Childhood cancer : Estimating regional and global incidence

Most of the world’s population is not covered by cancer surveillance systems or vital registration, and worldwide/UN-regional cancer incidence is estimated using a variety of methods. Quantifying the cancer burden in children (<15 years) is more challenging than in adults; childhood cancer is rare and often presents with non-specific symptoms that mimic those of more prevalent infectious and nutritional conditions.MethodsA Baseline Model (BM) was constructed comprising a set of quality assured sex- and age-specific cancer rates derived from the US Surveillance, Epidemiology and End Results (SEER) program, for diagnostic groups of the International Classification of Childhood Cancers (ICCC-3) 3rd edition, and information on a known risk factor for endemic Burkitt lymphoma and Kaposi’s sarcoma. These rates were applied to global country-level population data for 2015 to estimate the global and regional incidence of childhood cancer. Results were compared to GLOBOCAN 2018, extrapolations from the International Incidence of Childhood Cancer (IICC-3) and estimates from the Global Childhood Cancer (GCC) model (based on IICC-3 data combined with information on health care systems and other parameters).ResultsThe BM estimated 360,114 total childhood cancers occurring worldwide in 2015; 54% in Asia and 28% in Africa. BM estimated standardised rates ranged from ∼178 cases per million in Europe and North America, through to ∼218 cases per million in West and Middle Africa. Totals from GLOBOCAN and extrapolations from the IICC-3 study were lower (44.6% and 34.7% respectively), but the estimate from the GCC model was 10.2% higher. In all models, agreement was good in countries with very high human development index (HDI), but more variable in countries with medium and low HDIs; the discrepancies correlating with registration coverage across these settings.ConclusionDisagreements between the BM estimates and other sources occur in areas where health systems are insufficiently equipped to provide adequate access to diagnosis, treatment, and supportive care. Incorporating aetiological evidence into the BM enabled the estimation of the additional burden of Burkitt lymphoma and Kaposi sarcoma; similar adjustments could be applied to other cancers, as and when information becomes available.AbbreviationsSEERSurveillance, Epidemiology and End Results programIICC-3International incidence of childhood cancer study, 3rd volumeICCC-3International classification of childhood cancer, 3rd editionICD-10International classification of diseases, 10th RevisionBLBurkitt lymphomaBMBaseline modeleBLendemic Burkitt lymphomaEBVEpstein-Barr virusHDIHuman development index 2015KSKaposi sarcomaKSHVKaposi sarcoma-associated herpes virusGCCGlobal childhood cancer microsimulation modelKeywordsChildhood cancerIncidenceEstimatesGlobalCancer registryBurkitt lymphomaKaposi sarcomaGlobal estimate

Role of maternal diet in the risk of childhood acute leukemia: a systematic review and meta-analysis

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59–0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12–1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis

Acute leukemia commonly occurs in young children with peak incidence at the age of 2–5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case–control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76–0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937

Childhood cancer burden: a review of global estimates.

5-year net survival of children and adolescents diagnosed with cancer is approximately 80% in many high-income countries. This estimate is encouraging as it shows the substantial progress that has been made in the diagnosis and treatment of childhood cancer. Unfortunately, scarce data are available for low-income and middle-income countries (LMICs), where nearly 90% of children with cancer reside, suggesting that global survival estimates are substantially worse in these regions. As LMICs are undergoing a rapid epidemiological transition, with a shifting burden from infectious diseases to non-communicable diseases, cancer care for all ages has become a global focus. To improve outcomes for children and adolescents diagnosed with cancer worldwide, an accurate appraisal of the global burden of childhood cancer is a necessary first step. In this Review, we analyse four studies of the global cancer burden that included data for children and adolescents. Each study used various overlapping and non-overlapping statistical approaches and outcome metrics. Moreover, to provide guidance on improving future estimates of the childhood global cancer burden, we propose several recommendations to strengthen data collection and standardise analyses. Ultimately, these data could help stakeholders to develop plans for national and institutional cancer programmes, with the overall aim of helping to reduce the global burden of cancer in children and adolescents

