Neurofibromatosis Type 2: Natural History, Outcomes, and Treatment Patterns in a Large Contemporary Cohort

Introduction: Neurofibromatosis type II (NF2) is a challenging inherited cancer condition, which predisposes patients to bilateral vestibular schwannomas, cranial and spinal meningiomas, spinal ependymomas and peripheral nerve schwannomas. A large contemporary cohort of patients with NF2 was reviewed to assess the impact of present-day therapies upon the natural history of this disease.

Methods: A retrospective review of 54 patients with NF2 was performed using an IRB-approved brain tumor registry at Washington University in St. Louis over the last two decades. Data collection included demographics, age at diagnosis, burden of cranial and spinal disease, age at onset of deafness, treatments received (medical, surgical and radiation), and outcomes. Statistical analyses included a chi-square test used to compare early vs late age of diagnosis with respect to early vs late onset of unilateral deafness.

Results: Median age at diagnosis was 17.5 years (range 3–65); average age at last follow-up was 31 years (range 3–69) for 25 males and 29 females. Of 48 patients who had spinal imaging done, tumors were found in the cervical spine (85.4%), thoracic spine (72.9%), lumbar spine (81.3%), and throughout the spine (60.4%). Median lifetime tumor burden during the time period tracked for this cohort of patient was 6 (range 2–25) intracranial tumors and 6.5 (range 0–32) spinal tumors. The number of spinal tumors likely represents a conservative estimate of small spinal tumors, as many were “too numerous to count.” The median number of lifetime medical and surgical interventions to date related to NF2 was 5 (range 0–17), surgical interventions 3 (range 0–17). The median number of surgical interventions per year was 0.1 (range 0–1.75). Fifteen individuals (27.8%) underwent radiosurgical treatment (9 for meningiomas, 8 for vestibular schwannomas, 3 for both, 2 for other cranial schwannomas, and 2 for spinal tumors). Eleven (20.4%) received bevacizumab (Avastin), an intravenous antibody to vascular endothelial growth factor (VEGF) therapy, two (3.4%) received everolimus (Afinitor), and one (1.9%) received panzopanib (Votrient). Median duration of medical therapy was 16.5 months (range 3–58, n = 12). Four (7.4%) died due to progressive disease or complications of treatment; median age at death was 26.5 years (range 4–38). Median age of onset of unilateral deafness, Gardener-Robertson class 3 or higher, was 21 years (range 7–56, n = 31); median age of bilateral deafness was 24 years (range 13–61, n = 15). Using a chi-square test (p < .001), it was determined that patients diagnosed with NF2 at an early age (<=20 years) had earlier onset of unilateral deafness (median age 15, range 7–20), compared with those diagnosed at a later age (unilateral deafness in latter group at median age 31, range 21–56)

Conclusion: NF2 is a complex tumor predisposition disorder associated with bilateral vestibular schwannomas and numerous other tumors of the nervous system. NF2 patients typically undergo large numbers of surgical interventions and other treatments with an increasing number undergoing medical treatment such as bevacizumab in recent years. Patients diagnosed at a younger age are more likely to have an earlier age of onset of unilateral deafness.