Salvage Microsurgery for Vestibular Schwannoma after failed Stereotactic Radiosurgery: A Multicentric Retrospective Study

Salvage Microsurgery for Vestibular Schwannoma after failed Stereotactic Radiosurgery: A Multicentric Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Salvage Microsurgery for Vestibular Schwannoma after failed Stereotactic Radiosurgery: A Multicentric Retrospective Study Filippo Friso, Noa Ben Dor, Alfredo Conti, Alfredo Decio Fabbri, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7631342/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Purpose This study aimed to evaluate the clinical indications, technical characteristics, and outcomes of salvage microsurgery in patients with sporadic vestibular schwannomas (VS) primarily treated with Stereotactic radiosurgery (SRS). Methods This retrospective multicenter study included 28 patients who underwent salvage microsurgery between 2012 and 2022 at six European tertiary referral centers. Data on demographics, tumor characteristics, surgical approach, extent of resection, and functional outcomes were collected, with a focus on facial nerve preservation and postoperative complications. Results Tumor progression, with or without symptoms, was the predominant indication for surgery (60.7% of cases). The median interval between SRS and surgery was 42 months (range 24–120). Intraoperative findings revealed altered tumor consistency and limited mobility due to arachnoid adhesions or fibrosis in 19 patients (67.9%). Gross total resection was achieved in 53.6% of the cases, with near-total resection in 28.6% of the cases. No patient retained serviceable hearing, but postoperative facial nerve function improved over time, with 62.5% achieving House-Brackmann grade I at 12 months. The complication rate was 10.7%, with no procedure-related mortality observed. Conclusion Salvage microsurgery represents a viable and safe therapeutic option for managing VS following failed SRS. The timing of surgical intervention may be critical to optimizing outcomes. Favorable results in this cohort may reflect both the high-volume expertise of participating centers and a shared institutional preference for delayed intervention. Although technically more demanding than primary resection, acceptable morbidity and good functional outcomes can be achieved when function-preserving strategies are employed. Vestibular Schwannoma Acoustic Neuroma Recurrence Stereotactic Radiosurgery Radiation Therapy Salvage Microsurgery Oncology Figures Figure 1 Figure 2 Introduction Vestibular schwannomas (VS), also known as acoustic neuromas, are benign tumors that arise from Schwann cells in the vestibular division of the eighth cranial nerve. These lesions represent the most prevalent neoplasm of the cerebellopontine angle (CPA) and typically present with progressive unilateral hearing loss, tinnitus, and imbalance, and less commonly with facial weakness or trigeminal dysfunction [ 1 – 4 ]. The widespread application of high-resolution MRI has contributed to an increased detection rate of small, often asymptomatic tumors, particularly in older adults [ 3 , 5 ]. Historically, microsurgical resection was the primary treatment modality; however, the therapeutic landscape has evolved markedly with the advent and refinement of stereotactic radiosurgery (SRS) [ 6 – 8 ]. SRS is now widely accepted as a first-line intervention for small- to medium-sized VS, typically those measuring ≤ 2.5 to 3.0 cm in maximal extra-canalicular diameter—owing to its high long-term tumor control rates (91–98% at five years) and favorable safety profile in appropriately selected patients [ 5 , 9 ]. Despite its efficacy, treatment failure can occur in a subset of these patients. Reported failure rates range from 2.5% to 5%, with contributing factors including subtherapeutic marginal dosing, suboptimal isocenter distribution, and radioresistant tumor characteristics [ 5 , 9 – 16 ]. When failure is identified, salvage options include repeated radiosurgery or microsurgical resection. While repeat SRS has shown high tumor control rates, it carries a substantial risk of cranial nerve deficits and hearing deterioration [ 5 , 9 , 11 , 17 ]. Though definitive, microsurgical resection in the salvage setting is inherently more complex than primary surgery. Prior irradiation induces fibrosis, obliterates normal tissue planes, and increases adhesion to critical neurovascular structures, thereby increasing the risk of intraoperative morbidity [ 16 , 18 – 21 ]. These challenges require surgical expertise, advanced intraoperative monitoring, and