 59% [95% confidence interval (CI) 53–65] and 94% (95% CI 91–98), respectively. In the observation cohort, the number of SCCs was significantly higher than expected as the SIR was calculated to be 33·7 (P < 0·001). Conclusions: Increasing incidence warrants awareness and early diagnosis of CACs. Increased SCC incidence among patients with these tumours highlights the relevance of careful skin examination and follow-up.

Background Respond to alarms for possible cancer cluster is a public health problem, but the management of these alarms is difficult and sometime conflictual. Methods We reviewed the guidelines on the management of disease clusters developed in various countries and the approaches used in previous disease cluster episodes in Tuscany. Statistical approaches for cluster detection were also reviewed. We performed a clustering analysis (spatio or spatio-temporal when appropriate) on childhood leukemia using data from Tuscany Cancer Registry (RTT). We used spatial hierarchical Bayesian model on aggregate data at municipality level. We performed test for general clustering and cluster detection on individual data. Results More than 100 tests for clustering analysis has been identified in the literature. Bayesian analysis on aggregate data did not show areas at higher risk with the exception of the city of Florence for childhood cancer among males. We did not found clusters for leukemia. In previous studies on disease clusters in Tuscany, most investigations have been started from community concerns and in the majority of situations a multidisciplinary approach was used. In some case an increase of incidence rate was observed, but rarely specific cluster cancer tests were used. Conclusions Hierarchical Bayesian models to aggregate data provided useful to identify long range geographical patterns while clustering analysis on individual data is a useful tool for small scale patterns. Both represent important tools for epidemiological surveillance studies particularly on childhood cancer. The best test for all situations doesn't exist, but the choice is determined by the type of question being asked from the data, by different situations and by different approaches. The Tuscany cancer clusters survey and the review of the guidelines on the management of clusters developed in different countries, give us the opportunity to formulate some suggestions for the health agencies. Key messages Respond to alarms for cluster of cancer and suggest recommendations for epidemiological and statistical standardized approaches is a public health issue. Tuscany cancer clusters survey and the review of the guidelines on the management of clusters developed in different countries, give the opportunity to formulate some suggestions for health agencies.

The long-term survival of differentiated thyroid cancer (DTC) patients and the need to perform several treatments with radioiodine (131-I) lead to the question if the lifetime risk of developing a nonthyroidal second primary cancer (NTSPC) is increased in these patients. In our study, we assessed the prevalence of NTSPCs in thyroid cancer population and evaluated the possible causative role of 131-I treatment. We analyzed 1096 consecutive patients followed at our institution from 1964 to 1998. A total of 101 NTSPCs were observed in 92/1096 patients (8.4%) among which 17/101 (16.8%) diagnosed before DTC and 84/101 (83.2%) diagnosed after. The most frequent tumor sites observed were breast and bladder/urinary tract in the post-DTC group and breast and hematological system in the pre-DTC group. Regarding 131-I treatment, we did not observe any significant differences regarding either the number of treatments or the cumulative activity. The only significant parameter associated with an increased incidence of NTSPC was follow-up (P = .02): a longer follow-up period was associated with a higher number of NTSPCs. The mean latency between 131-I and NTSPC was 10.52 ± 7.69 years. Comparing with the general Italian population, independent of radioiodine treatment, the standard incidence ratio in our cohort was similar to that of the general population (SIR 1.07) and this result was confirmed by analyzing only the treated group. In conclusion, these results show that the risk of NTSPCs in the DTC patients' population is similar to that in the general population and 131-I treatment was not associated with an increased risk.

