Issues raised by the incidence and survival of childhood cancers
Authors: Philippe Autier
Journal: The Lancet Haematology (2017)

An Article by Audrey Bonaventure and colleagues1Bonaventure A Harewood R Stiller C et al.Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.Lancet Haematol. 2017; (published online April 11)http://dx.doi.org/10.1016/S2352-3026(17)30053-4PubMed Google Scholar in the Lancet Haematology provides international comparisons of 5-year net survival statistics of children diagnosed with leukaemia, and another Article by Eva Steliarova-Foucher and colleagues2Steliarova-Foucher E Colombet M Ries LAG et al.International incidence of childhood cancer, 2001–10: a retrospective, population-based registry study.Lancet Oncol. 2017; (published online April 11)http://dx.doi.org/10.1016/S1470-2045(17)30186-9PubMed Google Scholar in the Lancet Oncology is an exhaustive report on worldwide incidence rates of childhood cancers observed in 2001–10. Both are based on best-quality data from population-based cancer registries. The first Article by Bonaventure and colleagues1Bonaventure A Harewood R Stiller C et al.Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.Lancet Haematol. 2017; (published online April 11)http://dx.doi.org/10.1016/S2352-3026(17)30053-4PubMed Google Scholar documents the steady improvements in survival in children with leukaemia from 1995–2009. These improvements are essentially due to the combined effects of many factors including the increasing precision in diagnosis and the substantial progress in the management of children with cancer, including supportive care provided to children and their families. However, the accomplishment of 5-year net survival of around 80% in many high-income countries should not distract from the dire reality that about 80% of leukaemia cases in children occur in low-income and middle-income countries (LMICs) where there is little access to the sophisticated and costly specialised medical resources required for the optimum management of these conditions.3Sullivan R, Kowalczyk JR, Agarwal B, et al. New policies to address the global burden of childhood cancers. Lancet Oncol; 14: e125–35.Google Scholar From a worldwide perspective, it is the adoption by LMICS of affordable, locally adapted, multidisciplinary management programmes that is likely to translate into the largest gains in survival for children with haematological cancer.4Rodriguez-Galindo C Friedrich P Alcasabas P et al.Toward the cure of all children with cancer through collaborative efforts: pediatric oncology as a global challenge.J Clin Oncol. 2015; 33: 3065-3073Crossref PubMed Scopus (231) Google Scholar Steliarova-Foucher and colleagues2Steliarova-Foucher E Colombet M Ries LAG et al.International incidence of childhood cancer, 2001–10: a retrospective, population-based registry study.Lancet Oncol. 2017; (published online April 11)http://dx.doi.org/10.1016/S1470-2045(17)30186-9PubMed Google Scholar rightly extend on the many challenges faced by the registration of childhood cancers. Nonetheless, I believe that cancer registries could further enhance research efforts intended to improve survival if they also captured the likely cause of death, or the health problems associated with the deaths. Knowing the causes of death might inform about whether children died from the cancer itself, or from a consequence of their management, or from another cause. This knowledge might help reveal associations between health problems, treatments, socioeconomic status, and other factors. Moreover, the causes of death might vary across countries, socioeconomic groups, and age groups. For instance, the type and frequency of infectious diseases affecting children with impaired immunity are expected to differ between tropical and temperate climates. Another example is the deaths of children who survive less than 1 month after cancer diagnosis, before therapies can change the disease course;5Green AL Furutani E Ribeiro KB Galindo CR Death within 1 month of diagnosis in childhood cancer: an analysis of risk factors and scope of the problem.J Clin Oncol. 2017; (published online March 6. DOI:JCO.2016.70.3249)PubMed Google Scholar these early deaths account for 7·5% of all childhood cancer deaths and their causes are still obscure. They particularly affect children with haematological cancer aged younger than 1 year who belong to deprived families, an observation that partly explains the poorer 5-year net survival of children aged younger than 1 year when the diagnosis of leukaemia is made. The ascertainment of possible causes of death and the training of cause of death assessors would greatly benefit from internationally validated guidelines enabling the identification, characterisation and classification of health events possibly associated with cancer therapies.6Alexander S Pole JD Gibson P et al.Classification of treatment-related mortality in children with cancer: a systematic assessment.Lancet Oncol. 2015; 16: e604-e610Summary Full Text Full Text PDF PubMed Scopus (58) Google Scholar Steliarova and colleagues report a 13% increase in the overall incidence rates of childhood cancers from circa 1980 to 2001–10. The increase is found in all regions of the world except in Sub-Saharan Africa. Of the many statistics reported in the Article, this one is probably the most likely to attract attention. However, the Article does not present many possible reasons underlying this increase. In any case, the slow but steady raise in the incidence of many childhood cancers is real, especially for acute leukaemia in some areas.7Linet MS Brown LM Mbulaiteye SM et al.International long-term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0-19 years.Int J Cancer. 2016; 138: 1862-1874Crossref PubMed Scopus (67) Google Scholar Interpretation of these trends is hampered by the poor knowledge we have of risk factors associated with childhood cancer occurrence. Multiple factors that differ between tumour types are likely to be involved in the raising trends. Unfortunately, epidemiological studies have obtained consistent findings for few factors. For instance, children with Down syndrome have a 20-fold higher risk of developing acute leukaemia, while the risk of leukaemia decreases with repeated infections in early life and the onset of asthma.8Linabery AM Jurek AM Duval S Ross JA The association between atopy and childhood/adolescent leukemia: a meta-analysis.Am J Epidemiol. 2010; 171: 749-764Crossref PubMed Scopus (74) Google Scholar Additionally, congenital malformations seem to increase the risk of neuroblastoma.9Rios P Bailey HD Orsi L et al.Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: a pooled analysis of the ESCALE and ESTELLE French studies (SFCE).IntJ Cancer. 2016; 139: 1936-1948Crossref PubMed Scopus (19) Google Scholar But for major cancers like those of the central nervous system, the risk factors remain elusive, including environmental risk factors such as the parental exposure to pesticides.10Febvey O Schuz J Bailey HD et al.Risk of central nervous system tumors in children related to parental occupational pesticide exposures in three european case-control studies.J Occ EnvironMede. 2016; 58: 1046-1052Crossref PubMed Scopus (8) Google Scholar So, taken altogether, the few known factors explain at best 10% of all childhood cancers. Technological advances in medicine also play a role in raising trends, for instance the imaging techniques that have revolutionised the capacity to detect tumours, especially those of the central nervous system. Hence, our ignorance on the causes of childhood cancers is still immense and we should not compensate this ignorance with explanations that are not based on evidence. I declare no competing interests. Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countriesGlobal inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival. Full-Text PDF Open AccessInternational incidence of childhood cancer, 2001–10: a population-based registry studyThis unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research. Full-Text PDF Open Access