Modelling the effect of breast cancer screening on related mortality using French data.

INTRODUCTION: This study aimed at modelling the effect of organized breast cancer screening on mortality in France. It combined results from a Markov model for breast cancer progression, to predict number of cases by node status, and from relative survival analyses, to predict deaths. The method estimated the relative risk of mortality at 8 years, in women aged 50-69, between a population screened every two years and a reference population. METHODS: Analyses concerned cases diagnosed between 1990 and 1996, with a follow-up up to 2004 for the vital status. Markov models analysed data from 3 screening programs (300,000 mammographies) and took into account opportunistic screening among participants to avoid bias in parameter's estimates. We used survival data from cancers in the general population (n=918, 7 cancer registries) and from screened cancers (n=565, 3 cancer registries), after excluding a subgroup of screened cases with a particularly high survival. Sensitivity analyses were performed. RESULTS: Markov model main analysis lacked of fit in two out of three districts. Fit was improved in stratified analyses by age or district, though some lack of fit persisted in two districts. Assuming 10% or 20% overdiagnosed screened cancers, mortality reduction was estimated as 23% (95% CI: 4, 38%) and 19% (CI: -3, 35%) respectively. Results were highly sensitive to the exclusion in the screened cancers survival analysis. Conversely, RR estimates varied moderately according to the Markov model parameters used (stratified by age or district). CONCLUSION: The study aimed at estimating the effect of screening in a screened population compared to an unscreened control group. Such a control group does not exist in France, and we used a general population contaminated by opportunistic screening to provide a conservative estimate. Conservative choices were systematically adopted to avoid favourable estimates. A selection bias might however affect the estimates, though it should be moderate because extreme social classes are under-represented among participants. This modelling provided broad estimates for the effect of organized biennial screening in France in the early nineteen-nineties. Results will be strengthened with longer follow-up.

Multi-state Markov models in cancer screening evaluation: a brief review and case study.

This work presents a brief overview of Markov models in cancer screening evaluation and focuses on two specific models. A three-state model was first proposed to estimate jointly the sensitivity of the screening procedure and the average duration in the preclinical phase, i.e. the period when the cancer is asymptomatic but detectable by screening. A five-state model, incorporating lymph node involvement as a prognostic factor, was later proposed combined with a survival analysis to predict the mortality reduction associated with screening. The strengths and limitations of these two models are illustrated using data from French breast cancer service screening programmes. The three-state model is a useful frame but parameter estimates should be interpreted with caution. They are highly correlated and depend heavily on the parametric assumptions of the model. Our results pointed out a serious limitation to the five-state model, due to implicit assumptions which are not always verified. Although it may still be useful, there is a need for more flexible models. Over-diagnosis is an important issue for both models and induces bias in parameter estimates. It can be addressed by adding a non-progressive state, but this may provide an uncertain estimation of over-diagnosis. When the primary goal is to avoid bias, rather than to estimate over-diagnosis, it may be more appropriate to correct for over-diagnosis assuming different levels in a sensitivity analysis. This would be particularly relevant in a perspective of mortality reduction estimation.

[Prolonged exposure to atmospheric air pollution and mortality from respiratory causes]. / Exposition prolongée à la pollution atmosphérique et mortalité par pathologies respiratoires.

Different designs can be used to analyze the relationships between respiratory mortality and long term exposure to atmospheric pollution: epidemiological studies (cohort, prevalence study) demonstrate the reality of the relationship and toxicological studies explain it. Cohort studies have the advantage of being able to take into account many confounding factors and thus avoid biases (which is not the case with prevalence studies), but require significant human and financial resources. They were first adopted in the US, but are now more often applied in Europe. The results are relatively consistent, as they all show a statistically significant association between an increase in particulate pollution and cardiopulmonary mortality. Mortality from lung cancer is also associated with long term exposition to particles and sometimes to ozone or nitrogen oxides. Cerebrovascular diseases and sudden death of young children have also been associated with particulate pollution. The relationships are more powerful for long term than short term exposure but are also linear and without threshold. In order to explain these effects (today the causality of the relationship is certain) there are many possible factors, particularly regarding particulate exposures: an increase in cardiovascular risk biomarkers (fibrinogen, white blood cells, and platelets), atherosclerosis, chronic inflammation of lung tissues increased by acute exposure, etc. More and more studies address the interaction between gene and environment and even epigenetic phenomena which could be responsible of these effects. Public Health impact could be quantified. The European E&H surveillance program Apheis, for example, estimated that if PM2.5 levels remained below 15 microg/m(3), a 30 year old person could see his life expectancy increased by 1 month to 2 years, depending on the studied city. Finally, mortality is not the only relevant indicator for health effects of air pollution. ISAAC studies address asthma, allergic rhinitis and eczema among children.

