All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980-2018).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. METHODS: The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20-84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. RESULTS: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107-109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. CONCLUSIONS: For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Hepatic Artery Anomalies in Pancreaticoduodenectomy: Outcomes from a High-Volume Center.

INTRODUCTION: Hepatic artery anomalies (HAA) may have an impact on surgical and oncological outcomes of patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at our institution between July 2015 and January 2020 were retrospectively reviewed and classified into two groups: group 1, with presence of HAA, and group 2, with no HAA. A weighted logistic regression model was employed to assess the association between HAA and postoperative complications, and to assess the association between HAA and R status in patients with pancreatic cancer. RESULTS: 502 patients were considered for analysis, with 75 (15%) of them in group 1. They had either an accessory (n = 28, 40.8%) or replaced (n = 26, 36.6%) right hepatic artery. Most patients underwent surgery for a malignancy (n = 451; 90%); among them, vascular resection was performed in 69 cases (15%). The presence of a HAA was reported at preoperative imaging only in 4 cases (5%) and the aberrant vessel was preserved in 72% of patients. At weighted multivariable logistic regression analysis, HAA were not associated to higher odds of morbidity (odds ratio [OR]: 0.753, 95% confidence interval [CI]: 0.543-1.043) nor to R1 status in case of pancreatic cancer (OR: 1.583, 95% CI: 0.979-2.561). CONCLUSION: At our institution, the presence of HAA does not have an impact on postoperative outcomes or affects oncological clearance after PD. Hospitals', surgeons', volume and systematic review of preoperative imaging are all factors that help reduce possible adverse events.

Patient presentation, skin biopsy utilization and cutaneous malignant melanoma incidence and mortality in northern Italy: Trends and correlations.

BACKGROUND: The global increase in incidence of cutaneous malignant melanoma (CMM) occurring in the past decades has been partly attributed to increased diagnostic scrutiny of early lesions, with a potential phenomenon of overdiagnosis. The reported positive linear relation between skin biopsy rate and incidence of early CMM is compatible with this hypothesis. OBJECTIVES: We explored the ecological association between the trends in annual dermatologic office visit rates, skin biopsy rates, incidence rates of in situ and invasive CMM by tumour thickness category, and CMM mortality rates in the Emilia-Romagna Region (northern Italy). METHODS: Four cancer registries covering a population of 2,696,000 provided CMM incidence data for the years 2003-2017. Dermatologic office visit rates and skin biopsy rates were calculated using the Regional outpatient care database. All rates were age-standardized. Trends were described with the estimated average annual per cent change (EAAPC). Correlations were tested with the Spearman correlation coefficient. RESULTS: Incidence increased significantly. The increase was steeper for in situ CMM (EAAPC: men, 10.2; women, 6.9) followed by CMM <0.8 mm thick (9.1; 5.2), but the rates grew significantly for most subgroups of CMMs ≥0.8 mm thick. Mortality decreased significantly among women (-2.3) and non-significantly among men. For dermatologic office visit rate and skin biopsy rate the EAAPC were, respectively, 1.7 and 1.8 for men and 1.2 and 0.9 for women. Annual dermatologic office visit rate correlated with skin biopsy rate in both sexes. However, the proportion of skin biopsies out of dermatologic office visits was constant across the years (range: men, 0.182-0.216; women, 0.157-0.191). CONCLUSIONS: In Italy, the increasing CMM incidence trend is, at least in part, genuine. Overdiagnosis-if any-is due to an increased patient presentation at dermatologic offices and not to a lower dermatologic threshold to perform biopsy.

Applying competing risks analysis to recurrences of primary breast cancer.

