Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.

Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (ORadj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

BACKGROUND: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. METHODS: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. CONCLUSIONS: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

Registration, incidence patterns, and survival trends of central nervous system tumors among children in Germany 1980-2019: An analysis of 40 years based on data from the German Childhood Cancer Registry.

BACKGROUND: Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40 years. PROCEDURE: Including all CNS tumor cases in children diagnosed at ages 0-14 years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival. RESULTS: While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC = 2.7% in 1991-2010, AAPC = 0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%). CONCLUSIONS: Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing.

Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends.

Objective: To provide a comprehensive overview of geographical patterns (2001-2010) and time trends (1993-2012) of cancer incidence in children aged 0-19 years in Latin America and the Caribbean (LAC) and interpret the findings in the context of global patterns. Methods: Geographical variations in 2001-2010 and incidence trends over 1993-2012 in the population of LAC younger than 20 years were described using the database of the third volume of the International Incidence of Childhood Cancer study containing comparable data. Age-specific incidence per million person-years (ASR) was calculated for population subgroups and age-standardized (WSR) using the world standard population. Results: Overall, 36 744 unique cases were included in this study. In 2001-2010 the overall WSR in age 0-14 years was 132.6. The most frequent were leukemia (WSR 48.7), central nervous system neoplasms (WSR 23.0), and lymphoma (WSR 16.6). The overall ASR in age group 15-19 years was 152.3 with lymphoma ranking first (ASR 30.2). Incidence was higher in males than in females, and higher in South America than in Central America and the Caribbean. Compared with global data LAC incidence was lower overall, except for leukemia and lymphoma at age 0-14 years and the other and unspecified tumors at any age. Overall incidence at age 0-19 years increased by 1.0% per year (95% CI [0.6, 1.3]) over 1993-2012. The included registries covered 16% of population aged 0-14 years and 10% of population aged 15-19 years. Conclusions: The observed patterns provide a baseline to assess the status and evolution of childhood cancer occurrence in the region. Extended and sustained support of cancer registration is required to improve representativeness and timeliness of data for childhood cancer control in LAC.

Incidence of childhood leukemia before and after shut down of nuclear power plants in Germany in 2011: A population-based register study during 2004 to 2019.

The association between leukemia and proximity to nuclear-power-plants (NPPs) has been assessed in several countries with inconsistent results. A case-control study from Germany had shown an increased risk for childhood leukemia (diagnoses 1980-2003) near NPPs. Germany began shutting down nuclear reactors in 2011, following the Fukushima disaster. We tested whether the previously observed association between leukemia and proximity to NPP persisted despite the shutdown. We used an ecological study design to investigate the incidence of leukemia during 2004 to 2019 in children aged 0 to 14 years living near NPPs where at least one reactor was shut down in 2011. We defined study and control areas as municipalities whose surface area was at least 75% within 10 km or between 10 and 50 km of NPPs, respectively. We calculated age-standardized rates and incidence rate ratios (IRR) using control-areas as the reference. We also computed standardized incidence ratios (SIR) separately for each NPP using incidence rates of the German population as a reference. IRR decreased from 1.20 (95% confidence interval: 0.81-1.77) in 2004 to 2011 to 1.12 (0.75-1.68) in 2012 to 2019. Analyses of single plants showed an excess of childhood leukemia during 2004 to 2019 for the Unterweser-NPP, based only on three cases, and the Krümmel-NPP (n = 14; SIR: 1.98, 1.17-3.35). We found slightly decreasing of leukemia incidence rate ratios after the shutdown of nuclear reactors in 2011. Due to the small number of cases, risk estimates have large uncertainty. Further research including a longer follow-up is warranted. The consistent excess of incidence cases around Krümmel may require analytical epidemiological analysis.

Temporal patterns of childhood cancer survival 1991 to 2016: A nationwide register-study based on data from the German Childhood Cancer Registry.

Childhood cancer is the leading disease-related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long-term well-being remain primary goals. With this report, we provide the first long-term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years. Using data from the German Childhood Cancer Registry, we assessed temporal patterns of cancer survival among children (0-14 years) diagnosed in Germany from 1991 to 2016, by cancer type, age at diagnosis and sex. We calculated overall survival (OS) and average annual percentage changes of the respective 5-year OS estimates. OS improved across all cancer types, age groups as well as for boys and girls over time. Five-year OS for all childhood cancers combined increased from 77.8% in 1991-1995 to 86.5% in 2011-2016, with stronger improvements during the early 1990s. The most pronounced survival improvement was seen for acute myeloid leukaemia, at 2% annually and 5-year OS recently reaching 81.5%. Survival improvements for some diagnoses such as neuroblastoma, renal tumours and bone tumours have flattened out. Tremendous enhancements in diagnostics, treatment and supportive care have affected average survival improvements for most cancer types. Recently, survival improvements have decelerated overall and for some cancer types, it plateaued at an unsatisfactory level. As not all children benefited equally from the survival improvements, personal factors (eg, socioeconomic circumstances, health literacy, access to care) likely affect individual prognosis and warrant further investigation.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study.

