My career in pediatric oncology began 35 years ago in the exhilarating times when we were just beginning to learn how to use combinations of anti-cancer drugs to prevent recurrence of childhood cancer and death from cancer. The enduring theme of my work has been to improve cure rate through better chemotherapy while reducing side effects. My personal goal and that of The Children's Hospital of Philadelphia is for cancer patients to emerge from cancer treatment as least as good as they were before their therapy. Central to the goal of reducing side effects has been reducing the amount of radiation therapy needed to cure a tumor by replacing radiation with chemotherapy.
Over this time I have had the opportunity to direct many clinical trials at Children's Hospital or in the major national pediatric oncology research group, the Children's Oncology Group (COG) -- and at the same time to collaborate with scientists to discover better treatments with less serious side effects. My first research trials were in Hodgkin's disease. More chemotherapy and less radiation showed improved cure rates and eliminated the problem of growth failure in irradiated areas and long surgical procedures needed to locate all possible areas of involvement in the abdomen. This approach is now used in most children and many adults with Hodgkin's disease.
By the early 1980s, my research extended to trials in leukemia and then to trials in brain tumors -- and continues in these areas today. Radiation of the brain has been responsible for improving cure rates in children with acute lymphoblastic leukemia (ALL), the most common childhood cancer, and in brain tumors, the most common childhood solid tumor. However, the higher the dose of radiation and the younger the child, the more severe the side effects. The most serious side effect is cognitive impairment, specifically, problems in paying attention and then remembering, thinking, planning and doing all these things relatively quickly.
Reducing and eventually eliminating radiation for younger children with leukemia has to a large extent reduced problems with learning. However, some children with leukemia still need brain irradiation -- and some of the chemotherapy used in leukemia also impairs cognition. Additionally, children with brain tumors often have learning problems from the tumors themselves.
Many cognitive problems don't become evident immediately, particularly in leukemia survivors: what may become a progressive problem first manifests itself two or three or more years after treatment. There have been some trials to improve established cognitive deficits using either stimulant medications or cognitive psychotherapy and working with the special educational system. The results have been modest and limited to small numbers of children. Thus cognitive impairment is the most important unsolved problem in the area of cancer treatment complications.
I am one of a growing group of investigators at Children's Hospital and in COG committed to reshaping the field of cognitive impairment. There is emerging evidence that cancer survivors with established cognitive problems also can benefit from systematic cognitive re-education. This re-education can be accomplished with computer-based cognitive remediation programs that involve parent and child participation at home or in the outpatient clinic, with oversight by a trained coach. We are currently developing supervised computer-based trials for children known to have problems. This can be done with relatively low cost and can be made available to almost all children. We are also planning trials to use computer-based programs to diagnose cognitive problems earlier -- allowing us an opportunity to train young minds before the problem occurs. Our hope is to treat the problem before it occurs.
Essentially, we are using the same paradigm as we used when we began to use chemotherapy before a cancer recurs.
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