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.

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.

[Childhood cancer incidence in Apulia Region (Southern Italy), 2003-2008]. / Incidenza dei tumori maligni infantili in Puglia, 2003-2008.

OBJECTIVES: to investigate, for the first time, the incidence rates of malignant childhood cancers (children aged 0-14 years) in Apulia Region (Southern Italy) in the period 2003-2008. DESIGN: to compute incidence rates of childhood cancers from Apulia Region Cancer Registry database compared with the corresponding results published in 2012 by the Italian cancer registries network (AIRTUM),where data from the Apulia population were not included, because not available. SETTING AND PARTICIPANTS: we selected all incident cases of malignant tumours (behaviour: /3 of ICD-O-3 classification) in children aged 0-14 registered in the Apulia cancer registry. Local health unit (LHU) of Lecce (section of the Apulia cancer registry) collected data from 2003 to 2006; LHU of Taranto, BT, and Brindisi collected data from 2006 to 2008. MAIN OUTCOME MEASURES: we computed crude, age specific, and directly standardised rates (DSR), with 95% confidence intervals, of all malignant tumours, all categories and 5 subgroups of the ICCC-3 classification; standardised incidence ratios (SIR) for all childhood malignant tumours using the rates of the AIRTUM Pool 2003-2008 as reference . RESULTS: incident cases were 183. DSR (x106) of all childhood malignant tumours are: Apulia Region 169.7 (95%CI 145.9- 196.4); Brindisi 160.4 (95%CI 106.2-232.9); BT 177.7 (95%CI 122.7-248.7); Lecce 144.3 (95%CI 111.1-184.2); Taranto 216.2 (95%CI 163.0-281.4). SIR estimates are: Apulia Region 102.9 (95%CI 88.5-119.0); Brindisi 100.2 (95%CI 66.6-144.9); BT 105.4 (95%CI 73.0-147.2); Lecce 85.5 (95%CI 66.0-109.0); Taranto 134.6 (95%CI 101.7-174.8). Main incidence measures for all ICCC-3 categories and five subgroups of childhood cancers in Apulia are also reported. CONCLUSIONS: in Apulia Region, we estimated a DSR for all childhood malignant tumours very close to that of the AIRTUM Pool. DSRs for each ICCC-3 category look comparable with the data from the national survey too. When data of each LHU were analysed, the SIR estimate makes it evident an excess of all malignant childhood cancers in the LHU of Taranto. Other results of particular cancers and specific age groups also provide suggestions for further investigations.

Incidence of Non-Melanoma Skin Cancers in Salento (Southern Italy): A 15-Year Retrospective Analysis from the Cancer Registry of Lecce.

BACKGROUND AND OBJECTIVES: Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous-cell carcinoma (SCC), as well as a wide range of rare skin tumors. NMSCs is the most frequently diagnosed type of tumor among Caucasians. We aimed at estimating the incidence and mortality of NMSCs in the Salento area (Lecce province, Southern Italy), whose population is assumed to experience heavy and frequent sun exposure due to climatic/environmental factors, both for working and leisure activities. MATERIALS AND METHODS: We computed the incidence of NMSCs in the Province of Lecce by examining the comprehensive real-world data collected by the local cancer registry, which covers all the 830,000 inhabitants, over a period of fifteen years (from 2003 to 2017), with a focus on the latest 5 years (2013-2017) for the analysis of the different histologic morphologies of these tumors. The incidence of NMSCs has been described in terms of absolute frequencies, crude rates and age-adjusted direct standardized rates (DSR). Joinpoint analysis was used to examine temporal trends in the incidence of NMSCs and estimate annual percent changes (APCs). RESULTS: During the period of 2003-2017, the incidence of NMSCs reached a direct standardized rate (DSR) of 162.62 per 100,000 in men (mortality 1.57 per 100,000) and 89.36 per 100,000 in women (mortality 0.52 per 100,000), respectively. The incidence significantly increased among both men and women across the entire period. Basal cell carcinoma (BCC), with its different morphologies, represented about 67.6% of the NMSCs in men (n = 2139 out of a total of 3161 tumors observed between 2013 and 2017) and about 75.8% of the NMSCs in women (n = 1718 out of a total of 2264 tumors from 2013 to 2017), thus accounting for the vast majority of NMSCs. The results are consistent with the literature data carried out both at national and international level. CONCLUSIONS: Proper monitoring of this phenomenon through timely reporting and recording of all new NMSC cases is necessary to develop new preventive strategies.

