Highlight
• An international multicenter cohort (n=1,883) of patients with growing unilateral vestibular schwannoma (VS) treated first‑line with radiotherapy reported a 10‑year tumor control rate of 76.1% using a prespecified, clinically oriented growth definition.
• Tumor control estimates were highly sensitive to the radiologic growth threshold: 60.1% at 10 years using a ≥2 mm threshold, 78.3% using ≥3 mm, and 92.6% for conversion to surgery.
• Pretreatment size and intracanalicular vs extracanalicular location were not associated with failure, highlighting the need to consider measurement definitions and patient‑centered endpoints when counseling or designing studies.
Background: clinical context and unmet need
Vestibular schwannomas (VS; acoustic neuromas) are benign, usually slow‑growing tumors of the vestibulocochlear nerve. Management options include active surveillance, microsurgical resection, and radiotherapy (single‑fraction stereotactic radiosurgery or fractionated stereotactic radiotherapy). Decisions are individualized based on tumor size, growth behavior, symptoms (hearing, balance, cranial nerve function), patient age, comorbidity and preferences.
Most contemporary outcome data for radiotherapy in VS derive from mixed cohorts that include incidentally detected, small, or non‑growing tumors as well as growing lesions. Clinicians and patients increasingly ask whether radiotherapy is an appropriate definitive first‑line option for VS that are already documented to be growing. The natural history of VS varies and growth definitions are heterogeneous across centers, making treatment effect estimates difficult to interpret. High‑quality, large‑scale data focused specifically on radiologically growing tumors are therefore relevant to counseling and shared decision‑making.
Study design and methods
The paper by Sethi and colleagues reports an international, multicenter cohort study combining prospectively collected data from eight tertiary skull base referral centers covering patients treated between January 2000 and December 2023. Inclusion criteria were unilateral vestibular schwannoma with documented radiologic growth prior to treatment and radiotherapy used as first‑line therapy. Data were analyzed in June 2025.
Primary exposure: radiotherapy as initial treatment (the report does not subgroup by detailed dose/fractionation in the provided summary). The primary outcome (treatment failure) was predefined as VS growth after radiotherapy, operationalized as an increase in maximum intracranial tumor diameter (ICTD) of ≥3 mm within the first 2 years after radiotherapy or ≥2 mm thereafter. This hybrid definition attempts to account for early volumetric changes and late growth dynamics.
Secondary outcomes included alternative growth definitions: (1) increase in ICTD of ≥2 mm (uniform), (2) increase in ICTD of ≥3 mm, and (3) conversion to surgery (clinical endpoint). Kaplan‑Meier methods were used to estimate tumor control over time. The cohort size and prospective data capture are strengths for estimating real‑world outcomes in this specific population.
Key findings
The study included 1,883 patients (975 female, 51.8%); median age at diagnosis was 63 years (IQR 53–71 years).
Using the prespecified primary definition of treatment failure (≥3 mm ICTD within 2 years or ≥2 mm thereafter), the Kaplan‑Meier estimate of tumor control at 10 years was 76.1% (95% CI, 72.7%–79.2%).
Secondary growth definitions produced substantially different control estimates at 10 years:
- Uniform ≥2 mm increase: 60.1% tumor control (95% CI, 57.5%–64.3%).
- Uniform ≥3 mm increase: 78.3% tumor control (95% CI, 75.0%–81.2%).
- Conversion to surgery (clinical salvage): 92.6% (95% CI, 90.4%–94.3%).
Importantly, neither pretreatment tumor size nor tumor location (intracanalicular versus extracanalicular) was significantly associated with treatment failure in adjusted analyses. The relatively high rate of radiologic growth by smaller thresholds contrasted with the much lower rate of conversion to surgery, suggesting that radiographic progression does not always mandate operative intervention.
Interpretation and clinical implications
These results provide granular, clinically relevant evidence for a previously under‑studied subgroup: patients with VS that were actively growing before treatment. Key practical interpretations include:
- Radiotherapy achieves durable control (by the authors’ primary definition) in roughly three‑quarters of growing VS at 10 years. This supports radiotherapy as a reasonable first‑line option in many patients, particularly when balanced against age, comorbidity, and surgical risks.
- The choice of radiologic growth threshold materially changes reported control rates. A 2‑mm growth criterion yields much lower control estimates than 3 mm or the clinical endpoint of conversion to surgery. Measurement variability, interscan differences, and volumetric versus linear assessment contribute to this divergence.
- The large discrepancy between radiologic failure (by small thresholds) and the low proportion requiring salvage surgery emphasizes the difference between imaging‑defined progression and clinically meaningful failure. For patients and clinicians, the need for surgery, cranial nerve dysfunction, or declining quality of life are often the outcomes that drive management changes rather than modest increases in linear diameter alone.
