Principles in the Development of Contemporary Treatment of Childhood Malignancies: The First 75 Years.

Over the last 75 years, pediatric cancer has gone from nearly universally fatal, to having a >80% chance of long-term survival. Below we share highlights in this 75-year history, beginning with the "birth" of chemotherapy in treating childhood leukemia, through the development of multiagent chemotherapy, risk-stratified therapy, the use of molecular strategies in diagnosis and treatment, and adapting treatment to the needs of particularly vulnerable patient groups such as adolescents and young adults (AYAs). While pediatric leukemia treatment demonstrates the ever-improving cures achieved through iterative incorporation of novel discoveries, this experience is contrasted with that of osteosarcoma, where scientific advances made over recent decades have yet to be translated into meaningful improvements in long-term survival. We conclude with a brief overview of current areas of focus, including precision medicine, immunotherapy, and other treatment advancements, yet describe the need to couple these scientific breakthroughs with consideration of equitable access and evaluation of the long-term impacts of these "newer" therapies in survivorship. Substantial further work is needed to achieve our goal of curing all children with cancer as harmlessly as possible.