Prevalence of childhood cancer survivors in Europe: a scoping review.

Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors' needs.

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.

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.

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.

Risk factors for childhood brain tumours: A systematic review and meta-analysis of observational studies from 1976 to 2022.

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention. METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, during pregnancy and/or during post-natal period. Random effects meta-analysis was used to estimate summary effect sizes (ES) and 95% confidence intervals (CIs). We also quantified heterogeneity (I2) across studies. FINDINGS: A total of 4040 studies were identified, of which 181 studies (85 case-control and 96 cohort studies) met our criteria for inclusion. Of all eligible studies, 50% (n = 91) were conducted in Europe, 32% (n = 57) in North America, 9% (n = 16) in Australia, 8% (n = 15) in Asia, 1% (n = 2) in South America, and none in Africa. We found associations for some modifiable risk factors including childhood domestic exposures to insecticides (ES 1.44, 95% CI 1.20-1.73) and herbicides (ES 2.38, 95% CI 1.31-4.33). Maternal domestic exposure to insecticides (ES 1.45, 95% CI 1.09-1.94), maternal consumption of cured meat (ES 1.51, 95% CI 1.05-2.17) and coffee ≥ 2 cups/day (ES 1.45, 95% 95% CI 1.07-1.95) during pregnancy, and maternal exposure to benzene (ES 2.22; 95% CI 1.01-4.88) before conception were associated with CBTs in case-control studies. Also, paternal occupational exposure to pesticides (ES 1.48, 95% CI 1.23-1.77) and benzene (ES 1.74, 95% CI 1.10-2.76) before conception and during pregnancy were associated in case-control studies and in combined analysis. On the other hand, assisted reproductive technology (ART) (ES 1.32, 95% CI 1.05-1.67), caesarean section (CS) (ES 1.12, 95% CI 1.01-1.25), paternal occupational exposure to paint before conception (ES 1.56, 95% CI 1.02-2.40) and maternal smoking > 10 cigarettes per day during pregnancy (ES 1.18, 95% CI 1.00-1.40) were associated with CBT in cohort studies. Maternal intake of vitamins and folic acid during pregnancy was inversely associated in cohort studies. Hormonal/infertility treatment, breastfeeding, child day-care attendance, maternal exposure to electric heated waterbed, tea and alcohol consumption during pregnancy were among those not associated with CBT in both case-control and cohort studies. CONCLUSION: Our results should be interpreted with caution, especially as most associations between risk factors and CBT were discordant between cohort and case-control studies. At present, it is premature for any CBT to define specific primary prevention guidelines.

Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends / Incidencia del cáncer infantil en América Latina y el Caribe: cobertura de los registros, patrones y tendencias a lo largo del tiempo / Incidência de câncer infantil na América Latina e no Caribe: cobertura, padrões e tendências temporais

ABSTRACT 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.

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RESUMO Objetivo. Apresentar uma visão abrangente dos padrões geográficos (2001 a 2010) e das tendências temporais (1993 a 2012) da incidência de câncer em crianças e jovens de 0 a 19 anos na América Latina e no Caribe (ALC) e interpretar os resultados no contexto de padrões mundiais. Métodos. Foram descritas variações geográficas de 2001 a 2010 e tendências de incidência de 1993 a 2012 na população com menos de 20 anos da ALC usando informações comparáveis da base de dados do terceiro volume do estudo International Incidence of Childhood Cancer. Foram calculadas taxas de incidência específica por idade por milhão de pessoas-ano (ASR, na sigla em inglês) para subgrupos populacionais e taxas padronizadas por idade usando a população padrão mundial (WSR, na sigla em inglês). Resultados. No total, foram incluídos 36 744 casos únicos. No período de 2001 a 2010, a WSR para todos os tumores combinados na faixa etária de 0 a 14 anos foi de 132,6. Os diagnósticos mais frequentes foram leucemia (WSR de 48,7), neoplasias do sistema nervoso central (WSR de 23,0) e linfoma (WSR de 16,6). A ASR para todos os tumores combinados na faixa etária de 15 a 19 anos foi de 152,3, e a maior taxa foi a de linfoma (ASR de 30,2). A incidência foi maior no sexo masculino do que no sexo feminino e maior na América do Sul do que na América Central e no Caribe. De modo geral, em comparação com as estimativas mundiais, a incidência na ALC foi menor, exceto para leucemia e linfoma entre 0 e 14 anos e para outros tumores e tumores não especificados em qualquer idade. A taxa de incidência na faixa etária de 0 a 19 anos aumentou em 1,0% ao ano (IC de 95% [0,6, 1,3]) entre 1993 e 2012. Os registros incluídos cobriam 16% da população de 0 a 14 anos e 10% da população de 15 a 19 anos. Conclusões. Os padrões observados servem de referência para avaliar o status e a evolução da ocorrência de câncer infantil na região. É necessário garantir um apoio ampliado e consistente aos registros de câncer para aprimorar a representatividade e a disponibilidade das informações em tempo adequado para o controle do câncer infantil na ALC.