International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries

Despite improved survival rates, cancer remains one of the most common causes of childhood death. The International Cancer Benchmarking Partnership (ICBP) showed variation in cancer survival for adults. We aimed to assess and compare trends over time in cancer mortality between children, adolescents and young adults (AYAs) and adults in the six countries involved in the ICBP: United Kingdom, Denmark, Australia, Canada, Norway and Sweden. Trends in mortality between 2001 and 2015 in the six original ICBP countries were examined. Age standardised mortality rates (ASR per million) were calculated for all cancers, leukaemia, malignant and benign central nervous system (CNS) tumours, and non-CNS solid tumours. ASRs were reported for children (age 0-14 years), AYAs aged 15 to 39 years and adults aged 40 years and above. Average annual percentage change (AAPC) in mortality rates per country were estimated using Joinpoint regression. For all cancers combined, significant temporal reductions were observed in all countries and all age groups. However, the overall AAPC was greater for children (-2.9; 95% confidence interval = -4.0 to -1.7) compared to AYAs (-1.8; -2.1 to -1.5) and adults aged >40 years (-1.5; -1.6 to -1.4). This pattern was mirrored for leukaemia, CNS tumours and non-CNS solid tumours, with the difference being most pronounced for leukaemia: AAPC for children -4.6 (-6.1 to -3.1) vs AYAs -3.2 (-4.2 to -2.1) and over 40s -1.1 (-1.3 to -0.8). AAPCs varied between countries in children for all cancers except leukaemia, and in adults over 40 for all cancers combined, but not in subgroups. Improvements in cancer mortality rates in ICBP countries have been most marked among children aged 0 to 14 in comparison to 15 to 39 and over 40 year olds. This may reflect better care, including centralised service provision, treatment protocols and higher trial recruitment rates in children compared to older patients.</p

The PanCareSurFup consortium:research and guidelines to improve lives for survivors of childhood cancer

Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of$594 billion, producing a net benefit of $1986 billion on the global investment: a net return of$3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

Cancer incidence in children and young adults living in industrially contaminated sites: from the Italian experience to the development of an international surveillance system

BACKGROUND: this paper is based upon work from COST Action ICSHNet. Children's environmental health is on the 2030 Agenda for Sustainable Development. The incidence of childhood cancer is increasing worldwide and in Europe. Yet, the aetiology of most childhood cancers, including the role of environmental carcinogens, is still largely unknown. Contaminated areas, especially of industrial origin, are of high concern due to complex mix of hazardous pollutants and their potential health impacts on human populations, notably in children.OBJECTIVES: to describe cancer risk in children and young adults (YA) residing in national priority contaminated sites (NPCSs) in Italy and to provide a suitable framework for a development of cancer surveillance in industrially contaminated sites (ICSs) in Europe.METHODS: this study is based on a collaborative work of the Italian Institute of Health (ISS) and the Italian Association of Cancer Registries (AIRTUM), in the context of the SENTIERI project (Epidemiological study of residents in National Priority Contaminated Sites). Incidence rates were standardised according to the European standard population. The number of observed cases was compared to the expected cases derived from the age-, sex-, and cancer-specific incidence rates of the national pool of AIRTUM registries for the period 2006-2013. Standardized incidence ratios (SIRs) and 90% confidence intervals (CIs) were computed. The study reports the cancer profile in all combined 28 NPCSs covered by 22 cancer registries.RESULTS: 1,050 cases of malignant tumours (MTs) were recorded among 3,161,786 person-years in people aged 0-29 years in 28 NPCSs (SIR: 1.03; 90%CI 0.98-1.09), with an age-standardised incidence rate of 317 per million. Excess risks were observed for: MT of the central nervous system in the age-group <1 year (SIR: 3.2; 90%CI 1.4-6.3); soft tissue sarcoma in the age-group 0-14 years (SIR: 1.6; 90%CI 1.1-2.3); acute myeloid leukaemia in the agegroup 0-14 years (SIR: 1.7; 90%CI 1.1-2.4); non-Hodgkin lymphoma in the age-group 20-24 years (SIR 1.5; 90%CI 1.1-2.1), and germ cell tumours of male gonads in the age-group 20-29 years (SIR: 1.33; 90%CI 1.1-1.5). A deficit of cases was observed for Hodgkin lymphomas in the age-group 20-29 years (SIR 0.8; 90%CI 0.6-1.0).DISCUSSION: this study, which is based on standardized methods and accredited information sources, supports the hypothesis that living in an NPCS increases the risk of some cancer types in children and young adults. Further work will concern groups of NPCSs characterised by common sources of contamination/key carcinogenic pollutants. In fact, in a novel project proposal we aim to monitor the cancer profile in children living in ICSs in Europe. The new project, based on the SENTIERI-AIRTUM methodology, will build on the networking activities of the COST Action on Industrially Contaminated Sites and Health Networking (ICSHNet) and childhood cancer studies coordinated by the International Agency for research on Cancer (IARC)