Treatment Options for Neurofibromatosis Type 2
For patients with NF2, treatment should be stratified based on tumor type and disease severity: hearing-sparing microsurgery is the first-line approach for small vestibular schwannomas (VS) with preserved hearing, while bevacizumab is the primary medical therapy for progressive VS when surgery is not feasible or for patients with larger tumors and preserved hearing where surgical risk of hearing loss is high. 1, 2
Primary Treatment Modalities
Surgical Management
Surgery remains the cornerstone of NF2 management, with the specific approach determined by tumor characteristics and patient factors 3:
For minimally affected patients with preserved hearing and small tumors: Hearing-sparing microsurgery should serve as the first-line approach, as there is maximal opportunity for preserving hearing and cranial nerve function when tumors are small 1
For meningiomas: Surgery is indicated when there is significant growth, parenchymal edema, or clinical symptoms such as neurologic deficit, intractable seizures, or intracranial hypertension 1
For spinal tumors: Surgery is currently the only option when tumors are symptomatic, though NF2 ependymomas are usually indolent and rarely require surgery 1
Medical Therapy
Bevacizumab is the only drug currently proposed to selected NF2 patients in clinical practice 2:
Bevacizumab (anti-VEGF monoclonal antibody) induces hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas 2
In clinical experience, bevacizumab increases median time to tumor progression of VS from 5.6 months before treatment to more than 29.3 months 2
Primary drawbacks: Requires intravenous injections and carries long-term adverse events including hypertension, proteinuria, and hemorrhage 2
Optimal patient selection: Drug treatment may be the first therapeutic option for patients with larger tumors and preserved hearing due to higher risk of hearing loss with surgical therapy 1
Radiosurgery and Radiotherapy
The use of radiosurgery and radiotherapy for NF2 management is highly controversial 1:
Differences of opinion exist regarding whether observation, microsurgery, or radiosurgery is more effective for hearing preservation 1
Major concern: Radiosurgery and radiotherapy may induce malignancy, including secondary meningiomas and multiple small tumors 1
For cavernous sinus meningiomas specifically, surgery is not recommended, and radiosurgery may be helpful for rare symptomatic growing tumors 1
Critical caveat: The NF2 community lacks thorough data on the risks, benefits, and outcome of radiotherapy and radiosurgery beyond individual case reports 1
Treatment Algorithm by Clinical Scenario
Three Broad Patient Populations
Treatment should be tailored to disease severity 1:
Treatment naive patients (zero to one neurosurgical CNS procedure, no major complication except hearing loss or minor mononeuropathy): Consider early surgical intervention or watchful waiting with serial MRI 1
Patients with few treatments and/or some NF2 morbidity (two to three CNS surgeries, ambulant with no more than one major complication): Consider medical therapy or additional surgery based on tumor characteristics 1
Severe NF2 patients (multiple surgeries or severe morbidity): Drug treatment should be offered as adjunct to surgery or when surgery has been exhausted 1
Specific Clinical Scenarios
For patients with hearing deterioration after initial surgery: Consider enrollment in drug clinical trials 1
For patients with multiple tumors who cannot undergo further surgery: This represents a compelling group in desperate need of options where drug treatment should be offered 1
For post-surgery meningioma patients with residual tumor tissue: Drug treatment could be tested as an alternative to radiosurgery 1
Hearing Rehabilitation
When neither cochlear nerve is stimulated, a multichannel auditory brainstem implant (ABI) should be considered 1:
The ABI is effective and safe, providing useful auditory sensations in most deaf NF2 patients 1
ABI improves ability to communicate compared with lip reading only 1
ABI allows detection and recognition of many environmental sounds and can offer significant ability to understand speech using only sound from the ABI 1
Surveillance Strategy
For patients under observation without active treatment 1:
Clinical and radiological (MRI) follow-up required at 6 months, then yearly 1
Very few patients develop new meningiomas during surveillance 1
Imaging should be done at least every 6 months (every 3 months is preferred for patients in clinical trials) 1
Emerging Therapies with Limited Current Use
Other drugs have been evaluated but are not currently used in clinical practice 2:
Lapatinib: Showed volumetric response in 4/17 patients and hearing response in 4/13 in a single phase II trial, but not currently used 2
Erlotinib: Not associated with radiographic or hearing responses in phase II trial 2
Everolimus: Did not induce tumor shrinkage but may increase time to tumor progression in selected cases based on 3 phase II trials 2
Critical Management Pitfalls
Patients who have failed radiosurgery may have become therapy resistant, making them a more challenging population for treatment 1
NF2 patients may suffer from "burnout" after multiple surgeries and treatments, requiring careful consideration of treatment timing and patient engagement 1
Patients with multiple surgeries or radiation may need to be excluded from certain treatments due to risk for tumors to become malignant and impaired imaging/tumor monitoring from surgical artifacts 1