Survival of Patients with Sinonasal Cancers in a Population-Based Registry, Lombardy, Italy, 2008-2023.

Sinonasal cancers (SNCs) are rare malignancies associated with occupational exposures. The aim of this study was to analyse the survival of SNC patients using data from the population-based SNC registry of the Lombardy region (10 million people), Italy. We included epithelial SNC cases registered in 2008-2020 and followed-up for vital status until 31 July 2023. Multivariate flexible parametric models with time-dependent covariates were fitted to calculate excess hazard ratios (EHRs) and 95% confidence intervals (CIs) of death. Based on 827 cases (553 males, 274 females) and 514 deaths (345 males, 169 females), the 5-year observed survival was 49% and the net survival was 57%. Age had a substantial impact on survival, particularly within the first year (EHR, 1.35; 95% CI, 1.12-1.51 per 10 years). Compared with the nasal cavity, the EHR for paranasal sinuses was 4.70 (95% CI, 2.96-7.47) soon after diagnosis. Compared with squamous cell carcinomas, the EHR was 0.69 (95% CI, 0.52-0.91) for adenocarcinomas, 1.68 (95% CI, 1.20-2.35) for undifferentiated and unspecified carcinomas, and 1.78 (95% CI, 1.07-2.95) for neuroendocrine carcinomas. Age and cancer site showed time-dependent effects on prognosis, especially within the first month after diagnosis. Prognosis was also markedly affected by cancer morphology. No associations were found for gender and period of diagnosis.

COVID-19 vaccines coverage and effectiveness against SARS-CoV-2 infection among residents in the largest Health Authority of Lazio region (Italy): a population-based cohort study.

BACKGROUND: The waning of the protective effect of COVID-19 vaccines and timing of booster doses are debated. METHODS: Population-based cohort study in the largest Health-Authority of Lazio region, Italy, on 946,156 residents aged 12+ (study period: 1 January 2021-10 January 2022). Vaccine effectiveness (VE) against any SARS-CoV-2 infection (symptomatic or asymptomatic) was estimated through multivariable negative-binomial models using unvaccinated person-time as a reference. RESULTS: The primary vaccination cycle was completed by 81% of residents; of these, 45% received a booster dose. Vaccine coverages were lower for foreigners, and people living in deprived areas, families with children aged 0-11, and households size 1 or 6+. Overall, VE waned from 71% (95% Confidence Interval (CI) 70-73%) 1 month after the second dose to 43% (CI 41-45%) after 4 months and 24% (CI 21-27%) after 6 months, especially in the elderly aged 70+. We observed a prompt restore of VE 15-19 days after the booster dose (69%, CI 67-70%). CONCLUSIONS: Our results support the recommendation of a booster dose 4 months after completion of the primary cycle, giving priority to elderly and fragile individuals. The lower vaccine coverage among social disadvantaged subgroups suggests the need of targeted communication and interventions.

Effectiveness of the Comirnaty and the Vaxzevria vaccines in preventing SARS-CoV-2 infection among residents in Lazio region (Italy).

We estimated the effectiveness of Comirnaty and Vaxzevria vaccines among 371,423 residents in Lazio Region (Italy) vaccinated since 27/12/2020, and followed until diagnosis of SARS-CoV-2 infection or 25/4/2021, whichever came first. By the end of follow-up most of the Comirnaty-cohort (60%) had received the second dose at recommended time of 21 days (98%), while the Vaxzevria-cohort had received only one dose. Adjusted hazard ratios of SARS-CoV-2 infection at weekly intervals since the first dose were estimated through a Cox regression model using 0-13 days as reference time-interval. An increase in effectiveness with increasing time since administration was observed for Comirnaty (five-weeks = 81%, 95 %CI 71-88%; three-months = 94%, 95 %CI 84-98%). One dose of Vaxzevria showed an effectiveness of 63% (95 %CI 25-82%) after 7 weeks, although further analyses are needed after complete vaccination with two doses. These results could support the ongoing vaccination campaign by reinforcing evidence-based communication aimed at reducing vaccine hesitancy.

[Pitfalls on estimation of the cumulative risk of developing cancer]. / Le insidie nella stima del rischio cumulativo di ammalare di tumore.

