Publications by authors named "Giovanna Tagliabue"

81 Publications

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998-2012.

Cancer Med 2021 Sep 17. Epub 2021 Sep 17.

Mantova Cancer Registry, Epidemilogy Unit, Agenzia di Tutela della Salute (ATS) della Val Padana, Mantova, Italy.

Background: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC.

Methods: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer.

Results: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12-1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42-1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon-rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers.

Conclusions: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.
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http://dx.doi.org/10.1002/cam4.4193DOI Listing
September 2021

Variation of Cancer Incidence between and within GRELL Countries.

Int J Environ Res Public Health 2021 Sep 2;18(17). Epub 2021 Sep 2.

Romagna Cancer Registry, Romagna Cancer Institute (IRCCS Istituto Romagnolo Per Lo Studio dei Tumori (IRST) "Dino Amadori"), 47014 Meldola, Italy.

Variation in cancer incidence between countries and groups of countries has been well studied. However cancer incidence is linked to risk factors that may vary within countries, and may subsist in localized geographic areas. In this study we investigated between- and within-country variation in the incidence of all cancers combined for countries belonging to the Group for Cancer Epidemiology and Registration in Latin Language Countries (GRELL). We hypothesized that investigation at the micro-level (circumscribed regions and local cancer registry areas) would reveal incidence variations not evident at the macro level and allow identification of cancer incidence hotspots for research, public health, and to fight social inequalities. Data for all cancers diagnosed in 2008-2012 were extracted from Cancer Incidence in Five Continents, Vol XI. Incidence variation within a country or region was quantified as r/R, defined as the difference between the highest and lowest incidence rates for cancer registries within a country/region (r), divided by the incidence rate for the entire country/region × 100. We found that the area with the highest male incidence had an ASRw 4.3 times higher than the area with the lowest incidence. The area with the highest female incidence had an ASRw 3.3 times higher than the area with the lowest incidence. Areas with the highest male ASRws were Azores (Portugal), Florianopolis (Brazil), Metropolitan France, north Spain, Belgium, and north-west and north-east Italy. Areas with the highest female ASRws were Florianopolis (Brazil), Belgium, north-west Italy, north-east Italy, central Italy, Switzerland and Metropolitan France. Our analysis has shown that cancer incidence varies markedly across GRELL countries but also within several countries: the presence of several areas with high cancer incidence suggests the presence of area-specific risk factors that deserve further investigation.
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http://dx.doi.org/10.3390/ijerph18179262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431723PMC
September 2021

Municipality Data as a Rapid and Effective Tool to Analyse Spatial and Temporal Variations of All-Cause Mortality by Town District: The Experience in Genoa (Italy).

Int J Environ Res Public Health 2021 08 4;18(16). Epub 2021 Aug 4.

International Society of Doctors for the Environment (ISDE), Past Director of the Liguria Mesothelioma Registry, Ospedale Policlinico S. Martino, 16132 Genoa, Italy.

The main objective of this study was to analyse the space-time epidemiological differences by sex during the 2009-2020 period in the total mortality recorded among residents in each of the 25 districts of the Genoa municipality, net of the age effect. The analysis was based on official statistical data relating to total mortality and on the resident population. An estimate of the expected deaths was made to calculate the sex-specific age-standardised mortality ratio (SMR). The temporal trends and age-standardized death rates (SDRs) with respect to those of the European population specific to sex and calendar year were identified for each district. Over the entire observation period, the SMR for males ranged from 124.4 (Cornigliano) to 82.0 (Albaro); for females, the values ranged between 133.4 (Cornigliano) and 85.6 (Nervi-Quinto-S. Ilario). Between 2019 and 2020, Genoa recorded an increase in SDR of 24.5%, more pronounced in males (+26.7%) than in females (+22.4%). This epidemiological methodology is replicable and allows to quickly identify spatial, temporal, sex, and age differences in the general mortality within a municipality.
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http://dx.doi.org/10.3390/ijerph18168250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394076PMC
August 2021

Associations between dietary amino acid intakes and blood concentration levels.

Clin Nutr 2021 06 27;40(6):3772-3779. Epub 2021 Apr 27.

