The ALiCCS project
Cancer and its treatment during childhood and adolescence can result in a variety of long-term sequelae, such as impairment of growth and development, reproductive difficulties, chronic late morbidity, second cancers, increased mortality and psychosocial and familial problems.
Studies of late sequelae of childhood cancer require a large population of survivors and long periods of follow-up if they are to yield reliable estimates of the relative and absolute risks. Combined, the Nordic countries are an ideal study area for this type of clinical/epidemiological research, as a broad range of health care data are available from high-quality, nationwide population registers.
By the end of 2009 the Danish Research Council decided to support the establishment of a large, retrospective, inter-Nordic childhood cancer cohort (n = 55 000) in order to compare their morbidity-specific incidence and cause-specific mortality with those of a sample of the general populations of the Nordic countries (n = 275 000). The approved study plan included three case-control studies which are nested in the cohort with the purpose of investigating associations, including dose-response, between specific treatment regimens and selected outcomes.
The types of late effects initially selected for case-cohort studies are
cardiovascular and pulmonary diseases
renal and gastrointestinal disorders
The ultimate goals are to allow better planning of treatment protocols for Nordic childhood cancer patients, with fewer late effects, to contribute to preventive intervention strategies, to improve the basis for patient counseling and follow-up, and to educate a group of Nordic childhood oncologists/epidemiologists who become highly specialized in the prevention of late effects after treatment for childhood cancer.
Objectives of the research project
The first objective was to establish a complete, population-based series of children and adolescents in the Nordic countries in whom cancer was diagnosed during the period 1943 to 2008. The second objective was to set up a number of clinical case-cohort studies of childhood cancer patients and their offspring, in which cases were defined on the basis of selected serious outcomes.
The first objective was to establish a complete, population-based series of children and adolescents in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) in whom cancer was diagnosed during the period 1943 to 2008. The childhood cancer survivors were followed-up individually to the present in various health-related national registers in order to investigate a range of treatment-related late complications in both survivors themselves and in their offspring.
Large Cohort
As a result of this international collaboration, an extraordinarily large cohort of childhood cancer cases (n = 55 000) has been established, with a combined population-comparison cohort (n = 275 000) taken at random from the general populations of the Nordic countries. Accurate follow-up of patients and population controls were achieved through the civil registration systems of the Nordic countries, and use of large-scale record linkage techniques with national outcome registers provided a broad range of information on subsequent disease, independently of the persons status as a patient or a population control. The combined dataset constituted a new, comprehensive, powerful surveillance instrument for estimating relative and absolute risks for medically verified, chronic health conditions in childhood cancer survivors. This is especially important for survivors age ?40 years, for whom there is little information on non-malignant outcomes.
Late effects
The second objective was to set up a number of clinical case-cohort studies of childhood cancer patients and their offspring, in which cases were defined on the basis of selected serious outcomes. These studies were designed to investigate damaging late effects of specific treatment regimens in childhood. The purpose is to contribute to the identification and characterization of high-risk populations, as this information is critical for making evidence-based recommendations for long-term follow-up of survivors of childhood cancer. Thus, the case-cohort design was applied to the childhood cancer survivor cohort as a hypothesis-testing instrument. Some outcomes have been be selected a priori, but the screening phase in the first part of the study identified any important new questions to be investigated. Detailed information on childhood cancer treatment was obtained from the medical records of the patients and from other sources.