The late effects of therapy in an Australian cohort of childhood cancer survivors

In Australia, up to 80% of individuals diagnosed with childhood cancer are now expected to survive for more than five years after their initial diagnosis. However, survivors of childhood cancer are at risk of developing late sequelae as a consequence of therapies received during childhood. The aim of this study was to determine the incidence of selected late sequelae in a cohort of Australian childhood cancer survivors and identify treatment and genetic factors that may modify the risk of late sequelae in survivors. Our study included 1150 individuals treated for childhood cancer at the Sydney Children’s Hospital between 1962 and 1999, who had remained in remission >3 years and were confirmed to be alive. Rates of mortality and second cancers among survivors were compared against population rates to determine standardised mortality and incidence ratios. Survivors completed a questionnaire on the incidence of adverse health conditions and provided a buccal specimen. Real time PCR was used to detect polymorphisms in genes involved in drug detoxification and transport. Rates of mortality and secondary cancers were found to be 7.5-fold (95%CI 5.4-10.1) and 4.9-fold (95%CI 2.9-8.0) higher among survivors of childhood cancer relative to the general population, respectively, with the highest risks observed for those survivors previously treated for Hodgkin’s disease. Over 60% of survivors reported at least one cardiopulmonary, endocrine or sensory-motor condition following diagnosis of childhood cancer; the most frequently observed conditions included growth hormone deficiency, hypothyroidism, and hypertension. Late sequelae were most frequently reported by females and survivors of brain tumours. Genetic investigations showed that an increased risk of growth hormone deficiency was associated with homozygosity for the GSTM1 null polymorphism, while no gene associations were observed to influence the risk of second cancers among survivors. Our study demonstrates that survivors of childhood cancer are at risk of developing a variety of health conditions as a result of anti-cancer therapies received during childhood. Determining risk factors for late sequelae based on therapy type, lifestyle and genetic predisposition will enable the optimisation of treatment protocols and promote the future well-being of childhood cancer survivors