Aim: To evaluate the epidemiology of male breast cancer (MBC) in Italy and to describe incidence and survival data in relation to age, morphology, year of incidence, geographic area, and possible association with other cancers compared with female BC. Methods: Cases were extracted from 40 Italian Cancer Registries. Standardized incidence rates (SIR), age-specific rates, and 5-year survival were calculated. The association with second tumors was also evaluated. All data were compared with data from female BCs. Results: In the 2000–2014 period, 2175 new cases of MBC were registered, with an SIR of 1.7 × 100,000. The incidence showed a slight upward trend and increased with increasing age. The 5-year survival was 82% in the first two periods (2000–2004, 2005–2009), lower than in females (87%). The most frequent morphology was the ductal carcinoma (84%). Stage at diagnosis was 39.5% stage I, 33.1% stage II, 20.9% in stage III, and 6.4% in stage IV. Concerning receptor status, 96.4% had ER+ and 82.5% PR+; 46.5% had high Ki67 and 14.7% HER2 amplified. The risk of BC increased if the man had already had a previous tumor in any site (excess absolute risk, EAR = 2.7) and especially if he had had prostate cancer (EAR = 5.1). Instead, males with a previous diagnosis of BC had an increased risk of testicular, kidney and lung cancer. Conclusions: MBC requires more attention in terms of diagnosis and treatment as clinicians tend to follow the guidelines that have been developed for female BC management.

Aims: In Italy, incidence rates of thyroid cancer (TC) are among the highest world- wide 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 attribut- able to overdiagnosis. Methods: Data on TC cases reported to Italian cancer registries during 1998e2012 aged

The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population-based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow's thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86-89%) for women and 80% (78-82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56-0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown.

In 2009, the American Joint Committee on Cancer (AJCC) incorporated the tumor mitotic rate in the melanoma pathological TNM staging system. To investigate the effect of this change on the pT1 substaging of primary cutaneous melanomas, we reclassified the cases collected by a cancer registry according to the 6th and the 7th editions of AJCC melanoma staging.Patients with pathological T1 melanoma diagnosed in the period 2000-2008 were selected from Tuscan Cancer Registry. The histological reports were reviewed and pT1 melanomas classified according to both the 6th and the 7th editions of the AJCC staging system. The shift of melanomas between pT1 substages was analyzed.Among the 242 pT1 melanomas collected in the study period and with mitotic index available, there were 202 (83 % of all pT1) and 175 (72 %) pT1a, according to the 6th and the 7th editions of the AJCC melanoma staging, respectively. When the 7th edition was used, 20 % of all pT1a melanomas shifted to pT1b, and 32 % of all pT1b melanomas shifted to pT1a. A poor level agreement between the two TNM staging systems, measured by the Cohen's kappa coefficient, was found (K = 0.37).The addition of mitotic activity to the pathological staging resulted in an increase in pT1b proportion and in a change in the classification of some cases. This modification could influence the clinical approach, with a different use of the sentinel lymph node biopsy, and underlines the role of mitosis evaluation in the management of thin melanoma patients.

The role of progesterone (PR) expression in the management of breast cancer is controversial. The aim of this study is to evaluate the characteristics and prognosis of progesterone status among breast cancers patients in a population-based analysis. Through the Tuscan Cancer Registry data on all the invasive breast cancer cases diagnosed during the period 2004–2005 in the provinces of Florence and Prato, central Italy, were retrieved. Histological reports were re-examined to obtain information on the percentage of positive tumor cells for estrogen (ER), progesterone (PR) receptors, Ki67 marker and human epidermal growth factor 2 (HER2). Information on age, stage, differentiation grade were also obtained. Out of 1487 patients, 28% had PR− breast cancer. These patients were older (p 0.006) than PR+ cancer patients, with more frequently high Ki67 (p

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+.

Formal indicators for the evaluation of the quality of melanoma care are needed. We identified 13 process indicators, which encompassed early diagnosis, pathology reporting and surgical treatment. We evaluated the adherence to these indicators using a population-based series on incident skin melanomas (only primary melanomas) for the year 2004 (687 cases) and for the first semester of 2008 (539 cases). We compared the indicators for these 2 years. The melanoma incidence increased between 2004 and 2008. There were statistically significant increases in the percentage of thin (≤1 mm) melanomas (from 50.7 to 61.3%) and in the number of pathology reports that mentioned ulceration (from 61.4 to 84.6%) and margin status (from 76.8 to 84.3%). The percentage of patients staged by sentinel lymph node biopsy was stable (63%) and was higher for patients younger than 75 years of age (74%). The number of nodes almost invariably exceeded the proposed site-specific cutoff reference and, in 2008, the number of nodes removed was always reported for lymphadenectomy. From 2004 to 2008, surgical and pathological waiting times increased. Collection and analysis of these indicators would enable continuous evaluation of the quality of melanoma care in Tuscany and provide sources for a comparative study between Italy and elsewhere.