individualized treatment strategies. Although several retrospective studies and systematic reviews have enhanced the understanding of salvage surgery outcomes [ 5 , 9 , 16 , 17 , 19 ], large high-quality multicenter data are limited. The present study sought to address this gap by presenting a comprehensive multicenter retrospective analysis of patients who underwent microsurgical resection after failed SRS for sporadic VS. Our objective was to characterize the clinical indications, operative challenges, and functional outcomes in this setting, focusing on facial nerve preservation and long-term tumor control. Materials and Methods Study Design and Setting This retrospective multicenter study was conducted at six European tertiary referral centers in Bologna (Italy), Modena (Italy), Verona (Italy), Milan (Italy), Warsaw (Poland), and Bern (Switzerland). This study covered a ten-year period from January 2012 to December 2022. Patient records were reviewed to identify cases of VS in which patients underwent salvage microsurgical resection after the failure of primary SRS. Eligibility Criteria Eligible participants included adult patients (> 18-year-old) with unilateral sporadic VS who received SRS as the initial treatment and subsequently underwent microsurgical resection. Salvage surgery was indicated either because of radiological evidence of tumor regrowth (defined as an increase of more than 20% in tumor volume on follow-up MRI compared to the earliest post-SRS scan), or because of the development of neurological symptoms such as trigeminal neuralgia, facial pain, or hydrocephalus, even in the absence of radiological progression. Patients were excluded if they had undergone microsurgical resection prior to SRS, had a diagnosis of neurofibromatosis type 2 (NF2), showed malignant transformation of the tumor post-radiosurgery, or were treated with cerebrospinal fluid diversion alone without tumor removal. Data Collection and Variables Clinical and surgical data were retrospectively extracted from institutional databases. Demographic data included patient age and sex. Tumor characteristics, such as laterality and Koos classification [ 22 ], were recorded before radiosurgery and at the time of surgery for all the patients. Pretreatment and post-surgical hearing status was assessed according to the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) classification [ 23 – 25 ]. Information regarding SRS included the type of device used (Gamma Knife, CyberKnife, or LINAC), radiation dose delivered to the tumor margin, and the time interval between radiosurgery and surgical intervention. Surgical variables included the approach used, intraoperative findings, and extent of resection, which was evaluated based on postoperative imaging and classified into four categories. Gross Total Resection (GTR) was defined as complete radiographic removal of the tumor; Near-Total Resection (NTR) was characterized by a residual tumor volume of 2% or less; Subtotal Resection (STR) was defined as a residual volume greater than 2% but less than 5%; and Partial Resection (PR) indicated a residual volume of greater than 5%. Intraoperative findings were assessed based on the operative reports documented immediately after surgery, supplemented by a review of the corresponding intraoperative video recordings. Postoperative complications were also retrieved from patients’ charts and follow-up visits. Facial nerve function was typically evaluated at discharge and at 3, 6, and 12 months postoperatively, with variable timing according to each Institution, using the House-Brackmann (HB) grading scale [ 25 , 26 ]. Radiological follow-up was conducted regularly at participating centers, with MRI surveillance extending up to 5 years after salvage surgery. Although precise imaging dates were not uniformly documented, most patients received long-term radiologic monitoring to assess tumor control. Results The demographic, tumor, radiosurgery characteristics, and surgical outcomes of the study population are summarized in Table 1 . Patient and Radiation Characteristics A total of 28 patients met the inclusion criteria, with 21 males (75%) and 7 females (25%), resulting in a male-to-female ratio of 3:1. The median age at the time of SRS was 48 years (range, 24–70). Gamma Knife was the most commonly used modality, employed in 18 of 28 patients (64.3%), followed by CyberKnife in seven patients (25%), and LINAC in three patients (10.7%). The median dose to the tumor margin was 12 Gy (range 11–14). The Koos classification was documented both at the time of stereotactic