INTRODUCTION: in time-to-event analysis, competing risks are observed when a subject is at risk of multiple types of events. A competing risk is an event that prevents the event of interest from happening or modifies its chance to occur. OBJECTIVES: the purposes of this article are to provide an overview of competing risks analysis and to illustrate its application to the follow-up of breast cancer patients in order to estimate the risk of disease recurrence. DESIGN: cohort study. SETTING AND PARTICIPANTS: population-based random sample of patients with stage I-III primary female breast cancer diagnosed in 2000-2013, aged 15 years or older, resident in the Forlì health care district (northern Italy), treated surgically and with available information regarding disease laterality. MAIN OUTCOME MEASURES: subhazard ratio, hazard ratio and cumulative incidence function for loco-regional recurrences and distant metastasis during 10 years of follow-up. METHODS: breast cancer recurrences were evaluated taking into account death from any cause and occurrence of a second primary breast cancer as competing risks. Recent developments in competing risks methodology were used. The results obtained were compared with those from the Cox regression model, in which the competing risks were not accounted for. CONCLUSIONS: estimating the risk of recurrence without accounting for the competing risks resulted in a divergence of the hazard/subhazard functions. Competing risks analysis is preferable when the statistical assumption of independence of end-points may be violated.

How a faecal immunochemical test screening programme changes annual colorectal cancer incidence rates: an Italian intention-to-screen study.

BACKGROUND: This study aimed to evaluate the effectiveness of a biennial faecal immunochemical test (FIT) screening programme in reducing annual colorectal cancer (CRC) incidence in its dynamic target population. METHODS: The target population included over 1,000,000 persons aged 50-69 living in a region of northern Italy. The average annual response rate to invitation was 51.4%. Each observed annual age-standardised (Europe) rate per 100,000 persons between 2005, the year of introduction of the programme, and 2016 was compared with each expected annual rate as estimated with age-period-cohort (men) and age-period (women) models. RESULTS: For both sexes, the rates observed in 1997-2004 and those expected in 2005-2016 were stable. Observed rates increased in 2005, peaked in 2006 (the first full year of screening), dropped significantly below the expected level in 2009, and continued to decrease until 2013 (the eighth full year), after which no further significant changes occurred. In the pooled years 2013-2016, the observed incidence rate per 100,000 persons was 102.2 [95% CI: 97.4, 107.1] for men, 75.6 [95% CI: 71.6, 79.7] for women and 88.4 [95% CI: 85.3, 91.5] for both sexes combined, with an observed:expected incidence rate ratio of 0.68 [95% CI: 0.65, 0.71], 0.79 [95% CI: 0.76, 0.82] and 0.72 [95% CI: 0.66, 0.81], respectively. DISCUSSION: The study provided multiple consistent proofs of a causal relationship between the introduction of screening and a stable 28% decrease in annual CRC incidence after eight years.

Effects of Attendance to an Organized Fecal Immunochemical Test Screening Program on the Risk of Colorectal Cancer: An Observational Cohort Study.

BACKGROUND & AIMS: This cohort study compared colorectal cancer (CRC) incidence and mortality between people who participated in an Italian regional biennial fecal immunochemical test (FIT) screening program and people who did not. METHODS: The program started in 2005. The target population included over 1,000,000 people aged 50 to 69 years. The FIT was a one-sample OC-Sensor (Eiken Chemical Co, Tokyo, Japan) (cutoff, ≥20 µg hemoglobin/g feces). The average annual response rate to invitation was 51.4%. The records of people invited up to June 2016 were extracted from the screening data warehouse. Attenders were subjects who responded to the first 2 invitations or to the single invitation sent them before they became ineligible. Non-attenders were subjects who did not respond to any of these invitations. The records were linked with the regional CRC registry. People registered up to December 2016 were identified. Self-selection-adjusted incidence rate ratios (IRRs) and incidence-based CRC mortality rate ratios (MRRs) for attenders to non-attenders, with 95% confidence intervals (CIs), were calculated. RESULTS: The cohort generated 2,622,131 man-years and 2,887,845 woman-years at risk with 4490 and 3309 CRC cases, respectively. The cohort of attenders was associated with an IRR of 0.65 (95% CI, 0.61-0.69) for men, 0.75 (95% CI, 0.70-0.80) for women and 0.69 (95% CI, 0.66-0.72) for both sexes combined. The self-selection-adjusted IRR was 0.67 (95% CI, 0.62-0.72) for men and 0.79 (95% CI, 0.72-0.88) for women. The IRR for stage I, II, III, and IV CRC was 1.35 (95% CI, 1.20-1.50), 0.61 (95% CI, 0.53-0.69), 0.60 (95% CI, 0.53-0.68) and 0.28 (95% CI, 0.24-0.32) for men and 1.64 (95% CI, 1.43-1.89), 0.60 (95% CI, 0.52-0.69), 0.73 (95% CI, 0.63-0.85) and 0.35 (95% CI, 0.30-0.42) for women. The overall incidence-based CRC MRR was 0.32 (95% CI, 0.28-0.37) for men, 0.40 (95% CI, 0.34-0.47) for women and 0.35 (95% CI, 0.31-0.39) for both sexes combined. The adjusted MRR was 0.35 (95% CI, 0.29-0.41) for men and 0.46 (95% CI, 0.37-0.58) for women. CONCLUSIONS: Attendance to a FIT screening program is associated with a CRC incidence reduction of 33% among men and 21% among women, and a CRC mortality reduction of 65% and 54%, respectively.

