6 Natural History and Management Options of Vestibular Schwannomas

Jordan Jones, Andrew H. Kaye, and Andrew Morokoff

Abstract

An understanding of the natural history as well as the effectiveness of treatment modalities is essential when managing patients diagnosed with vestibular schwannomas. In this chapter, we review the literature pertaining to the rate and predictive features of growth in both sporadic and neurofibromatosis type 2 associated vestibular schwannomas. We then summarize the outcomes following surgery, stereotactic radiosurgery, and a combination of subtotal resection and adjuvant radiosurgery.

Vestibular schwannomas (VS; acoustic neurinomas) are benign tumors that typically arise from the vestibular division of the vestibulocochlear nerve.1 They account for approximately 6 to 8% of all primary intracranial tumors and are responsible for between 78 and 85% of tumors that arise within the cerebellopontine angle.^{2,​ 3} The incidence of VS is best estimated by the Danish epidemiology study by Tos et al at 9.4 tumors per year per million inhabitants.⁴ A more recent review of their database in 2004 indicated that this was increasing to a peak of 23 tumors per year per million, likely reflecting the improved diagnostic capabilities of modern magnetic resonance imaging (MRI).⁵ Post mortem studies have found a higher incidence of VS from 1.7 to 2.4%, suggesting a substantial number remain asymptomatic or undiagnosed and follow a benign course.^{6,​ 7}

VS are sporadic and unilateral in 96% of cases (Fig. 6.1a). Bilateral VS (Fig. 6.1b) are far less common and are associated with the inherited condition neurofibromatosis type 2 (NF2). NF2, first described by the Scottish surgeon Wishart in 1822, results from a mutation in the tumor suppressor nf2 gene located on chromosome 22q12.2 that encodes for the Merlin protein. Merlin exerts its tumor suppressor effects primarily through maintaining membrane stability and by promoting cell contact inhibition.¹

Unilateral sensorineural hearing loss, tinnitus, and disequilibrium are the most common presenting symptoms in VS; however, only 10% of patients with these symptoms will be found to have a VS.⁸ Unilateral hearing loss that is present for a median of 1 to 3 years is the most common symptom (94–96%), followed by disequilibrium (77%), tinnitus (71%), headache (20–85%), otalgia (28%), facial numbness (7%), and diplopia (7%), with cerebellar dysfunction and facial hypoesthesia more common in larger tumors.^{9,​ 10,​ 11} Recently, there has been an increase in the detection of asymptomatic tumors (5–12%) found incidentally on neuroimaging.¹²

Prior to management decisions, all patients should have appropriate neuroimaging with MRI and computed tomography (CT), baseline audiometry assessment, and evaluation of facial nerve function.

6.2 Selected Papers on Natural History

●Paldor I, Chen AS, Kaye AH. Growth rate of vestibular schwannoma. J Clin Neurosci 2016;32:1–8

●Stangerup SE, Caye-Thomasen P, Tos M, Thomsen J. The natural history of vestibular schwannoma. Otol Neurotol 2006;27(4):547–552

●Hunter JB, Francis DO, O’Connell BP, et al. Single institutional experience with observing 564 vestibular schwannomas: factors associated with tumor growth. Otol Neurotol 2016;37(10):1630–1636

●Moffat DA, Kasbekar A, Axon PR, Lloyd SK. Growth characteristics of vestibular schwannomas. Otol Neurotol 2012;33(6):1053–1058

6.3 Natural History

There is wide variability in the reported natural history of untreated VS (Table 6.1). In sporadic tumors, the incidence of tumor growth during follow-up has been reported to be between 12 and 85% of cases. A total of 7,581 tumors were reported in the 50 series of non-NF2 VS; of these, 2,816 (37%) were reported as growing, during a median follow-up of 39 months. The duration of follow-up affects the incidence of growth as suggested by Paldor et al in their systematic review, in which approximately one-third of patients demonstrated growth in a follow-up period of 1 to 3 years; however, that increased to 50% when follow-up extended beyond 5 years.¹³

Table 6.1 Selective series reporting on the natural history of vestibular schwannomas

6.3.1 Rate of Growth

The reported rate of growth is also highly variable, typically less than 2 mm/y with an average of 1.48 mm/y in reports on non-NF2 VS. A small subset of patients though will demonstrate more rapid growth as reported by Charabi et al who found that 8% will grow greater than 10 mm/y,¹⁴ similar to that reported by Modugno et al, where 12% grew by greater than 9 mm/y.¹⁵ The pattern of growth is also not always constant with up to 40% showing exponential growth compared to linear enlargement.¹⁶ Growth in the first few years of follow-up tended to be more rapid and suggestive of continued enlargement, whereas several reports have suggested a slow or absent pattern of growth for 3 years indicates that future growth is unlikely to be of significance.

6.3.2 Risk Factors for Growth

Forty-one of the 56 reports attempted to identify predictive features of growth. Both patient and tumor factors were identified and included the following:

●Age: Younger patients are more likely to grow at an increased rate.

●Tumor size: Larger tumors demonstrated greater tendency for growth, but not at a faster rate.

