This article is a review of Pediatric Cancers in the New Millennium: Dramatic Progress, New Challenges
In his essay on "Reason in Common Sense," the philosopher Santayana said that "Those who cannot remember the past are condemned to repeat it." When one reads the comprehensive review on the history and current status of curing cancer in children by McGregor et al, one might conclude that repeating the success of the past half-century would not be so bad.
A Job Well Done
As the review points out, overall survival for children with cancer has gone from less than 25% to approximately 80%. For some forms of cancer, the cure rate is in the mid to high 90% range. McGregor et al cover most of the waterfront of pediatric oncology successes along with some thoughts on future directions. A notable omission is the absence of a discussion of acute myelogenous leukemia (AML), in which pediatric oncologists have contributed a significant amount of innovative thinking and new approaches to small-molecular and immunotherapeutically targeted therapies.
The authors appropriately point out the important model of collaborative translational and clinical trials that have characterized pediatric oncology from its inception as well as the extension of such models into other areas of medicine, including medical oncology. For example, pediatric cooperative clinical trials groups continue to set the standard for enrolling a large percentage of patients on randomized clinical trials. Adolescents and young adults, however, represent an important exception, as they enter clinical trials at a significant lower percentage than young children.[2,3]
Another area in which pediatric oncology has been out in front of the curve includes efforts to improve the outcome of children with cancer in developing countries. Several programs have initiated twinning centers in developed countries with those in developing countries. These programs have already begun to show improved survival of children with cancer, particularly those with diseases such as acute lymphoblastic leukemia (ALL).[4-9] Important components of such programs involve introducing standardized treatment protocols along with the means to decrease the critically high percentage of children who abandon treatment for a variety of reasons such as economic and travel obstacles.
These programs have also recognized the importance of governmental and public education. An astonishing example is retinoblastoma, a pediatric tumor of the retina, whose analysis coincidently led to the "two-hit hypothesis" of cancer development as well as the identification of Rb, the first true tumor-suppressor gene.[11,12] In developed countries, children with retinoblastoma have a greater than 90% cure rate with excellent preservation of vision, whereas in developing countries, the results are considerably inferior. Important factors in this discrepancy include the lack of recognition of the early signs and symptoms of retinoblastoma as well as the lack of multidisciplinary centers in which children can be appropriately treated. The formation of partnerships between centers in developed and developing countries should be an important advance in the improvement of outcomes for all children with cancer.
And yet, despite the extraordinary advances that have been made over the past 50 years in pediatric oncology, cancer remains the leading cause of death by disease in children. To that end, one might be justified in reconsidering just how successful we have actually been in addition to what major challenges need to be addressed in order to eradicate childhood cancer.
A Job Not Yet Done
Mark Twain stated that "Twenty years from now you will be more disappointed by the things that you didn't do than by the ones you did do." While it is always more uncomfortable to focus on what we have not done and the obstacles that prevent progress, it is critical that we focus on these very issues. I do not pretend to be like Wayne Gretzky, who once explained that "The difference between me and other players is that they know where the puck is, while I know where the puck is going to be." Nevertheless, I will try to gauge where the puck is going to be in pediatric oncology.