Childhood cancer survival in France, 2000-2008.

This paper reports the latest survival data for French childhood cancer patients at the national level. Data from the two French National Registries of Childhood Cancer (Haematopoietic Malignancies and Solid Tumours) were used to describe survival outcomes for 15,479 children diagnosed with cancer between 2000 and 2008 in mainland France. The overall survival was 91.7% at 1 year, 86.9% at 2 years and 81.6% at 5 years. Relative survival did not differ from overall survival even for infants. Survival was lower among infants for lymphoblastic leukaemia and astrocytoma, but higher for neuroblastoma. For all cancers considered together, 5-year survival increased from 79.5% in the first (2000-2002) diagnostic period to 83.2% in the last (2006-2008) period. The improvement was significant for leukaemia, both myeloid and lymphoid, central nervous system tumours (ependymoma) and neuroblastoma. The results remained valid in the multivariate analysis, and, for all cancers combined, the risk of death decreased by 20% between 2000-2002 and 2006-2008. The figures are consistent with various international estimates and are the result of progress in treatment regimens and collaborative clinical trials. The challenge for the French registries is now to study the long-term follow-up of survivors to estimate the incidence of long-term morbidities and adverse effects of treatments.

Childhood leukemia around French nuclear power plants--the Geocap study, 2002-2007.

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose-based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0-3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR)=1.9 [1.0-3.2]). These results were similar for all the 5-year-age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990-2001 and over the entire 1990-2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002-2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.

Spatial variations of childhood acute leukaemia in France, 1990-2006: global spatial heterogeneity and cluster detection at 'living-zone' level.

Childhood acute leukaemia (AL) accounts for a third of childhood cancers. Analysing the spatial distribution of the incidence of AL and its lymphoblastic and myeloblastic subtypes may contribute to the identification of risk factors. This national registry-based study aimed to evaluate global spatial heterogeneity in the incidence rates of AL and to detect clusters in France over the period 1990-2006 on the 'living-zone' scale. Between 1990 and 2006, 7675 cases of AL were registered in the National Registry of Childhood Haematopoietic malignancies. Their spatial distribution in the 1895 'living zone' was first evaluated with two tests for global spatial heterogeneity (Potthoff-Witthinghill and Rogerson's tests) and then with the SaTScan and FleXScan methods, which aim to locate spatial and space-time clusters. Over 1990-2006, no spatial heterogeneity of AL or its subtypes was evidenced. In addition, none of the most likely clusters identified with SaTScan and FleXScan over the whole period was significant, and the systematic search for space-time clusters yielded nonsignificant results. However, when three subperiods were considered, five statistically significant nonoverlapping spatial clusters were identified. This study did not find evidence of any global spatial heterogeneity of AL incidence rates in France over the period 1990-2006. Although no significant spatial cluster was detected over the whole period, the study identified a few significant spatial clusters in specific periods. Even though the significance levels of those clusters do not strongly support the existence of local risk factors, the clusters may still reflect a slight impact of shared risk factors, including background environmental exposures, which require further investigation.

Detection of clusters of a rare disease over a large territory: performance of cluster detection methods.

BACKGROUND: For many years, the detection of clusters has been of great public health interest. Several detection methods have been developed, the most famous of which is the circular scan method. The present study, which was conducted in the context of a rare disease distributed over a large territory (7675 cases registered over 17 years and located in 1895 units), aimed to evaluate the performance of several of the methods in realistic hot-spot cluster situations. METHODS: All the methods considered aim to identify the most likely cluster area, i.e. the zone that maximizes the likelihood ratio function, among a set of cluster candidates. The circular and elliptic scan methods were developed to detect regularly shaped clusters. Four other methods that focus on irregularly shaped clusters were also considered (the flexible scan method, the genetic algorithm method, and the double connected and maximum linkage spatial scan methods). The power of the methods was evaluated via Monte Carlo simulations under 27 alternative scenarios that corresponded to three cluster population sizes (20, 45 and 115 expected cases), three cluster shapes (linear, U-shaped and compact) and three relative risk values (1.5, 2.0 and 3.0). RESULTS: Three situations emerged from this power study. All the methods failed to detect the smallest clusters with a relative risk lower than 3.0. The power to detect the largest cluster with relative risk of 1.5 was markedly better for all methods, but, at most, half of the true cluster was captured. For other clusters, either large or with the highest relative risk, the standard elliptic scan method appeared to be the best method to detect linear clusters, while the flexible scan method localized the U-shaped clusters more precisely than other methods. Large compact clusters were detected well by all methods, with better results for the circular and elliptic scan methods. CONCLUSIONS: The elliptic scan method and flexible scan method seemed the most able to detect clusters of a rare disease in a large territory. However, the probability of detecting small clusters with relative risk lower than 3.0 remained low with all the methods tested.

Incidence of childhood cancer in France: National Children Cancer Registries, 2000-2004.

The French National Registry of Childhood Haematopoietic Malignancies and the French National Registry of Childhood Solid Tumours jointly ensure the surveillance of cancer in children aged less than 15 years in mainland France. During the period 2000-2004, the registries recorded a total of 8473 cases: 3446 cases of haematological malignancies and 5027 cases of solid tumours. The average number of sources per case was 2.7 and diagnosis was documented by cytology/histology in 94% of cases, ensuring high quality data. The age-standardized incidence rate for all cancers combined was 156.6 cases per million children per year, with a sex ratio of 1.2. The most frequent cancers were leukaemia (29%), central nervous system tumour (23%), lymphoma (12%) and neuroblastoma (8%). In France, an estimated one out of every 440 children presents with cancer before the age of 15 years. The incidence rates are close to those of other industrialized countries, but somewhat higher than those estimated by the French local registries for the period 1990-1999, probably because of improved methodology or perhaps a real increase in some rates. The French National Registries of Childhood Cancer have shown that they are able to fulfil public health surveillance missions satisfactorily and support the national programme for research on childhood cancer.

