Natural History of Plexiform Neurofibromas

There is great clinical variability in plexiform neurofibromas (pNFs), making it challenging to design an intervention and prove efficacy. The NTAP pNF Natural History initiative is designed to develop a clearer understanding of the clinical behavior of these tumors and has two concurrent efforts: (1) support the ongoing prospective NF1 natural history study at the Pediatric Oncology branch of The National Cancer Institute and (2) bring together a consortium of global researchers to combine clinically-obtained longitudinal data to assess large numbers of pNFs over time.

The initiative will generate a uniform, open-source dataset that will act as a baseline against which the impact of potential therapies can be evaluated.

To date, NTAP has collaborated with the Pediatric Oncology Branch of the National Cancer Institute (POB-NCI) to analyze key elements of their long-standing natural history study. This analysis yielded key data to help establish endpoints to be considered by the FDA for upcoming clinical trials including: a median growth rate of pNF of 12.4%/year (range -8.5%/year to 246.7%/year) with none of the 82 individual pNF analyzed having spontaneous regression >20% over 5 years. [Akshintala S, et al Growth patterns and predictors of plexiform neurofibroma (PN) growth in patients with neurofibromatosis 1 (NF1) based on volumetric Magnetic Resonance Imaging (MRI analysis), CTF, 2014]. This allowed regression of tumor >20% to be an established end point for single arm studies seeking regulatory approval. Moreover, this work showed that faster growth rates were associated with younger patients with diffuse lesions, but that there was a distinct subset of tumors that had different behavior termed “nodular lesions” suggesting a subtype of pNF. There was no statistically significant relationship between pNF growth rate and patient’s sex, race, type of germline NF1 mutation or tumor location.