Stereotactic radiosurgery for sporadic vestibular schwannoma

Tumor control

VS are typically slow-growing tumors, with a substantial proportion remaining radiographically stable over long-term follow-up. Accordingly, a conservative “wait-and-see” approach has traditionally been preferred initial management strategy for asymptomatic, small tumors confined to the internal auditory canal (IAC). However, in cohorts managed with observation, approximately 40% of patients required additional intervention due to tumor progression within 5 years, and among these, 42% underwent SRS. These findings suggest that while conservative observation may be safe for a period, a non-negligible proportion of cases ultimately require therapeutic intervention [8,9].

Following SRS for intracanalicular VS, tumor control rates have been consistently reported at 95–98%, with sustained long-term efficacy beyond 5 years [10]. Recent comparative studies and meta-analyses have demonstrated that the upfront SRS group showed favorable outcomes over the observation group, with significantly lower rates of tumor progression (6% vs. 40%) and reduced need for subsequent treatment (1% vs. 25%) [11,12].

Hearing preservation

With the increasing early detection of intracanalicular VS, hearing preservation has emerged as a main objective in treatment decision-making. Pennings et al. [13] reported that approximately 50% of patients with VS experience progressive hearing decline during the natural course of VS. Even some patients with favorable baseline hearing may eventually lose serviceable hearing over time. Notably, hearing deterioration does not always correlate with tumor growth. It may occur independently of tumor progression [8,13]. Therefore, hearing status should be considered to determine whether upfront SRS is indicated.

A recent international multicenter matched cohort study compared long-term hearing outcomes between patients managed with upfront SRS and those undergoing observation. Serviceable hearing preservation rates did not differ significantly between the two groups. At 3 years, the preservation rates were 73.5% in the SRS group and 82.9% in the observation group. At 5 years, these declined to 70.1% and 53.4%, respectively. By 8 years, hearing preservation was observed in 44.6% of the SRS group and 26.7% of the observation group. Despite these trends, no statistically significant difference was found over the full follow-up period (log-rank test, p=0.33) [11,14].

Several factors have been identified as predictors of hearing preservation following SRS, including tumor size and anatomical location, pre-treatment hearing status, radiation dose [11,14]. Among these, pre-treatment hearing status is the most important prognostic factor. Patients classified as Gardner–Robertson class I or II demonstrate the highest likelihood of maintaining serviceable hearing post-treatment. A pure tone average exceeding 30 dB has been associated with a significantly increased risk of post-treatment hearing decline, suggesting greater vulnerability to radiation-induced damage in patients with pre-existing hearing decline. Tumor size is also a critical determinant. Although most intracanalicular lesions range from 0.05 to 0.2 cm³, subtle differences in size and spatial positioning could impact outcomes. Specifically, tumor volumes exceeding 0.15 cm³ have been associated with a 4-fold increased risk of hearing deterioration (p=0.045), likely due to transient volume expansion and subsequent compression of the cochlear nerve within the limited space of the IAC [15].

A recent study involving 37 patients with small intracanalicular VS and serviceable hearing demonstrated hearing preservation rates of 86%, 82%, and 70% at 1, 2, and 3 years, respectively, following SRS. Notably, in patients with tumor volumes ≤0.05 cm³ treated with a single 4-mm shot with a marginal dose of 12 Gy, hearing was preserved in all cases. These findings support the safety and efficacy of early SRS in selected patients with small-volume tumors and good baseline hearing [16].

Others

SRS demonstrates an excellent safety profile with respect to facial nerve preservation. Long-term follow-up data report that the incidence of persistent facial nerve palsy is less than 0.1%, with transient facial weakness being similarly rare. This favorable outcome significantly contributes to the maintenance of patient quality of life following treatment. Other neurological complications are also infrequently reported. In selected studies, vertigo was observed in approximately 5% of patients (range: 4.3–8%), while additional adverse events such as facial spasms have been reported in less than 1% of cases [10,17].

In conclusion, SRS for intracanalicular VS offers comparable outcomes to observation in terms of hearing preservation, while providing superior tumor control and long-term neurological safety. In patients with small tumor volumes and favorable baseline hearing (Gardner–Robertson class I), upfront SRS may offer a distinct advantage in hearing preservation. Conversely, in patients with baseline hearing decline, tumor volumes exceeding 0.15 cm³, or radiation dose exceeding 12 Gy, the likelihood of hearing preservation is reduced. These factors should therefore be carefully considered and integrated into a patient-specific treatment plan.