radiosurgery and prior to salvage surgery in 22 patients, as summarized in Fig. 1 . Before radiosurgery, the majority of patients were classified as Koos grade III (n = 7/22, 31.8%) or IV (n = 9/22, 40.9%). At the time of salvage surgery, a higher proportion of high-grade tumors was observed, with 8 patients (29.6%) classified as grade III and 17 patients (63.0%) as grade IV. This shift suggests that tumor progression is a significant factor prompting surgical intervention. Surgical Indication and Management The median interval between radiosurgery and salvage microsurgery was 42 months (range 24–120). The most frequent indication for surgery was asymptomatic tumor regrowth, which accounted for 17 patients (60.7%). Tumor regrowth with symptoms such as hydrocephalus or trigeminal neuralgia occurred in 10 patients (35.7%), and one patient underwent surgery due to symptomatic worsening in the absence of tumor growth (3.6%). Microsurgical resection was performed via the retrosigmoid approach in 24 patients (85.7%), translabyrinthine approach in 3 patients (10.7%), and transpromontorial approach in one patient (3.6%). Intraoperative findings revealed firm, poorly mobile tumors due to arachnoid adhesions or post-radiation changes, as observed in 67.9% of patients. Gross total resection was achieved in 15 patients (53.6%), near-total resection in eight patients (28.6%), subtotal resection in two patients (7.1%), and partial resection in three patients (10.7%). Surgical Outcomes and Complications Postoperative complications were observed in 3 patients (10.7%). These included one case of meningitis, one case of cerebrospinal fluid leak, and one case of atrial fibrillation. Among the 14 patients with audiometric follow-up available post-revision surgery (50%), all were classified as AAO-HNS Class D, indicating non-serviceable hearing. The median duration of facial nerve follow-up was 64 months (range: 3–120 months), based on data from 14 patients. Facial nerve function at discharge was grade I in two patients (7.1%), grade II in ten patients (35.7%), grade III in five patients (17.9%), grade IV in six patients (21.4%), grade V in three patients (10.7%), and grade VI in two patients (7.1%). At the 12-month follow-up, among the 16 patients with available data (57%), 10 (62.5%) had recovered to HB grade I, one (6.3%) to grade II, one (6.3%) to grade III, and four (25%) remained in HB grades V or VI. These trends are illustrated in Fig. 2 . Table 1 Summary of Study Cohort (N = 28) Characteristic Subgroup No. (%) Sex Female 7 (25%) Male 21 (75%) Age at radiosurgery, median (range), y 48 (24–70) Interval from radiosurgery to surgery, median (range), months 42 (24–120) Primary SRS modality Gamma Knife 18 (64.3%) CyberKnife 7 (25%) LINAC 3 (10.7%) Koos grade at revision surgery Grade II 2 (7.4%) Grade III 8 (29.6%) Grade IV 17 (63.0%) Surgical approach Retrosigmoid 24 (85.7%) Translabyrinthine 3 (10.7%) Transpromontorial 1 (3.6%) Extent of surgical resection Gross total 13 (46.6%) Near-total (≤ 2%) 6 (21.4%) Subtotal (> 2–5%) 8 (28.5%) Partial (> 5%) 1 (3.5%) Postoperative complications Any complication 3 (10.7%) Meningitis 1 (3.6%) CSF leak 1 (3.6%) Atrial fibrillation 1 (3.6%) Discussion This multicenter retrospective study contributes to the expanding body of literature addressing the outcomes of salvage microsurgery for VS after failed SRS. As SRS continues to be widely adopted as a primary management strategy for small- to medium-sized VS, the frequency of salvage surgical interventions, although still relatively uncommon, may increase over time. In this evolving landscape, a deeper understanding of the indications, technical challenges, and outcomes of salvage procedures is warranted. Indications and Timing for Salvage Intervention In our cohort, radiological tumor progression, with or without associated symptoms, was the predominant indication for salvage microsurgery (60.7%). These findings are in concordance with the most recent systematic review and meta-analysis by Ribeiro et al. [ 5 ] and are further supported by earlier studies [ 9 , 19 , 27 ]. The median interval between SRS and surgical intervention was 42 months, reflecting the clinical preference for delayed surgery in the absence of acute neurological deterioration, consistent with evolving clinical standards [ 5 , 9 , 28 , 29 ]. This preference for deferred intervention is grounded in the evolving understanding of post-radiation tumor behavior and its impact on surgical morbidity. Within the first 6–18 months, transient tumor swelling, often referred to as pseudoprogression, is