The cumulative risk (CR) of developing cancer is a measure of the spread of cancer in a population used because it is intuitive to understand. However, there are various methods to calculate it leading to results with different interpretations. With real data we calculated the CR of developing any tumour in males and females to age 84 using three approaches. With the former, which uses only the cancer incidence, a CR to age 84 is estimated equal to 51.7% in males and 36% in females. With the second, which takes into account the competing risk of dying for other causes, the CR to age 84 is estimated equal to 44% in males and 32.9% in females. Finally, after adjusting for multiple primaries in the same person, the CR to age 84 boils down to 37.7% in males and 29.2% in females. Only methods taking into account the competing risk of dying for other causes and adjusting for multiple primaries in the same person are appropriate to estimate the real risk of developing any tumour in the course of life. For estimating the real risk of developing a specific form of cancer we must take into account the competing risk of dying while the adjustment for the occurrence of multiple primaries should be considered only for some long-survival sites. KEYWORDS: cumulative risk; cancer incidence; competing risks.

Estimation of age-standardized net survival, even when age-specific data are sparse.

BACKGROUND: Age-standardization is vital in international comparison studies of cancer patient survival, but standard approaches can fail to produce estimates in the case of sparsity. METHODS: The purpose of this paper is to demonstrate that using a standardization pre-weighting approach is a viable alternative approach for external age-standardization in population-based cancer data and performs well in cases of sparsity. We further de;1;scribe how the pre-weighting approach to age-standardization can be coupled with the Pohar Perme estimator in both a cohort and period analysis setting. For period analysis, we compare approaches for defining the internal age distribution. We use SEER public use data to illustrate our approach and estimate survival for Connecticut and by race to create a scenario with sufficient sparsity. RESULTS: The pre-weighting approach gives comparable estimates to traditional age-standardization in cases with sufficient data and produces estimates throughout follow-up in cases of sparsity when a traditional approach would fail. CONCLUSION: International comparison studies and other national population-based survival studies that need to age-standardize estimates for comparability purposes should adopt the Pohar Perme estimator with pre-weighting. This approach avoids issues of non-estimation in the case of sparsity and will allow more consistent comparisons across the produced estimates.

[Risk profiling in cancer surveillance in contaminated sites: an example from the ISS-AIRTUM collaborative study]. / Sintesi del profilo di incidenza di tumore nei SIN: un esempio dallo studio collaborativo ISS-AIRTUM.

Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.

Mortality trends for primary liver cancer in Puglia, Italy.

In the region of Puglia, Italy, the mortality rates from primary liver cancer (PLC) show a considerable geographical variability. In an area including the city of Bari and the northern province [high-risk (HR) area] the mortality rates are significantly higher than elsewhere in the region [low-risk (LR) area]. The aim of this study is to analyze mortality because of PLC from 1980 to 2002 in the HR and LR areas using an age-period-cohort model to identify their respective trend characteristics and the differences that emerge from their comparison. Attention was focused on the identifiable effects, which are on the drift and on the deviations from this regular trend (curvature), specifically attributable to the cohort and the period effects by applying the method recently proposed by Carstensen. The HR area is characterized by a more marked increase in the mortality trend compared with that observed in the LR area, as indicated in the model by a greater drift effect. In both areas the cohort (curvature) effect shows a decreasing trend starting from the early 1930s whereas the period effect shows a peak in the first half of the 1990s. Despite the correspondence of the trends, the rate ratio of death from PLC between the two areas is not constant and tends to rise uniformly by age, birth cohort, and period of time: in 2002, the rate ratio of death was 1.40 [confidence interval (CI): 1.15-1.70] at 40 years old, 1.73 (CI: 1.55-1.93) at 60 years old, and 2.14 (CI: 1.92-2.38) at 80 years old.

Hemochromatosis in Italy in the last 30 years: role of genetic and acquired factors.