BACKGROUND: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. METHODS: In this population-based study, we analysed 135 847 children (aged 0-14 years) diagnosed during 2000-13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. FINDINGS: 5-year survival for all childhood cancer combined in Europe in 2010-14 was 81% (95% CI 81-82), showing an increase of three percentage points compared with 2004-06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60-79] to 87% [77-93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010-13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73-75) in 1998-2001 to 80% (79-81) in 2010-13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74-100) for retinoblastoma to 60% (58-63) for CNS tumours and reached 90% (95% CI 87-93) for lymphoid leukaemia and 70% (67-73) for acute myeloid leukaemia. INTERPRETATION: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. FUNDING: European Commission.

Incidences and characteristics of primary lung malignancies in childhood in Germany: An analysis of population-based data from German cancer registries.

BACKGROUND: Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany. MATERIALS AND METHODS: Pseudonymized data of cases recorded at the German Center for Cancer Registry Data (ZfKD) between 1990 and 2017 were retrieved. Primary lung malignancies were identified using the ICD- and ICD-O classification. Numbers were compared to those reported to the German Childhood Cancer Registry (GCCR). Crude incidence rates were calculated using the ZfKD database. RESULTS: A total of 168 patients diagnosed with primary lung malignancies in the age below 19 years were identified from the ZfKD. The median age at diagnosis was 13 years. The most common tumor entities were lung carcinoids (n = 49), lung carcinoma (n = 36), and pleuropulmonary blastoma (n = 14). An unexpected accumulation of lung cancer cases was noted in the first year of life without a clearly specified histopathological diagnosis. A substantial discrepancy in the numbers of primary lung malignancies between ZfKD and GCCR was found. CONCLUSIONS: We present population-based data on the occurrence of primary childhood lung malignancies in Germany, which were more frequent than previously anticipated but likely remained underreported. For better understanding and optimal treatment of these entities, cancer registration needs to be improved through mandatory reporting to the GCCR and regular data sharing between GCCR, population-based and clinical cancer registries.

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971-2008 in Denmark, Finland, and Sweden: A population-based cohort study.

OBJECTIVE: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. METHODS: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971-2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. RESULTS: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0-42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6-17.2) for survivors diagnosed during 1971-1981, to 2.5% (95% CI: 1.3-3.7) for those diagnosed during 2002-2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7-16.1) for survivors diagnosed during 1971-1981 to 1.9% (95% CI: 0.9-2.8) for those diagnosed during 2002-2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26-61) 5-9 years from diagnosis, and 4.4 (95% CI: 3.4-5.6) ≥10 years from diagnosis. CONCLUSIONS: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death.

Residential road traffic and railway noise and risk of childhood cancer: A nationwide register-based case-control study in Denmark.

BACKGROUND: The aetiology of most childhood cancers remains poorly understood. We conducted a nationwide register-based case-control study to assess the association between residential road traffic and railway noise exposure and risk of childhood cancers. METHODS: We identified all cases of first cancers diagnosed in children aged 0-19 years in 1985-2013 from the Danish Cancer Registry (N = 3962) and sampled four individually matched (by sex and date of birth) controls per case (N = 14,790) using the Central Population Register. We estimated time-weighted exposure averages of residential road traffic and railway noise at the most (Lden max) and least (Lden min) exposed façades from birth to index-date (for additional analysis: in utero period) based on the individual address history for the respective time windows. We fitted conditional logistic regression models to estimate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: ORs varied by noise estimate and cancer type, with generally wide CIs mostly including 1.00. We found a tendency of higher ORs with increasing railway and road traffic noise for Hodgkin lymphoma (ORs for railway and road Lden min were 1.63 (95% CI 1.00; 2.66) and 1.14 (95% CI 0.87; 1.48) per 10 dB), as well as a tendency of higher ORs with increasing railway noise for non-Hodgkin lymphoma. For embryonal CNS tumours and astrocytoma and other glioma we observed also some weak suggestions of a positive association. Analysing exposure to traffic noise in utero revealed similar patterns to those of the main analyses. CONCLUSIONS: This nationwide study with minimal risk of bias suggests no strong associations between traffic noise and risk of most childhood cancers. We found however some suggestive evidence for a positive association with Hodgkin lymphoma, non-Hodgkin lymphoma and some CNS tumours. Further research is warranted to confirm these associations in other populations and elucidate the underlying biological mechanisms.