[Incidence of lung cancer in Bas-Rhin, France: trends and projection for 2014]. / Incidence du cancer du poumon dans le Bas-Rhin: tendance et projections en 2014.

INTRODUCTION: In France lung cancer is the second most common cancer in men and the fourth most common in women. In the department of Bas-Rhin the incidence is increasing by 0.1% per annum in men and by 4.4% in women. The aim is to analyse and predict the trend of lung cancer incidence in Bas-Rhin from 1975 to 2014. METHODS: The incidence data from 1975 to 1999 were extracted from the Bas-Rhin cancer registry. Population estimates (2594 years) were made for the period 1975-2014. Predictions were based on a Bayesian age-period-cohort model. RESULTS: Between 1975 and 1999 the incidence of lung cancer increased by 4.5% p.a. in women. In men it increased by 1.6% p.a. between 1975 and 1989 and then diminished. For the periods 2000-2004, 2005-2009 and 2010-2014 respectively the rates should reach 25.6, 32.9 and 42.8 per 100,000 in women and 117.5, 111.6 and 110.1 per 100,000 in men. CONCLUSIONS: Increasing tobacco smoking among women and a reduction among men could be one of the reasons for the respective increasing and decreasing incidences.

Deaths from chronic obstructive pulmonary disease in France, 1979-2002: a multiple cause analysis.

BACKGROUND: A study was undertaken of deaths with an underlying or associated cause of chronic obstructive pulmonary disease (COPD), and trends in COPD mortality from 1979 to 2002 in France were analysed. METHODS: Data were obtained from the Centre of Epidemiology on the Medical Causes of Death (CépiDc) for individuals aged 45 years and over. Owing to implementation of ICD-10 in 2000 for recording causes of death, two separate periods were analysed (1979-99 and 2000-2). RESULTS: In 2000-2, COPD was the underlying cause of 1.4% of deaths (deaths from COPD) and was mentioned on the death certificate in 3.0% (deaths with COPD). The other main underlying causes in these cases were cardiovascular diseases (32.0%) and cancers (24.5%). In 1979-99, age standardised rates of death with COPD remained stable in men (-0.01%/year) and increased in women (+1.7%/year). The mean annual rates of death with COPD per 100 000 were 84 for men and 19 for women in 2000-2. CONCLUSION: Multiple cause analysis improved the estimate of COPD related mortality. In 1979-99, COPD related mortality rates in France were stable in men but increased in women. Implementation of ICD-10 in 2000 introduced substantial discontinuities in mortality trends.

[Lung cancer mortality among women in France. Trend analysis and projection between 1975 and 2014, with a bayesian age-cohort model]. / Mortalité par cancer du poumon chez les femmes françaises. Analyse de tendance et projection à l'aide d'un modèle âge-cohorte bayésien, de 1975 à 2014.

BACKGROUND: With 4,500 deaths in year 2000, female lung cancer mortality rates increased by 3% every year over the last two decades in France. This trend, not observed among males, is attributed to the regular increase of female smoking. In order to answer French Health decider's concerns, we estimated the future female lung cancer mortality rates and numbers of deaths for the next fifteen years, in France and its regions. METHODS: Analyses were based on numbers of female deaths from lung cancer observed between 1975 and 1999, and on past and future population estimates for 1975-2014, at national and regional levels. Mortality rates and numbers of deaths in France and its regions by 5-year periods and 5-year age groups were given in the 1975-1999 death certificate data base, and were projected for 2000-2014. The analysis used a bayesian approach of the age-cohort model with auto-regressive constraints on parameters. Estimated mortality rates were standardized on truncated 20-85 + world population. RESULTS: French female lung cancer mortality increased by 3% every year between 1975 and 1999. In period 1995-1999, truncated 20-85 + mortality rates, and number of deaths per year were respectively 11.4 per 100,000 and 4,000. Mortality rates increased in all regions but variations were maximum in Corsica (+ 314%) and minimum in Auvergne (+ 37%). For the whole of France, the estimated truncated 20-85 + standardized rate, was respectively, 14.1 and 22.5 per 100,000 in period 2000-04 and period 2010-14, which represents a 60% increase between these two time periods. At the regional level, the maximum variation was found in Languedoc-Roussillon (107%), the minimum in Nord-Pas-de-Calais (40%). CONCLUSIONS: The bayesian approach of the age-cohort model is increasingly used because it produces stable projections, without having to include other cancer parameters. Nevertheless, it would be interesting to extend this model by incorporating a tobacco consumption component, in order to assess scenarios based on consumption decreases.

