52.1 Introduction

Long-term audiometric and vestibular outcomes after stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) for vestibular schwannoma (VS) remain a contentious issue. The primary challenges are to distinguish treatment effect from the natural history of disease and to decipher which factors best predict outcomes and how those factors interact (Table 52‑1 ). The current literature pertaining to this topic is frequently mired by heterogeneity in outcome reporting and imperfect methodology, making data interpretation and inter-study comparison difficult.

The primary objective of the current chapter is to review factors that influence hearing and balance after SRS for VS. Priority is given to the most recent and relevant data and only those studies that present data using standard reporting guidelines including the American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) and Gardner–Robertson (GR) hearing classification systems—both designating serviceable hearing as greater than 50% on word recognition testing and less than a 50-dB pure-tone average (PTA; Table 52‑2 ).s. Literatur ^,​ s. Literatur

52.2 Patient-Related Factors

Patients with normal or mild hearing loss prior to treatment tend to retain functional hearing longer following radiation treatment than patients with greater degrees of hearing loss. Hasegawa et al. found that 64% of patients with GR class I hearing retained serviceable at 5 years following treatment, compared to only 24% in patients who started with GR class II hearing.s. Literatur Furthermore, even among patients with GR class I or AAO–HNS class A hearing, even mild hearing loss and subtle asymmetry predicts poorer long-term audiologic outcome compared to those with normal hearing.s. Literatur ^,​ s. Literatur Mousavi et al. classified 68 patients with pretreatment GR class I hearing into groups, with or without subjective hearing loss. At 3-year follow-up, the patients without subjective hearing loss had 100% maintenance of serviceable hearing, compared to 57% in patients with subjective hearing loss.s. Literatur In a follow-up study, the authors divided 166 patients with GR class I hearing into three groups based on the level of PTA asymmetry: no asymmetry, less than 10 dB difference, and more than 10 dB difference. After 5-year posttreatment, follow-up serviceable hearing was maintained in 98, 73, and 33% of patients, respectively.s. Literatur Carlson et al. proposed that each 10-dB increase in pretreatment PTA results in a twofold increased risk of posttreatment hearing loss.s. Literatur The correlation between pretreatment hearing thresholds and posttreatment time to nonserviceable hearing has also been supported by multivariate analyses.s. Literatur ^,​ s. Literatur

Paralleling the aforementioned data, studies on the natural history of hearing loss with VS also report different trajectories for maintenance of serviceable hearing once hearing loss has started, even if that loss is mild. In a study by Stangerup et al., audiometric data were available for 932 patients managed with a “wait-and-scan” approach. Patients with an initial speech discrimination score (SDS) of 100% had a significantly higher rate of long-term hearing preservation than patients with an initial SDS between 99 and 90% (87 vs. 54%).s. Literatur These data further support that subdivisions may exist within patients classified as “good” according to either the GR or AAO–HNS scales. Whether discussing the natural disease history or treatment outcomes, the early signs of hearing loss predict eventual hearing decline in all treatment cohorts. The specific role of radiation effect versus natural history remains undetermined.

Patient age has also been identified as a potential predictor for hearing preservation after SRS. Kano et al. demonstrated that age less than 60 years was associated with better hearing preservation.s. Literatur Franzin et al. showed that age less than 54 years predicts better hearing preservation, while Tamura et al. reported that age less than 50 years was the statistical cutoff point distinguishing hearing outcomes.s. Literatur ^,​ s. Literatur Other studies showed no correlation between age and hearing preservation.s. Literatur ^,​ s. Literatur ^,​ s. Literatur The selection of a specific cutoff age is often arbitrary and use of appropriate statistical methodology is critical to control for other confounding variables. The study by Franzin et al. highlights this issue. Their age cutoff of 54 years was statistically significant on univariate analysis but not with multivariate regression. Age-related hearing loss, with or without the added complexity of the presence of a VS, incorporates many variables that are ideally analyzed with multivariate analysis. When reviewing the VS treatment literature, it is crucial to consider these subtleties, particularly if inferences are made regarding causality or clinical significance.

Data regarding vestibular function after SRS are less robust than reports on hearing outcomes. Vestibular outcomes, like hearing outcomes, must be compared against the natural history of disease and changes associated with aging.s. Literatur ^,​ s. Literatur ^,​ s. Literatur Wackym et al. compared pre- and posttreatment vestibular function in 54 patients managed with SRS. All patients had at least 6-month follow-up and 27 patients were followed up for longer than 60 months. The majority of patients did not experience long-term change in vestibular function as measured by electronystagmography or the dizziness handicap inventory (DHI). The mean pretreatment DHI was 15.5 compared to the mean posttreatment DHI of 13.5. A subset of patients older than 65 years were more likely to have improvement in their DHI scores. Vestibular function fluctuated the most after the first 6 months of treatment. This early posttreatment window may represent a critical period for vestibular rehabilitation.s. Literatur Another study identified severe headaches as predictive of severe dizziness (DHI > 26). This association was maintained among cohorts of patients treated with observation, microsurgery, and SRS. After a mean follow-up of 7.7 years, nearly 60% of patients experienced some degree of dizziness, although the majority had only mild symptoms. Multivariate analysis found an association between poor DHI scores and increasing age, tumors greater than 20 mm, pretreatment dizziness, frequent headaches, and severe headaches. Migraine features were significant in univariate analysis only.s. Literatur

52.3 Tumor-Related Factors

Hearing preservation after SRS may be affected by tumor-related factors such as VS size, tumor location in relationship to the cochlear nucleus or cochlea, tumor enlargement after treatment, growth rate, cytokine secretions, or cystic characteristics.

