Brain and Spinal Cord Cancer

Tumors Common in Children

Brain tumors in children account for one in five cases of childhood cancer. The incidence of primary CNS tumors, particularly the astrocytic lesions, increased in children during the first half of the 1990s; since then, the incidence has leveled off, perhaps because of the added diagnostic sensitivity of MRI.68 Pediatric brain tumors arise most often in the posterior fossa. Posterior fossa tumors often produce symptoms and signs of increased intracranial pressure because the growing tumor obstructs the flow of CSF through the fourth ventricle. Ataxia often accompanies pressure-related headaches and morning vomiting. Brainstem gliomas cause cranial nerve palsies, ataxia, and long-tract signs, including lateralizing weakness and sensory deficits.

Supratentorial tumors occur in the cerebral hemispheres and the central or deep-seated areas of the thalamus, hypothalamus, suprasellar area, and pineal–third ventricular region. Symptoms are local and include lateralizing neurologic deficits and seizures, which are associated with hemispheric and thalamic tumors; visual and endocrine changes; and specific oculomotor findings, which are associated with tumors of the pineal region.

Primary tumors of the spinal cord account for only 5% of tumors in children. Metastasis to the CNS is uncommon in childhood cancer. Contiguous extradural compression within the spinal canal or at the base of the skull (e.g., in neuroblastoma, rhabdomyosarcoma, primary bone tumors) is more common than hematogenous metastasis to the brain.

Common primary intracranial tumors diagnosed in children are listed in Table 33-1.The histologic classification of pediatric brain tumors has been relatively standardized by the World Health Organization (WHO).The most common tumors are the astrocytic lesions (i.e., astrocytomas, malignant gliomas, and brainstem gliomas). Medulloblastoma, which accounts for 20% of all childhood CNS tumors, is part of the broader category of supratentorial primitive neuroectodermal tumors (PNETs) and other embryonal CNS tumors (i.e., cerebral neuroblastoma, ependymoblastoma, and pineoblastomas).

TABLE 33-1 Relative Incidence of Brain Tumors in ChildrenModified from Duffner PK, Cohen ME, Myers MH, et al. Survival of children with brain tumors: SEER program, 1973-1980. Neurology 1986;36:597-601; Childhood Brain Tumor Consortium. A study of childhood brain tumors based on surgical biopsies from 10 North American institutions: sample description. J Neurooncol 1988;6:9-23.

Biologic findings increasingly define the nature of CNS tumors in children, providing some associations with tumor aggressiveness and outcome. Medulloblastoma, for example, is often associated with gene deletions in chromosomal region p17; expression of the EGFR gene (formerly designated ERBB1), which encodes the epidermal growth factor receptor, and NTRK3 (formerly called TRKC), which encodes the neurotrophic tyrosine kinase receptor type 3, are negatively and positively correlated with outcome, respectively. Several other molecular markers, such as cyclin-dependent kinase 6, MYC, apurinic or apyrimidinic endonuclease activity, and members of the WNT pathway, also have prognostic significance. Several investigators have proposed combining information on gene expression patterns and clinical stage for stratifying risk groups in medulloblastoma.

Tumors Common in Adults

Malignant Gliomas: Anaplastic Astrocytoma and Glioblastoma Multiforme

The dominant primary intracranial tumors that occur in adults in terms of frequency and mortality are the malignant gliomas. These tumors occur in the cerebral hemispheres as sizable, rapidly growing lesions with a characteristic ringlike, enhancing appearance on CT or MRI, with central necrosis, infiltrating margins, and surrounding low-density changes (Fig. 33-14). Malignant gliomas occur in all age groups but predominate in the fifth and sixth decades, and they account for 35% to 45% of all adult brain tumors.

Radiation Therapy Technique

Radiation therapy remains the most effective single agent in prolonging survival in patients with malignant gliomas. It should consist of standard EBRT with wide local coverage of the neoplasm. Anatomic studies of tumor extent, imaging analyses of patterns of recurrence, and clinical trials have shown that the appropriate initial target volume should extend 2 to 3 cm beyond the low-density periphery shown on CT scans or 2 cm beyond the abnormal signal shown on T2-weighted MRI studies. Margins of less than 2 cm are theoretically inadequate because of the histologic nature of the tumor301 and the way in which the initial sites of disease progress.

The use of limited high-dose treatment volumes delivered by three-dimensional conformal or proton radiation may be associated with a relative increase in the peripheral failure rate. Central or intralesional disease progression is less common in patients with interstitial implants. Studies of patterns of failure in series of patients treated with brachytherapy have shown that disease recurs primarily in the tumor margin, often within 2 cm of the high-dose implant; the incidence of distant intracranial recurrence is also relatively high.

Dose-response data were established early in clinical trials involving patients with malignant gliomas. Walker and colleagues showed that median survival time improved from 28 weeks for patients given 50 Gy in 25 to 28 fractions to 42 weeks for patients given 60 Gy in the first Brain Tumor Study Group studies (Fig. 33-15). Three-dimensional conformal and proton-based regimens have made it possible to escalate doses to 70 to 90 Gy; however, although central tumor control may be improved, no increase in survival has been found. As summarized earlier, none of the altered fractionation regimens has been shown to improve outcome over that achieved with conventionally fractionated radiation to 60 to 65 Gy (in 1.8- to 2-Gy fractions given once daily). No data exist to suggest that these recommendations for radiation therapy for adults be adjusted for children; however, the requirement for high-dose radiation to reasonably large volumes limits the use of this modality in young children with malignant gliomas.