International Agency for Research on Cancer, Nutrition and Metabolism Section, 69372, Lyon CEDEX 08, France.

Background And Aims: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations.

Results: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results.

Conclusions: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.
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http://dx.doi.org/10.1016/j.clnu.2021.04.036DOI Listing
June 2021

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs.

Birth Defects Res 2021 Jul 18;113(12):945-957. Epub 2021 Mar 18.

Child Population and Translational Health Research, Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, Australia.

Background: Esophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions.

Methods: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s.

Results: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies.

Conclusions: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.
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http://dx.doi.org/10.1002/bdr2.1891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273078PMC
July 2021

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

Int J Cancer 2021 02 28;148(4):835-844. Epub 2020 Aug 28.

Romagna Cancer Registry, Romagna Cancer Institute, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì, 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.
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http://dx.doi.org/10.1002/ijc.33259DOI Listing
February 2021

Risk Prediction for Renal Cell Carcinoma: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Prospective Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 03 17;30(3):507-512. Epub 2020 Dec 17.

School of Public Health, Imperial College London, London, United Kingdom.

Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives.

Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure.

Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679-0.721]). Our model had slightly improved discrimination (0.714 [0.694-0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025.

Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population.

Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1438DOI Listing
March 2021

A multi-country study of prevalence and early childhood mortality among children with omphalocele.

Birth Defects Res 2020 12 17;112(20):1787-1801. Epub 2020 Oct 17.

International Center on Birth Defects, International Clearinghouse for Birth Defects Surveillance and Research, Rome, Italy.

Background: Omphalocele is the second most common abdominal birth defect and often occurs with other structural and genetic defects. The objective of this study was to determine omphalocele prevalence, time trends, and mortality during early childhood, by geographical region, and the presence of associated anomalies.

Methods: We conducted a retrospective study with 23 birth defect surveillance systems in 18 countries who are members of the International Clearinghouse for Birth Defects Surveillance and Research that submitted data on cases ascertained from 2000 through 2012, approximately 16 million pregnancies were surveyed that resulted in live births, stillbirths, or elective terminations of pregnancy for fetal anomalies (ETOPFA) and cases with omphalocele were included. Overall prevalence and mortality rates for specific ages were calculated (day of birth, neonatal, infant, and early childhood). We used Kaplan-Meier estimates with 95% confidence intervals (CI) to calculate cumulative mortality and joinpoint regression for time trend analyses.

Results: The prevalence of omphalocele was 2.6 per 10,000 births (95% CI: 2.5, 2.7) and showed no temporal change from 2000-2012 (average annual percent change = -0.19%, p = .52). The overall mortality rate was 32.1% (95% CI: 30.2, 34.0). Most deaths occurred during the neonatal period and among children with multiple anomalies or syndromic omphalocele. Prevalence and mortality varied by registry type (e.g., hospital- vs. population-based) and inclusion or exclusion of ETOPFA.

Conclusions: The prevalence of omphalocele showed no temporal change from 2000-2012. Approximately one-third of children with omphalocele did not survive early childhood with most deaths occurring in the neonatal period.
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http://dx.doi.org/10.1002/bdr2.1822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722785PMC
December 2020

Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses.

BMC Med 2020 09 3;18(1):229. Epub 2020 Sep 3.

Public Health Directorate, Asturias, Spain.

Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.

Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.

Results: The associations between circulating UCB levels and CRC risk differed by sex (P = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P ≥ 0.2).

Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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http://dx.doi.org/10.1186/s12916-020-01703-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469292PMC
September 2020

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

J Adolesc Young Adult Oncol 2021 06 30;10(3):309-315. Epub 2020 Jul 30.

