Summary Background Accurate estimates of childhood cancer incidence are important for policy makers to inform priority setting and planning decisions. However, many countries do not have cancer registries that quantify the incidence of childhood cancer. Moreover, even when registries do exist, they might substantially underestimate the true incidence, since children with cancer might not be diagnosed. We therefore aimed to provide estimates of total childhood cancer incidence accounting for underdiagnosis. Methods We developed a microsimulation model to simulate childhood cancer incidence for 200 countries and territories worldwide, taking into account trends in population growth and urbanicity, geographical variation in cancer incidence, and health system barriers to access and referral that contribute to underdiagnosis. To ensure model results were consistent with epidemiological data, we calibrated the model to publicly available cancer registry data using a Bayesian approach in which the observed data are fixed and the model parameters (cancer incidence and probabilities of health system access and referral) are random variables. We estimated the total incidence of childhood cancer (diagnosed and undiagnosed) in each country in 2015 and projected the number of cases from 2015 to 2030. Findings Our model estimated that there were 397 000 (95% uncertainty interval [UI] 377 000–426 000) incident cases of childhood cancer worldwide in 2015, of which only 224 000 (95% UI 216 000–237 000) were diagnosed. This finding suggests that 43% (172 000 of 397 000) of childhood cancer cases were undiagnosed globally, with substantial variation by region, ranging from 3% in western Europe (120 of 4300) and North America (300 of 10 900) to 57% (43 000 of 76 000) in western Africa. In south Asia (including southeastern Asia and south-central Asia), the overall proportion of undiagnosed cases was estimated to be 49% (67 000 of 137 000). Taking into account population projections, we estimated that there will be 6·7 million (95% UI 6·3–7·2) cases of childhood cancer worldwide from 2015 to 2030. At current levels of health system performance, we estimated that 2·9 million (95% UI 2·7–3·3) cases of childhood cancer will be missed between 2015 and 2030. Interpretation Childhood cancer is substantially underdiagnosed, especially in south Asia and sub-Saharan Africa (including western, eastern, and southern Africa). In addition to improving treatment for childhood cancer, health systems must be strengthened to accurately diagnose and effectively care for all children with cancer. As countries expand universal health coverage, these estimates of total incidence will hopefully help guide efforts to appropriately increase health system capacity to ensure access to effective childhood cancer care. Funding Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard T H Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, and Union for International Cancer Control.

Estimating the total incidence of global childhood cancer: a simulation-based analysis

The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% in WGS only and 25.0% in RNAseq only). Of these patients, 93.7% had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 central nervous system tumors, methylome analysis confirmed diagnosis in 71.1% of patients and contributed to a change of diagnosis in two patients (2.6%). To date, 43 patients have received a recommended therapy, 38 of whom could be evaluated, with 31% showing objective evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, leading to clinical benefit in some patients.

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer.

http://digital.csic.es/bitstream/10261/230651/1/Intact_Vicente_PV_Art2020.pdf

An intact gut microbiome protects genetically predisposed mice against leukemia

Background: China's lung cancer (LC) burden plays a pivotal role in the global cancer epidemic. Comparing LC burden and population attributable fractions (PAFs) of risk factors between China and other countries/regions is essential to inform effective intervention. The Global Burden of Disease (GBD) study provides a unique opportunity for such comparisons. Methods: We extracted the number of LC deaths, age-standardized death rates (ASDRs), age-standardized disability-adjusted life-year (DALY) rates, and PAFs of risk factors for LC deaths between 1990 and 2017 from GBD 2017. The annual percentage change (APC) was used to quantify the trends of LC ASDRs and age-standardized DALY rates. The relationship between the APC of LC ASDR and Socio-demographic Index was assessed among China and other countries. Results: Globally, the ASDR for LC decreased in men (APC, −0.66% [95% CI, −0.69 to −0.62]) but increased in women (APC, 0.31% [95% CI, 0.26 to 0.36]) from 1990 to 2017. The ASDRs in China increased both for men (APC, 1.12% [95% CI, 1.03 to 1.20]) and women (APC, 0.80% [95% CI, 0.70 to 0.89]). The increased LC death numbers among men (312,798) and women (139,115) in China accounted for 59.39% and 43.01% of global increases. LC years of life lost accounted for the majority of LC DALYs globally and in China. The risk factors with the highest PAFs of LC death in China were smoking and ambient particulate matter. The ASDRs for LC associated with ambient particulate matter in China ranked second globally. Conclusions: The trends of LC ASDRs and age-standardized DALY rates and the PAFs of risk factors vary markedly by region, indicating a need for tailored measures to reduce LC burden and improve health equality. China's LC ASDRs are among the highest in the world, and the primary intervention priorities in China should be control of ambient particulate matter and tobacco usage.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.33078

Global, regional, and national burden of lung cancer and its attributable risk factors, 1990 to 2017.

Despite substantial improvements in survival from childhood cancer during the last decades, there are indications that survival rates for several cancer types are no longer improving. Moreover, evidence accumulates suggesting that socioeconomic and sociodemographic factors may have an impact on survival also in high-income countries. The aim of this review is to summarize the findings from studies on social factors and survival in childhood cancer. Several types of cancer and social factors are included in order to shed light on potential mechanisms and identify particularly affected groups. A literature search conducted in PubMed identified 333 articles published from December 2012 until June 2018, of which 24 fulfilled the inclusion criteria. The findings are diverse; some studies found no associations but several indicated a social gradient with higher mortality among children from families of lower socioeconomic status (SES). There were no clear suggestions of particularly vulnerable subgroups, but hematological malignancies were most commonly investigated. A wide range of social factors have been examined and seem to be of different importance and varying between studies. However, potential underlying mechanisms linking a specific social factor to childhood cancer survival was seldom described. This review provides some support for a relationship between lower parental SES and worse survival after childhood cancer, which is a finding that needs further attention. Studies investigating predefined hypotheses involving specific social factors within homogenous cancer types are lacking and would increase the understanding of mechanisms involved, and allow targeted interventions to reduce health inequalities.

/pdf/survival-after-childhood-cancer-social-inequalities-in-high-1y25mjs6r5.pdf

Survival After Childhood Cancer-Social Inequalities in High-Income Countries.

Summary 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.

/pdf/changing-geographical-patterns-and-trends-in-cancer-4l6ecx120x.pdf

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

Staffan Khan

Papers

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