Neurofibromatoses predispose to the development of sarcomas. The mechanisms responsible for this are still under investigation. The incidence of neurofibromatoses appears to be highest in Caucasians, whereas Asians have a higher predisposition towards multiple neurofibromas.
We need a larger population-based study and a better way of assessing neurofibromas so that we can accurately calculate the number of people being diagnosed with this tumor annually in the US.
The signs of neurofibromatoses are varied and depend on the type of neurofibroma. Signs and symptoms are usually present in the first 2 to 3 years of infancy and vary in complexity over time. Neurologic signs include loss of motor function, and developmental delay. Cognitive and behavioral changes may emerge later. Diagnosis is usually made by screening of family members for neurofibromas. Ultrasonography has been extensively used for diagnosis.
The first symptom of NF is a solitary neurofibroma, the most common malformation in neurofibromatosis. NF tumors occur in different locations, such as the extremities (like leg or arm), the torso or back. Most NF-associated tumors can be removed completely, so most need no treatment. However, some can form in places where surgery is difficult and risky, such as the brain; as NF tumors in the brain tend to be tumor-like, NF can cause some types of neurofibromatosis (pNF) in addition to NF. With the right treatment, most pNF patients can also live a normal life span, with occasional problems with nerves, skin, or bones.
Neurofibromatosis type 2 and von Schwartzen-Löffler disease are the only forms of neurofibromatosis that have a curative treatment. The other neurofibromatosis forms are often effectively treated but are unlikely to disappear completely.
Most NF patients are treated only with surgery or with radiotherapy if the patient needs surgery and has no cancer. In our experience, all patients with neurofibromas in NF1 have tumors that are malignant and require surgery. In addition, all patients with plexiform neurofibromas need some sort of treatment because they will develop cancer. All individuals with Lisch nodules need to be followed and treated because they are malignant. Finally, patients with optic pathway gliomas require surgery and irradiation, if the tumor is resectable.
This is another exciting field that is slowly getting better as science-based medicine is starting to catch up to our clinical practice. We should learn new things on a regular basis and keep up with this ever-expanding research field.
The overall 5-year survival rate for neurofibromatosis in patients younger than 5 years old and 5-years younger is about 67% to 80%, while the 10-year survival rate for neurofibromatosis in patients 20 years of age or older is about 30% to 50% depending on the type of neurofibromatosis.
The development of the novel bsmTK inhibitor binimetinib (Musekino) is an important innovation since prior generation bsmTK inhibitors, (e.g., axitumomab transthyretin) did not exhibit sufficient TK potency to exert efficacy in refractory neurofibromatosis.
Findings from a recent study suggest that it is important to ensure early diagnosis of neurofibromatoses and to provide the patient with information about the course of the disease so that he or she can make the best and most informed care decisions at the beginning of the disease.
Binimetinib is a novel, covalently-linked inhibitor of the vascular endothelial growth factor receptor-1, so called VEGFR-1 ligand. It has potent antitumor activity in preclinical models of solid tumors and has a favorable safety profile. Initial clinical testing as a single agent or in combination has demonstrated activity in both breast and NSCLC. Binimetinib has an active dose-range profile, with antitumor activity seen across a broad range of pediatric and adult disease indications. Clin Cancer Res; 21(29); 5873-89. ©2015 AACR.