The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population-based investigation.

BACKGROUND: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor. OBJECTIVES: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy. METHODS: Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors. RESULTS: Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017. CONCLUSIONS: For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

Five-year annual incidence and clinico-molecular features of breast cancer after the last negative screening mammography at age 68-69.

OBJECTIVE: The European Commission Initiative on Breast Cancer recommendation for triennial screening of women aged 70-74 is based on very weak evidence. A cohort of Italian women who had their last biennial screening mammography at age 68-69 was followed up for 5 years, assumed to represent the interval to another hypothetical screening mammography, in order to determine the annual proportional incidence of interval breast cancer. METHODS: The cohort included 118,370 women. They had their last mammography between 1997 and 2008. Incident breast cancers were identified by record-linking the cohort with the regional breast cancer registry. The expected incidence in the age range 65-74 was estimated with an age-period-cohort model. The number of interval cancers was divided by the expected number to obtain their proportional incidence. RESULTS: Overall, there were 298,658 woman-years at risk with 371 interval cancers versus 988.8 expected. In the first, second, third, fourth, and fifth interval year, the proportional incidence was 0.09 (95% confidence interval, 0.06-0.13), 0.32 (0.25-0.39), 0.60 (0.49-0.73), 0.75 (0.60-0.92), and 0.81 (0.60-1.07), respectively. Between the second and the fifth year, tumour stage and molecular subtype did not change significantly. CONCLUSION: Though not supported by these findings, the proposal of triennial screening for women aged 70-74 merits further research, because the 95% confidence interval of the third-year proportional incidence of interval cancer included 0.50-the maximum limit considered acceptable for women aged 50-69. KEY POINTS: • The third-year incidence of breast cancer relative to the expected one was 0.60 (95% confidence interval, 0.49-0.73). • Between the second and the fifth year, tumour stage and molecular subtype did not change significantly (p >0.10). • The proposal of a 3-year screening interval at age 70-74 merits further evaluation.

[Update of survival of cancer patients in Italy: geographical comparisons and focus on patients with cancers targeted by screening programmes, childhood cancers, and smoking-associated cancers]. / Aggiornamento della sopravvivenza dei pazienti con tumore in Italia: confronti geografici e focus su pazienti con tumori oggetto di screening, pediatrici e associati al fumo.