Rare pediatric tumors in Germany - not as rare as expected: a study based on data from the Bavarian Cancer Registry and the German Childhood Cancer Registry.

Very rare pediatric tumors (VRTs) pose a challenge for treating physicians as little is known about the best diagnostic assessment and therapeutic decision-making in these malignancies. A large proportion of these cancers occur in adolescence. Therefore, the established structures of pediatric oncology including cancer registration may partly be circumvented. This may lead to an underregistration in clinical cancer registries of yet unclear extent. The aim of this study is to increase the knowledge on the occurrence of VRTs in pediatric patients in Germany. Pseudonymized data of cases recorded in the Bavarian Cancer Registry (BCR) between 2002 and 2014 were retrieved. VRTs according to the definition of the European Cooperative Study Group for Pediatric Rare Tumors were identified using the ICD and ICD-O classification. The numbers of registered patients were compared to those reported to the German Childhood Cancer Registry (GCCR). 6.3% (n = 290) of all malignancies (n = 4615) in the age below 18 years were classified as VRTs. Median age at diagnosis was 15 years (range 0-17 years). The most common tumor types included malignant melanoma, skin carcinoma, and gonadal tumors. During the same period, 49 pediatric patients from Bavaria with matchable VRTs were reported to the GCCR, accounting for 17% of cases reported to the BCR. CONCLUSIONS: The frequency of VRTs in Germany is underestimated in the national GCCR. With this study, we present population-based data on the incidence of VRTs in Germany for the first time. In order to gain additional knowledge about these malignancies, registration of VRTs must be improved through enhanced data exchange between the GCCR, the public cancer registries, and the clinical Registry for Rare Pediatric Tumors (STEP). WHAT IS KNOWN: • Rare pediatric tumors pose a challenge for treating physicians as limited knowledge is available on these malignancies for diagnostic and therapeutic decision-making. • Little is known about the frequency of these rare tumors in pediatric patients. WHAT IS NEW: • The frequency of rare pediatric tumors in Germany is distinctly underestimated in the German Childhood Cancer Registry. • We present population-based data on the incidence of these rare pediatric cancers for the first time.

Rare Tumors in Children and Adolescents - the STEP Working Group's Evolution to a Prospective Registry.

Background Very rare tumors (VRT) in children and adolescents have such a low incidence that until recently, they have not been integrated into the clinical and scientific network of pediatric oncology. Data is very limited and consistent treatment strategies are missing. Thus, VRTs are classic orphan diseases. To counteract this problem, the Arbeitsgemeinschaft für Seltene Tumorerkrankungen in der Pädiatrie (STEP) was founded. Here we report on patient recruitment during the first 10 years. Patients Patients aged up to 18 years and not included in any other clinical trial or GPOH registry were included in this analysis. Methods Data was collected from 2008 to 2018 by means of a standardized form. The recorded diagnoses were descriptively analyzed focusing on histology, localization, and year of report. Results A total of 623 patients with VRTs were registered. During 2008-2014, the annual number of registrations was around 40 and is around 90 since 2015. Most frequent diagnoses included tumors of the skin (n=150), tumors of the gastrointestinal tract (n=102), tumors of the gonads (n=77), the ENT region (n=68), and miscellaneous tumors (n=107). Discussion With the establishment of central structures for clinical consultation and documentation of VRTs, the number of registrations increased. Comprehensively, VRTs are as common as other classic pediatric oncology tumors, but extremely heterogeneous in terms of localization, histology, and prognosis. By a centralized and complete registration and analysis of VRTs, also in collaboration with international partners, it is possible to develop treatment strategies and thus greatly increase treatment quality.

[The 41,000 long-term survivor cohort of the German Childhood Cancer Registry]. / Die Kohorte der 41.000 Langzeitüberlebenden des Deutschen Kinderkrebsregisters.

