The Economic Cost of Thyroid Cancer in France and the Corresponding Share Associated With Treatment of Overdiagnosed Cases.

OBJECTIVES: Thyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases. METHODS: Multiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21 departments using data from the French network of cancer registries and extrapolated to the whole country; medical records from 6 departments were used to refine the diagnosis and care pathway. RESULTS: Between 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer, with mean cost per capita of €6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to overdiagnosis. The total cost of thyroid cancer patient management was €203.5 million (€154.3 million for women and €49.3 million for men), of which between €59.9 million (or 29.4% of the total cost, lower bound) and €115.9 million (or 56.9% of the total cost, upper bound) attributable to treatment of overdiagnosed cases. CONCLUSIONS: The management of thyroid cancer represents not only a relevant clinical and public health problem in France but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important role on the total costs of thyroid cancer management.

Use of a case-mix approach to study the trends in the incidence of second primary cancers.

PURPOSE: To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution. METHODS: Cases registered by 13 French cancer registries between 1989 and 2010 and followed-up until June 2013 were included. The person-year approach was used to compute standardized incidence ratios (SIRs) of metachronous SPC. Usual SIRs and cancer site-specific weighted SIRs called "case-mix SIRs" (cmSIRs) were estimated by sex and calendar period of first cancer diagnosis. Calendar trends in SIRs and cmSIRs were compared. RESULTS: More than 2.9 million person-years at risk were included. Among males, SIRs dropped from 1.49 to 1.23 between 1989-1994 and 2005-2010, while cmSIRs decreased from 1.40 to 1.27. This difference seems mainly related to a stronger representation of prostate cancers (at lower risk of SPC) and a weaker contribution of bladder and head and neck cancers (at higher risk of SPC) in recent periods of diagnosis. Among females, both SIRs and cmSIRs have remained stable at around 1.22 and 1.21, respectively. CONCLUSIONS: The cmSIR is an indicator that is not influenced by changes in first cancer site distribution. Its use should be encouraged to assess second cancer incidence control.

Socioeconomic status and site-specific cancer incidence, a Bayesian approach in a French Cancer Registries Network study.

The aim of this study was to identify and compare cancer sites whose incidence is influenced by social deprivation. The study population comprised 189 144 cases of cancer diagnosed between 2006 and 2009, recorded in member registries of the French Network of Cancer Registries. Social environment was assessed at an aggregate level using the European Deprivation Index. The association between incidence and socioeconomic status was assessed by a geographical Bayesian Poisson model enabling a reduction of the overall variability and smoothing of the relative risks by sharing information provided by multiple geographic units. For cancers of the stomach, liver, lips-mouth-pharynx, and lung, a higher incidence in deprived populations was found for both sexes as well as for cancers of the larynx, esophagus, pancreas, and bladder in men and cervical cancer in women. For melanoma, prostate, testis, ovarian, and breast cancer, a higher incidence was observed in affluent populations. The highest relative risks of the lowest social class compared with the highest social class were found for larynx [relative risk (RR)=1.67 (1.43-1.95)], lips-mouth-pharynx [RR=1.89 (1.72-2.07)], and lung cancer [RR=1.59 (1.50-1.68)] in men and for cervix [RR=1.62 (1.40-1.88)] and lips-mouth-pharynx [RR=1.56 (1.30-1.86)] cancer in women. By estimating the burden of social deprivation on cancer incidence throughout France, this study enables us to measure the gains that could be achieved by implementing targeted prevention efforts.

Breast cancer incidence: Decreasing trend in large tumours in women aged 50-74.