[Cervical cancer in Bas-Rhin: trend and prediction of the incidence in 2014]. / Cancer du col de l'utérus dans le Bas-Rhin: tendance et projection de l'incidence jusqu'en 2014.

BACKGROUND: In the world, the cervix cancer is the second commonest cancer in women. Its incidence is decreasing but it is still too frequent. The aim of this study was to predict the incidence of cervix cancer among women in the Department of Bas-Rhin. METHODS: Incidence data were provided by the Bas-Rhin Tumor Registry. The incidence of in situ tumors and invasive cancers was predicted in 2010-2014 by using an age - period - cohort model and a Bayesian approach. RESULTS: The incidence rates predicted by the model, standardized to the European population, were 99.7 per 10(5)population in 2000-2004 (CI 95%: [82.7-118.5]) and 177.1 per 10(5) population in 2010-2014 (CI 95%: [103.7-288.5]) for in situ and 13.0 per 10(5) population (CI 95%: [9.5-17.2]) in 2000-2004 and 11.1 per 10(5)population (CI 95%: [4.5-22.7]) in 2010-2014 for invasive tumors. CONCLUSIONS: The decrease of invasive tumors is due to screening. The improvement of the quality of the screening and treatment of in situ tumors would allow the number of incident cases of cervix cancer to decrease.

[Short-term relationships between urban atmospheric pollution and respiratory mortality: time series studies]. / Relations à court terme entre la pollution atmosphérique urbaine et la mortalité respiratoire: la place des études temporelles.

Time series studies conducted in the field of air pollution aim at testing and quantifying short-term relations which can exist between daily air pollution levels and daily health effects. The method used for this type of survey has sometimes been misunderstood mainly because individual factors and indoor exposure to air pollutants were not taken into account. The adjustment on these individual confounding factors commonly used in classic epidemiologic studies (case-control studies, cohort studies) is not adequate to times series studies which are based on aggregate data. This is different for those factors that change over time according to the levels of air pollution (meteorological conditions, influenza epidemics, trend of health cases) which, when being analysed, must be taken into account either indirectly through time modelling or directly through non-linear modelling processes. During this last decade, numerous studies using the time series method have been published and have found short-term associations between daily levels of air pollution commonly observed and daily respiratory mortality. The consistency of the numerous results published in the international literature are more arguments in favour of non-confounding short-term relations between air pollution and respiratory mortality.

[Incidence of colorectal cancer in Bas-Rhin, trend and prediction in 2009]. / Incidence du cancer colorectal dans le Bas-Rhin: tendance et projection jusqu'en 2009.

The colorectal cancer is one of the three most frequent cancers. It concerns more and more men and women and is a of heavy consequence for mortality and treatment. This study attempted to predict the incidence and the number of incident cases of colorectal cancer. The analysis is a Poisson regression based on an age-period-cohort model. The predicted value of the incidence of colon cancer, standardized on the world population (25-89 years old), is increasing with time: it is, in 2005-2009, 41.5 for 100,000 for the women and 104.9 for 100,000 for the men. For rectum cancer, the predicted value of incidence is, in 2005-2009, 22.9 for 100,000 for the women and 37.2 for 100, 000 for the men. During the period 2005-2009, the number of incident cases is, for colon, 1,195 women (the mean increase, every ten years, is 31%) and 2,254 men (the mean increase, every ten years, is 65%). During the same period, the number of incident cases is, for rectum, 640 women (the mean increase, every ten years, is 24%) and 807 men (the mean increase every ten years is 14%). These results are similar to those of other studies in Europe and in the World.