Chemotherapy

Given the long-term side effects associated with radiation therapy, chemotherapy is recommended as first-line therapy for most pediatric patients who require adjuvant therapy after surgery.

Chemotherapy may result in objective tumor shrinkage and help avoid, or at least delay, the need for radiation therapy in most patients.[20-22] Chemotherapy is also an option for adolescents with optic nerve pathway gliomas to delay or avoid radiation therapy.[23][Level of evidence C2] 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.[24]

The most widely used regimens to treat tumor progression or symptomatic nonresectable, pediatric low-grade gliomas are the following:

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 without NF1 using one of two regimens: carboplatin and vincristine (CV) or TPCV. The 5-year EFS rate was 39% (± 4%) for patients who received the CV regimen and 52% (± 5%) for patients who received the TPCV regimen. Toxicity rates between the two regimens were relatively comparable.[20] In the same study, children with NF1 were nonrandomly assigned to receive treatment with CV. The 5-year EFS rate for children with NF1 was markedly better, at 69% (± 4%), than it was for children without NF1 who received CV. In multivariate analysis, NF1 was an independent predictor of better EFS but not OS.[31] In a separate study that included 100 patients with WHO grade 2 diffuse gliomas, a subset of patients (n = 16) were treated with CV, and some patients also received etoposide. This subset of patients had a 5-year PFS rate of 38% when patients with histone H3 variants were excluded.[14][Level of evidence B4]

Other chemotherapy approaches that have been employed to treat children with progressive or symptomatic nonresectable, low-grade astrocytomas include the following:

Among children who received chemotherapy for optic pathway gliomas, those without NF1 had higher rates of disease progression than those with NF1, and infants had higher rates of disease progression than children older than 1 year.[21,22,29] Visual status (including acuity and field) is an important measure of outcome and response to treatment. Vision function can be impaired; it is variable even in patients with radiographic responses and is often less than optimal. More than one-third of patients successfully treated with chemotherapy have poor vision in one or both eyes, and some patients lose vision despite radiographic evidence of tumor control (response or stability). In most series, children with sporadic visual pathway gliomas have poorer visual outcomes than do children with NF1.[29]; [38,39][Level of evidence C1] Better initial visual acuity, older age, and absence of postchiasmatic involvement are associated with improved or stable vision after chemotherapy.[40,41]