OBJECTIVES: to update the Italian estimates of survival for patients with a paediatric cancer, tobacco smoke-associated cancers, and cancers targeted by screening; to assess geographical differences. DESIGN: population-based descriptive study. SETTING AND PARTICIPANTS: incident cancer cases diagnosed in 2010-2014, with follow-up to 2018, from 17 Italian cancer registries (covering 31% of the national population; 43% of the population residing in the North-Centre of the country and 8% of the population living in the South and Islands). MAIN OUTCOME MEASURES: age-standardized 5-year net survival (NS) by cancer site or type, sex, age, and geographical area. RESULTS: NS of patients aged ≥15 years with breast, prostate, colorectal, and lung cancers was higher in the North-Centre than in the South and Islands. The overall survival of people diagnosed with cancer in childhood (0-14 years) was 84.3%, with similar values among the geographical macro-areas and between males and females. Women with breast cancer within the current target age of the screening programmes and those in the younger age groups (45-49 years) show similar survival values; the same is true for women with colorectal cancer. In both cases, survival decreased in the age groups after the age of cessation of screening programmes. Survival of patients with tobacco smoke-associated cancers varies according to cancer site (from 11.1% for patients with pancreatic cancer to 79.7% for those with bladder cancer). For most cancer sites, women have higher survival than men. CONCLUSIONS: for adults, a geographical survival gap persists. The results may contribute to the debate on extending the target age for screening programmes and to support initiatives to encourage tobacco smoking cessation even after cancer diagnosis. For patients who receive a cancer diagnosis in childhood, survival similar to highest values internationally.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Results of Compliant Participation in Five Rounds of Fecal Immunochemical Test Screening for Colorectal Cancer.

BACKGROUND & AIMS: We investigated the magnitude and temporal patterns of the decreasing trend in main performance measures of fecal immunochemical test (FIT) screening for colorectal cancer (CRC) observed in second and subsequent rounds. METHODS: We followed up 494,187 participants from the first round of a regional biennial FIT screening program in Italy (cut-off value for positivity, 20 µg hemoglobin/g feces) for 5 total rounds (2005-2016). At each round, only compliant participants were eligible. Performance measures from the first, third, fourth, and fifth rounds were compared with those from the second round (the first incidence round) using rate ratios from multivariate Poisson regression models and relative risk ratios from multinomial logistic regression models. RESULTS: Between the second and the third rounds, a significant 20% to 30% decrease was found in the proportion of men with a positive FIT result (from 5.2% to 4.3%) and in detection rates of advanced adenoma (from 13.4 to 10.2 per 1000), CRC (from 1.7 to 1.4 per 1000), and advanced neoplasia (from 15.1 to 11.6 per 1000). Positive predictive values (PPVs) decreased by 10% or less between the second and third rounds. Detection rates and PPVs for adenoma stabilized by the fourth and fifth rounds. The PPVs for advanced adenoma, CRC, and advanced neoplasia decreased slightly in men and women by the fourth and fifth rounds. The detection rate of proximal colon cancer stabilized after the second round, whereas the detection rate of distal colon cancer decreased until the fourth round in men (from 0.7 to 0.3 per 1000), and the fifth round in women. CONCLUSIONS: These findings support the notion that FIT screening prevents progression of a subset of advanced adenomas. Screening intensity could be modulated based on results from previous rounds, with a risk-based strategy.

COVID-19 outbreak investigation and response in a penitentiary setting: the experience of a prison in Italy, February to April 2020.

Prisons are high-risk settings for COVID-19 and present specific challenges for prevention and control. We describe a COVID-19 outbreak in a large prison in Milan between 20 February and 30 April 2020. We performed a retrospective analysis of routine data collected during the COVID-19 emergency in prison. We analysed the spatial distribution of cases and calculated global and specific attack rates (AR). We assessed prevention and control measures. By 30 April 2020, 57 confirmed COVID-19 cases and 66 clinically probable cases were recorded among a population of 1,480. Global AR was 8.3%. The index case was a custodial officer. Two clusters were detected among custodial staff and healthcare workers. On 31 March, a confirmed case was identified among detained individuals. COVID-19 spread by physical proximity or among subgroups with cultural affinity, resulting in a cluster of 22 confirmed cases. Following index case identification, specific measures were taken including creation of a multidisciplinary task-force, increasing diagnostic capacity, contact tracing and dedicated isolation areas. Expanded use of personal protective equipment, environmental disinfection and health promotion activities were also implemented. Outbreaks of COVID-19 in prison require heightened attention and stringent comprehensive measures.

