LESSONS FROM OUR CHILDREN

While the incidence of cancer is increasing among both children and adults, mortality rates have decreased for children, while they have increased for adults. Of children diagnosed with cancer today, 80% are predicted to be long-term survivors. Although there are differences between children and adults with respect to the tumor types, biology, and outcome, there are common lessons which we can learn from our children regarding the genetics of cancer, its management and treatment, and the importance of longitudinal studies of the survivors. Specific pediatric cancers, such as retinoblastoma, have led to the recognition of tumor suppressor genes, now also observed among adult tumors including sarcomas, breast, lung, and bladder cancer. The presence of the tumor suppressor gene provides an understanding for the incidence of second malignant tumors among patients with heritable diseases. Furthermore, cancer prone families, such as those with the Li-Fraumeni syndrome, also carry the p 53 tumor suppressor gene; the presence of which greatly increases the risk of developing invasive cancer. Childhood cancer is rare; it represents only 1% of the total US cancer problem. However, 53% of all children with cancer, but only 2% of all adults, are studied via the NCI cooperative group mechanism. For some specific childhood tumors such as rhabdomyosarcoma and Wilms' tumor, as many as 70-85% of all cases are managed via NCI sponsored trials. Essentially all pediatric cancer is treated by interdigitating radiation with surgical resection and systemic chemotherapy. This approach has contributed to high cure rates. Finally, our understanding of the late effects of being a cancer survivor have come from longitudinal studies of children. The most severe long-term effects related to radiation in childhood pertain to growth and development, infertility, and second malignant tumor induction. Here the children treated for Hodgkin's disease have taught us the dose and volume effects on axial skeletal and soft tissue growth. Infertility issues are also treatment-related and may often be obviated by using gonadal shielding. The risk of secondary leukemia is related to dose and class of specific chemotherapeutic agents administered; it is 5.5% among children receiving 6 cycles of MOPP. There is a 22-fold risk at 30 years of age of solid tumor induction following radiotherapy for children with Hodgkin's disease. These serious concerns have been offset by current therapeutic approaches of using lower doses and smaller volumes of radiation with fewer cycles of less toxic chemotherapeutic agents. Childhood cancer ranks high among number of person-years of potential life saved annually. Currently, 1:1000 persons aged 15-45 is a cancer survivor, and in a decade more than 1% of the country's work force will be a cancer survivor. The genetics, management and treatment, and follow-up of childhood cancer serves as an ideal model for our approach to adult cancer.