New treatment modalities in NF-related neuroglial tumors

The management of low-grade gliomas (LGGs) and other neuroglial tumors in children with neurofibromatosis type 1 (NF1) has not changed over the past 2-3 decades. With the widespread utilization of chemotherapy for younger children with progressive LGGs, outcomes have been good for most patients who have required treatment. However, some may progress after the initiation of chemotherapy and others, although radiographically responding or with stable disease, may develop progressive neurologic and visual deterioration. Molecular-targeted therapy has become an option for patients who have progressed after receiving chemotherapy and the mTOR inhibitors and bevacizumab have already shown some degree of efficacy. However, the greatest impact has been the introduction of the MEK inhibitors. A variety of different MEK inhibitors are in clinical trials and have already demonstrated the ability to result in radiographic tumor shrinkage in the majority of children with NF1 and progressive LGGs. Because of this efficacy, the MEK inhibitors have moved rapidly from phase I studies to ongoing phase III studies comparing their benefit directly to that of chemotherapy. The long-term ability of these agents to not only control disease, but improve visual and/or neurological function, as well as their short- and long-term safety, are open questions that can only be answered by well-constructed prospective, often randomized, clinical trials.