[Show abstract][Hide abstract] ABSTRACT: With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring.
We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression.
Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95% confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest.
Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.
International Journal of Cancer 11/2014; 25(10). DOI:10.1002/ijc.28854 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To assess the risk of childhood central nervous system (CNS) tumors associated with parental occupational exposure to polycyclic aromatic hydrocarbons (PAH), diesel motor exhaust (DME), asbestos, crystalline silica, and metals, which are established carcinogens in adults.
We pooled data from three population-based case-control studies from Germany, France, and the UK. Cases were children aged up to 15 years and diagnosed with CNS tumor, and controls were frequency-matched by age and sex. Socio-demographic data and parental occupation around conception/pregnancy and at diagnosis were collected using standardized interviews, face-to-face or by telephone. A general population job-exposure matrix was used to assign a level of exposure to each job. Logistic regression models were fitted to compute odds ratios and 95 % confidence intervals.
Our study included 1,361 cases of CNS tumors and 5,500 controls. Paternal exposure to PAH, asbestos, and metals around conception was associated with an increased moderate risk of CNS tumors, although statistically non-significant. The association with exposure to asbestos around conception and diagnosis was stronger when fathers were exposed to high levels. Paternal exposure to DME and silica, and maternal exposure to PAH, DME, asbestos, silica, and metals, were not associated with an increased risk of CNS tumors.
Our large pooled study showed weak evidence of a modest association between paternal occupational exposure to PAH and CNS tumor risk. Our findings need further exploration in the future studies.
Cancer Causes and Control 10/2014; 25(12). DOI:10.1007/s10552-014-0465-4 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype.
We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center.
Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester).
Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.
[Show abstract][Hide abstract] ABSTRACT: Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.
[Show abstract][Hide abstract] ABSTRACT: Radiotherapy (RT) has been associated with the development of solid second malignant neoplasms (SMNs) in childhood cancer survivors. The aim of this study was to analyse the effect of cumulative doses of previous RT received at the SMN body region, at all other body regions and at body regions adjacent to the SMN, on the risk of developing a solid SMN. A total of 190 cases diagnosed with a solid second malignant neoplasm in 1980-2002 were matched with 368 controls with single neoplasm from the database of the German Childhood Cancer Registry (GCCR) (33,809 patients at cut-off date). The GCCR registers approximately 97 % of all childhood malignancies which occur at an age of less than 15 years in Germany since 1980. It was found that 147 (77.4 %) cases had received RT compared to 208 (56.6 %) controls with cumulative focus doses from 8 to 110 Gy. Fifty per cent of the SMNs and 60 % of RT affected the head region. RT was shown to increase the risk of a solid second tumour within the body region of radiation by 5.3 % per Gy (odds ratio 1.053; 95 % confidence interval 1.036-1.071). With increasing age at diagnosis and with more recent treatment eras, this effect decreased. Cumulative RT doses received at all other body regions or only at body regions adjacent to the SMN did not show an additional effect on the risk of developing an SMN. It is thus concluded that RT is the main risk factor for the development of SMNs within the irradiated body region. Late effects surveillance of former patients should give special attention to the originally irradiated parts of the body.
[Show abstract][Hide abstract] ABSTRACT: Sex, age, immunophenotype and white blood cell count at diagnosis are well accepted predictors of survival from acute lymphoblastic leukaemia (ALL) in children. Less is known about the relationship between socio-economic determinants and survival from paediatric ALL, studied here for the first time in German children.
ALL cases were diagnosed between 1992 and 1994 and their parents interviewed during a previous nationwide case-control study. Children were followed-up for 10years after diagnosis by the German Childhood Cancer Registry. Cox proportional hazards models estimating hazard ratios (HRs) were calculated to assess the impact of selected socio-demographic characteristics on overall and event-free survival.
Overall survival was 82.5%, with a higher proportion of girls than boys surviving (85% versus 81%). We found a non-linear relationship between age at diagnosis and survival, with poorer survival in infants and children aged >5years. There was no association between socio-economic factors and survival or risk of relapse. For five levels of increasing family income, all HRs were close to one. No relationship was seen with parental educational level.
Socio-economic determinants did not affect ALL survival in West German children, in contrast to studies from some other countries. Dissimilarities in social welfare systems, including access to health care, lifestyle and differences in treatment may contribute to these differences in findings. Our observation of no social inequalities in paediatric ALL survival is reassuring, but needs continued monitoring to assess the potential impact of evolvement of treatment options and changes in paediatric health service.
European journal of cancer (Oxford, England: 1990) 02/2014; 50(7). DOI:10.1016/j.ejca.2014.01.028 · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Summary
Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007.
We analysed survival data for 157 499 children (age 0—14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers.
We analysed 59 579 cases. For all cancers combined for children diagnosed in 2000—07, 1-year survival was 90·6% (95% CI 90·2—90·9), 3-year survival was 81·0 % (95% CI 80·5—81·4), and 5-year survival was 77·9% (95% CI 77·4—78·3). For all cancers combined, 5-year survival rose from 76·1% (74·4—77·7) for 1999—2001, to 79·1% (77·3—80·7) for 2005—07 (hazard ratio 0·973, 95% CI 0·965—0·982, p<0·0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65·2% (95% CI 63·1—67·3) in 1999—2001, to 70·2% (67·9—72·3) in 2005—07. Europe-wide average yearly change in mortality (hazard ratio) was 0·939 (95% CI 0·919—0·960) for acute lymphoid leukaemia, 0·959 (0·933—0·986) for acute myeloid leukaemia, and 0·940 (0·897—0·984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005—07).
Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe.
Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.
The Lancet Oncology 12/2013; DOI:10.1016/S1470-2045(13)70548-5 · 24.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Ensuring adequate parental consent is a key issue of ethical practice in pediatric oncology. In Germany, however, knowledge about parental comprehension and satisfaction with the informed consent procedure is limited, and representative data on parents' perspectives are still missing. Based on data collected by means of a population-based survey, we evaluated the parental recall of the informed consent process for pediatric clinical trials, and how they rated the consent process retrospectively.
A standardized survey was carried out among 1,465 parents whose children were first diagnosed in 2005 with a disease defined by ICCC-3 in the German Childhood Cancer Registry (response: 55.1%). The survey's primary objective was to assess how well parents were able to recall of the informed consent process. To evaluate the results, we set up a second survey among 581 parents who had given consent recently for their child's participation in a clinical trial (response: 53.5%).
Approximately 81% of the parents in the population-based survey correctly remembered whether or not their child had been enrolled in a clinical trial or treated off-trial. The ability to recall accurately is significantly lower if the parents have a migration background or if their child was not a trial participant. However, parents who recalled the child's trial participation status incorrectly felt as adequately informed as parents who recalled it correctly.
Our results identified weak points and vulnerable subgroups in the parental consent process in pediatric oncology in Germany.