BACKGROUND AND OBJECTIVES: One-third of childhood cancer long-term survivors suffer from severe late effects (e.g., secondary cancer and cardiovascular diseases). The German Childhood Cancer Registry (GCCR) holds approximately 70,000 registered cancer cases, of which more than 41,000 are long-term survivors, with recent follow-up and contact information that can be used for scientific studies on late effects. The characteristics of this cohort are presented, previous late effects studies with the support of the GCCR are described, and the respective participation rates are reported. METHODS: For all patients who developed cancer between 1980 and 2019 and were in long-term observation at the GCCR, the distribution of diagnoses, current age, observation time, and number of secondary cancers as of 16 July 2021 was determined. The rates of patients who responded to history queries were computed. The influence of determinants on the participation rate were calculated using generalized estimating equations. RESULTS: The cohort comprises 41,466 long-term survivors. Of these, 10% are older than 40 years and 40% had their cancer diagnosis more than 20 years ago. The participation rates range between 30 and 60% and depend on age at diagnosis, the complexity of the study, and the number of previously conducted surveys. A time interval of at least four years between two consecutive contacts seems optimal. CONCLUSIONS: Our unique cohort enables population-based research on late effects after childhood cancer. To define a sensible time interval for contacting survivors is essential. In order to ensure that survivors are not contacted too frequently, the number of survivors included in research projects should be as small as possible.

Is the risk of childhood leukaemia associated with socioeconomic measures in Denmark? A nationwide register-based case-control study.

The aetiology of childhood leukaemia is poorly understood. Knowledge about differences in risk by socioeconomic status (SES) may enhance etiologic insights. We conducted a nationwide register-based case-control study to evaluate socioeconomic differences in the risk of childhood leukaemia in Denmark and to access whether associations varied by different measures of SES, time point of assessment, leukaemia type and age at diagnosis. We identified all cases of leukaemia in children aged 0 to 19 years, born and diagnosed between 1980 and 2013 from the Danish Cancer Registry (N = 1336) and sampled four individually matched controls per case (N = 5330). We used conditional logistic regression models for analysis. Medium and high level of parental education was associated with a higher risk of acute myeloid leukaemia (AML) in the offspring, mainly driven by children diagnosed at ages 0 to 4 years [odds ratio (OR) for high maternal education = 3.07; 95% confidence interval (CI): 1.44-6.55]. We also observed a modestly increased risk for lymphoid leukaemia (LL) in association with higher level of parental education, but only in children diagnosed at ages 5 to 19 years. Higher parental income was associated with an increased risk of LL but not AML among children aged 5 to 19 years at diagnosis (OR for high maternal income = 2.78; 95% CI: 1.32-5.89). Results for neighbourhood SES measures indicated null associations. Bias or under-ascertainment of cases among families with low income or basic education are unlikely to explain the observed socioeconomic differences. Future research addressing explicitly the underlying mechanisms of our results may help to enhance etiologic insights of the disease.

Number of siblings and survival from childhood leukaemia: a national register-based cohort study from Sweden.

BACKGROUND: Previous studies suggest worse leukaemia survival for children with siblings, but the evidence is sparse, inconsistent and does not consider clinical factors. We explored the associations between number of siblings in the household, birth order and survival from childhood acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML). METHODS: In this nationwide register-based study we included all children aged 1-14, diagnosed with ALL and AML between 1991-mid-2015 in Sweden (n = 1692). Using Cox regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) according to number of siblings and birth order, adjusting for known prognostic and sociodemographic factors. RESULTS: A tendency towards better ALL survival among children with one, or ≥2, siblings was observed, adjHRs (95% CI): 0.73 (0.49-1.10) and 0.63 (0.40-1.00), respectively. However, this was mainly limited to children with low risk profiles. An indication of better AML survival among children with siblings was seen, adjHRs (95% CI) 0.68 (0.36-1.29) and 0.71 (0.34-1.48) but diminished after adjusting for birth order. CONCLUSION: Our results do not support previous findings that a larger number of siblings is associated with poorer survival. Inconsistencies might be explained by underlying mechanisms that differ between settings, but chance cannot be ruled out.

Socioeconomic position and prediagnostic health care contacts in children with cancer in Denmark: a nationwide register study.