Objective A decrease in advanced breast cancer incidence is considered an early indicator of breast cancer mortality reduction in a screening programme. We describe trends in breast cancer incidence according to tumour size and age in three French administrative areas, where an organized screening programme was implemented during the 1990s. Methods Our study included all 28,092 invasive breast cancers diagnosed from 2000 to 2010 in women living in three areas (Hérault, Isère, Loire-Atlantique). Age, year of diagnosis, and size of tumour at diagnosis was provided by the three area cancer registries. Poisson regression models were fitted to estimate changes in incidence over time, after adjustment for age and administrative area. Results From 2000 to 2010, the incidence rate of large (tumour size >20 mm) breast cancer linearly decreased in women aged 50-74 (target age of the screening programme) from 108.4 to 84.1/100,000 (annual percent change = -1.9%, p < 0.001). No change in large breast cancer incidence rate was found in women aged 20-49, or older than 74. Conclusions A decreasing trend in incidence of large tumour size breast cancer in the target age of the screening programme is demonstrated for the first time in France. The overall 20.9% linear decrease over 11 years in these three areas is encouraging and should be closely monitored and extended to other areas of France, where the screening programme was generally implemented only in 2004.

Impact of socioeconomic inequalities on geographic disparities in cancer incidence: comparison of methods for spatial disease mapping.

BACKGROUND: The reliability of spatial statistics is often put into question because real spatial variations may not be found, especially in heterogeneous areas. Our objective was to compare empirically different cluster detection methods. We assessed their ability to find spatial clusters of cancer cases and evaluated the impact of the socioeconomic status (e.g., the Townsend index) on cancer incidence. METHODS: Moran's I, the empirical Bayes index (EBI), and Potthoff-Whittinghill test were used to investigate the general clustering. The local cluster detection methods were: i) the spatial oblique decision tree (SpODT); ii) the spatial scan statistic of Kulldorff (SaTScan); and, iii) the hierarchical Bayesian spatial modeling (HBSM) in a univariate and multivariate setting. These methods were used with and without introducing the Townsend index of socioeconomic deprivation known to be related to the distribution of cancer incidence. Incidence data stemmed from the Cancer Registry of Isère and were limited to prostate, lung, colon-rectum, and bladder cancers diagnosed between 1999 and 2007 in men only. RESULTS: The study found a spatial heterogeneity (p < 0.01) and an autocorrelation for prostate (EBI = 0.02; p = 0.001), lung (EBI = 0.01; p = 0.019) and bladder (EBI = 0.007; p = 0.05) cancers. After introduction of the Townsend index, SaTScan failed in finding cancers clusters. This introduction changed the results obtained with the other methods. SpODT identified five spatial classes (p < 0.05): four in the Western and one in the Northern parts of the study area (standardized incidence ratios: 1.68, 1.39, 1.14, 1.12, and 1.16, respectively). In the univariate setting, the Bayesian smoothing method found the same clusters as the two other methods (RR >1.2). The multivariate HBSM found a spatial correlation between lung and bladder cancers (r = 0.6). CONCLUSIONS: In spatial analysis of cancer incidence, SpODT and HBSM may be used not only for cluster detection but also for searching for confounding or etiological factors in small areas. Moreover, the multivariate HBSM offers a flexible and meaningful modeling of spatial variations; it shows plausible previously unknown associations between various cancers.

Risk assessment of second primary cancer according to histological subtype of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of diseases that are known to carry a considerable risk of second primary cancer (SPC). However, little attention has been paid to SPC risk assessment according to NHL subtypes. Data from 10 French population-based cancer registries were used to establish a cohort of 7546 patients with a first diagnosis of NHL (eight subtypes) between 1989 and 2004. Standardized incidence ratios (SIRs) of metachronous SPC were estimated. Among the 7546 patients diagnosed with a NHL, the overall SPC risk was 25% higher than that in the reference population (SIR = 1.25, 95% confidence interval 1.15-1.36). In univariate analysis, the SPC risk differed by lymphoma subtype. Interestingly, multivariate analysis showed that SPC risk did not differ significantly across NHL subtypes after adjustment for the other covariates (p = 0.786). Patients with NHL have an increased risk of SPC that is not influenced by the histological NHL subtype.

