[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Increasing Therapy Related Myeloid Neoplasms in Multiple Myeloma

© 2018 Stichting European Society for Clinical Investigation Journal Foundation. This document is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc /4.0/ This document is the submitted version of a published work that appeared in final form in European Journal of Clinical Investigation.Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28‐year follow‐ up period (1991‐2018) in a tertiary single institution. Material and Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs. Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapyrelated myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months). Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)

© 2022.This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the published version of a published work that appeared in final form in CancersThe assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals

Physical activity of subjects aged 50–64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objective: To describe physical activity of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A cross-sectional analysis of baseline data of a European prospective cohort study. Subjects: This analysis was restricted to participants in the age group 50-64 years, which was represented in all EPIC centres. It involved 236 386 participants from 25 centres in nine countries. In each EPIC centre, physical activity was assessed by standardised and validated questions. Frequency distribution of type of professional activity and participation in non-professional activities, and age-adjusted means, medians and percentiles of time dedicated to non-professional activities are presented for men and women from each centre. Results: Professional activity was most frequently classified as sedentary or standing in all centres. There was a wide variation regarding participation in different types of non-professional activities and time dedicated to these activities across EPIC centres. Over 80% of all EPIC participants engaged in walking, while less than 50% of the subjects participated in sport. Total time dedicated to recreational activities was highest among the Dutch participants and lowest among men from Malmo (Sweden) and women from Naples (Italy). In all centres, total time dedicated to recreational activity in the summer was higher than in the winter. Women from southern Europe spent the most time on housekeeping. Conclusions: There is a considerable variation of physical activity across EPIC centres. This variation was especially evident for recreational activities in both men and women

Autoimmunity plays a role in the onset of diabetes after 40 years of age

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood

Autoimmunity plays a role in the onset of diabetes after 40 years of age

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood

Is hospital discharge administrative data an appropriate source of information for cancer registries purposes? Some insights from four Spanish registries

<p>Abstract</p> <p>Background</p> <p>The use of hospital discharge administrative data (HDAD) has been recommended for automating, improving, even substituting, population-based cancer registries. The frequency of false positive and false negative cases recommends local validation.</p> <p>Methods</p> <p>The aim of this study was to detect newly diagnosed, false positive and false negative cases of cancer from hospital discharge claims, using four Spanish population-based cancer registries as the gold standard. Prostate cancer was used as a case study.</p> <p>Results</p> <p>A total of 2286 incident cases of prostate cancer registered in 2000 were used for validation. In the most sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most predictive algorithm (that using five diagnostic and five surgical codes) Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3% (CI95% 67.0-80.6). The most frequent reason for false positive cases was the number of prevalent cases inadequately considered as newly diagnosed cancers, ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for false negative cases was related to the number of cases not attended in hospital settings. In this case, figures ranged from 34.4% to 69.7% of false negative cases, in the most predictive algorithm.</p> <p>Conclusions</p> <p>HDAD might be a helpful tool for cancer registries to reach their goals. The findings suggest that, for automating cancer registries, algorithms combining diagnoses and procedures are the best option. However, for cancer surveillance purposes, in those cancers like prostate cancer in which care is not only hospital-based, combining inpatient and outpatient information will be required.</p

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations.PMD was supported by the fellowship Ramón Areces Foundation. JAH was funded by the National Institute of General Medical Sciences, Award U54GM088558, and the National Institutes of Health Director’s Early Independence, Award DP5-OD028145. ML was supported by the Morris-Singer Fund and by a subcontract from the Carnegie Mellon University under an award from the US Centers for Disease Control and Prevention, Award U01IP001121). MS was supported by the National Institute Of General Medical Sciences, Award R01GM130668-02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Intake of individual fatty acids and risk of prostate cancer in the European prospective investigation into cancer and nutrition

The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-hour recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (Pheterogeneity <0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD =1.08; 95%CI=1.01-1.15; P-trend=0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR1SD =1.05; 1.00-1.11; P-trend=0.048) and eicosapentaenoic acid (20:5n-3c; HR1SD =1.07; 1.00-1.14; P-trend=0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk. This article is protected by copyright. All rights reserved