- Because pretreatment size and intracanalicular location did not predict failure, radiotherapy may be considered across a broad range of growing lesions; however, individual factors (hearing status, tumor‑brainstem relationships) still matter for personalized decisions.
Strengths and limitations
Strengths
Large multicenter cohort with prospectively collected data focused specifically on growing tumors; explicit prespecified primary outcome that accounts for early versus late measurement thresholds; long follow‑up enabling 10‑year estimates; clinically useful secondary outcomes including conversion to surgery.
Limitations
Heterogeneity in radiotherapy technique, dose and fractionation across centers is likely and not fully characterized in the summary, which could influence control and toxicity. The study used linear diameter thresholds rather than volumetric assessment; linear measures are easier to implement but can be vulnerable to small measurement error. Functional outcomes (hearing preservation, facial nerve function), radiation‑related toxicity, and quality‑of‑life measures were not emphasized in the summary; these are central to shared decision‑making. Although data were prospectively collected, the observational design leaves potential for selection and ascertainment bias: patients chosen for radiotherapy may differ from those undergoing early surgery. Finally, median age of 63 years may limit generalizability to younger patients where long‑term risk–benefit calculus differs.
How this fits with prior evidence
Historically, reported tumor control after stereotactic radiosurgery or fractionated stereotactic radiotherapy in mixed VS cohorts has been high in the medium term, often quoted in the 80–95% range at 5–10 years depending on definitions and cohorts. The current study shows that in lesions already demonstrating growth, control estimates are lower when strict radiologic thresholds are used, but the majority of patients still avoid surgery long term. This underscores the importance of cohort definitions and growth criteria when interpreting the literature and counseling patients.
Practical recommendations for clinicians
- When counseling patients with documented tumor growth, discuss both imaging‑based control rates and clinically oriented outcomes (need for salvage surgery, functional decline). Explicitly describe how choice of growth threshold affects the probability of documented progression.
- Use a shared‑decision approach that includes patient values (e.g., tolerance for monitoring vs. desire for definitive surgery), baseline hearing and balance function, age, and comorbidity. For older patients or those with comorbidity, radiotherapy remains an attractive organ‑sparing option with a low rate of subsequent surgery.
- Standardize imaging protocols and measurement methods in local practice (prefer volumetrics where feasible) to reduce measurement variability and to align surveillance thresholds with clinical decision points.
- Ensure comprehensive informed consent includes realistic expectations about radiographic progression, the potential need for long‑term surveillance, and the relative rarity of conversion to surgery observed in this cohort.
Research and policy implications
Future work should prospectively capture functional outcomes (hearing, facial nerve), patient‑reported quality of life, and long‑term toxicity across standardized radiotherapy protocols. Studies comparing fractionation strategies, doses, and modalities (single‑fraction radiosurgery vs. hypofractionation vs. conventional fractionation) in growing tumors would aid optimization. Consensus on radiologic progression definitions (preferably volumetric thresholds linked to clinical events) would improve comparability across studies and translate better to patient care.
Conclusion
Sethi et al. provide important, pragmatic data on outcomes after radiotherapy in patients with radiologically growing vestibular schwannomas. Using a prespecified growth definition intended to reflect clinically meaningful change, about 76% of growing tumors remained controlled at 10 years, while over 92% of patients avoided conversion to surgery. These results argue that radiotherapy is a reasonable first‑line option for many patients with growing VS, but the interpretation of tumor control depends critically on the growth definition applied. Clinicians should integrate these data with functional outcomes and patient preferences when advising individual patients.
Funding and clinicaltrials.gov
Funding: Study funding details were not provided in the summary presented here; see the full manuscript (Sethi et al., JAMA Otolaryngol Head Neck Surg. 2025) for acknowledgments and funding statements.
ClinicalTrials.gov: Not applicable (multicenter observational cohort using prospectively collected clinical data).
References
1. Sethi M, Gowrishankar S, Tysome J, et al. Radiotherapy for Growing Vestibular Schwannomas. JAMA Otolaryngol Head Neck Surg. 2025 Oct 1;151(10):931-937. doi:10.1001/jamaoto.2025.1953. Erratum in: JAMA Otolaryngol Head Neck Surg. 2025 Nov 13. doi:10.1001/jamaoto.2025.4615. PMID: 40906473; PMCID: PMC12412036.
Note: Additional background literature on vestibular schwannoma natural history and radiosurgery outcomes is extensive; readers should consult comprehensive reviews and local multidisciplinary tumor board guidance when applying these findings to clinical practice.