Long-term Morbidity and Socioeconomic Outcome among Nordic Childhood Cancer Survivors

Sammanfattning: Survival after childhood cancer has improved dramatically during the past four decades, resulting in a five-year survival rate of 80% in children recently treated for cancer in the Nordic countries. However, these advances in treatment and survival has come at a price, and many survivors face significant treatment-induced sequelae, most of which only become clinically apparent many years after the child has been cured. Previous studies have highlighted the need for better characterization of these late complications and their risk factors, in order to improve the basis for individual patient counselling and optimal long-term follow-up care. The main objective of the studies presented in this thesis was to investigate some of the diseases that contribute to long-term morbidity in childhood cancer survivors, as well as the late socioeconomic effects after treatment for acute lymphoblastic leukaemia (ALL) in childhood. All the studies presented in this thesis are population-based, retrospective cohort studies. Studies I and II are register-based studies of late socioeconomic effects and hospital-related morbidity, respectively, among 213 five-year survivors of ALL in the southern region of Sweden, compared to a population comparison cohort. Studies III–V included 33,160 one-year survivors of childhood cancer diagnosed between the start of cancer registration in the 1940s and 1950s up to and including 2008, identified in the national cancer registries of Denmark, Finland, Iceland, Norway and Sweden, and 212,892 comparison subjects, selected from national population registers. The study subjects in Studies III–V were linked to the national hospital registers and standardized hospitalization rate ratios and absolute excess risks of specific diseases were calculated. ALL survivors were married, had children, attained a high level of education and were employed to a lesser extent than the comparison subjects. Young age at diagnosis and cranial radiotherapy were risk factors for these negative late socioeconomic effects. Increased morbidity among ALL survivors, measured in terms of health care utilization, was primarily confined to those treated with cranial irradiation. Nordic childhood cancer survivors exhibited an increased risk of diabetes mellitus, which persisted throughout life. In addition, survivors were found to have a substantially increased risk of other endocrine disorders. The diagnoses of pituitary hypofunction, hypothyroidism and dysfunction of the gonads were the most frequent endocrine disorders found among the survivors. Childhood cancer survivors also showed an increased risk of various autoimmune diseases; increased risk ratios were seen in survivors of leukaemia, Hodgkin’s lymphoma, renal tumours and central nervous system neoplasms. The findings of these studies underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.