●Tumor location: VS with extension into the cerebellopontine angle reported to more likely grow and at a faster rate compared to purely intracanalicular VS.

●Tumor features: Cystic tumors and those that have demonstrated hemorrhage show increased rate and tendency to grow.

●Presenting symptoms: Disequilibrium and tinnitus were reported in a small number of studies to be predictive of tumor growth. Hearing loss and vertigo as presenting symptoms were not found to be risk factors. Tumors found incidentally were reported either to have no effect on natural history¹⁷ or to behave more indolently.¹⁸

●Previous growth: VS growth within the first year was reported in five studies to be a significant predictor of further tumor growth. Similarly, the longer a tumor remains stable, the likelihood of subsequent growth also reduces; Sethi et al recently demonstrated the risk of growth after 4 years of stability to be less than 2%.¹⁹ On the other hand, a separate report by Macielak et al found that 3.9% of all observed tumors and 8.1% of previously reported growing tumors have delayed growth beyond 5 years arguing for lifelong surveillance of all untreated VS.²⁰

Although a number of risk factors for tumor growth were identified, the results were not consistent across all studies and 10 series found no features that were predictive of growth during follow-up. The clinical significance of tumor growth was also mixed with symptom progression or need for retreatment ranging from 23 to 42% when reported.^{18,​ 21,​ 22,​ 23,​ 24} Nevertheless, the majority of these studies were limited by selection bias whereby tumors deemed high risk for growth, including larger tumors, or tumors with symptom progression, were excluded from surveillance.

6.3.3 Growth in Neurofibromatosis Type 2 Vestibular Schwannomas

The growth of VS in patients with NF2 differs to that of non-NF2 patients due to underlying differences in tumor biology and the fact that they occur in a younger population. In six studies, the rate of growing tumors ranged from 32 to 100% of cases. Overall in 468 VS in NF2 patients, 263 (56%) were reported to grow during a median follow-up of 53 months. Growth rates were variable, with three series reporting younger age of onset as a risk factor for tumor growth and the median time to tumor progression was significantly shorter than the median time to hearing decline when reported.25^{,​ 26}

6.4 Selected Papers on Treatment

●Goldbrunner R, Weller M, Regis J, et al. EANO guideline on the diagnosis and treatment of vestibular schwannoma. Neuro-Oncol 2020;22(1):31–45²⁷

●Ben Ammar M, Piccirillo E, Topsakal V, Taibah A, Sanna M. Surgical results and technical refinements in translabyrinthine excision of vestibular schwannomas: the Gruppo Otologico experience. Neurosurgery 2012;70(6):1481–1491, discussion 1491

●Johnson S, Kano H, Faramand A, et al. Long term results of primary radiosurgery for vestibular schwannomas. J Neurooncol 2019;145(2):247–255

●Golfinos JG, Hill TC, Rokosh R, et al. A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas. J Neurosurg 2016;125(6):1472–1482

●Chung L, Nguyen T, Sheppard J, Lagman C. A systematic review of radiosurgery versus surgery for neurofibromatosis type 2 vestibular schwannomas. World Neurosurg 2018;109:47–58

6.5 Treatment

There are four main treatment strategies in patients with VS: conservative management with tumor monitoring, microsurgical resection, stereotactic radiosurgery (SRS) or a planned combination of subtotal resection and adjuvant SRS. Treatment decisions must consider tumor morphology and size, patient symptoms and comorbidities, as well as the experience of the treating team.

6.5.1 Microsurgery

The first reported successful operation on a cerebellopontine angle tumor was by Sir Charles Ballance in 1894 and early series were complicated by high morbidity and mortality.¹ Current advances in anesthesia, facial nerve electromyographic (EMG) monitoring, and microsurgical techniques, as described by House in 1964 and others, have resulted in significant reductions in mortality rates and high rates of anatomical facial nerve preservation. In general, there are retrosigmoid and presigmoid approaches with the choice dependent on tumor characteristics, hearing status, bony and venous sinus anatomy, and expertise of treating surgeons.

In the last 26 years, 114 studies have reported on outcomes following surgical resection of sporadic non-NF2 VS (Table 6.2). The total number of patients included was 28,470 patients with median follow-up of 37 months. A gross macroscopic resection was reported in 42 to 100% of cohorts with Ahmad et al reporting 93.8% gross total resection in a large cohort of 2,400 VS.²⁸ Larger tumors and cystic characteristics were associated with lower rates of GTR^{29,​ 30}; however, several series reported high rates of GTR despite these features.³¹ Along with the good chance of complete resection, tumor control was high and the need for retreatment was low in most reported series. Ben Ammar et al in a series of 1,865 patients reported 99.5% tumor control during a median follow-up of 68 months.³² Subtotal resection was associated with higher rates of retreatment (Fig. 6.2) as was cystic tumors,^{30,​ 33,​ 34} although in a series of 131 solid versus 131 matched cystic tumors there was minimal differences between the two groups.³⁵

Table 6.2 Summary of the literature regarding treatment of vestibular schwannoma

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