Although decreased rates of hearing preservation would be suspected with larger tumors, the effect of tumor size alone on hearing preservation is inconclusive. Interpretation of the data regarding tumor size is often difficult because of the variability in measurement techniques. Multiple reports demonstrate total tumor size has no effect on hearing preservation.s. Literatur ^,​ s. Literatur ^,​ s. Literatur However, other studies have demonstrated tumor size predicts hearing preservation after SRS.s. Literatur ^,​ s. Literatur ^,​ s. Literatur Carlson et al. showed a 2.4-fold increased risk of progression to nonserviceable hearing in tumors that contacted the brainstem compared to smaller tumors.s. Literatur

Hearing decline after SRS is strongly associated with radiation dose delivered to the cochlea. As a result, the volume and location of tumor within the internal auditory canal (IAC) will largely determine the amount of radiation the cochlea will receive. Massager et al. evaluated the effects of intracanalicular tumor volume on hearing preservation in 82 patients treated with 12 Gy at the 50% isodose line. The authors demonstrated that intracanalicular tumor volume and radiation dose were predictive of hearing preservation. Patients with preserved hearing had a mean tumor volume of 136.16 mm³ (range of 0–556 mm³) compared to a mean tumor volume of 220.01 mm³ (range of 46.5–555 mm³) in patients who demonstrated hearing decline. The authors conclude SRS delivered with an intracanalicular volume of greater than 100 mm³ has a 3.5-fold rate of hearing degradation when compared to tumor volumes less than 100 mm³. In this study, total tumor volume did not predict hearing preservation.s. Literatur

Niranjan et al. analyzed hearing preservation in 15 patients with purely intracanalicular tumors and serviceable hearing, with a median follow-up of 33 months (range, 9–65 months). At last follow-up, 73% maintained serviceable hearing after SRS. Use of 4-mm collimators and a tumor diameter less than 4 mm was associated with improved hearing preservation. Position of the tumor within the IAC and tumor length did not correlate with maintenance of hearing. Patients who received ≤ 14 Gy to the tumor margin also had better hearing outcomes.s. Literatur

The natural history of hearing loss in relation to tumor growth is controversial. Hajioff et al. followed up 72 patients for a median of 10 years. The majority of patients had tumor growth of less than 1 mm/year. Forty patients had audiometric data and all showed some degree of hearing decline with no correlation to tumor growth.s. Literatur In contrast, an institutional review and a systematic analysis by Sughrue et al. showed that tumor growth rate was inversely correlated with hearing preservation. Specifically, 75% of patients with tumor growth less than 2.5 mm/year maintained functional hearing at the time of last follow-up, while only 32% of patients with tumor growth greater than 2.5 mm/year had preserved hearing.s. Literatur ^,​ s. Literatur The poor correlation between tumor growth and hearing status implies that other factors may be involved. One factor is whether or not tumors secrete cytokines that may influence the health of the cochlea or cochlear nerve. Using a cytokine microarray from surgically excised tumor specimens, high levels of fibroblast growth factor 2 (FGF2) corresponded to a 3.5-fold higher rate of better hearing.s. Literatur Biomarkers, like FGF2, may someday help us predict the natural course of hearing. Another factor for hearing loss may be the buildup of proteinaceous material within the cochlea or CSF fundal cap. Three-dimensional fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging has the ability to detect increased protein concentrations within the cochlea perilymph. An increased FLAIR signal within the cochlea has been correlated with worse hearing in VS, as well as other disease processes such as sudden idiopathic sensorineural hearing loss, Ramsay Hunt syndrome, and radiation toxicity.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur

Tumor swelling after radiation treatment may also have an effect on hearing decline. Nearly 50% of VS will have at least 1 mm of mean diameter expansion after radiation and 17% will have greater than 2 mm of expansion.s. Literatur This posttreatment edema is often transient, although delayed cyst formation may have a more refractory course.s. Literatur ^,​ s. Literatur Kim et al. showed more hearing deterioration in patients who demonstrated ≥ 20% tumor enlargement after radiosurgery.s. Literatur It is unclear whether transient tumoral edema causes hearing deterioration through acute compression or traction of the cochlear nerve or its blood supply, from tumor cytokine release or other unknown factors.