Evaluative Epidemiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study describes treatment for RMS in patients more than 10 years old and examines to what extent treatment contributes to explain the different age-related survival observed and to what extent treatment centers impact treatment appropriateness. A retrospective population-based study was developed considering 104 RMS cases (excluding the pleomorphic subtype) diagnosed in Italy between 2000 and 2015. Patients were grouped by age (10-19 vs. 20-60 years old) and scored according to whether or not their chemotherapy was consistent with the schemes used in pediatric protocols (score 1 = chemotherapy in line with pediatric protocols). Treatment centers were grouped according to whether or not they have a pediatric-dedicated unit affiliated to the national pediatric oncology network (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]). Older patients were more likely to have tumors at unfavorable sites ( = 0.045). A treatment score of 1 was assigned to 85% of younger patients, but only to 32% of older patients ( < 0.001). Furthermore, the proportion of score 1 was higher in younger patients treated in centers with an AIEOP Unit. A multivariate model confirmed age as a significant prognostic factor (Hazard rate ratio [HR] = 2.06;  = 0.04) and showed a significant impact of treatment on survival (HR = 2.13;  = 0.03). Adult RMS patients are still relatively unlikely to be treated with pediatric protocols and in centers with a pediatric oncology expertise. This may explain the survival gap between older and younger patients.
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http://dx.doi.org/10.1089/jayao.2020.0043DOI Listing
June 2021

Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study.

Int J Cancer 2021 02 28;148(3):609-625. Epub 2020 Aug 28.

Public Health Directorate, Asturias, Spain.

Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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http://dx.doi.org/10.1002/ijc.33236DOI Listing
February 2021

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

Thorac Cancer 2020 06 4;11(6):1661-1669. Epub 2020 May 4.

Trapani Cancer Registry, Trapani, Italy.

Background: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions.

Methods: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department.

Results: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department.

Conclusions: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services.

Key Points: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions.

What This Study Adds: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.
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http://dx.doi.org/10.1111/1759-7714.13456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262944PMC
June 2020

An application of the Toronto Childhood Cancer Stage Guidelines in three population-based cancer registries: The case of central nervous tumors.

Pediatr Blood Cancer 2020 06 17;67(6):e28303. Epub 2020 Apr 17.

Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital and Centre for Cancer Prevention, Turin, Italy.

Background: Cancer stage is a determinant of survival of childhood central nervous system (CNS) cancers and could help the interpretation of survival variability among countries. Consensus guidelines to stage childhood malignancies in population cancer registries ("Toronto Childhood Cancer Stage Guidelines") have been recently proposed with the goal of data comparability. Indeed, stage is not systematically recorded in all registries and, when it is, different classification systems are used. We applied the Toronto Childhood Cancer Stage Guidelines to CNS cancer cases of three population-based cancer registries with the aim of evaluating the feasibility of staging this type of cancer and the critical points in the classification of CNS tumors.

Procedures: The Toronto Childhood Cancer Stage Guidelines were applied to 175 CNS patients, diagnosed from January 1, 2002 to December 31, 2014 in three cancer registries in Italy, and the percentage of cases that could be staged was assessed.

Results: One hundred eight of 126 (86%) medulloblastomas and other embryonal CNS cancers and 22 of 49 (45%) ependymomas were staged. Using these guidelines, survival of children with localized tumors could be discriminated from that of children with metastatic disease.

Conclusions: The use of the Toronto Childhood Cancer Stage Guidelines is feasible for staging medulloblastoma in Italian population-based cancer registries, whereas it is more difficult for ependymomas. In Italy, cerebrospinal fluid examination, one of the decisive tests to stage CNS tumors, is not routinely performed as a first-line diagnosis procedure in ependymoma pediatric patients. A similar exercise by a larger number of cancer registries in different countries could suggest improvements in the childhood cancer staging system.
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http://dx.doi.org/10.1002/pbc.28303DOI Listing
June 2020

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

J Adolesc Young Adult Oncol 2020 10 13;9(5):586-593. Epub 2020 Apr 13.

Epidemiology Unit, Cancer Registry, ASL BAT, Barletta, Italy.

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. 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. 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. 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.
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http://dx.doi.org/10.1089/jayao.2019.0170DOI Listing
October 2020

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

Gynecol Oncol 2020 06 7;157(3):656-663. Epub 2020 Apr 7.

Catania, Messina, and Enna Cancer Registry, Catania, Italy.

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.
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http://dx.doi.org/10.1016/j.ygyno.2020.03.013DOI Listing
June 2020

Epidemiology and biological characteristics of male breast cancer in Italy.

Breast Cancer 2020 Jul 29;27(4):724-731. Epub 2020 Feb 29.

