Amy E. Armstrong, MD, Angela Hirbe, MD, PhD - ReiNForcing Care Pathways in NF1-PN: Solutions to Improve Outcomes Across the Patient Journey With MEK Inhibition and Shared-Care Models

So neurofibromatosis type 1 affects about 120,000 Americans and 2 million people worldwide.

It's a genetic neurocutaneous disorder that predisposes individuals to develop both benign and malignant tumors.

And it's caused by a mutation in the NF1 gene, which codes for neurofibromin.

And neurofibromin functions as a tumor suppressor, so losing this results in overactivation of various growth signaling pathways.

Plexiform neurofibromas happen in almost half of patients with NF1, and we think that these are congenital, although they may not manifest in infancy.

We may not know about them until later in life.

They're composed of Schwann cells, which we believe are the tumor cell, but there's also fibroblasts infiltrating mast cells, endothelial cells, all around several nerves.

These can cause significant disfigurement and motor dysfunction.

They can be deep, nodular, not visible, and symptoms can be pain, limited mobility, and neurologic deficits.

Sometimes they can be life-threatening, so there can be mechanical compression of the trachea, large blood vessels, or the spinal cord.

And we know that there's a risk of malignant transformation into malignant peripheral nerve sheath tumors.

So the graph that you see in this figure is really just meant to help illustrate that these tumors tend to grow most in the pediatric population.

So you're looking at age here and tumor size here.

And again, these lines are growing in the pediatric population most in this zero to 10 year range.

When you start getting into adults, you really expect these to plateau.

This is kind of an anomaly here.

And if I see this in an adult patient, I'm more worried about malignant transformation.

So this is some data from the NCI natural history study where patients were followed for seven years, assessed for plexiform neurofibroma volume, as well as morbidities.

And again, they found that plexiforms grew most rapidly in patients aged three to five years.

And at baseline, most common plexiform neurofibroma-related morbidities were pain, having to have a surgery, and then motor dysfunction.

And you can kind of see some of these morbidities and numbers of surgeries in the graph.

So these are all some of the challenges I think that we have to deal with in caring for NF1 plexiform patients.

So certainly there's disease complexity and there can be fragmented care.

There's multi-system involvement.

There's an unpredictable course.