Tumor control

SRS has established as a primary treatment modality for small to medium-sized (a maximum diameter of ≤3 cm) VS. It consistently achieves high tumor control rates, with most studies reporting long-term control exceeding 90%. A meta-analysis comparing SRS and microsurgery demonstrated tumor control rates greater than 90% in both cohorts, with long-term outcomes showing 98% control in the microsurgery group and 92% in the SRS group [18]. Although microsurgery allows for complete tumor removal, it is associated with a potential risk of facial nerve dysfunction and other surgery-related morbidities. As a result, SRS is increasingly favored in clinical practice, owing to its advantages in functional preservation and patient preference. A randomized controlled trial comparing upfront SRS with conservative observation demonstrated a statistically significant benefit of SRS in suppressing tumor growth. At 4-year follow-up, the mean tumor volume ratio (V4:V0) was 0.87 in the SRS group, indicating volumetric reduction, whereas the observation group exhibited a mean ratio of 1.51, reflecting substantial tumor growth (p=0.002). These findings suggest that upfront SRS may reduce the need for future therapeutic intervention by effectively limiting tumor growth [19,20].

SRS not only inhibits tumor growth but is associated with gradual volume reduction over time. However, transient tumor expansion, known as pseudoprogression, is frequently observed within the first 2 years post-treatment, occurring in approximately 20–80% of cases. This phenomenon is reported to result from radiation-induced apoptosis, vascular injury, and immune-mediated responses, leading to transient volume expansion (TVE). Histopathologically, pseudoprogression is characterized by the presence of foamy macrophages, myxoid degeneration, and necrosis [21,22]. Importantly, such volume increases do not necessarily indicate treatment failure and typically resolves or stabilizes spontaneously over time. Recent studies have reported cases in which TVE persists for more than 5 years. In the absence of brainstem compression or progressive neurological deficits, prolonged conservative surveillance is generally recommended [23,24].

Hearing preservation

Hearing preservation is a critical determinant of quality of life in patients with VS, particularly in those with small- to medium-sized tumors. In such cases, SRS requires careful balancing between tumor control and functional preservation. Despite numerous studies, the precise mechanisms underlying hearing loss following SRS remain incompletely understood. Several hypotheses have been proposed:

- Radiation-induced injury: Radiation may cause direct damage to the cochlear nerve, cochlea, or cochlear nucleus. Among these, the radiation dose delivered to the cochlea has been identified as a critical factor in hearing preservation. Several studies have reported higher preservation rates when the mean cochlear dose is maintained below 4 Gy, with some suggesting thresholds as low as 3.1 or 4.2 Gy. However, other studies have failed to demonstrate a clear correlation between cochlear dose and hearing outcomes, potentially due to variability in dosimetric techniques and cochlear dose measurement methods [25,26].

- Transient volume expansion and increased intracanalicular pressure: Volume expansion following SRS may increase pressure within the IAC, leading to compression of the cochlear nerve or disruption of microvascular perfusion, thereby contributing to hearing deterioration. TVE is currently considered one of the most significant predictors of hearing decline. TVE in patients with loss of serviceable hearing was larger than in patients with intact hearing. Some studies have shown that favorable baseline auditory brainstem responses, correlate well with intracanalicular pressure, are associated with hearing preservation. Additionally, the degree of tumor filling within the IAC on pre-treatment MRI has been proposed as a surrogate marker for intracanalicular pressure and a potential predictor of hearing loss [15,27,28].

- Tumor biology and microenvironment: Beyond mechanical compression and radiation effects, intrinsic biological activity of the tumor may contribute to hearing loss. Inflammatory cytokines such as tumor necrosis factor-α and MMP-14, released following irradiation, have been implicated in ototoxic injury. Moreover, tumor-associated macrophage-mediated inflammatory responses may also play a role. Elevated protein concentrations in endolymphatic fluid, as observed on FLAIR MRI sequences, have been suggested as another marker associated with hearing decline [29,30].

These mechanisms likely interact in a multifactorial manner, and further research is needed to elucidate the precise pathophysiology of post-SRS hearing loss. Some studies have demonstrated that the timing of TVE often overlaps with the onset of acute hearing decline, typically within 12 months post-treatment. In this context, corticosteroid administration has shown potential benefit in mitigating acute auditory deterioration. Therefore, close hearing monitoring during this period, combined with timely corticosteroid intervention, and may help prevent irreversible hearing loss [31].

Additionally, hearing preservation rates after SRS decline over time. While 5-year preservation rates range from 57–74%, they decrease to 24–44% at 10 years. Although outcomes may differ depending on baseline hearing status and tumor size, progressive hearing decline over time remains a possibility. Therefore, individualized strategies should be guided by careful assessment of contralateral hearing status and consideration of long-term hearing prognosis.

Tumor control

Although evidence supporting the use of SRS for large VS, particularly those classified as Koos grade IV, has been limited, a recent international multicenter study by Pikis et al. [32] has provided substantive data supporting its efficacy. This study analyzed outcomes from 627 patients with large VSs who underwent single-session SRS, with a median tumor volume of 8.7 cm³. Over a median follow-up period of 38 months, tumor stability and regression were observed in 47.7% and 46.4% of patients, respectively, yielding an overall tumor control rate of 94.1%. The 5- and 10-year progression-free survival rates were 92.3% and 87.6%, respectively—comparable to those reported for smaller tumors.