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s12282-020-01068-1DOI Listing
July 2020

A Case-Crossover Study to Investigate the Effects of Atmospheric Particulate Matter Concentrations, Season, and Air Temperature on Accident and Emergency Presentations for Cardiovascular Events in Northern Italy.

Int J Environ Res Public Health 2019 11 21;16(23). Epub 2019 Nov 21.

Pneumology Department, Humanitas Research Hospital, 20089 Rozzano, Italy.

Atmospheric particulate matter (PM) has multiple adverse effects on human health, high temperatures are also associated with adverse health outcomes, and the frequency of cardiovascular events (CVEs) varies with season. We investigated a hypothesized increase in PM-related accident and emergency (A&E) presentations for CVE with high temperature, warm season, days of high influenza incidence, and in people with a cancer diagnosis, using a time-stratified case-crossover study design. Outcomes were associations of A&E presentation for CVE with atmospheric PM ≤ 10 μm (PM), season, and air temperature. PM levels in the municipality of residence (exposure variable) were estimated by modeling data from local monitoring stations. Conditional logistic regression models estimated odds ratios (OR) with 95% confidence intervals (CI) for presentations in relation to supposed influencers, adjusting for confounders. Study participants were all who presented at the A&E of a large hospital near Milan, Italy, for a CVE (ICD-9: 390-459) from 1st January 2014 to 31st December 2015. There were 1349 A&E presentations for CVE in 2014-2015 and 5390 control days. Risk of A&E presentation was significantly increased on hot days with OR 1.34 (95%CI 1.05-1.71) per 10 μg/m PM increment (as mean PM on day of presentation, and 1 and 2 days before (lags 0-2)), and (for lag 0) in autumn (OR 1.23, 95%CI 1.09-1.37) and winter (OR 1.18, 95%CI 1.01-1.38). Risks were also significantly increased when PM was on lag 1, in people with a cancer diagnosis in the spring and summer months (1.88, 95%CI 1.05-3.37), and on days (lags 0-2) of high influenza incidence (OR 2.34, 95%CI 1.01-5.43). PM levels exceeded the 50 μg/m "safe" threshold recommended by the WHO and Italian legislation for only 3.8% of days during the warm periods of 2014-2015. Greater risk of A&E presentation for CVE in periods of high PM and high temperature suggests that "safe" thresholds for PM should be temperature-dependent and that the adverse effects of PM will increase as temperatures increase due to climate change.
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http://dx.doi.org/10.3390/ijerph16234627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926530PMC
November 2019

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

Paediatr Perinat Epidemiol 2019 11 21;33(6):436-448. Epub 2019 Oct 21.

International Center on Birth Defects, International Clearinghouse for Birth Defects Surveillance and Research, Rome, Italy.

Background: Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains.

Objectives: To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries.

Methods: We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution.

Results: Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America.

Conclusions: Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.
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http://dx.doi.org/10.1111/ppe.12589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899817PMC
November 2019

Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis.

Am J Med Genet A 2019 12 30;179(12):2382-2392. Epub 2019 Sep 30.

IBDSP (Israel Birth Defect Surveillance and Research program), Tel Aviv, Israel.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.
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http://dx.doi.org/10.1002/ajmg.a.61365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848757PMC
December 2019

Neoadjuvant therapy for breast cancer.

Tumori 2019 Dec 9;105(6):488-493. Epub 2019 Sep 9.

Epidemiology Unit, Azienda Unità Sanitaria Locale-IRCCS Reggio Emilia, Reggio Emilia, Italy.

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I-III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area.

Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009-2013). Included were 3546 women aged <85 years (groups <50, 50-69, 70-64, and 75+) with stage I-III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables.

Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83-5.18), luminal B (OR 1.87; 95% CI 1.27-2.76), triple-negatives (OR 1.88; 95% CI 1.15-3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13-3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37-3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24-0.68).

Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care.
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http://dx.doi.org/10.1177/0300891619869505DOI Listing
December 2019

Changes in life expectancy for cancer patients over time since diagnosis.

J Adv Res 2019 Nov 16;20:153-159. Epub 2019 Jul 16.

Editorial Board "Epidemiologia & Prevenzione", 20148 Milano, Italy.