Aim : Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. Methods : A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003–2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Results : Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna – where sophisticated diagnostic examinations were performed more often – had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60–61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02–1.48) than Modena (reference). Conclusions : Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes.

Objective. To evaluate the quality of patients care, a set of indicators of the standards of cancer care were defined. Design, Setting, Participants. We developed a set of indicators to assess the implementation in daily practice of recommendation produced by a regional network (Istituto Toscano Tumori). This set was tested in a retrospective study in the resident population of the Tuscany Region; the regional health system is organized on 12 local health authorities which refer to three macro areas (Area Vasta). The study included incident colorectal, lung and breast cancer cases listed in 2004 for the Tuscan Cancer Registry, a population-based registry which collected tumor cases diagnosed in all residents in Tuscany. Electronic data from registry database were used to determine the compliance with each indicator for patients in 2004. To validate the results, an ad hoc clinical survey including the same geographical area for the year 2006 was performed. Intervention. None. Main Outcome Measures. The proportion of patients who fulfilled each of the indicators. Results. Our study showed the feasibility of the evaluation of the quality of cancer care using cancer registry populationbased data and major computerized information systems. The estimation of the selected indicators confirmed a good homogeneity among areas, and globally revealed a good intraregional performance. Conclusions. Further work is needed to develop specific quality measures, particularly about structural data and to continually revise indicators of quality of care. Data from a cancer registry, however, can be useful to evaluate quality of cancer care

Neuroendocrine tumors are considered rare tumors: recently an increased incidence and an improvement in survival were described. We explore distribution, incidence and survival of neuroendocrine tumors using population based registry data. We extracted from the Tuscan Cancer Registry neuroendocrine tumors from 1985-2005, and we evaluated distribution, incidence ad survival according to sex, site of tumor, age and stage at diagnosis. 455 cases of neuroendocrine tumors were identified. The overall incidence increased over the study period from 0.7 per 100,000 per year to 1.6 among men (APC +3.6) and from 0.3 to 2.1 among women (APC +4.8). The anatomic distribution of tumors was lung 25.7%, small intestine 23.5%, appendix 10.9%, colon 10.3%, pancreas 9.4%, stomach 7.4%, and rectum 5.2%. Neuroendocrine tumors were more frequent among males and incidence rate increased with age. We observed increased incidence of neuroendocrine tumors, while survival did not change over time. Prognosis varied with age, stage and localization; females had better survival than males. The increase number of neuroendocrine tumors may be due, at least in part, to better registration and to improvement of diagnosis.

Recently, an increasing incidence of brain tumors has been reported from multiple studies. Brain tumors diagnosed in the period 1985-2005 were identified through the Tuscan Cancer Registry, a population-based registry active since 1985 in the area of Florence and Prato. Age-standardized incidence rates and average annual percent change (APC) was calculated for the entire period from 1985 to 2005 for sex and behavior. A total of 4,417 brain tumors was registered, 1,900 (43%) in male and 2,517 (57%) in female patients. Malignant and benign tumor incidence rates were 8.3 and 4.1, respectively, among males and 6.4 and 7.2, respectively, among females. The age-adjusted annual incidence rate of all brain tumors was 13.9, with a statistically significant increasing rate throughout the period (APC: +3.2, CI 2.2-4.2). The annual incidence rate remained stable for malignant brain tumors but increased significantly for benign brain tumors (APC: +6.2, CI 4.5-7.9). In our population-based study, the incidence of brain tumors increased from 1985 to 2005 overall and for benign tumors, but not for malignant tumors. Part of the temporal variations may be attributed to improvement in diagnostic imaging techniques and, particularly for benign tumors, in changes in registration practice.