However, tumor volume expansion occurred in 10.7% of patients within 36 months post-treatment, and 18 patients (2.9%) ultimately required surgical resection. In large tumors with limited anatomical reserve, such early post-SRS volume expansion may result in brainstem compression. Accordingly, appropriate pre-treatment warning and patient education regarding this potential risk is warranted.

Single-session SRS in large tumors may increase the risk of radiation-induced toxicity. To mitigate this, hSRS has emerged as an alternative approach [33,34]. hSRS involves delivering the total radiation dose in 3–5 fractions, taking advantage of the differential radiobiological responses of normal tissues to mitigate toxicity while maintaining therapeutic efficacy. Common fractionation regimens include 18 Gy in three fractions, 21 Gy in three fractions, and 25 Gy in five fractions. These regimens provide a biologically effective dose, comparable to 12–13 Gy in a single fraction, while potentially reducing radiation exposure to critical structures such as the cochlea, brainstem, and facial nerve.

Recent studies (Table 1) [33,35-39] have reported 5-year tumor control rates of 80–100% with hSRS in large VS—slightly lower but generally comparable to the 90–97% reported with single-session SRS. In terms of functional outcomes, hSRS has demonstrated a favorable safety profile, with no reported cases of facial nerve palsy or trigeminal sensory disturbance. This contrasts with the 1–5% incidence of transient facial nerve dysfunction and trigeminal paresthesia occasionally observed following single-session SRS, suggesting that fractionated regimens may provide better protection for sensitive neuroanatomical structures. Moreover, some meta-analyses suggest that hSRS may offer advantages in hearing preservation by more effectively limiting cochlear radiation exposure. However, given the limited sample sizes and study heterogeneity, further validation through large-scale randomized controlled trials is necessary.

Table 1.

Hypofractionated stereotactic radiosurgery studies

Facial nerve preservation

Facial nerve function preservation is a key clinical objective in the management of large VS. In a multicenter study, deterioration of facial nerve function, defined as worsening of the House-Brackmann grade, was reported in 3.0% of patients following SRS [32,40]. The majority (93.6%) maintained their pre-treatment facial nerve function, and improvement was reported in 3.3% of cases. Risk factors for post-treatment facial nerve dysfunction included a prescription dose of ≥13 Gy (p=0.03, hazard ratio [HR]=4.8) and early tumor volume expansion (p=0.04, HR=5.0). These findings support the recommendation to limit the marginal dose to below 13 Gy when feasible in order to optimize facial nerve preservation in large tumors. Long-term outcomes remain favorable, with facial nerve preservation rates of 97.3% at 5 years and 91.9% at 10 years—comparable to those observed in small- and medium-sized tumors.

Others

In the management of large VS, notable complications associated with SRS include adverse radiation effects (AREs), trigeminal neuropathy, and hydrocephalus [32,40,41]. AREs comprise a spectrum of post-radiosurgical changes such as T2 hyper intensity on MRI, cyst formation, and radiation necrosis. Clinically, these may present as headache, focal neurological deficits, or gait disturbances. Although often mild and transient, AREs can, in some cases, result in persistent neurological impairment. In large VS, the incidence of AREs following SRS has been reported at 14.7%, with 5.4% of patients requiring intervention, such as corticosteroid administration or surgical management. High prescription doses (≥13 Gy) and early post-treatment tumor volume expansion have been identified as independent risk factors for AREs. Accordingly, for large VSs, it is recommended to limit the marginal dose to ≤12–13 Gy. Furthermore, meticulous treatment planning is essential to minimize radiation exposure to adjacent critical structures, particularly the brainstem.

Trigeminal neuropathy has been observed in 5–8% of patients treated with SRS for large VS. The risk is elevated when tumors extend toward Meckel’s cave or when higher radiation doses are used. Pre-existing trigeminal neuropathy has been observed in 7.7–32.4% of cases, and in some patients, SRS has led to symptomatic improvement. However, a subset may develop chronic neuropathic pain post-treatment. For patients in whom trigeminal neuralgia relief is a primary therapeutic goal, microsurgical decompression may be a more appropriate option, offering immediate relief [42].

Hydrocephalus may result from fourth ventricle compression by the tumor or from post-radiosurgical changes such as edema, cyst formation, or pseudoprogression. In select cases, cerebrospinal fluid diversion via ventriculoperitoneal shunting may be required. Notably, communicating hydrocephalus can occur independently of tumor growth, highlighting the importance of comprehensive pre-treatment risk assessment when considering SRS.

Although microsurgery remains the standard initial treatment for many large VS—particularly in cases of refractory trigeminal neuralgia, progressive ataxia, or brainstem compression—SRS is increasingly recognized as a viable alternative in patients without life-threatening mass effect and with stable clinical status. With meticulous patient selection and optimized dose planning, SRS can be a safe and effective treatment option even in the setting of large VS. Nonetheless, given the risk of hydrocephalus or neurological deterioration from post-treatment volume expansion, careful post-SRS surveillance and timely surgical intervention, when indicated, are critical components of optimal patient management.