Optic pathway gliomas may involve the optic nerve, chiasm, and optic radiations and tracks. Isolated optic nerve tumors, especially in patients with neurofibromatosis type 1, can often be observed without any specific intervention for many years. For those patients with isolated optic nerve tumors and complete loss of vision, surgical resection is possible. For other clinical situations, chemotherapy and, less frequently, radiotherapy may be initial treatment. In this article, the author reviews the treatment approaches for these tumors and the efficacy of treatment. He also focuses on the therapeutic implications of new insights into the biology of these tumors.
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• Visual pathway gliomas may occur sporadically, but 50% are associated with neurofibromatosis type 1 (NF1).
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• Most visual pathway gliomas are pilocytic astrocytomas.
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• Mutations in BRAF, most commonly an activating fusion, occurs in the majority of patients with non-NF1-related visual pathway pilocytic tumors.
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• Chemotherapy is frequently effective in delaying, if not obviating, the need for radiotherapy in “non-operable” lesions.
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• Molecular-targeted therapy is playing a larger role in management of progressive lesions.
Historical note and terminology
Chiasmatic gliomas arising in childhood have been the subject of many reports, with various recommendations for treatment (44; 24; 78). The first descriptions of the various types of orbital tumors were by Byers (17). Hudson was the first to suggest that optic pathway tumors were hamartomatous rather than neoplastic (46), a concept that was debated heatedly over the next several decades. The surgical accessibility of these lesions was initially described by Martin and Cushing (66).
At times, lesions of the chiasm have been discussed as a singular entity, and at other times, as a subgroup of diencephalic tumors or visual pathway tumors. Although chiasmatic gliomas may remain relatively limited to the chiasm, there is often contiguous involvement of other brain stem structures. In children with neurofibromatosis, chiasmatic gliomas usually extend to 1 or both optic nerves or posteriorly to the optic tracts or optic radiations (74). Patients without neurofibromatosis may have isolated globular chiasmatic lesions, but also may have tumors that extend into other regions of the diencephalon, such as the hypothalamus and thalamus. It is unclear whether separation of chiasmatic lesions from other diencephalic or visual pathway gliomas is of prognostic significance. Prior to the advent of magnetic resonance imaging, chiasmatic tumors were often arbitrarily classified as being anterior, involving the chiasm and optic nerve, or posterior, involving the chiasm plus hypothalamus or other parts of the visual pathway (70). This distinction was used for prognostic reasons, on the belief that patients with anterior lesions had a more favorable prognosis. Since the introduction of magnetic resonance, such arbitrary distinctions have diminished importance, as the extent of tumor can be more clearly delineated.
Another change concerning concepts of chiasmatic gliomas has been the identification, primarily through screening programs for children with neurofibromatosis, of lesions in asymptomatic patients or children with minimal, apparently, static symptomatology. Although a proportion of patients with neurofibromatosis and asymptomatic, radiographically confirmed lesions will develop progressive disease, the majority remain stable for months or years. This has given more credence to the contention that some chiasmatic gliomas are not truly tumors, but are rather hamartomatous masses without growth potential. Longitudinal studies following patients over many years or decades are needed to clarify the growth potential of chiasmatic lesion in children with neurofibromatosis. However, it is well-documented that isolated optic nerve lesions in children with neurofibromatosis may remain quiescent for many years (44).
Predominantly arising in a chiasm, a pilomyxoid variant of pilocytic astrocytoma has been identified, demonstrating monomorphous pilomyxoid features. It is believed to have a poorer prognosis and a higher tendency to disseminate throughout the nervous system than the classical pilocytic astrocytoma (56). The 2017 WHO classification does not identify it as a distinct entity, although molecular studies have demonstrated that it has a different molecular profile than classic pilocytic tumors and a tendency to “mature” into the more classical tumor (64).
Anaplastic astrocytoma with piloid features is still another entity. This clinically more aggressive lesion is seen in both patients with and without neurofibromatosis 1 and is associated with other concomitant genetic alterations in tumor tissue (86).