Objective: Our aim was to evaluate the best intrathoracoscopic localization technique between hookwire and radio-guided surgery, in patients with pulmonary nodule. Methods: From January 2000 to January 2005 we enrolled in this study 50 patients with a solitary pulmonary nodule, prospective randomized in two groups, well matched for diameter and depth of the pulmonary lesion. In 25 patients we performed the hookwire technique (Group A), whereas in the other 25 patients radio-guided localization was adopted (Group B). In both groups the localization technique was compared with finger palpation. In Group A, 9 lesions were in the left and 16 in the right lung; in Group B, 14 nodules were in the left lung and 11 in the right one. In both groups, the distance of the nodule from the pleural surface with lung inflated was 2.5 cm (1.5-2.5 cm in 12 patients, and >2.5 cm for the remaining 13). The mean size of the nodules in both groups was 1.1, range 0.6-1.9 ( 1 cm n = 7 patients). Results: All patients underwent thoracoscopic wedge resection, and 23 patients with a primary pulmonary lesion underwent thoracotomy for lobectomy and radical mediastinal lymphadenectomy. In Group A the hookwire technique localized the nodule in 21 of 25 patients (84%) whereas finger palpation localized it in 7 of 25 patients (28%). In Group B, radio-guided surgery localized the nodule in 24 of 25 patients (96%) whereas finger palpation localized it in 6 of 25 (24%). In Group A we registered 6 cases of pneumothorax compared to 1 case observed in the radio-guided group. Postoperative hospital stay required an average of 4 days in both groups. Conclusions: In our experience radio-guided surgery has therefore been proven efficacious in the diagnosis of solitary pulmonary nodule and video-assisted thoracoscopic surgery allows the removal of pulmonary nodules without complications. Hookwire was also shown to be efficacious but demonstrated complications linked primarily to external technical factors.

Background A retrospective study including all patients with non-small cell lung cancer carcinoma in a population-based registry was performed to characterize gender differences in lung cancer and to analyze the factors influencing prognosis in women. Methods We retrieved through the Tuscan Cancer Registry (RTT) archive 2523 lung tumor cases diagnosed during the period 1996–1998 in the provinces of Florence and Prato, central Italy. We compared the prognosis within 464 non-small lung cancer women and 1798 men in a population-based case series. The influence of the following variables on postoperative survival were analyzed: age, cell type, pathologic T and N status, site of tumor and type of surgical resection. Results The age at diagnosis was similar in women and in men. Women were significantly more likely to have adenocarcinoma but less likely to have squamous cell carcinoma compared with men. Fewer pneumonectomies were performed in women than in men. Nevertheless, prognosis was similar in both sexes and type of surgical resection was significant prognostic factor. Conclusions Lung cancer was more frequent in men than in women, but overall survival is similar. Differences in lung cancer histology and rate of pneumonectomies were found between men and women.

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9% were screen-detected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended.

Objective To evaluate the relationship between diameter and Breslow's thickness in skin melanoma. Methods 2,071 skin melanomas incident in the area of activity of the Tuscany Cancer Registry (central Italy) were analyzed. Pearson's linear correlation coefficient r was computed between diameter and Breslow's thickness. Results There was a statistically significant, but rather small, correlation between diameter and Breslow (r = 0.39). The same was true for men and women, for older and younger patients, and for skin subsites. 22.3% of the examined skin melanomas had a diameter ≤6 mm. Conclusions There was a statistically significant, but small, correlation between Breslow's thickness and diameter in skin melanomas. Moreover, a non-negligible proportion of small lesions were thick and/or nodular.

Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS-mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the NRASQ61R mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of NRAS mutation were retrieved from a multicentric database. Formalin-fixed and paraffin-embedded melanoma tissues were analyzed for BRAF and NRAS mutations by independent, blinded observers using both conventional DNA molecular techniques and immunohistochemistry with the novel anti-human N-Ras (Q61R) monoclonal antibody (clone SP174). The antibody showed a sensitivity of 100% (14/14) and a specificity of 100% (83/83) for detecting the presence of an NRASQ61R mutation. Of the NRAS-mutated cases, none of the non-Q61R cases stained positive with the antibody (0/7). There were three cases with discordant NRAS mutational results. Additional molecular analysis confirmed the immunohistochemically obtained NRAS result in all cases, suggesting that a multiple analytical approach can be required to reach the correct sample classification. The reported immunohistochemical method is an accurate, rapid, and cost-effective method for detecting NRASQ61R mutation in melanoma patients, and represents a valuable supplement to traditional mutation testing. If validated in further studies, genetic testing would only be required for immunohistochemistry-negative patients to detect non-Q61R mutations.

Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement.The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection.The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor.N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.

Cerebellar liponeurocytoma is a rare and newly identified neoplasm found in adults which is reputed to be benign. Its salient morphological characteristics are advanced neuronal/neurocytic differentiation, the presence of lipomatous areas, low mitotic rate, and the absence of necrosis, pleomorphism and vascular hyperplasia. Reported is a case of relapsing liponeurocytoma which occurred 3 and a half years after the radical excision of the primary lesion. Histopathological aggressive features (mitoses and a high proliferation index as evaluated by MIB-1) were shown in the primary lesion and recurrence of the tumor. We suggest that liponeurocytoma is an uncertain malignant potential lesion when mitoses are present and the MIB-1 positive cells are more than 10%.

We present an unusual case of intracranial plasma cell granuloma in a 70-year-old man with a 6-month history of progressive visual disturbance. The lesion extensively involved the cranial base, extended into the frontal region, and reached the floor of the third ventricle in the suprasellar area. Microscopic examination of multiple diagnostic transsphenoidal biopsies showed an inflammatory proliferation with a predominance of cells that were immunohistochemically determined to be polyclonal plasma cells. Ultrastructural analysis confirmed the presence of numerous mature plasma cells in a mixed inflammatory proliferation. In situ hybridization for Epstein-Barr viral RNA revealed no evidence of viral expression. The patient was treated with steroid therapy and radiotherapy, without any appreciable reduction of the lesion's size. He is alive with persistent severe visual disturbance 14 months after the diagnosis. We discuss the etiopathogenetic, diagnostic, and therapeutic issues related to this entity, and review the literature.

Primary pulmonary meningiomas are rare and their occurrence has been reported only sporadically. The diagnosis of such tumors should be accepted only after the presence of an intracranial or intraspinal meningioma has been excluded. The morphological and immunohistochemical features are similar to those of intracranial meningiomas. A case of primary pulmonary meningioma along with a review of the literature and discussion of other lesions in the differential diagnosis of this rare neoplasm are here presented.

A 31-year-old woman with a large placental tumor underwent a caesarean section. After delivery, the lesion, detected by ultrasound examination, was found to originate from the umbilical cord. A live female infant with cyanosis, hypotonia and diffuse edema was delivered. A review of the literature, which revealed 31 cases of umbilical cord hemangioma, showed that this tumor has a polymorphous presentation. Some fetuses and infants died from various causes, indicating that a close follow-up is necessary in these pregnancies

Summary Oncocytic meningioma is a recently described rare variant of meningothelial neoplasms that typically occurs as a large cell tumor with granular cytoplasm. The distinct histological features of numerous cells with granular cytoplasm and the ultrastructural evidence of numerous mitochondria in the cytoplasm differentiate this tumor from other neoplasms with granular appearance. We report an additional case of oncocytic meningioma investigated by ultrastructural and immunohistochemical methods.

