Archive | 2019
Evolution in the Management of Childhood Low-Grade Gliomas and Neuronal/Mixed Neuronal-Glial Tumors
Abstract
Gliomas comprise the majority of tumors occurring in those less than 18 years of age and unlike the situation in adulthood, the majority of pediatric gliomas are low-grade. Since demonstration of the benefits of chemotherapy by multiple single-arm and randomized prospective studies, there has been a shift in management of unresectable, progressive low-grade gliomas (LGGs) from initial treatment with radiation therapy to the employment of chemotherapy in attempts to delay and in some cases obviate the need for radiation therapy or potentially damaging «definitive» surgery [1, 2]. A variety of different chemo-therapeutic approaches have been utilized, most attempting to use relatively non-mutagenic agents such as the combination of carboplatin and vincristine, carboplatin alone or vinblastine alone [1, 2]. Although such therapies are successful in delaying the need for radiation therapy or other interventions in 80% or more patients with LGGs while on treatment or during the first 1–2 years off treatment, 5-year progression-free survival rates for children with sporadic LGGs after treatment with chemotherapy are only 30–40% [1, 2]. The degree of disease control is better in patients with NF1, as children with NF1-associated pilocytic astrocytomas (PAs) have approximately a 70% 5 years progression-free survival after treatment with chemotherapy [1, 2]. The benefits of chemotherapy as regards functional improvements are less well documented and the majority of patients do not clinically improve after treatment [1–3]. This is especially true for children with tumors of the visual pathway [3]. Also, for many patients with LGGs, because of the tendency of these tumors to relapse within the first 5 years after treatment, patients may cycle from one form of chemotherapy to another or ultimately receive radiation therapy in attempts to gain longer term tumor control. For those children with the closely aligned neuronal and mixed neuronal glial tumors, approaches to treatment are even less straightforward. Lesions such as gangliogliomas (GGs) and dysembryoplastic neuroephitilial tumors (DNETs) often present with seizures. The mainstay of treatment is surgery and complete surgical removal results in excellent long-term control and often complete cessation of seizures. However, in those tumors in eloquent regions of brain not amenable to complete or near total resections, management is less straightforward. Many tumors seem to remain quiescent for years, while others slowly progressed with suboptimal seizure control. Given the benign nature of these tumors, there is reluctance to utilize radiotherapy unless the tumor had anaplastic features. The relative rarity of progressive GGs, DNETs, or other neuro-glial lowgrade tumors makes prospective clinical trials difficult to mount and the benefits of chemotherapy as regards tumor control or control of symptomatology are very unclear.