This retrospective analysis of 175 patients treated with stereotactic radiotherapy for vestibular schwannoma provides a robust long-term assessment of tumor control, symptomatic evolution, and toxicity profiles, with a particular focus on comparing single-fraction radiosurgery (SRS) and normofractionated stereotactic radiotherapy (NFSRT). With a median follow-up of 46 months, our data affirm the high efficacy of modern SRT while unveiling nuanced insights into dose–response relationships, symptom dynamics, and the late effects of treatment. These findings contribute significantly to the ongoing refinement of personalized therapeutic strategies for VS.

The cornerstone of any radiotherapy treatment is durable tumor control. Our study demonstrates exemplary outcomes in this regard, with an in-field progression-free survival (IFPFS) rate of 94.3% and an out-field progression-free survival (OFPFS) rate of 99.4% over the follow-up period. These figures are squarely in line with modern published series for both SRS and FSRT with photon and proton irradiation, which consistently report 5‑ and 10-year control rates exceeding 90%. Table 3 provides an overview of existing data from the past two decades using various fractionation schemes as well as photon and proton radiotherapy. Across numerous institutions and techniques, SRT provides control rates comparable to those of microsurgery but with a different profile of associated risks and benefits [7].

However, the most intriguing and potentially practice-informing finding of our analysis is the apparent dose–response relationship observed within the NFSRT cohort. Contrary to the conventional oncological principle that higher radiation doses yield superior tumor control, our univariate Cox model indicated that increasing total dose was a significant predictor of higher in-field progression rates (HR = 2.97; p = 0.003). All 10 recurrences occurred in patients receiving doses between 55.8 and 56 Gy in 1.8–2.0 Gy per fraction. This finding presents a fascinating paradox, and while it may initially seem counterintuitive, it potentially reflects the unique radiobiology of benign tumors like VS. The primary goal of SRT is not to eradicate every cell but rather to induce terminal growth arrest through mechanisms like vascular endothelial and DNA damage, leading to reproductive cell death [25]. Excessive dose beyond what is required to trigger this arrest may not provide additional benefit and could theoretically incite a proinflammatory or profibrotic tumor microenvironment that, in rare instances, might paradoxically support regrowth or treatment resistance [26, 29]. This observation challenges historical data that suggested improved control with doses at the higher end of the spectrum [10] and aligns with a growing body of evidence indicating that moderate doses are sufficient for excellent control [30, 31]. For instance, Meijer et al. [30] found no significant difference in tumor control between biologically different fractionation schedules of 20 × 2.5 Gy (50 Gy) and 25 × 2 Gy (50 Gy), suggesting a plateau in the dose–response curve. Our data imply that for NFSRT, this plateau may be reached at or even below 55.8 Gy, and exceeding it could be detrimental. This warrants serious consideration for protocol adjustment, potentially adopting a lower dose range of 50–54 Gy for standard fractionation, which has been shown to be highly effective while potentially improving the therapeutic ratio [30, 32]. Adding to this, no significant differences were found regarding tumor volumes in that group, although our standard was to treat larger tumors with lower doses to allow better OAR sparing.

Hearing preservation remains one of the most critical quality of life metrics in VS management. Our cohort had a high baseline rate of useful hearing impairment (86.9%), which remained stable at final follow-up (88.0%). This indicates that while SRT is highly effective at halting tumor progression and preventing further neurological decline, it rarely reverses pre-existing auditory deficits. This underscores the critical importance of early intervention while hearing is still serviceable, a conclusion strongly supported by prospective studies [9]. The high baseline impairment rate in our study precludes definitive comparison of hearing preservation rates between SRS and NFSRT, as there was little functional hearing left to preserve in many patients. This is a common challenge in retrospective series. The ongoing debate regarding a potential advantage of fractionated regimens for hearing preservation, based on the radiobiological principle of a more favorable alpha/beta ratio for neural tissue, therefore remains unresolved by our data [11, 33]. Prospective trials specifically enrolling patients with good baseline hearing are needed to definitively answer this question.

The analysis of symptom evolution before and after SRT revealed a generally stable or improving picture for most neurological symptoms. The rates of facial paralysis (7.4% before to 6.9% after SRT) and trigeminal neuralgia (1.1% before to 2.9% after SRT) were low and stable, reinforcing the superior facial nerve preservation profile of SRT compared to historical surgical series showing rates of up to 38% of facial nerve affection [34, 35]. Regarding trigeminal function, SRS in our series seems equal to surgical reports [36, 37]. This excellent safety profile is a direct result of steep dose gradients and rigorous adherence to modern dose constraints for the cranial nerves [38]. Nonetheless, the observed associations of higher age with lower rates of vertigo or tinnitus should be interpreted cautiously. Given the low event rates and retrospective design, such findings may reflect chance variation, reporting bias, or incomplete documentation rather than true biological effects. These signals are best considered hypothesis generating and warrant confirmation in prospective studies with standardized symptom assessment.