We read with great interest the article by Denkert et al. [1] about the prognostic role of Ki67 among breast cancer patients treated with neoadjuvant therapy. We think, however, that the different composition of population in clinical practice in comparison with population in the trial could be kept in mind. Among the 1475 cases of breast cancer diagnosed in 2004– 2005 in residents in the area of Firenze and Prato, collected by Tuscan Cancer Registry, and with Ki67 score available, we found a low Ki67 expression (≤15%) in more than half of the cases (58% of total); moreover, in this population-based database, the luminal A cases constituted 70% of the series [2] while, in the trial by Denkert [1], they were 53% of the total. Probably, in the population by trial, the low-risk breast cancer patients are underrepresented, and this feature can influence the results about the prognostic effect of Ki67 in this group. We carried out an ROC curve to assess the best cutoff of Ki67 for predicting overall survival among the luminal A and B cases

Few studies have investigated rectal cancer management at the population level. We compared how rectal cancers diagnosed in Italy (2003-2005) and France (2005) were managed, and evaluated the extent to which management adhered to European guidelines.Samples of 3938 Italian and 2287 French colorectal cancer patients were randomly extracted from 8 and 12 cancer registries respectively. Rectal cancer patients (860 Italian, 559 French) were analysed. Logistic regression models estimated odds ratios (ORs) of being treated with curative intent, receiving sphincter-saving surgery, and receiving preoperative radiotherapy.Similar proportions of Italian and French patients were treated with curative intent (70% vs. 67%; OR=0.92 [0.73-1.16]); the respective proportions receiving sphincter-saving surgery were 21% and 33% (OR=1.15 [0.86-1.53]). In about 50% of those treated with curative intent, ≥ 12 lymph nodes were harvested in both countries. The proportion receiving postoperative radiotherapy was higher in Italy than in France (25% vs. 11%, p0.01), but French patients were more likely to receive preoperative radiotherapy (52% vs. 21%; OR=4.06 [2.79-5.91]).The proportions of patients receiving preoperative radiotherapy and the numbers of lymph nodes sampled were low in both countries. Centralising treatment and potentiating screening would be practical ways of improving outcomes and adhering to guidelines.

Original, population-based estimates of indicators of long-term survival and cure in cancer patients are provided. More than a quarter of cancer patients in Italy have reached death rates similar to those of the general population. Nearly three quarters of them will not die as a result of cancer. These estimates are potentially helpful to health-care planners, clinicians, and patients., Background Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. Patients and methods Data on 818 902 Italian cancer patients diagnosed at age 15–74 years in 1985–2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. Results The cure fractions ranged from >90% for patients aged 95% were both reached in 95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained 25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. Conclusions A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective.

We analysed presentation, treatment and survival in a representative population-based sample of 3753 Italian colorectal cancer cases, diagnosed 2003–05: 70% were >65 years, 44% stage I-II, 27% stage IV and 92% received surgery. Chemotherapy was given to 58% of stage III colon cases, radiotherapy to 25% of rectal cases. Four percent of surgical cases underwent endoscopic polypectomy, and in 57% ≥11 lymph nodes were examined. Five-year relative survival was good (60%), independent of sex and site. Adherence to treatment guidelines was satisfactory, but wider use of faecal blood testing and colonoscopy will anticipate stage at diagnosis and likely improve survival.

Conflicting results on the shift of right-left ratio in colon cancer incidence have been reported. We examine incidence trends by subsite in a population-based study.Colorectal cancer cases diagnosed in the 1985-2005 period were identified through the Tuscany Cancer Registry. Colon subsite was defined as proximal and distal; gender, age at diagnosis, histology, and stage were analyzed. Average annual incidence and age-specific rates according to subsite were calculated.A total of 21,160 colorectal cancer cases were extracted; in 18,311 cases, the subsite was identified: 6,916 rectal, 5,239 proximal, and 6,156 distal. A larger proportion of distal colon cancers presented as early stage when compared with proximal. Incidence of rectal and distal colon cancer remained stable, while proximal colon cancer incidence increased.Proximal colon cancer incidence rate increased through the period. Temporal variations in the incidence rate by subsite could suggest different carcinogenic pathways of right- and left-sided colon cancer.

Purpose Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries. Methods Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers. Results Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER–PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER–PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%). Conclusions Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.