Central nervous system (CNS) neoplasms are, as a group, the most common solid tumors of childhood, second only to the leukemias as a cause of cancer in children. Despite improvements in diagnosis and management, more children will die of brain tumors than of any other type of pediatric cancer. Although the prognosis for children with certain CNS tumors, such as medulloblastoma, has been improved through a combination of surgical advances and refinements in radiotherapy and chemotherapy, other groups, such as those with diffuse intrinsic pontine gliomas (DIPGs), continue to have a poor outcome. Children who experience long-term survival after therapy are at risk for sequelae from the tumor or its treatment that may adversely impact their quality of life. Current cooperative group studies are attempting to address these issues, focusing on improving survival results in children with tumor types that historically have been resistant to therapy, as well as on improving quality of life for children with treatment-responsive tumors. Increasingly, these studies also incorporate new insights regarding molecular subsets of tumors to facilitate risk-adapted treatment stratification.
PATHOGENESIS AND EPIDEMIOLOGY
Brain tumors occur at an incidence of 3.1 per 100,000 children per year. There is no gender bias, with a male-to-female ratio of 1.2:1.0 in white children and 0.9:1.0 in African-American children. The incidence of brain tumors, as reflected in data from the Surveillance, Epidemiology, and End Results (SEER) Registry of the National Cancer Institute and the Central Brain Tumor Registry of the United States (CBTRUS), has increased over the past 30 years. While some absolute increase in childhood brain tumors may exist, an analysis of the data, which identified a 35% increase in pediatric brain tumors between 1973 and 1994, demonstrated a particular jump in the incidence of brain tumor diagnoses in the mid-1980s coincident with the introduction and subsequent widespread use of magnetic resonance imaging (MRI), suggesting improved or earlier detection of previously undiagnosed lesions.
Genetic Causes of Brain Tumors
A number of familial syndromes and diseases have been identified that predispose the patient to a variety of nervous system and other tumors. The most common of these disorders is neurofibromatosis type 1 (von Recklinghausen disease). Additional examples include neurofibromatosis type 2, tuberous sclerosis complex (TSC), von Hippel–Lindau (VHL) syndrome, Cowden disease, Li-Fraumeni syndrome, Turcot syndrome, and Gorlin syndrome. Summary information on each of these syndromes is detailed in Table 456-1.
TABLE 456-1GENETIC SYNDROMES ASSOCIATED WITH PEDIATRIC BRAIN TUMORS ||Download (.pdf) TABLE 456-1GENETIC SYNDROMES ASSOCIATED WITH PEDIATRIC BRAIN TUMORS
|Syndrome ||Incidence/Diagnostic Criteria/Clinical Features || |
|Genetics ||Presumptive Mechanism of Disease |
|NF1 || |
Two of the following:
- 6+ café-au-lait macules
- 2+ neurofibromas or 1 plexiform neurofibroma
- Axillary or inguinal freckling
- Optic pathway glioma
- 2+ Lisch nodules
- Sphenoid dysplasia or other osseous abnormalities...