The aims of this study were to provide life expectancy (LE) estimates of cancer patients at diagnosis and LE changes over time since diagnosis to describe the impact of cancer during patients' entire lives. Cancer patients' LE was calculated by standard period life table methodology using the relative survival of Italian patients diagnosed in population-based cancer registries in 1985-2011 with follow-up to 2013. Data were smoothed using a polynomial model and years of life lost (YLL) were calculated as the difference between patients' LE and that of the age- and sex-matched general population. The YLL at diagnosis was highest at the youngest age at diagnosis, steadily decreasing thereafter. For patients diagnosed at age 45 years, the YLL was above 20 for lung and ovarian cancers and below 6 for thyroid cancer in women and melanoma in men. LE progressively increased in patients surviving the first years, decreasing thereafter, to approach that of the general population. YLL in the long run mainly depends on attained age. Providing quantitative data is essential to better define clinical follow-up and plan health care resource allocation. These results help assess when the excess risk of death from tumour becomes negligible in cancer survivors.
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http://dx.doi.org/10.1016/j.jare.2019.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710558PMC
November 2019

Hypospadias Prevalence and Trends in International Birth Defect Surveillance Systems, 1980-2010.

Eur Urol 2019 10 9;76(4):482-490. Epub 2019 Jul 9.

Public Health Agency of Canada, Ottawa, Ontario, Canada.

Background: Hypospadias is a common male birth defect that has shown widespread variation in reported prevalence estimates. Many countries have reported increasing trends over recent decades.

Objective: To analyze the prevalence and trends of hypospadias for 27 international programs over a 31-yr period.

Design, Setting, And Participants: The study population included live births, stillbirths, and elective terminations of pregnancy diagnosed with hypospadias during 1980-2010 from 27 surveillance programs around the world.

Outcome Measurements And Statistical Analysis: We used joinpoint regression to analyze changes over time in international total prevalence of hypospadias across programs, prevalence for each specific program, and prevalence across different degrees of severity of hypospadias.

Results And Limitations: The international total prevalence of hypospadias for all years was 20.9 (95% confidence interval: 19.2-22.6) per 10000 births. The prevalence for each program ranged from 2.1 to 39.1 per 10000 births. The international total prevalence increased 1.6 times during the study period, by 0.25 cases per 10000 births per year (p<0.05). When analyzed separately, there were increasing trends for first-, second-, and third-degree hypospadias during the early 1990s to mid-2000s. The majority of programs (61.9%) had a significantly increasing trend during many of the years evaluated. Limitations include known differences in data collection methods across programs.

Conclusions: Although there have been changes in clinical practice and registry ascertainment over time in some countries, the consistency in the observed increasing trends across many programs and by degrees of severity suggests that the total prevalence of hypospadias may be increasing in many countries. This observation is contrary to some previous reports that suggested that the total prevalence of hypospadias was no longer increasing in recent decades.

Patient Summary: We report on the prevalence and trends of hypospadias among 27 birth defect surveillance systems, which indicate that the prevalence of hypospadias continues to increase internationally.
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http://dx.doi.org/10.1016/j.eururo.2019.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265200PMC
October 2019

Prenatal diagnosis and prevalence of critical congenital heart defects: an international retrospective cohort study.

BMJ Open 2019 07 2;9(7):e028139. Epub 2019 Jul 2.

Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.

Objectives: To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality.

Setting: Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia.

Participants: Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014.

Results: 18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases.

Discussion And Conclusions: Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future.
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http://dx.doi.org/10.1136/bmjopen-2018-028139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609145PMC
July 2019

Prognosis and cure of long-term cancer survivors: A population-based estimation.

Cancer Med 2019 08 17;8(9):4497-4507. Epub 2019 Jun 17.

Department of Oncology and Molecular Medicine, Italian National Institute of Health (ISS), Rome, Italy.

Background: Increasing evidence of cure for some neoplasms has emerged in recent years. The study aimed to estimate population-based indicators of cancer cure.

Methods: Information on more than half a million cancer patients aged 15-74 years collected by population-based Italian cancer registries and mixture cure models were used to estimate the life expectancy of fatal tumors (LEFT), proportions of patients with similar death rates of the general population (cure fraction), and time to reach 5-year conditional relative survival (CRS) >90% or 95% (time to cure).

