Incidence Patterns and Trends of non-Central Nervous System Solid Tumours in Children and Adolescents. A Collaborative Study of the Spanish Population Based Cancer Registries

Objective: To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. Methods: Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. Results: The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95% CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95% CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. Conclusions: Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence in adolescents increased significantly over the whole period 1983-2007. Several specific tumour groups showed significant rises or decrements in childhood or adolescence, although the small number of cases precludes showing significant trends or inflexion points

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.

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. 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. 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]). 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. Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project.

The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia

Survival from cancer in teenagers and young adults in England, 1979–2003

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13–24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30 000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979–84 to 74% during 1996–2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13–16, 17–20, 21–24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges

Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project.

The interpretation of reports of clusters of childhood leukaemia is difficult, first because little is known about the causes of the disease, and second because there is insufficient information on whether cases show a generalized tendency to cluster geographically. The EUROCLUS project is a European collaborative study whose primary objective is to determine whether the residence locations of cases at diagnosis show a general tendency towards spatial clustering. The second objective is to interpret any patterns observed and, in particular, to see if clustering can be explained in terms of either infectious agents or environmental hazards as aetiological agents. The spatial distribution of 13351 cases of childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been analysed using the Potthoff-Whittinghill method. The overall results show statistically significant evidence of clustering of total childhood leukaemia within small census areas (P=0.03) but the magnitude of the clustering is small (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2-3.1). The clustering is most marked in areas that have intermediate population density (150-499 persons km[-2]). It cannot be attributed to any specific age group at diagnosis or cell type and involves spatial aggregation of cases of different ages and cell types. The results indicate that intense clusters are a rare phenomenon that merit careful investigation, although aetiological insights are more likely to come from investigation of large numbers of cases. We present a method for detecting clustering that is simple and readily available to cancer registries and similar groups

What can we learn from geographical comparisons of childhood cancer survival?

With improvements in treatment for childhood cancer, comparisons of survival rates between countries have become important to inform future health policies and treatment strategies. Population-based cancer registry data are viewed as the gold standard for such comparisons, but even these have potential confounding factors. Here, we review the interpretation of recent geographical comparisons of childhood cancer survival from the viewpoint of the British Isles, a region with a 45-year record of national population-based cancer registration and a national childhood cancer clinical trials organisation in place for nearly 30 years. Using national data on referral patterns to tertiary paediatric oncology centres, we explore some of the reasons for lower survival rates in the past for some tumour groups and anticipate continued improvement in the next decade. Participation in international clinical trials coincided with rapid gains in survival for hepatoblastoma. This exemplifies the potential benefits of international collaborative clinical research, particularly for rare subgroups

The histology of brain tumors for 67 331 children and 671 085 adults diagnosed in 60 countries during 2000-2014: a global, population-based study (CONCORD-3).

BACKGROUND: Global variations in survival for brain tumors are very wide when all histological types are considered together. Appraisal of international differences should be informed by the distribution of histology, but little is known beyond Europe and North America. METHODS: The source for the analysis was the CONCORD database, a program of global surveillance of cancer survival trends, which includes the tumor records of individual patients from more than 300 population-based cancer registries. We considered all patients aged 0-99 years who were diagnosed with a primary brain tumor during 2000-2014, whether malignant or nonmalignant. We presented the histology distribution of these tumors, for patients diagnosed during 2000-2004, 2005-2009, and 2010-2014. RESULTS: Records were submitted from 60 countries on 5 continents, 67 331 for children and 671 085 for adults. After exclusion of irrelevant morphology codes, the final study population comprised 60 783 children and 602 112 adults. Only 59 of 60 countries covered in CONCORD-3 were included because none of the Mexican records were eligible. We defined 12 histology groups for children, and 11 for adults. In children (0-14 years), the proportion of low-grade astrocytomas ranged between 6% and 50%. Medulloblastoma was the most common subtype in countries where low-grade astrocytoma was less commonly reported. In adults (15-99 years), the proportion of glioblastomas varied between 9% and 69%. International comparisons were made difficult by wide differences in the proportion of tumors with unspecified histology, which accounted for up to 52% of diagnoses in children and up to 65% in adults. CONCLUSIONS: To our knowledge, this is the first account of the global histology distribution of brain tumors, in children and adults. Our findings provide insights into the practices and the quality of cancer registration worldwide

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

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global 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 survival