SummaryBackgroundCancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control.MethodsThis population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001–10. Incidence rates per million person-years for the 0–14 years and 0–19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0–4 years, 5–9 years, 10–14 years, and 15–19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0–14 years were compared with comparable data obtained in the 1980s.FindingsOf 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001–10. 385 509 incident cases in children aged 0–19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0–14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15–19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0–14 years has increased from 124·0 (95% CI 123·3–124·7) to 140·6 (140·1–141·1) per million person-years.InterpretationThis 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.FundingInternational Agency for Research on Cancer and the Union for International Cancer Control.

The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.

Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% -93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% -99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% -81%) and specificity (61% -88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% -43%) and positive predictive value (24%, 95% CI: 12 -39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% -98%) and specificity (58%, 95% CI: 42% -73%) for predicting clinical signs of sepsis. Key words: C-reactive protein, procalcitonin, interleukin-6, presepsin, fever, sepsisBacterial infection is the most common treatment-related complication in patients with haematological malignancies [1]. Documented mortality associated with paediatric febrile neutropenia is 2% [2]. The potential for early diagnosis of bacteraemia through serum biomarkers has been the subject to extensive research [3]. In 2012 Phillips et al published large meta-analysis of 25 studies exploring 14 different biomarkers in 3,585 episodes of febrile neutropenia. CRP, PCT and IL-6 were subject to quantitative meta-analysis. The bivariate estimates of diagnostic precision of these biomarkers and outcomes were done. Data were available for meta-analysis for CRP for microbiologically or clinically documented infection (results: cut off > 50mg/dl, sensitivity 65%, specificity 73%), for PCT assessing microbiologically or clinically documented infection (results: cut off > 0.2 mg/ml, sensitivity 96%, specificity 85%), for IL-6 reporting microbiologically or clinically documented infection (results: cut off > 235 pg/ml, sensitivity 68%, specificity 94%), and gram-negative bacteraemia (results: cut off > 1000 pg/ml, sensitivity 78%, specificity 96%). Huge inconsistencies and heterogeneity in the studies included in this review were the most important limiting factors [...