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Management of Neurofibromatosis Type 1 with Plexiform Neurofibromas (NF1 with PNs) - Episode 5

Therapeutic Options for NF1 With PNs

Kaleb H. Yohay, MD: One of the treatment options for plexiform neurofibromas is an attempt at surgical removal. There are some plexiform neurofibromas that are well encapsulated and are approachable in the sense that we think we can remove essentially the whole tumor or the majority of the tumor. In some cases, we will attempt a total resection. However, the majority of the time these tumors are so complicated, and they interact with surrounding organs as well as with the nervous system in such a way that total removal isn’t possible. In this case debulking is an option. Debulking is the process of selecting a portion of the tumor that can be resected safely with minimal risk to the patient but provides some benefit, either by alleviating some amount of pressure on surrounding tissue or by improving cosmetic appearance.

There are a number of factors that contribute to whether a tumor can be resected completely or debulked. One is location. Often these tumors can be located in areas that aren’t approachable from a surgical standpoint safely so that the entire tumor can be removed. For instance, if there’s a plexiform neurofibroma that involves the face, it may involve the facial nerve as well as the internal carotid artery. The risk to those structures is such that it isn’t feasible to resect those tumors. However, if a tumor is more discrete and isolated from other vital structures, those tumors may be easier to approach surgically. Therefore, we might approach them earlier than we would ones that are more difficult areas to reach safely.

The risk of resecting a plexiform neurofibroma is based on several factors. One is that many of these tumors have highly complex vascular systems. These tumors can have both arterial and venous components, and resection can sometimes lead to bleeding that can be difficult to manage.

In addition to the risk of bleeding, there’s also significant risk to neurologic function. These tumors grow within nerves, and the axons are often splayed out throughout the tumor. Resection of the tumor almost always necessitates sacrifice of some portion of a nerve. Depending on where the tumor is and which nerve is impacted, it can result in some amount of neurologic dysfunction. For instance, if a sciatic nerve tumor is resected, it’s possible to lose function of the leg below the sciatic nerve. For a more superficial tumor on the chest, you might lose just sensation to that area of skin. The amount of nerve injury depends both on the location, which nerve it arises from, as well as how the tumor is associated with that specific nerve.

Herbert B. Newton, MD, FAAN: For enlarging, painful, and otherwise symptomatic plexiform neurofibromas, surgical resection is usually the first option for treatment in these patients. For tumors that are accessible and amenable to surgical resection, using a laser or electrocautery is at the discretion of the surgeon who’s doing the operation. Most of the time when they’re using that, they’re trying to control bleeding and close off vessels that are oozing or leaking blood around the surgical sites. It’s something the surgeon decides at the moment during the procedure, whether they need to use that type of approach to handle bleeding on site from tumor removal.

In terms of the role of radiation therapy or chemotherapy, as a general rule most specialists with NF [neurofibromatosis] would not recommend using radiation therapy as a routine treatment option. The main reason is if you use that for a plexiform neurofibroma, you have the chance of having the radiation cause a malignant transformation of that tumor in a number of years and convert it into a malignant peripheral nerve sheath tumor, which again is a dangerous sarcomatous cancer. Sometimes we would consider using radiation for treating a malignant peripheral nerve sheath tumor, but the data are not very strong for radiation even in that setting and it doesn’t seem to help prolong survival very much.

In terms of chemotherapy, prior to April of 2020, there were no FDA-approved forms of chemotherapy for plexiform neurofibromas. Until that time, chemotherapy was used once in a while for refractory, unresectable tumors. Some of the chemotherapies that have been evaluated include pegylated interferon and imatinib, in which both were found to have some limited activity. Recently some molecular drugs, including inhibitors of mTOR, such as rapamycin, everolimus, as well as MEK inhibitors—some of the first ones like trametinib—were also thought to have some activity.

Kaleb H. Yohay, MD: The choice to use imaging modalities to either diagnose or monitor plexiform neurofibromas is up to the clinician. There aren’t specific guidelines at the moment for how best to diagnose and monitor these tumors. There is some thought that there could be benefit to performing a whole body MRI for patients with neurofibromatosis type 1 to identify neurofibromas before they become symptomatic, but there is not yet consensus about whether that is worthwhile. For symptomatic tumors, we will definitely image when surgery is being considered or if treatment is being considered to establish a baseline and to assess the viability of surgical resection. For tumors that are less symptomatic and treatment is not being considered, we don’t typically image those tumors unless the clinical scenario changes over time. The optimal imaging for neurofibromas includes MRI of the area, specifically with STIR [short inversion time inversion-recovery] imaging. Contrast can be helpful as well.