BACKGROUND: While underlying mechanisms and pathways of social inequalities in cancer survival have been extensively examined in adults, this is less so for children with cancer. Hypothesized mechanisms include prediagnostic utilization of and navigation through the health care system, which may differ by socioeconomic resources of the families. In this nationwide register-based study we investigated the association between measures of family socioeconomic position in relation to prediagnostic health care contacts and stage of disease at diagnosis in children with cancer in Denmark. METHODS: We identified all children diagnosed with a cancer at ages 0-15 years in 1998-2016 (N = 3043) from the Danish Childhood Cancer Registry. We obtained comprehensive information on measures of socioeconomic position, parental health and prediagnostic contacts to both general practitioners and hospitals 24 months prior to diagnosis from various national registries. We fitted multivariable conditional logistic regression models for the association of family socioeconomic and health-related variables with firstly, frequent health care contacts and secondly, advanced stage. RESULTS: We found higher odds ratios (OR) of frequent both overall and emergency health care contacts in the last 3 months before diagnosis in children from households with short parental education and mixed affiliation to work market, when compared to children with high family socioeconomic position. Further, children of parents with depression or of non-Western origin, respectively, had higher OR for frequent overall and emergency contacts. We found no association between socioeconomic position, parental health and stage of disease. CONCLUSION: Families with socioeconomic disadvantage, non-Western origin or depression more frequently utilize prediagnostic health care services, both generally and in the acute setting, indicating that some disadvantaged families may struggle to navigate the health care system when their child is sick. Reassuringly, this was not reflected in disparities in stage at diagnosis. In order to improve the diagnostic process and potentially reduce health care contacts, attention and support should be given to families with a high number of health care contacts over a short period of time.

Mental health and health-related quality of life in preschool-aged childhood cancer survivors. Results of the prospective cohort study ikidS-OEVA.

OBJECTIVES: Long-term survivors of childhood cancer are at increased risk for sequelae such as poor mental health (MH) or impaired health-related quality of life (HrQoL). We aimed to evaluate early adverse effects on MH and HrQoL in young childhood cancer survivors (YCCS) before school entry. METHODS: In a nationwide prospective cohort study, children with cancer other than brain tumors diagnosed at preschool age and completed cancer treatments were identified from the German Childhood Cancer Registry. The comparison group was children of the same age without a cancer diagnosis who participated in the prospective population-based health survey ikidS. MH problems and HrQoL were assessed by parental versions of the Strengths and Difficulties Questionnaire (SDQ) and the questionnaire for health-related quality of life in children (KINDL), respectively. Associations between cancer and MH as well as HrQoL were analyzed by multivariable linear regression. RESULTS: Of 382 YCCS contacted, 145 were enrolled (mean age 6.6 years) and 124 analyzed. Compared to children without a cancer diagnosis (3683 contacted, 2003 enrolled, 1422 analyzed), YCCS had more MH problems (13% vs. 3%) and slightly worse HrQoL (median 78.7 vs. 80.2 points). In the adjusted analysis, YCCS had higher SDQ scores (2.2 points, 95% confidence interval [CI] 1.3, 3.0) and lower KINDL scores (-2.4 points, 95% CI -3.7, -1.1) compared to children without cancer diagnosis. CONCLUSION: Already at preschool age, YCCS may be at increased risk of MH problems and impaired HrQoL. This could have impacts on subsequent school performance and educational attainment. Follow-up health care for YCCS may include early screening for MH problems and reasons for HrQoL deficits.

The impact of childhood cancer on parental working status and income in Denmark: Patterns over time and determinants of adverse changes.

Having a child with cancer may affect the socioeconomic situation of the parents. We aimed to assess the impact of childhood cancer on parental working status and income and to identify determinants of adverse changes after the child's cancer diagnosis by calendar period. We conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer in 1982-2014 (n = 12,418) were matched with comparison parents of cancer-free children (n = 125,014). We analysed annual working status (working/not working) and annual disposable income (lowest quintile/not lowest quintile) of case and comparison parents over a period of 10 years after diagnosis by calendar period (1982-1999 vs. 2000-2014). Logistic regression models were used to identify determinants of adverse changes after diagnosis. Mothers of children diagnosed in 1982-1999 were more likely not working or having a low income than comparison mothers up to 10 years after diagnosis. This risk of not working or low income was lower in mothers of children diagnosed in 2000-2014 compared to 1982-1999 in the first years after diagnosis (pinteraction < 0.05). We observed no consistent patterns among fathers. Low parental education, diagnosis of lymphoid leukaemia and younger age of the child at diagnosis were the main determinants of adverse changes in working status or income after diagnosis. Childhood cancer adversely interfered with parents' socioeconomic situation in the earlier calendar period, particularly among mothers. The absence of such an effect in more recent years emphasises the supportive role of a countries' welfare system alongside the general advances in childhood cancer treatment.