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Pediatric Cancers in the New Millennium: Dramatic Progress, New Challenges

Pediatric Cancers in the New Millennium: Dramatic Progress, New Challenges

Over the past 50 years, great strides have been made in diagnosis, treatment, and survival of childhood cancer. In the 1960s the probability of survival for a child with cancer was less than 25%, whereas today it may exceed 80%. This dramatic change has occurred through significant and steady progress in our understanding of tumor biology, creation of specialized multidisciplinary care teams, incremental improvements in therapy, establishment of specialized centers with research infrastructure to conduct pivotal clinical studies, and the evolution of a cooperative group mechanism for clinical research. Most children with cancer in the United States, Europe, and Japan receive appropriate diagnosis and treatment, although access is limited in developing countries. The price of success, however, is the growing population of survivors who require medical and psychosocial follow-up and treatment for the late effects of therapy. Here we review the progress made in pediatric oncology over the past 3 decades and consider the new challenges that face us today.

Cancer is the second leading cause of death (after accidents) in children and adolescents in the United States despite significant progress in diagnosis, treatment, and survival.[1] Mortality rates have declined approximately 2% per year over the past 3 decades, and survival rates for many childhood cancers have greatly improved (Figure 1). The overall 5-year survival rate for childhood cancer now exceeds 79%.[2] Most notable is the progress in treating acute lymphoblastic leukemia (ALL), which represents about a third of all cases of pediatric cancer (Figure 2). Improved critical care, infectious disease management, and nutritional support and the widespread use of central venous catheters have increased survival overall for children with malignancies. Approximately 1 in every 250 adults is expected to be a childhood cancer survivor by 2010. The potential social, economic, and medical impact of this advance is second only to that of the treatment of adult breast cancer.[3]

Overview of Childhood Cancers

Childhood cancers comprise a spectrum of malignancies that differ in histologic type, site of origin, and incidence across age groups. Importantly, they also differ from adult cancers in significant ways. Whereas most adult cancers are epithelial and may be influenced by environmental factors (eg, smoking and diet), most pediatric cancers are dysontogenic in nature. Therefore, screening or prevention programs are less likely to be effective. Further, tolerance of therapy is quantitatively and qualitatively different in children and adults because of dissimilar host characteristics, such as physiology and organ maturation.

Because childhood cancer is rare, successful therapy depends on focused, collaborative clinical research supported by governmental agencies and public philanthropy.[4] This model is anchored in a strong clinical research infrastructure and the effective collaboration of a multidisciplinary team composed of pediatric oncologists, surgeons, radiation therapists, and other professionals. Paramount to these efforts is the contribution of basic and translational scientists who define important biologic and genetic components of childhood cancer that can guide risk-based therapy.

The international community has made significant contributions to this success. Collaborative pediatric oncology research models have also laid the foundation for research alliances for the treatment of asthma, cystic fibrosis, AIDS, and other chronic childhood diseases. Further, fundamental principles gained through protocol-based treatment of pediatric cancer have translated to improved management of adult cancers. These key principles are summarized in Table 1 and further elaborated below.

Many challenges remain. Survival remains poor for children with tumors such as disseminated neuroblastoma or diffuse pontine glioma, and for others we have reached a survival plateau. There is poor understanding of the biology of some tumor subtypes. The physical, psychosocial, and financial consequences of effective therapy have created a need for specialized care for survivors and new venues for research. There is room for improvement in the collection of late effects and outcome data. There is little financial incentive or support for the development of new drugs and biologic therapies. There are disparities in outcomes in adolescents and young adults, and many children worldwide lack access to effective therapy. This article will review specific examples of progress, the challenges that remain across the spectrum of childhood cancer, and future areas of work.

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