Abstract
Individuals with NF1 are prone to the development of both benign and malignant tumors of the central nervous system, including Schwann cell tumors (e.g. neurofibromas) and glial cell tumors (e.g. astrocytomas). Although the most common tumor in children with NF1 is an optic pathway glioma (OPG), astrocytomas may occur throughout the central nervous system most notably in the brainstem. The greatest risk period for the development of OPG is in the first 6 years of life. Symptomatic NF1-associated OPG generally present in one of two ways- ophthalmologic symptoms and signs or the development of precocious puberty. Progressive disease after diagnosis of NF1-associated OPG requiring treatment occurs in 23–52% of cases. Although tumors involving the post-chiasmatic optic tracts and optic radiation have been associated with a worse prognosis, predicting the natural history of an individual OPG is impossible. As low grade astrocytomas in children with NF1 may remain quiescent following diagnosis, therapeutic decisions regarding these tumors must incorporate the presence or absence of NF1 into the decision-making process. Surgery of an intraorbital OPG should be limited to improving cosmetic appearance or reducing the risk of corneal exposure of a proptotic eye. Given the real risk of secondary malignancies and cerebral vasculopathy, there is virtually no role for radiation therapy in the treatment of NF1-associated OPG. The combination of carboplatin and vincristine is standard first-line therapy for symptomatic NF1-associated OPG which require treatment. Insights derived from studying the pathophysiology and biochemical basis for glioma formation and visual loss have uncovered new opportunities for therapeutic intervention including anti-neoplastic cell therapies that target the RAS/mTOR/STAT3 pathway, treatments that target the tumor microenvironment, including microglia and microglia-derived glioma growth factors, and neuro-protective strategies that reduce the collateral damage to neurons resulting from tumor formation or cancer treatment.
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We thank Ms. Samantha Higer for generating the illustrations used in this chapter.
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Listernick, R., Gutmann, D.H. (2012). Pediatric Low-Grade Glioma: The Role of Neurofi bromatosis-1 in Guiding Therapy. In: Hayat, M. (eds) Pediatric Cancer, Volume 2. Pediatric Cancer, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2957-5_27
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