Treatment options should be considered not only to improve survival but also to stabilize visual function. Children with isolated optic nerve tumors have a better prognosis than those with lesions that involve the chiasm or that extend along the visual pathway.[1,2,3] Children with neurofibromatosis type 1 (NF-1) also have a better prognosis, especially when the tumor is found in asymptomatic patients at the time of screening.[1] Observation is an option for patients with NF-1 or nonprogressive masses.[1,2,4] Spontaneous regressions of optic pathway gliomas have been reported in children both with and without NF-1.[5,6] For children with isolated optic nerve lesions and progressive symptoms, complete surgical resection or local radiation therapy may result in prolonged progression-free survival.[1]

Radiation therapy results in long-term disease control for most children with chiasmatic and posterior pathway chiasmatic gliomas, but may also result in substantial intellectual and endocrinologic sequelae, cerebrovascular damage, and possibly an increased risk of secondary tumors.[1,3,7,8] An alternative to immediate radiation therapy is subtotal surgical resection, but it is unclear how many patients will have stable disease and for how long.[7] For those children with low-grade glioma for whom radiation therapy is indicated, conformal radiotherapeutic approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality.[9,10,11]

Chemotherapy may result in objective tumor shrinkage and will delay the need for radiation therapy in most patients.[4,12,13,14,15] The most widely used regimen to treat progression or symptomatic nonresectable, low-grade gliomas is a combination of carboplatin and vincristine.[4,15] Other chemotherapy approaches have been employed to treat children with progressive optic pathway gliomas, including multiagent platinum-based regimens [12,16] and nitrosourea-based regimens.[13]

Reported 5-year progression-free survival rates have ranged from approximately 35% to 60% for children receiving platinum-based chemotherapy for optic pathway gliomas,[12,15] but most patients ultimately require further treatment. Among children receiving chemotherapy for optic pathway gliomas, those without NF-1 have higher rates of disease progression than those with NF-1, and infants have higher rates of disease progression than do children older than 1 year.[12,15,16] Given the side effects associated with radiation therapy, chemotherapy may be particularly appropriate for patients with NF-1 and for younger children. Younger children are at higher risk for radiation-associated intellectual and endocrinologic sequelae. Children with NF-1 may be at higher risk for radiation-associated secondary tumors and morbidity due to vascular changes. 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.[17]

The Children's Oncology Group (COG) completed a randomized phase III trial, COG-A9952,[18] that treated children younger than 10 years with low-grade chiasmatic/hypothalamic gliomas on 1 of 2 regimens: carboplatin and vincristine or thioguanine (6-thioguanine), lomustine, and procarbazine hydrochloride given with vincristine. Children with NF-1 were only treated on the carboplatin and vincristine arm. Study results are pending.