Results: Between 1990 and 2000, the median LEFT increased >1 year for breast (from 8.1 to 9.4 years) and prostate cancers (from 5.2 to 7.4 years). Median LEFT in 1990 was >5 years for testicular cancers (5.8) and Hodgkin lymphoma (6.3) below 45 years of age. In both sexes, it was ≤0.5 years for pancreatic cancers and NHL in 1990 and in 2000. The cure fraction showed a 10% increase between 1990 and 2000. It was 95% for thyroid cancer in women, 94% for testis, 75% for prostate, 67% for breast cancers, and <20% for liver, lung, and pancreatic cancers. Time to 5-year CRS >95% was <10 years for testis, thyroid, colon cancers, and melanoma. For breast and prostate cancers, the 5-year CRS >90% was reached in <10 years but a small excess remained for >15 years.

Conclusions: The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.
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http://dx.doi.org/10.1002/cam4.2276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675712PMC
August 2019

Microenvironment and tumor inflammatory features improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms.

J Pathol Clin Res 2019 10 9;5(4):217-226. Epub 2019 Jul 9.

Department of Research, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.

Microenvironment-related immune and inflammatory markers, when combined with established Ki-67 and morphology parameters, can improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Therefore, we evaluated the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP-NENs. For this purpose, formalin-fixed paraffin-embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN-, and fibroblast-related markers. A total of 314 patients were used to generate overall survival (OS) and disease-free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5-year OS and DFS. A total of 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 versus G3 GEP-NENs showed phenotypic divergence with immune-inflammatory markers. HLA, CD3, CD8, and PD-1/PD-L1 IHC expression separated G3 into two sub-categories with high versus low adaptive immunity-related features. MoTIFs PI for OS based on COX-2 > 4, PD-1 > 0, CD8 < 1, and HLA-I < 1 was associated with worst survival (hazard ratio [HR] 2.50; 95% confidence interval [CI], 2.12-2.96; p < 0.0001). MoTIFs PI for DFS was based on COX-2 > 4, PD-1 > 4, HLA-I < 1, HLA-I < 2, HLA-DR < 6 (HR 1.77; 95% CI, 1.58-1.99; p < 0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30-10.15; p < 0.001) and Ki-67 (HR 11.32; 95% CI, 5.28-24.24; p < 0.001) for OS, and morphology (PI = 0: HR 10.23; 95% CI, 5.67-18.47; PI = 5: HR 2.87; 95% CI, 1.21-6.81; p < 0.001) and MoTIFs PI for DFS in well-differentiated GEP-NENs (HR 6.21; 95% CI, 2.52-13.31; p < 0.001). We conclude that G1/G2 to G3 transition is associated with immune-inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki-67 improve 5-year DFS prediction in GEP-NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints.
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http://dx.doi.org/10.1002/cjp2.135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817832PMC
October 2019

[Formaldehyde in electronic cigarettes and in heat-not-burn products: let's make the point].

Epidemiol Prev 2018 Sep-Dec;42(5-6):351-355

Struttura semplice dipartimentale pneumologia e centro antifumo, Fondazione IRCCS Istituto nazionale dei tumori, Milano.

The spread of electronic cigarettes (e-cigs) and of the so-called heat-not-burn (HnB), also known as heated tobacco products, presented as a less harmful alternative to traditional cigarettes, required further in-depth studies to demonstrate the real benefits or possible risks linked to this type of habit among smokers and possible new smokers. There are numerous harmful substances produced by these devices, such as metals, organic compounds, and aldehydes. The presence of formaldehyde is particularly worrying: its indoor concentration is 2.7, 1.2, and 40 µg/m3 for HnB, e-cigs, and traditional cigarettes, respectively. The evidence of this substance, which numerous epidemiological studies have already shown to be harmful to health (in particular, the International Agency for Research on Cancer classified it as a group 1 carcinogen), would lead to the need to modify the legislation with more restrictive rules on the use of these devices in public environment and in particular in the presence of more susceptible subjects, such as minors and pregnant women.
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http://dx.doi.org/10.19191/EP18.5-6.P351.104DOI Listing
June 2019

Effectiveness of First-Line Bevacizumab in Metastatic Colorectal Cancer: The Observational Cohort Study GRETA.