Determinants of participation in organized colorectal cancer screening in Isère (France).

BACKGROUND AND AIMS: In France, participation in organized colorectal cancer screening remains low. The objective of this study was to identify the determinants of participation in colorectal cancer screening in Isère, a French administrative entity. METHODS: This study examined the target population invited for screening between 2007 and 2008 in Isère. The statistical analysis method was based on a two-level logistic regression model: the first was the individual level relative to the individuals invited for screening and the second was an aggregate level corresponding to the socioeconomic level of an invited person's residence area (IRIS: "Ilot regroupé pour l'Information Statistique"; Regrouped statistical information block). The evaluation of the socioeconomic level was based on the Townsend deprivation. RESULTS: Participation varied depending on sex, age, and health insurance plan. The people residing in the least deprived IRISes participated more than individuals residing in the most deprived IRISes. The multilevel analysis showed a 24% difference in participation between the least and the most deprived IRISes. CONCLUSIONS: The use of socioeconomic data on the IRIS geographical unit has identified, socially and geographically, the populations that participate the least, although this reflects "mean" behaviors. These results could be used to set up targeted actions to encourage participation in these populations.

Cancer incidence estimation at a district level without a national registry: a validation study for 24 cancer sites using French health insurance and registry data.

BACKGROUND: District-level cancer incidence estimation is an important issue in countries without a national cancer registry. This study aims to both evaluate the validity of district-level estimations in France for 24 cancer sites, using health insurance data (ALD demands--Affection de Longue Durée) and to provide estimations when considered valid. Incidence is estimated at a district-level by applying the ratio between the number of first ALD demands and incident cases (ALD/I ratio), observed in those districts with cancer registries, to the number of first ALD demands available in all districts. These district-level estimations are valid if the ratio does not vary greatly across the districts or if variations remain moderate compared with variations in incidence rates. METHODS: Validation was performed in the districts covered by cancer registries over the period 2000-2005. The district variability of the ALD/I ratio was studied, adjusted for age (mixed-effects Poisson model), and compared with the district variability in incidence rate. The epidemiological context is also considered in addition to statistical analyses. RESULTS: District-level estimation using the ALD/I ratio was considered valid for eight cancer sites out of the 24 studied (lip-oral cavity-pharynx, oesophagus, stomach, colon-rectum, lung, breast, ovary and testis) and incidence maps were provided for these cancer sites. CONCLUSION: Estimating cancer incidence at a sub-national level remains a difficult task without a national registry and there are few studies on this topic. Our validation approach may be applied in other countries, using health insurance or hospital discharge data as correlate of incidence.

Breast cancer incidence using administrative data: correction with sensitivity and specificity.

OBJECTIVE: To estimate breast cancer incidence in the general population using a method that corrects for lack of sensitivity and specificity in the identification of incident breast cancer in inpatient claims data. STUDY DESIGN AND SETTINGS: Two-phase study: phase 1 to identify incident cases in claims data, and phase 2 to estimate sensitivity and specificity in a subset of the population. Two algorithms (1: principal diagnosis; 2: principal diagnosis+specific surgery procedures) were used to identify incident cases in claims of women aged 20 years or older, living in a French district covered by a cancer registry. Sensitivity and specificity were estimated in one district and used to correct incident cases identified. RESULTS: The sensitivity and specificity for algorithms 1 and 2 were 69.0% and 99.89%, and 64.4% and 99.93%, respectively. In contrast to specificity, the sensitivity for both algorithms was lower for women younger than 40 years and older than 65 years. Cases reported by cancer registries were closer to cases identified with algorithm 2 (-3.2% to +20.1%) and to corrected numbers with algorithm 1 (-1% to +15%). CONCLUSION: To obtain reliable estimates of breast cancer incidence in the general population, sensitivity and specificity, which reflect medical and coding practice variations, are necessary.

Uncertainty and sensitivity analysis in assessment of the thyroid cancer risk related to Chernobyl fallout in Eastern France.