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.

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.

Childhood and adolescent cancer in Germany - an overview.

Background: Childhood and adolescent cancer constitutes only a very small fraction of the cancer cases in Germany and throughout the world, but it is the most frequent cause of disease-related death in children. The diagnostic spectrum differs markedly from that of adults. More than 90% of all cases of childhood and adolescent cancer in Germany are treated according to centralised protocols or in therapy studies. Methods: The main epidemiological data for this group are collected by the German Childhood Cancer Registry (GCCR) since 1980. Based on this data, three typical diagnoses and their incidence and prognosis are described in exemplary manner: Lymphoid leukaemia (LL), astrocytoma and neuroblastoma. Results: Approximately 2,250 new cancers are diagnosed in children and adolescents under the age of 18 in Germany every year. In this age group, leukaemia and lymphoma account for almost 50% of all new cancer cases, predominately acute forms. Overall, the prognosis is considerably better than in adults. Conclusions: There is relatively little consistent evidence available on external factors as risk factors for childhood cancer, despite decades of research. For LL, the immune system and infections are assumed to play a role, as early training of the immune system appears to be protective. To an increasing degree, research is identifying genetic risk factors for many types of childhood and adolescent cancer. The therapy is sometimes very intensive and leads to a variety of late effects for at least 75% of the survivors, which may occur soon after the primary diagnosis, but also decades later.

Income disparities between adult childhood cancer survivors and their peers-A register-based cohort study from the SALiCCS research programme.

BACKGROUND: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers. METHODS: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses. RESULTS: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently. CONCLUSIONS: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system.

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.

Equivalent doses for anticancer agents used in pediatric oncology: A literature review and evaluation of a novel approach for conversion factors.

BACKGROUND: Epidemiological research on late effects of therapy shows the necessity to aggregate chemotherapy agents to substance classes. This requires using conversion factors by substance classes. AIMS: The aim of this study was to identify previously used conversion factors from the literature, to present a novel approach for additional factors, and to compare these approaches. METHODS AND RESULTS: A literature review was performed, which identified two main principles of deriving conversion factors: effect-equivalence and equimolar. Thirty-five articles presenting effect equivalence-based factors in the widest sense were found in the literature. Ten articles presented the equimolar approach which can be applied to almost all chemotherapy substances. Based on a comprehensive list of treatment protocols used in German pediatric oncology, we derived alternative conversion factors from typical doses. We compared the conversion factors using Pearson correlation coefficients and linear regression. At least two types of conversion factor were available for each of the 49 substances included. The equivalent effect-based and the typical dose-based factors were highly correlated with a regression coefficient close to 1. The equimolar factors are independent. CONCLUSIONS: For substances for which no conversion factor based on some type of effect equivalence has been published so far, a factor based on a typical doses-approach may be used in epidemiological late effects research. Doses aggregated based on the equimolar approach may not be compatible with doses aggregated based on equivalent effects.

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.

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.

Patient-reported long-term outcome following allogeneic hematopoietic stem cell transplantation in pediatric chronic myeloid leukemia.