However, it is notable that the headache prevalence rose from 14.3% at baseline to 22.3% at final follow-up (p = 0.02). Post-SRT headache is a well-documented, though not fully understood, phenomenon. Carlson et al. [6] reported a 50% incidence of headaches up to 8 years after VS SRT, noting that they can be a delayed effect. This underscores the necessity of thorough patient counseling prior to treatment, setting realistic expectations not only for acute effects but also for potential long-term quality of life changes. The management of these patients may benefit from a multidisciplinary approach involving neurologists or pain specialists.

The transient nature of acute toxicities like fatigue and alopecia—showing a higher association with NFSRT—which were significant at the first (T1) but had resolved by the final follow-up (T2), is an important counseling point. Patients opting for a fractionated course should be reassured that these side effects, while common during treatment, are typically self-limiting.

Our analysis revealed that patients who had undergone prior partial resection were more prone to reporting vertigo at the final follow-up (OR = 0.3; p = 0.005). This is an insightful observation that speaks to the complex interplay between treatment modalities and functional outcomes. Surgery in the cerebellopontine angle can cause vestibular disruption by damaging the vestibular nerve or its vascular supply [21]. This, combined with the subsequent effects of radiotherapy on any remaining vestibular function, may impair the brain’s ability to fully compensate, leading to persistent dizziness and imbalance. This finding reinforces the argument for primary SRT in eligible patients, as it may offer a better chance of preserving vestibular function and facilitating neural compensation compared to a combined-modality approach that introduces the traumas of both surgery and radiation [22]. It also highlights the paramount importance of dedicated vestibular rehabilitation programs for all VS patients, particularly those undergoing multimodality treatment, to promote central compensation and improve functional outcomes [22].

The very low incidence of radionecrosis (0.6%) in our series is testament to the advancements in treatment planning and delivery. The use of high-resolution MRI fusion (including CISS/FIESTA sequences for superior nerve delineation), precise immobilization with thermoplastic masks, and daily image-guided verification ensure highly conformal dose distributions that spare critical organs at risk. This result is consistent with modern literature, where the risk of symptomatic radionecrosis is consistently reported at below 2% when established dose–volume constraints for the brainstem are meticulously adhered to [23, 38]. Interestingly though, the differentiation between progression, pseudoprogression, and radionecrosis remains challenging and demands interdisciplinary efforts [16,17,18]. In sum, the excellent safety profile makes SRT a very attractive option for patients.

The interpretations of this study must be contextualized within its limitations. The retrospective, single-institution design introduces inherent potential for selection bias and unmeasured confounding. While we statistically adjusted for factors like PTV size, other unaccounted-for variables may have influenced outcomes. The evolution of institutional techniques and dose prescriptions over the 25-year inclusion period is another confounding factor, reflecting the natural progression in the field but making direct comparisons over time less straightforward. The lack of standardized, prospectively collected quality of life data (e.g., using PANQOL or SF-36 questionnaires) is a significant limitation, as it restricts our analysis to physician-reported symptoms rather than patient-reported outcomes, which are increasingly recognized as paramount [24]. Furthermore, toxicity data were derived from long-term follow-up assessments, which may be subject to reporting and recall bias. Moreover, toxicity grading was not consistently harmonized (dichotomous documentation, VAS, or CTCAE), potentially limiting comparability and the statistical robustness of symptom analyses. Missing data at the first follow-up (T1) for some symptoms that were not routinely assessed at that time further complicates a complete understanding of the acute phase and insights into when symptoms form following SRT. Likewise, it would have been desirable to have had the PTV for all patients, in order to confidently assess the influence of the PTV on clinical outcomes. Lastly, we chose to analyze late toxicity as a fluid endpoint counted at the time of last FU. Therefore, the reported toxicity was assessed between 6 and 282 months after RT. This could introduce significant bias, as early-late and delayed-late toxicity may differ.

Despite these limitations, the study has considerable strengths, including a relatively large, well-characterized patient cohort; a robust median follow-up duration; and a detailed analysis of a wide array of symptoms and toxicities over time. The homogenous treatment within two clear modality groups (SRS and NFSRT) also adds clarity to the comparisons.