For children with low-grade glioma for whom radiation therapy is indicated, conformal radiation therapy or stereotactic radiosurgery approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality. Care must be taken in separating radiation-induced imaging changes from disease progression during the first year after radiation, especially in patients with pilocytic astrocytomas.[33,34,35]; [Level of evidence: 2A]; [Level of evidence: 2C]; [Level of evidence: 3iiiDi]; [Level of evidence: 3iiiDii]; [23,39][Level of evidence: 3iiiDiii]
Given the side effects associated with radiation therapy, chemotherapy may be particularly appropriate for patients with NF1 and for younger children.
Chemotherapy may result in objective tumor shrinkage and will delay the need for radiation therapy in most patients.[27,28,40,41] Chemotherapy has been shown to shrink tumors in children with hypothalamic gliomas and the diencephalic syndrome, resulting in weight gain in those who respond to treatment.
The most widely used regimens to treat progression or symptomatic nonresectable, low-grade gliomas are carboplatin with or without vincristine [27,28,43] or a combination of thioguanine, procarbazine, lomustine, and vincristine (TPCV).; [Level of evidence: 1iiA] The COG reported the results of a randomized phase III trial (COG-A9952) that treated children younger than 10 years with low-grade chiasmatic/hypothalamic gliomas using one of two regimens: carboplatin and vincristine (CV) or TPCV. The 5-year event-free survival rate was 39% ± 4% for the CV regimen and 52% ± 5% for the TPCV regimen. Other chemotherapy approaches have been employed to treat children with progressive low-grade astrocytomas, including multiagent platinum-based regimens [28,40,45]; [Level of evidence: 2Diii] and temozolomide.[47,48]
Reported 5-year PFS rates have ranged from approximately 35% to 60% for children receiving platinum-based chemotherapy for optic pathway gliomas,[28,40] but most patients ultimately require further treatment. This is particularly true for children who initially present with hypothalamic/chiasmatic gliomas that have neuraxis dissemination.[Level of evidence: 3iiiDiii]
Among children receiving chemotherapy for optic pathway gliomas, those without NF1 have higher rates of disease progression than those with NF1, and infants have higher rates of disease progression than do children older than 1 year.[28,40,45] Whether vision is improved with chemotherapy is unclear.[50,51][Level of evidence: 3iiiC]
Most children with tuberous sclerosis have a mutation in one of two tuberous sclerosis genes (TSC1/hamartin or TSC2/tuberin). Either of these mutations results in an overexpression of the mTOR complex 1. These children are at risk for the development of subependymal giant cell astrocytomas (SEGA), in addition to cortical tubers and subependymal nodules. For children with symptomatic SEGAs, agents that inhibit mTOR (e.g., everolimus and sirolimus) have been shown in small series to cause significant reductions in the size of these tumors, often eliminating the need for surgery.[Level of evidence: 2C]; [Level of evidence: 3iiiC] Whether reduction in size of the mass is durable, obviating the need for future surgery, is currently unknown.