PEDS CNS: High Grade Gliomas
Background
High grade gliomas are WHO Grade III/IV astrocytomas. Supratentorial malignant gliomas are approximately 6% of all childhood brain tumors. Children have a higher percentage of anaplastic astrocytomas and may have a longer survival. The tumors are biologically separate from adult malignant gliomas. Adult malignant gliomas arise de novo and are associated with PTEN and EGFR genes. Less commonly in adults, HGG evolve from conversion of LGG, primarily infiltrating astrocytoma, WHO Grade II. These tumors typically have TP53 mutations. Although p53 overexpression and TP53 mutations have been noted in childhood HGG, EGFR is less commonly seen.
Supratentorial tumors arise primarily in the cerebral hemispheres, 20% to 30% present centrally in the thalamus or basal ganglia. Imaging characteristics are similar to those in adults with poorly defined margins, ring enhancement on CT and MRI, associated with surrounding edema (white matter changes). The enhancement correlates with cellular vascular periphery of the tumor complex. Adult HGG have shown infiltrate into the perilesional low density areas on CT or areas of abnormal T2 MRI. HGG have significant infiltrative characteristics and aggressive surgery and high dose local radiation techniques should be used with caution. The patterns of failure show both a direct relationship between the degree of resection and the duration of tumor control as well as a pattern of failure that is overwhelmingly at the primary target volume even after high dose focal radiation therapy.
Treatment
Surgery
Maximum possible surgical resection improves surivival. Surgery is limited by the extent of poorly defined margins and nature of the tumor. A large CCG series found that GTR and NTR (> 90%) was achieved in only 37% with 49% arising in the superficial cerebral hemispheres, 45% arising in the cerebellum and 8% in the central structures. There is a significant correlation between the degree of resection and the median survival with GTR/NTR doubling PFS-5 to 44% (Grade III-Anaplastic Astrocytoma) and 26% (Grade IV GBM).
Radiation Therapy
As per adults, the intial treatment volume is the T2/FLAIR edema signal plus 2 cm margin to 50-54 Gy followed by a boost to the T1 enhancing margin plus 1 cm margin. The bulk of the failures remain local, infield.
Chemotherapy
Unfortunately, the use of temozolomide has not demonstrated particular effectiveness in children as it has in adults. Molecular targeting agents may have promise, such as bevasuzimab and EGFR blockers either concurrent with RT or sequentially.