80.1 Introduction

Bilateral vestibular schwannomas (VSs) are the hallmark of neurofibromatosis type 2 (NF2) and are present in 90 to 95% of patients with NF2.s. Literatur VSs are slow-growing benign tumors and inescapably cause bilateral deafness in most patients. To critically evaluate the results of the available treatments, the authors have reviewed the published natural history of VS in NF2, focusing on the patterns and factors influencing tumor growth and the patterns and mechanisms of hearing loss.

80.2 Growth Rate and Growth Patterns

During the last decade, the evolution of imaging techniques has led to the consensus that three-dimensional volumetric measurements are significantly more sensitive to change than single linear diameter measurements.s. Literatur Linear measures underestimate the volumetric growth of VS. This finding was seen for overall growth rates, annual growth rates, and determination of tumor progression. While linear measurements are performed for ease of use and are suitable for most malignant lesions that rapidly change in size, they are inappropriate for benign slow-growing tumors such as VSs, for which volumetric analysis of MRIs has been recommended.s. Literatur

The natural history of bilateral VS in NF2 has been thoroughly described in several studies, emphasizing their highly variable growth ratess. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur (Table 80‑1 ). In publications focusing on patients treated with conservative management, the mean VS growth rates ranged from 0.4 mm/years. Literatur to 1.8 mm/year.s. Literatur In other cohorts, the mean annual growth rates of NF2-related VS were higher (Harris et als. Literatur: 8.9 mm/year, Dirks et als. Literatur: 8.4 mm/year). The first two cohorts suffer from selection bias, as fast-growing tumors ineligible for conservative treatment were excluded from their studies. The last two cohorts suffer from a small cohort size—15 and 18 tumors, respectively. When attempting to classify enlarging VSs according to growth rate, 31% may be defined as slow-growing (growth rate: < 1 mm/year) and 25% as fast-growing (growth rate: > 3 mm/year), while 44% have intermediate growth rates.

Several studies have reported that linear diameter growth rates, but not volumes, of left- and right-sided VS in the same patient are strongly correlated.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Conversely, in their cohort of 29 patients harboring 58 VSs, Slattery and colleaguess. Literatur found a significant relationship between the sizes of left and right VS at a precise time point (baseline and end of follow-up) but not between the growth rates of the tumors. In a 2013 publication from our center, we showed that before the first surgery, bilateral VSs tend to have similar growth rates. We postulated that despite their intrinsic similar growth rates, bilateral VSs often present at different sizes at diagnosis, depending on the timing of the second hit leading to biallelic inactivation of the NF2 gene (the first hit being the germline or mosaic mutation).s. Literatur However, we believe that this small correlation does not validate the use of a contralateral VS as an internal control for studies evaluating unilateral radiosurgery effects on tumor growth, as previously reported.

In a recent study by Dirks et al with long-term follow-up of VS in NF2 patients, the authors suggested that all VSs eventually grow over time.s. Literatur Despite long follow-up (mean: 9.5 years), this study suffers from a small cohort size (17 patients) and from selection bias with most patients presenting with more severe phenotypes and high tumor burden.

Spontaneous shrinkage can also occur during radiological follow-up, which must be taken into consideration when examining the efficacy of radiosurgery and medical therapy. In our study, we found that 14% (13/92) displayed shrinkage or no growth but with a shorter radiological follow-up (mean: 4.2 years).s. Literatur Similarly, others have shown that VS may spontaneously decrease in size over time.s. Literatur In a series of 56 patients with 84 VSs, Slattery et al found some degree of size regression in 19% of tumors (16 of 84): 7 of 16 decreased less than 1 mm in size and 13 tumors less than 2 mm. Most interestingly, one tumor regressed almost 7 mm in short-term follow-up. In the most recent and largest study to date on 102 patients, Plotkin et als. Literatur reported a 25% rate of spontaneous tumor shrinkage, defined as a decrease in tumor volume of 20% or greater. However, about one-third of tumors failed to maintain tumor shrinkage during follow-up and 25% of concerned patients demonstrated tumor shrinkage only at their last study visit, questioning the durability of such a phenomenon. Dirks et al demonstrated the existence of saltatory growth patterns for 47% of VSs and suggested that previous studies may have incorrectly classified tumors as nongrowing while they were actually quiescent over the course of the study.s. Literatur However, this observation relies on a small number of tumors (18 tumors in 12 patients) and nonvolumetric analysis of growth.