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.