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.

Estimating the impact of an organised screening programme on cervical cancer incidence: A 26-year study from northern Italy.

The impact of the organised cervical cancer (CC) screening programmes implemented in Europe since the 1990s has been insufficiently evaluated. We investigated the changes in CC incidence following the introduction of a screening programme in the Emilia-Romagna Region (northern Italy). The study period was 1988-2013. The programme, targeting women aged 25-64 years (1,219,000 in 2018), started in 1998. The annual incidence rates that would be expected in 1998-2013 in the absence of screening were estimated, first, by analysing the annual rates in 1988-1997 with a log-linear model and, second, by analysing the annual rates in 1988-2013 with an age-period model in which the period effect was enforced to be linear. Cervical adenocarcinoma incidence trend over the entire period was used to validate both estimates. Observed annual rates were compared to the two series of expected ones with the incidence rate ratio (IRR). Incidence remained stable during 1988-1997, peaked in 1998 and then decreased until 2007, when it stabilised. The two series of expected rates were virtually coincident and their trends roughly paralleled the stable adenocarcinoma incidence trend. After 2007, the median IRR was 0.60 (95% confidence interval, 0.45-0.81) based on the log-linear model and 0.58 (95% confidence interval, 0.34-0.97) based on the age-period model. Thirty-six to seventy-five CC cases were prevented annually for an average annual frequency of 6.5 per 100,000 women in the target population. In summary, consistent circumstantial evidences were obtained that the organised screening programme brought about a 40% reduction in annual CC incidence after 10 years.

Sources of Uncertainty in Biotransformation Mechanistic Interpretations and Remediation Studies using CSIA.

Compound-specific isotope analysis (CSIA) is a powerful tool to understand the fate of organic contaminants. Using CSIA, the isotope ratios of multiple elements (δ13C, δ2H, δ37Cl, δ15N) can be measured for a compound. A dual-isotope plot of the changes in isotope ratios between two elements produces a slope, lambda (Λ), which can be instrumental for practitioners to identify transformation mechanisms. However, practices to calculate and report Λ and related uncertainty are not universal, leading to the potential for misinterpretations. Here, the most common methods are re-evaluated to provide the basis for a more accurate best-practice representation of Λ and its uncertainty. The popular regression technique, ordinary linear regression, can introduce mathematical bias. The York method, which incorporates error in both variables, better adapts to the wide set of data conditions observed for dual-isotope data. Importantly, the existing technique of distinguishing between Λs using the 95% confidence interval alone produces inconsistent results, whereas statistical hypothesis testing provides a more robust method to differentiate Λs. The propensity for Λ to overlap for a variety of conditions and mechanisms highlights the requirement for statistical justification when comparing data sets. Findings from this study emphasize the importance of this evaluation of best practice and provide recommendations for standardizing, calculating, and interpreting dual-isotope data.

Annual mammography at age 45-49 years and biennial mammography at age 50-69 years: comparing performance measures in an organised screening setting.

