5.6Management of Neurofibromatosis Type 1

5.6.1Introduction

5Due to the variable clinical manifestations of NF1, treatment must be tailored to the patient and not the disease. A multidisciplinary approach is important for optimizing patient care by incorporating the diagnostic and management skills of other medical services such as genetics, neurooncology, ophthalmology, neuroophthalmology, plastic surgery, otolaryngology, orthopedics, general surgery, and developmental psychiatry/psychology.

5.6.2Medical Management of Neurofibromas

Although there has been some success in treating OPGs with chemotherapy or radiation, the management for optic nerve gliomas in the orbit has been primarily surgical when treatment for severe proptosis has been determined necessary. For plexiform neurofibromas, however, because of their marked vascularity, numerous chemotherapeutic agents are being tested as potential treatments. A clinical trial with alfa-interferon has had poor results [50]. Thalidomide has also had poor results with plexiform neurofibromas but has shown more promise in treating malignant peripheral nerve sheath tumors [17]. AZD2171, a small molecule VEGF-like vascular endothelial growth factor (VEGF) receptor, is currently under phase I study [3]. Tipifarnib, a drug specifically targeting tumor cells, is also currently in phase II trials. This is a farnysyl transferase inhibitor that affects intracellular Ras activity and has shown some promise in phase I trials in both children and adults [49].

The antifibrotic agent pirifenidone (5-methyl-1-phenyl- 2-[1H]-pyridone) is now in phase II trials. This medication attenuates cytokine release by fibroblasts thus weakening the cellular support of neurofibromas [1]. At the Children’s Hospital of Philadelphia, the effectiveness of methotrexate with Velban for suppressing NF1 tumor growth is currently being evaluated as well as an NF consortium study using rapamycin. Although there is as yet no published data, anecdotally, however, it appears that there may be some slowing of growth but little evidence of regression [4].

Unfortunately, to date an effective “home run” medical regimen has not been found for managing plexiform neurofibromas [4]. For this reason, surgical debulking and reconstruction still remain the best option for orbitofacial rejuvenation from the disfiguring tumors associated with NF1. The following section outlines our current approach to the surgical management of orbitofacial tumors associated with NF1.

Summary for the Clinician

■First-line therapy for OPGs is proper imaging and chemotherapy.

■Medical therapy for neurofibromas is currently under clinical trials; however, initial data do not point to a home run therapy. and surgery should always be considered a primary treatment.

5.7Surgical Management of Orbitofacial Tumors in NF1

5.7.1Introduction

Surgical intervention to help restore function and improve cosmesis in patients with orbitofacial involvement of neurofibromatosis has been well described in the literature. Jackson et al., in their series of 24 patients with NF1, defined three treatment groups [19]:

1.Orbital soft tissue involvement with a seeing eye

2.Orbital soft tissue and significant bony involvement with a seeing eye

3.Orbital soft tissue and significant bony involvement with a blind or absent eye

Lee et al., in their series of 33 patients with NF1, elaborated on this classification by describing additional findings to these treatment groups [28]:

1.Brow ptosis

2.Upper lid infiltration with ptosis

3.Lower lid infiltration

4.Lateral canthal disinsertion

5.Conjunctival and lacrimal gland infiltration

5.7.2Timing of Surgery

It is critical to recognize the emotional stress and psychosocial implications of NF1 deformities not only on the affected individuals but also on their families and friends. Social withdrawal due to disfigurement and chronic pain must be considered when evaluating the need for and timing of surgical intervention. Some authors suggest delaying intervention if possible due to the higher rate of “recurrence” in younger patients. In the periorbital region, these tumors really do not represent recurrences, however, but rather continued progression of sheath and cutaneous tumors in particular. In our experience, most families are extremely motivated to begin treatment, including surgical intervention, even though cautioned