Background: Pediatric CML is very rare. Before the introduction of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (HSCT) from a donor -if available- was the standard cure attempt. Data on the long-term outcome and health-related quality of life (HRQOL) in former pediatric CML patients undergoing HSCT are lacking. Study question: We investigated long-term survivors' self-reporting to a questionnaire sent out to patients formerly enrolled in pediatric CML-HSCT trials. Methods: Individuals with CML transplanted at age <18 years were identified from the German Childhood Cancer Registry database. Long-term survivors received a questionnaire based on the SF-36 and FACT-BMT asking them to self-report HRQOL issues. (Ethical vote #541_20 B, Medical Faculty, University of Erlangen-Nürnberg). Results: 111/171 (64.9%) individuals survived HSCT long-term and 86/111 (77.5%) fulfilled all inclusion criteria and received the questionnaire. 37/86 (43%) participants (24 female, 13 male, median age at HSCT 12 years [range 2-18], median age at the time of the survey 29 years [range 18-43]) responded after a median follow-up period of 19 years (range 4-27) after HSCT. 10/37 (27%) participants underwent no regular medical follow-up examinations. Self-reported symptoms like chronic graft-versus-host disease (cGvHD)-associated organ impairments and conditioning regimen consequences could causatively not sharply be separated in each case. Complains comprised hypothyroidism (N=11, 30%), infertility (N=9, 24%), lung problems, dry eyes (each N=7, 19%), skin alterations (N=6, 17%), hair problems (N=4, 11%), and sexual dysfunction (N=3, 9%). 10 (27%) participants experienced 13 CML relapses after a median interval from HSCT of 31 months (range 2-93). Only one patient underwent 2nd SCT after failure of relapse treatment with TKIs. Six secondary malignancies (dysplastic melanocytic nevus and ALL, basal cell carcinoma (N=2), rhabdomyosarcoma, and thyroid carcinoma developed in 5 (13%) participants. As assessed by the SF-36 questionnaire, impaired physical health was mainly associated with cGvHD. The mental component summary score showed that also participants without cGvHD scored significantly lower than the general population. When assessed by the FACT-BMT, participants with cGvHD scored significantly lower while participants without cGvHD scored even 5 points higher than the data from controls. 18 (49%) participants considered the sequelae of HSCT an obstacle to education. Out of the total cohort, N=20 (54%), N=7 (19%), N=5 (14%), and N=4 (11%) participants worked full time, part-time, were unemployed, or had not yet finalized their education, respectively. 20 (54%) participants lived as singles, 8 (22%) lived in a partnership, 6 (16%) were married, and 3 (8%) had been divorced. Four (11%) participants reported a total number of 7 children. Conclusion: This first assessment of HRQOL in former pediatric patients with CML surviving HSCT for more than two decades demonstrates self-reported satisfactory well-being only in the absence of cGvHD. Research-based on self-reported outcomes sheds light on former patients' perspectives and provides an additional layer of valuable knowledge for pediatric and adult hematologists. Regular follow-up examinations are mandatory helping to avoid that late secondary neoplasias, CML-relapse, and disorders forming the broad range of possible long-term consequences of HSCT are not detected too late.

Patterns and temporal trends in the incidence of childhood and adolescence cancer in Cyprus 1998-2017: A population-based study from the Cyprus Paediatric Oncology Registry.

BACKGROUND: Despite its rarity, cancer in children and adolescents (CAC) is a major health issue worldwide. The lack of appropriate cancer registries is an obstacle for defining its incidence and survival, and informing cancer control. As in Cyprus, CAC epidemiology has not previously been comprehensively examined, we determined incidence rates and temporal trends of cancer in the 0-19 age group during 1998-2017. METHODS: We established the population based Paediatric Oncology Registry of Cyprus (PORCY) for the period 1998-2017. World age standardised incidence rate per million children and adolescents per year (ASRW) were calculated and time trends were assessed using Joinpoint regression analysis. Comparisons were made with other countries using the International Incidence of Childhood Cancer, third volume. RESULTS: For all cancers combined, for ages 0-19-years, ASRW was 203.54 (95% CI 189.49, 217.59) one of the highest rates globally. The most frequent CAC were leukaemias followed by lymphomas, specified epithelial neoplasms and central nervous system tumours, differing to what is described in most other countries. For all cancers, both combined and individual types, except thyroid carcinoma (where incidence was rising), no significant temporal variation was found. CONCLUSIONS: To inform cancer control activities, we conducted the first ever population-based epidemiological study of childhood and adolescent cancer (0-19 years) in Cyprus. The striking findings indicate high overall incidence rates that are among the world's highest, a higher frequency of lymphomas and thyroid cancer than brain tumours, and rising incidence for thyroid, but not for other, cancers. These novel findings, will help the formulation of hypotheses to provide explanation for the high rates for all CAC in Cyprus and may contribute to the global efforts for improving prevention of cancer in this age group.