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.

Risk Factors for Lung Cancer in the Province of Lecce: Results from the PROTOS Case-Control Study in Salento (Southern Italy).

In the province of Lecce (southern Italy), a higher incidence of lung cancer (LC) among men compared to regional and national data was reported. In a sub-area in the center of the province (cluster area), the incidence and mortality for LC was even higher. PROTOS is a case-control study aimed at investigating possible risk factors for LC in the province area. A total of 442 patients with LC and 1326 controls matched by sex and age living in the province of Lecce for at least 10 years were enrolled and georeferenced; they filled in a questionnaire with their personal information and exposures. For each risk factor, an Odds Ratio adjusted for all the other variables was calculated. The risk of LC increased with excessive use of alcohol in women, for those subjects with a family cancer history, for each increase in pack/year of cigarettes, for men more exposed considering the industrial district in the cluster area, and for those using pesticides in agriculture without wearing personal protective equipment. The higher incidence of adenocarcinoma in both sexes suggests that, in addition to cigarette smoking, concurrent exposures to other environmental, occupational, and life-style factors may play a role in increased cancer risk and should be more deeply explored.

Population-based incidence of gastrointestinal stromal tumors in Puglia.

INTRODUCTION: This study presents the incidence of gastrointestinal stromal tumors (GISTs) in an Italian region of over 4 million inhabitants monitored for 10 years and is the largest incidence study of this type of cancer conducted so far in Italy. METHODS: In order to ensure the registration of all GISTs, including those with nonmalignant behavior, a cancer list was integrated with the cases found through an ad hoc data mining process that covered all the pathologic reports of Puglia. Case distributions by sex, age groups, site, and prognostic groups according to Miettinem and Lasota classification and crude and age-standardized incidence rates were produced. RESULTS: In the 10-year period 2006 to 2015, 708 cases of GIST were recorded in Puglia. The average crude incidence rate was 1.7 per 100,000 person-years and the age-standardized incidence rate, using 2013 European standard population, was 1.8 per 100,000 person-years (95% confidence interval [CI], 1.6-1.9). Incidence was higher in men than in women: crude incidence rate was 2.0 per 100,000 person-years and age-standardized incidence rate 2.2 per 100,000 person-years (95% CI, 2.0-2.4) in men and 1.5 per 100,000 person-years and 1.4 per 100,000 person-years (95% CI, 1.2-1.6) in women. DISCUSSION: Our incidence rates are comparable with those of other international studies and they are located in the medium to high end of the range. The comparisons are affected by a different capacity of the cancer registries to intercept and record GISTs with nonmalignant behavior. Distribution of cases for sex, age groups, sites, and prognostic risk groups are consistent with previous results.

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.

Estimates of cancer burden in Puglia.

AIMS AND BACKGROUND: A regional population-based cancer registry that provides incidence and survival data has become active only recently. Since it is important to know the time trends of basic epidemiological indicators to understand the cancer burden in the region, this paper will provide incidence, prevalence and mortality estimates in the region for seven major cancers for the period 1970-2015. METHODS: The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries. RESULTS: The incidence rates are estimated to be still increasing for female breast cancer, colorectal cancer in men and skin melanoma in both sexes. By contrast, the incidence rates indicate a decreasing trend for cervix uteri cancer and stomach cancer, the latter both in men and women. For these cancers an analogous trend is observed for mortality, confirming the reduction of the risk factors related to these cancer types. The incidence rates for lung cancer and prostate cancer in men were estimated to rise, reach a peak, and then decrease in the last part of the considered period. Prevalence increased for all the considered cancers except cervix cancer. The increase was striking for breast cancer and less pronounced for stomach cancer in both genders. CONCLUSION: This paper provides a description of the burden of the major cancers until 2015. The results highlight the need to reinforce effective preventive measures to contrast cancers related to an unhealthy lifestyle and to increase the compliance with organized screening programs to reduce the colorectal and breast cancer burden.