a well-documented phenomenon [ 30 – 32 ]. This phase is characterized by treatment-related edema, inflammation, and early fibrosis, which can mimic true progression both radiologically and symptomatically. Crucially, surgical intervention during this period is associated with increased operative risk owing to obscured anatomical planes and heightened vulnerability of adjacent neurovascular structures. As such, delayed surgery—ideally beyond 24 to 36 months—has become the preferred strategy in patients without urgent clinical deterioration, offering improved operative conditions and a lower-risk profile [ 10 , 29 – 31 , 33 – 35 ]. Considerations on Pre-Radiosurgery Tumor Volume A noteworthy characteristic of our salvage cohort is the substantial tumor volume present at the time of initial SRS. Among the patients with available pre-treatment data, a significant majority were classified with Koos grade III or IV tumors before receiving radiation. Of the 22 patients for whom this data was available, the majority were classified as either Koos grade III (7 patients) or Koos grade IV (9 patients) at the time of their primary SRS treatment. This means that 16 of these 22 patients (approximately 73%) already had large tumors with significant mass effect prior to receiving radiation. This finding is particularly relevant given that the literature supports SRS as a first-line intervention primarily for small- to medium-sized vestibular schwannomas, typically those measuring ≤ 2.5 to 3.0 cm, where its safety profile and efficacy are most favorable [ 46 ]. While this study was not designed to identify risk factors for SRS failure, the prevalence of large tumors in this cohort of treatment failures warrants consideration. It underscores the importance of careful patient selection for primary SRS and suggests that applying this modality to larger tumors may carry a higher risk of requiring future salvage microsurgery. Operative Challenges and Functional Outcomes The intraoperative findings in our cohort highlight the inherent complexity of salvage microsurgery for previously irradiated VS. Radiation-induced alterations, most notably fibrosis and arachnoid adhesions, were encountered in 67.9% of cases. These phenomena have been well documented in the literature and are known to obscure surgical planes, increase operative time, and elevate the risk of cranial nerve injury [ 15 , 18 , 19 , 32 , 33 , 36 – 40 ]. Salvage procedures require meticulous dissection techniques, comprehensive intraoperative monitoring, and experience with distorted microsurgical anatomy. An important adjunct to these observations was the documented progression in the Koos classification between radiosurgery and surgery. Among the 22 patients with complete data, 27.3% were initially classified as Koos grades I–II, whereas only 7.4% remained at grade II at the time of surgical intervention. The proportion of Koos grade IV tumors increased substantially from 40.9% to 63.0%. This progression likely reflects not only true volumetric growth, but also increased brainstem involvement and mass effect, factors that critically influence surgical approach and morbidity. The Koos classification has traditionally served as a radiological staging tool and guide for treatment selection [ 22 ]. However, in the salvage setting, the Koos grade may underrepresent the intraoperative complexity posed by radiation-induced anatomical distortion [ 33 , 41 ]. In our experience, several tumors initially graded as Koos II demonstrated surgical characteristics typical of grade IV lesions, including dense adhesions to the brainstem and facial nerve, loss of arachnoidal planes, and friable tumor consistency. These findings suggest that static imaging-based classifications may not reliably reflect the surgical risk in previously irradiated patients and that appropriate counselling with the patient on this topic is crucial. The clinical implications of this mismatch are reflected in the surgical outcomes. In our series, GTR was achieved in only 46.6% of cases, which is considerably lower than the rates reported for non-irradiated Koos I–III tumors, where GTR typically exceeds 70% [ 9 , 33 , 42 ]. Accordingly, STR and NTR were deliberately pursued in anatomically unfavorable cases, particularly where tumor adherence to critical neurovascular structures was evident. This approach is increasingly supported in the literature, where long-term control has been demonstrated even in the absence of GTR [ 2 , 5 , 9 , 11 , 12 , 38 , 43 ]. Facial nerve outcomes were encouraging; although only 7.1% of