Long-Term Survivors of Childhood Cancer: The Late Effects of Therapy

The successful treatment of pediatric malignancy by multimodality therapy has improved the outcome for children with cancer. It has been estimated that 0.1% of individuals 20 years of age are survivors of childhood cancer. This represents a large cohort nationally who, with maturation, may be increasingly beset by the medical and social consequences of treatment. The study of long-term effects of cancer chemotherapy has grown enormously in the past decade. Any side effect that does not resolve after the completion of therapy is a long-term effect of therapy. Side effects recognized during the therapeutic period are usually addressed by the treating physicians. More problematic are those effects of therapy that are subclinical at completion of therapy but manifest years later. These are the true late effects of therapy and are the focus of this review. The cytotoxic effects on maturing tissues become apparent only with development. Thus physical, intellectual and pubertal development as well as reproductive potential may be impossible to assess for a decade or more, depending upon the age at the time of treatment. Nonetheless, the ability to predict the likelihood of a given adverse outcome is enormously helpful to the survivor and may allow for the mitigation of severe effects. Organ injury may also be subclinical initially. With aging and additional stress, compensatory mechanisms may fail. The development of effective screening methodologies may be essential for early interventions. Lifestyle changes may reduce exposure to further toxins and mutagenic agents such as alcohol and cigarette smoke that may lead to secondary malignancy, particularly if compounded in some instances by genetic predisposition. Programs for survivors of childhood cancer were developed within pediatric oncology. As the children become adults, the likelihood of continued care at the initial treating institution decreases. Oncologists and other health care professionals who become responsible for the health care of this maturing cohort will need to understand the risks engendered by childhood cancer therapy.