Oncologist 2019 03 10;24(3):358-365. Epub 2018 Aug 10.

National Centre of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.

Background: Scant real-world data exist on the clinical outcomes associated with the use of bevacizumab-containing chemotherapy (B+CT) in patients with metastatic colorectal cancer (mCRC). The primary objective of the GRETA cohort study was to compare the overall survival (OS) of patients with mCRC treated with first-line B+CT versus chemotherapy (CT) alone, in an Italian clinical practice setting.

Materials And Methods: Incident patients with mCRC were identified during the period 2010-2012 from five population-based cancer registries in Italy. Cases were linked to regional health care utilization databases to obtain the entire spectrum of health services provided to each patient. Patients starting a first-line treatment with B+CT or CT alone within 90 days from the diagnosis were included in the study cohort. A propensity score (PS) method was applied to account for residual confounding.

Results: Of 480 patients with mCRC included in the study cohort, 21.0 received first-line B+CT, and 79.0% received CT. Patients receiving B+CT were younger ( < .001) and underwent surgery more frequently ( = .001). The median OS was 22.5 and 14.6 months for B+CT and CT, respectively ( = .011). The corresponding hazard ratios adjusted by multivariate modeling and PS matched analysis were 0.82 (95% confidence interval [CI], 0.62-1.08) and 0.86 (95% CI, 0.56-1.33), respectively. Similar results were observed after subgrouping by age and surgery.

Conclusion: In this Italian real-world setting of unselected mCRC, the OS of patients treated with B+CT was consistent with previous observational and patient-registry studies. However, definitive evidence of an improvement in OS cannot be drawn.

Implications For Practice: Bevacizumab is a well-established first-line treatment for metastatic colorectal cancer. However, there is scarce evidence in the literature about its effectiveness in clinical practice. Evaluating this topic should be of interest for both clinicians and regulatory agencies. In this study, the median overall survival of the bevacizumab cohort was strikingly coherent with that reported in large observational series of unselected patients, thus suggesting a consistent and reproducible effect of the drug in clinical practice. Although consistent results were observed both in the overall population and in age and surgery subgroups, the present study did not offer definitive evidence of an improvement in OS.
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http://dx.doi.org/10.1634/theoncologist.2017-0314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519764PMC
March 2019

Tau Mutations Serve as a Novel Risk Factor for Cancer.

Cancer Res 2018 07 24;78(13):3731-3739. Epub 2018 May 24.

Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.

In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. In addition, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathologic roles of mutated tau. This study reveals a novel role for tau as a risk factor for cancer, providing new insights beyond its role in neurodegeneration. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-3175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031304PMC
July 2018

Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.

Endocr Relat Cancer 2018 05 28;25(5):583-593. Epub 2018 Mar 28.

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin, Bcl-2, p16, Rb1, ALDH, mismatch repair proteins and CD117) were investigated separately in both components, genomic (, , ) alterations were searched for on the entire tumor. Data were correlated with overall survival (OS). MANEC sites were: 92 colorectal, 44 gastroesophageal and 24 pancreatobiliary. Median OS was 13.2 months. After adjustment for primary site, Ki67 index of the NEC component (but not of the non-NEC component) was the most powerful prognostic marker. At multivariable analysis, patients with Ki67 ≥ 55% had an 8-fold risk of death (hazard ratio (HR) 7.83; 95% confidence interval (CI) 4.17-14.7;  < 0.0001) and a median OS of 12.2 months compared to those with Ki67 < 55% (median OS 40.5 months). MC (HR 1.51; 95% CI 1.03-2.20,  = 0.04) was a weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11-2.32;  = 0.01) was significantly associated with poorer survival. No single immunomarker, in either component, was statistically significant. This retrospective analysis of a large series of digestive system MANECs, showed that the NEC component, particularly its Ki67 index, was the main prognostic driver.
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http://dx.doi.org/10.1530/ERC-17-0557DOI Listing
May 2018

Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2018 08 30;143(4):801-812. Epub 2018 Mar 30.

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.
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http://dx.doi.org/10.1002/ijc.31367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481554PMC
August 2018
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