The increase in the thyroid cancer incidence in France observed over the last 20 years has raised public concern about its association with the 1986 nuclear power plant accident at Chernobyl. At the request of French authorities, a first study sought to quantify the possible risk of thyroid cancer associated with the Chernobyl fallout in France. This study suffered from two limitations. The first involved the lack of knowledge of spontaneous thyroid cancer incidence rates (in the absence of exposure), which was especially necessary to take their trends into account for projections over time; the second was the failure to consider the uncertainties. The aim of this article is to enhance the initial thyroid cancer risk assessment for the period 1991-2007 in the area of France most exposed to the fallout (i.e., eastern France) and thereby mitigate these limitations. We consider the changes over time in the incidence of spontaneous thyroid cancer and conduct both uncertainty and sensitivity analyses. The number of spontaneous thyroid cancers was estimated from French cancer registries on the basis of two scenarios: one with a constant incidence, the other using the trend observed. Thyroid doses were estimated from all available data about contamination in France from Chernobyl fallout. Results from a 1995 pooled analysis published by Ron et al. were used to determine the dose-response relation. Depending on the scenario, the number of spontaneous thyroid cancer cases ranges from 894 (90% CI: 869-920) to 1,716 (90% CI: 1,691-1,741). The number of excess thyroid cancer cases predicted ranges from 5 (90% UI: 1-15) to 63 (90% UI: 12-180). All of the assumptions underlying the thyroid cancer risk assessment are discussed.

Projecting the time trend of thyroid cancers: its impact on assessment of radiation-induced cancer risks.

The incidence of thyroid cancer, which may be induced by ionizing radiation, has been rising in most Western countries for more than 20 years. In France, public worry about this increase and its possible connection with the fallout from Chernobyl led the government to ask for an evaluation of the health impact of this accident and an assessment of the feasibility of an epidemiological study. These requests raise two methodological questions: Which risk model should be used to relate exposure to risk? What is known about the spontaneous incidence rate of thyroid cancers? This article analyzes the impact of the time trend in the spontaneous incidence of thyroid cancers over the past 20 years in France when evaluating the risk of radiation-induced cancer. Age-period-cohort models were used to model the trend of spontaneous incidence from 1978 through 1997 and then to apply two scenarios for projections up to 2007: one with a constant incidence, the other using the trend observed over the past 20 years. Then the risk was assessed for a hypothetical population of 30,000 children aged 0 to 15 y, exposed to a hypothetical 0.1 Gy thyroid dose. The analysis shows that consideration of the trend instead of a constant spontaneous incidence can yield substantial differences in the risk estimates for thyroid cancer.

Prognostic assessment of PTK activity in T1-T2, N0-N1, M0 breast cancer: a multicentric retrospective study.

Protein tyrosine kinases (PTKs) play a major role in the transduction of intracellular mitogenic signal. PTKs are also involved in the process of cellular transformation. A number of studies have reported increased PTK activities in cytosolic fractions from human breast carcinoma. However, the possible pronostic value of these activities is difficult to establish from these studies, mostly conducted on limited numbers of patients. In order to clear up the issue, we have investigated a large series of patients with a long follow-up, using a retrospective multicentric study (894 breast cancers T1-T2, N0-N1, M0; median follow-up: 67 months). PTKs were measured using a radioenzymatic assay as described in our previously report. We confirmed the already observed correlation between PTK activities and Scarff-Bloom grading (p < 10(-5)), negative estrogen receptor (ER), and progesterone receptor (PR) status. By contrast, we found in this study a correlation between PTK values and clinical nodal status (p = 0.00027) not showed in our precedent analysis. In Cox multivariate analysis, PTK activity does not emerge as a significant pronostic parameter. On the other hand, tumor PTK activity assay may prove of great interest in clinical research using newly developed tyrosine kinase inhibitors in order to assess their biological impact and eventually to predict the responsiveness to these new therapeutic agents.