Geographical variations in the incidence of childhood acute leukaemia in France over the period 1990-2004.

Spatial variations in childhood acute leukaemia (AL) incidence rates were investigated by département, in mainland France, over the period 1990-2004. This is the first spatial study of this incidence to cover a 15-year period. French National Registry of Childhood Haematological Malignancies data and population counts by type of leukaemia (AL, acute lymphoblastic leukaemia, acute myeloblastic leukaemia), time period (1990-2004, 1990-1994, 1995-1999 and 2000-2004), sex, and age group (0-14, 0-4, 5-9 and 10-14 years of age) were considered. The overall homogeneity of the relative risks of leukaemia was tested, as well as comparison to 1 of each relative risk by the exact Poisson test. To give a more stable estimate of the underlying relative risk pattern than that provided by the local standardized incidence ratios (SIRs), Bayesian hierarchical models using four different spatial priors have been produced: the parametric BYM and CAR models, and two semiparametric models. Very slight overall heterogeneity was observed on the whole AL data set (SIR overdispersion 18.6%, P=0.10). Irrespective of the model, the ranges of the smoothed SIRs exhibited considerable shrinkage relative to the ranges of the local SIRs. The associated maps were slightly heterogeneous; the smoothed SIRs of overall acute lymphoblastic leukaemia of the south-west départements were slightly higher than those of the north-east. The results, however, did not remain stable when investigated by leukaemia type, time period, sex or age group. No spatial heterogeneity of childhood AL incidence on the département scale was observed but that does not exclude spatial heterogeneity on other scales.

Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004.

INTRODUCTION: Childhood Langerhans cell histiocytosis (LCH) is a rare and poorly understood multisystemic disease. The French National Registry of Childhood Hematopoietic Malignancies (NRCH) has recorded LCH cases of all subtypes since 2000. The present study describes the data on LCH collected on a national scale over a 5-year period. MATERIALS AND METHODS: The cases were children aged less than 15 years, diagnosed with LCH of any type between 2000 and 2004, and residing in mainland France at the time of diagnosis. Completeness was evaluated by capture-recapture after cross-checking against the database compiled by the French Langerhans Cell Histiocytosis Study Group. RESULTS: Two hundred fifty-eight cases of LCH were registered. The completeness of the NRCH was estimated to be 97%. The annual incidence rate was 4.6/10(6) children aged less than 15 years and the sex ratio was 1.2. Bone and skin were the most commonly involved organs at diagnosis. The incidence rate decreased with age from 15.3/10(6) before 1 year to 2.0/10(6) after 10 years. The disease was mainly unifocal (2.6/10(6)) and rarely disseminated (0.6/10(6)), but disseminated forms predominated in infants. The overall 2-year survival rate was 99% (95%CI: [97; 100]). About 30% of the LCH cases were enrolled in a clinical trial at first onset. No case was treated by radiotherapy. CONCLUSION: This study evidenced the main features of LCH incidence in the overall population and was consistent with previous studies. The NRCH thus appears to be a very promising tool for further elucidation of LCH.

Childhood cancer survival in France, 1990-1999.

The aim of this study was to describe the overall survival after childhood cancer in France using follow-up data from regional population-based registries. The survival of children (aged under 15 years) diagnosed with a cancer during 1990-1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4-91.3] at 1-year, 75.2% [73.8-76.6] at 5 years and 72.2% [70.7-73.7] at 10 years. During the 1990s, the average improvement in the 5-year survival was +1.2% per year. Adjusted for gender, age, area of residence and stage, children with cancer diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with those whose cancer had been diagnosed between 1990 and 1994. The increase of survival at the population level reflects a global improvement in childhood cancer care. The Paediatric Registries, in association with the French Society of Childhood Cancer, are now collecting data to quantify on a national basis the other events, at least relapse and second cancers.

Cancer incidence among children in France, 1990-1999.

BACKGROUND: Cancer is the second most important cause of death for children aged less than 15 years in France, unintentional injuries being the leading cause. The aim of the present study was to estimate the incidence of childhood cancer from six Childhood Cancer Registries covering 32% of France. PROCEDURE: Incident cancer cases diagnosed between 1990 and 1999 in children (0-14 years) resident in the administrative areas covered by each Registry were included. Annual age-standardized rates (ASRs) were adjusted by the world population. The estimated annual percent change (EAPC) was used to measure trend towards changes in the annual age-standardized incidence rate. RESULTS: With 4234 registered cases, the ASRs per million children were 137.5 for all cancers combined, 42.3 for leukemia, 29.1 for central-nervous-system tumors, 15.6 for lymphomas, 14.1 for sympathetic-nervous-system tumors, and 9.1 for renal tumors. The ASR of all cancers combined was slightly higher in males (145.8 per million children) than in females (128.7 per million children) with an M/F ratio of 1.2. No significant incidence trend was observed, with an EAPC of +0.2% [IC 95% (-2.5; +3.0); P = 0.89]. CONCLUSIONS: The estimated incidence rates are similar to those reported in previous studies in European and North American countries. These results will contribute to the development of National Registration of Childhood Cancer in France and support the national research program on childhood cancer.