Brain Tumors Across the Age Spectrum: Biology, Therapy, and Late Effects

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The clinical difference between brain tumors in adults and children is striking. Compared with adults, pediatric tumor types (mostly glial and neuronal) are more sensitive to adjuvant irradiation and chemotherapy. Pediatric tumors more often require craniospinal irradiation based on their propensity to disseminate within the neuraxis. The spectrum of side effects is broader in the child based on age and extent of treatment: radiation therapy brings increased risk of severe long-term sequelae affecting neurologic, endocrine, and cognitive function. In this review of glioma, ependymoma, and medulloblastoma, we highlight the differences between adults and children, including the higher incidence of spinal cord ependymoma and supratentorial high-grade glioma in the adult and a higher incidence of medulloblastoma in the child. With the exception of completely resected low-grade glioma, radiation therapy remains a standard of care for most patients. In some settings, the radiation oncologist should suggest further surgery or additional adjuvant therapy in an effort to optimize local tumor control. An effort is underway to better characterize adult and pediatric brain tumors biologically with an emphasis on improving our understanding of tumor genesis, malignant transformation, and some of the similarities and differences between tumor types and their response to conventional therapy.

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Epidemiology

The distribution of tumors and tumor locations by age is a fascinating aspect of brain tumor epidemiology.1 For certain tumor types, such as medulloblastoma, ependymoma, and pilocytic astrocytoma, the incidence decreases with age (Fig. 1). Although the differences by age in the proportion of patients with ependymoma is much less than observed for medulloblastoma and low-grade glioma, it is important to note that posterior fossa ependymoma, supratentorial ependymoma, and spinal cord ependymoma

Pathobiology

Medulloblastoma and low-grade gliomas are among the tumors featured in the recent revision of the World Health Organization (WHO) classification of brain tumors.2 An expanded view of medulloblastoma now includes large-cell medulloblastoma, anaplastic medulloblastoma, medulloblastoma with extensive nodularity, and desmoplastic/nodular medulloblastoma in order of decreasing risk of treatment failure using standard therapy. There is increased agreement that these subtypes will be used in the

Disease Presentation

Radiation oncologists are important gatekeepers in the treatment of patients with brain tumors. Critical evaluation of diagnostic information and the ability to choose from a variety of radiation delivery modalities place the radiation oncologist in a position to affect outcome. In the treatment of brain tumors, assessing the extent of resection before radiation therapy serves as a critical example of the radiation oncologist in this pivotal position. Because radiation therapy is generally

Medulloblastoma

Medulloblastoma is first among central nervous system embryonal tumors and malignant brain tumors in children when it comes to understanding the efficacy of available therapy, tumor biology, and the acute and late effects of radiation therapy. After decades of successful treatment using craniospinal irradiation, significant late effects observed in long-term survivors led to trials hoping to reduce or eliminate radiation therapy. Chemotherapy has been successfully used to reduce radiation dose

Late Effects

Understanding where the risks of normal tissue irradiation are high or low can be used effectively in the planning process to minimize the risk or impact of side effects. Patients with brain tumors are vulnerable to wide-ranging side effects from radiation therapy that are magnified in young children and enhanced by tumor and treatments preceding radiation therapy. Side effects range from treatable deficits that rarely impact long-term function to severe and debilitating side effects that

Conclusions

Brain tumor is a well recognized diagnosis in pediatric oncology and these patients represent everything that is positive and negative about current treatment: increasing cure rates, the promise of new treatments, deleterious effects of therapy, and a lack of understanding about the impact of current treatment on long-term survivorship. The impact of long-term sequelae on functional outcome is also important in adults, particularly those with low-grade lesions, who may be expected to have

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