Scott R. Plotkin, Massachusetts General Hospital; Boston, MA

Neurofibromatosis 1 (Nfl) is a complex neurogenetic disorder with features of a tumor-suppressor syndrome and a rasopathy. The condition is characterized by a predisposition to multiple tumor types, learning disability, bony lesions, and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and in some cases malignancy. With increasing knowledge of the biology and pathogenesis of NFl, clinical trials with targeted agents directed at NFl-related complications have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NFl (compared to cancers) require the development of new designs and endpoints to perform meaningful clinical trials.

The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children’s Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials with a specific emphasis on endpoints. The REiNS Collaboration includes seven working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. The working groups have made the first series of recommendations on behalf of the REiNS collaboration. The hope is that these recommendations will be adopted by the broader research community to standardize the measurement of outcomes and thus improve clinical trials for patients with NFl. Ultimately, the REiNS collaboration plans to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for NFl patients.