What are the management and treatment options for neurofibromatosis (NF)?

Management and Treatment Options for Neurofibromatosis (NF)

The management of neurofibromatosis requires a specialized, coordinated approach with targeted surveillance and treatment of specific manifestations, with MEK inhibitors like selumetinib now approved for symptomatic, inoperable plexiform neurofibromas in children ≥2 years old. 1, 2

Types of Neurofibromatosis and Initial Management

Neurofibromatosis has multiple types with different management needs:

• NF1: Most common form (1/2,000-1/3,000 prevalence)
• NF2: Less common, characterized by bilateral vestibular schwannomas
• Schwannomatosis: Rarest form, multiple schwannomas without vestibular involvement

Core Management Recommendations:

• Referral to specialized NF clinic for coordinated care 1, 2
• Regular clinical assessment by providers familiar with NF complications
• Genetic counseling for 50% offspring recurrence risk 2

Tumor Management in NF1

Plexiform Neurofibromas (PNs)

• Present in ~50% of NF1 patients
• FDA-approved treatments:
  • Selumetinib: For symptomatic, inoperable PNs in children ≥2 years 1, 2
  • Trametinib: Alternative MEK inhibitor where selumetinib unavailable 1
  • Cabozantinib: Approved for patients ≥16 years with NF1 PNs 1

Malignant Peripheral Nerve Sheath Tumors (MPNSTs)

• Life-threatening complication with poor prognosis if advanced
• Warning signs: Pain, rapid growth, neurologic symptoms 1, 2
• Management:
  • Surgical resection with clear margins is cornerstone of treatment 2
  • Consider referral to high-volume specialized centers 1
  • MRI preferred over CT for imaging to reduce radiation exposure 1
  • Consider 18F-FDG PET/CT for suspicious lesions (SUV max >3.5 warrants biopsy) 1, 2

Central Nervous System Tumors

• Optic Pathway Gliomas (OPGs):

  • Most common CNS tumor in NF1 (~20%)
  • Usually present before age 8 (median 4-5 years)
  • Treatment:
    • Observation for asymptomatic lesions (most don't progress)
    • Chemotherapy for symptomatic/progressive tumors
    • MEK inhibitors showing promise in clinical trials 1
    • Avoid radiation due to vascular complications 1

• Brainstem Gliomas:

  • Present in <10% of NF1 individuals
  • Only ~5% require treatment
  • Biopsy may be needed if malignant transformation suspected 1

Surveillance Recommendations

Imaging

• Baseline MRI for known/suspected plexiform neurofibromas 1, 2
• Regular clinical assessment for tumor growth/symptoms
• Annual mammograms starting at age 30 for women (higher breast cancer risk) 1, 2
• Consider breast MRI with contrast between ages 30-50 years 2

Clinical Monitoring

• Annual ophthalmologic exams in children, less frequent in adults 1
• Regular developmental assessment in children 1
• Regular blood pressure monitoring for hypertension (pheochromocytoma risk) 1, 2
• Pain assessment using validated scales 1

Management of Other Complications

Pain Management

• Chronic pain is common and underrecognized 1
• Approach:
  • Medication
  • Physical therapy
  • Surgery for compressive tumors
  • Referral to pain clinics for complex cases 1

Glomus Tumors

• Painful fingertip tumors requiring surgical intervention 1
• Present with localized tenderness, severe paroxysmal pain, and cold sensitivity

Neurological Complications

• Migraine, seizures, sleep disorders: Treat as in non-NF1 population 1
• NF1 neuropathy: Consider medication, physical therapy, or surgery for compression 1

Special Considerations

Pregnancy and Contraception

• Higher maternal morbidity (hypertension, preeclampsia, growth restriction) 1
• Most oral contraceptives appear safe; high-dose depot progestogens may stimulate neurofibroma growth in rare cases 1

Quality of Life Assessment

• Regular structured assessments using validated questionnaires 2
• Address psychosocial impacts of disease

Pitfalls to Avoid

• Delayed MPNST diagnosis: Maintain high clinical suspicion for pain or rapid tumor growth
• Unnecessary radiation: Prefer MRI over CT when possible
• Missed screening: Adhere to recommended surveillance schedules
• Inadequate pain management: Address chronic pain proactively
• Failure to consider NF1-specific cancer risks: Particularly breast cancer in young women

The management of NF requires lifelong monitoring with age-specific attention to potential complications, with early intervention being key to improving outcomes and quality of life.