OBJECTIVE: To compare the results of 5 years of annual mammography screening at age 45-49 with the results of 5 years of biennial screening at age 50-54 and 55-69. METHODS: In an Italian screening programme, data from 1,465,335 mammograms were analysed. Recall rates, invasive assessment rates, surgical biopsy (including excisional biopsy and definitive surgical treatment) rates, and cancer detection rates were calculated for the first screen (first) and, cumulatively, for the second and subsequent screens (second+). RESULTS: The rate ratios between younger women and the two groups of older ones were (in parentheses, original figures per 1000 mammograms if not otherwise specified): recall rate: first 1.11 (103.6 vs. 93.5) and 1.11 (vs. 93.2), second+ 2.10 (208.9 vs. 99.7) and 2.77 (vs. 75.5); invasive assessment rate: first 0.94 (23.0 vs. 24.5) and 0.94 (vs. 24.6), second+ 1.63 (35.8 vs. 22.0) and 1.56 (vs. 23.0); surgical biopsy rate: first 0.68 (5.9 vs. 8.6) and 0.45 (vs. 13.2), second+ 1.35 (11.5 vs. 8.5) and 0.88 (vs. 13.0); total detection rate: first 0.63 (4.3 vs. 6.7) and 0.37 (vs. 11.7), second+ 1.30 (8.9 vs. 6.8) and 0.74 (vs. 12.0); total positive predictive value of surgical biopsy: first 0.93 (72.8% vs. 78.0%) and 0.82 (vs. 88.9%), second+ 0.96 (77.2% vs. 80.5%) and 0.83 (vs. 92.7%). CONCLUSION: Younger women experienced two to threefold higher cumulative recall rates at second+ screens and limited differences in surgical biopsy rate. Albeit encouraging, these results must be completed with further investigation, especially on interval cancer incidence. KEY POINTS: • At repeated screens, cumulative recall rate was two- to threefold higher for younger women. • Differences in cumulative surgical referral and surgical biopsy rates were moderate. • Differences in positive predictive value of surgical biopsy were particularly small.

Patterns and determinants of receipt of follow-up mammography and/or clinical examination in a cohort of Italian breast cancer survivors.

Information regarding the use of mammography by breast cancer survivors is limited. This study aimed at evaluating the compliance to surveillance mammography and/or clinical breast examination and the associated factors among patients living in northern Italy. A cancer registry-based cohort of 1304 patients living in the Health Care District of Forlì was followed up for 10 years. Eighty percent of patients had a mammogram and/or clinical breast examination during the first year after treatment. The proportion decreased to 67 % at 10 years of follow-up. Three demographic characteristics were independently associated with lower odds of having an annual mammogram and/or clinical breast examination: age at diagnosis [odds ratio (OR) 0.51, 95 % confidence interval (CI) 0.41-0.63 for patients aged 65-74 years; and OR 0.14, 95 % CI 0.11-0.18, for patients ≥75 years versus patients aged <64 year]; socio-economic status (OR 0.81, 95 % CI 0.65-1.00, for deprived patients versus patients of the reference class); and hospital travel time greater than 30 min (OR 0.44, 95 % CI 0.29-0.68 versus ≤15 min). With respect to clinical and disease characteristics, lower odds were observed for patients treated with mastectomy (OR 0.79, 95 % CI 0.65-0.97), for patients diagnosed with in situ breast cancer (OR 0.68, 95 % CI 0.46-0.99) as well as with stage II + breast cancer (OR 0.77, 95 % CI 0.63-0.94), and for patients with ≥3 Elixhauser comorbidities (OR 0.43, 95 % CI 0.26-0.71). Adherence to follow-up declined over time. Knowledge of associated factors may assist in improving access to care for breast cancer survivors.

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

INTRODUCTION: This cross-sectional study was aimed at estimating the number of Italian incident cancer patients in 2020 eligible for, and respondent to, immune checkpoint inhibitors (ICI). METHODS: The study is based on publicly available data: the ICI approved until August 2022 by the Italian Medicines Agency (AIFA) with their specific indications and overall observed responses, rther details can be found in the Online Supplementary Materi cancer incidence estimates at 2020 and observed cancer deaths, and published papers with estimates on the frequency of different cancer stage/histology/markers etc. corresponding to AIFA authorizations. RESULTS: In the analyzed period, a total of seven ICI were authorized in Italy for 20 cancer types. The estimated number of ICI-eligible patients in 2020 was 48,400, 14.3% of those tumors (including skin epitheliomas) that may fit AIFA-indications, and 10.5% of all the incident malignant tumors, including skin epitheliomas. The number of patients who may benefit from ICI therapy was 24,052, 49.7% of the ICI-eligible ones, or 5.2% of the overall estimated incident cancers in 2020. CONCLUSIONS: In conclusion, although the number of ICI-eligible patients is a relatively small proportion of the yearly burden of cancers, about half of them may respond to ICI-treatment.