UNLABELLED: The clinical presentation of hereditary hemochromatosis has changed markedly in recent years. The aim of this study was to analyze a large series of consecutive Italian patients with hemochromatosis diagnosed between 1976 and 2007 to determine whether the genetic background and the presence of acquired risk factors influenced the severity of iron overload and the natural history of the disease. A cohort of 452 Italian patients with iron overload-338 HFE-related (C282Y homozygotes or compound C82Y/H63D heterozygotes) and 114 non-HFE-related-were followed prospectively for a median of 112 months. Alcohol intake, smoking habits, and iron removed to depletion were similar in patients with and without HFE-related iron overload. Hepatitis B virus (4% and 9%; P = 0.04) and hepatitis C virus (6% and 19%; P = 0.002) infections were more frequent in patients with non-HFE-related iron overload. Seventy-three percent of patients with HFE and 61% of patients with non-HFE-related disease had no acquired risk factor. Cirrhosis was significantly more frequent in non-HFE patients independent of the presence of acquired risk factors (P = 0.02). Sex, alcohol intake, prevalence of smoking, hepatitis C virus infection, glucose, lipids, iron-related parameters, and prevalence of C282Y/H63D differed significantly over the years. At enrollment, cirrhosis was present in 145 cases and was significantly more frequent in the first decade (80%, 47%, and 13%; P = 0.001). Survival did not differ across the decades in cirrhotic patients; hepatocellular carcinoma occurred similarly in HFE and non-HFE patients. CONCLUSION: Patients with HFE and non-HFE-related iron overload have comparable iron overload and similar clinical history. Patients who were diagnosed during the last 10 years and were not identified as cirrhotic at enrollment have less severe disease and lower prevalence of acquired risk factors, independent of genetic background.

Evaluation of service mammography screening impact in Italy. The contribution of hazard analysis.

12,987 invasive breast cancer cases were diagnosed in women aged 50-69 upto the year 2001 in nine Italian areas where a screening programme was active. Cases were followed up in 2005 for a total of 1921 breast cancer failures. The 10-year survival rates were 85.3% for the invited group against 75.6% for the non-invited. A time dependent analysis was performed using 5-year intervals. Crude hazard ratios for the invited group in comparison to the not invited group were 0.52 and 0.64 respectively in the (0-5) year and [5-10] year time windows. Hazard ratio adjusted for tumour characteristics was 0.96 in the [5-10] year time window, suggesting minimal or any length bias. Consistent with the results of randomised trials, these analyses of service screening data document a mortality reduction of 36% at 5-10 years after diagnosis.

[The hazard function]. / La funzione dell'hazard.

In cohort studies the event occurrence is usually described by the incidence rate and the survivor function. In comparison with these estimators the plot of the hazard function has the advantage to show the variations of the occurrence of the event along the period of observation, which often are important to be highlighted. Furthermore, when comparing individuals with different characteristics, the hazard function is a valuable support to check the assumption and to interpret the results of a Cox regression model. This paper illustrates the method for estimating the hazard function and an example is given from a real case by using the survival data of the breast cancers collected in the IMPACT study, aimed to detect the efficacy of the mammographic screening program. The relationship between the usual estimators and the hazard function is shown and its role in the survival regression modelling is emphasized. In the example the estimate of the hazard function allows to point out that the mortality rate of breast cancer in the first year after the diagnosis is lower than later and that the difference between the hazards of the invited cases and those of the not invited cases is approximately constant along the whole l0 years follow up, two important remarks both demonstrating the usefulness of the application of this function in the analysis of cohort studies.

[Statistical approaches to test for spatial heterogeneity of relative risks of cause-specific mortality in Alto Vicentino Municipalities (years 1991-2000)]. / Valutazione dell'eterogeneità nei rischi relativi di mortalità per causa: un'applicazione ai Comuni dell'ULSS Alto Vicentino (decessi 1991-2000).

OBJECTIVE: To review the statistical approaches to test for spatial heterogeneity of relative risks. Three different statistical tests (Gail, Martuzzi-Hills and Potthoff-Whittinghill) are reviewed and applied--as motivating example--to the analysis of cause-specific mortality records (years: 1991-2000) of the Municipalities belonging to the Local Health Unit Alto Vicentino. METHODS: Spatial heterogeneity was found in 17 (Martuzzi-Hills) and 18 (Gail, Potthoff-Whittinghill) among 70 selected causes of death. Cohens Kappa test was chosen to assess the agreement among the tests (k = 0.596; p < or = 0.001). CONCLUSION: Spatial heterogeneity must be interpreted with great caution, taking into account the available evidence about risk factors for specific causes of death and carefully evaluating available exposure data.