patients had House-Brackmann (HB) grade I function at discharge, this improved to 62.5% at 12 months. These data are consistent with those of other studies, highlighting the potential for delayed facial nerve recovery after salvage surgery [ 14 , 27 , 32 ]. As expected, none of the patients in our cohort retained serviceable hearing following surgery, and all patients were classified as AAO-HNS class D postoperatively. This outcome is expected in the salvage context, where prior cochlear radiation exposure and the nature of the surgical approach limit the possibility of functional cochlear preservation [ 13 , 42 , 44 , 45 ]. In this context, hearing preservation should not be considered a realistic goal of salvage surgery. Our complication rate was relatively low (10.7%) and included only one case each of meningitis, cerebrospinal fluid leak, and atrial fibrillation. This compares favorably with published reports [ 5 , 15 , 17 , 19 ] and likely reflects careful patient selection and experience in high-volume centers. Importantly, no procedure-related mortality occurred, consistent with the experience of other high-volume centers and underscoring the safety of salvage MS when performed by experienced teams with appropriate patient selection criteria [ 11 , 38 ]. Long-term follow-up was available in most patients, with median FN monitoring of 64 months and radiological surveillance often extending beyond five years post-surgery. The durable functional outcomes reported here underscore the value of prolonged monitoring, particularly in patients undergoing complex salvage procedures after stereotactic radiosurgery. Limitations This study had several limitations due to its retrospective design. The relatively small sample size, although reflective of the rarity of salvage microsurgery after failed SRS, did not permit formal statistical analysis and limited the scope of the inferential interpretation. Additionally, heterogeneity in surgical techniques, perioperative management, and follow-up duration across participating centers may introduce variability that affects the generalizability of the findings. Functional outcomes, particularly those related to long-term facial nerve recovery, were assessed based on clinical documentation and follow-up availability, which may be subject to institutional differences in reporting and retrospective nature of the study. The present rate of data attrition could potentially influence the reported outcomes; therefore, the findings on functional recovery should be interpreted with appropriate caution as they may not be generalizable to the entire cohort. The absence of a control group (e.g., patients undergoing primary microsurgery or repeat SRS) also limits comparative assessment. Future prospective studies with standardized outcome measures and larger multicenter cohorts are essential to validate and expand these findings. Conclusions Salvage microsurgery represents a viable and safe therapeutic option for managing VS following failed SRS. The timing of surgical intervention is critical to optimizing outcomes. Favorable results in this cohort may reflect both the high-volume expertise of participating centers and a shared institutional preference for delayed intervention. Although technically more demanding than primary resection, acceptable morbidity and good functional outcomes can be achieved when function-preserving strategies are employed. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests : The authors have no relevant financial or non-financial interests to disclose. Author Contributions : All authors contributed to the study conception and design. Material preparation and data collection were performed by Filippo Friso, Alfredo Decio Fabbri, Federico Calvaruso, Virginia Dallari, Franco Federico Bochicchio, Emanuele La Corte, Kazimierz Niemczyk, Adrian Drożdż, Lukas Anschuetz, Giacomo Pavesi, Barbara Masotto, and Francesco DiMeco. Data analysis and first draft writing was performed by Noa Ben Dor. All authors commented on previous versions of the manuscript. Supervision was provided by Giulia Molinari, Livio Presutti, Paolo Ferroli, Francesco DiMeco, and Alfredo Conti. All authors read and approved the final manuscript. Data Availability : The dataset analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval : The study was conducted in accordance with the Declaration of Helsinki and approved by the Comitato Etico di Area Vasta Emilia Centro (IRCCS Azienda Ospedaliero–Universitaria di Bologna, Policlinico di Sant’Orsola). Approval Code: 436/2023/Oss/AOUBo; date of approval: February 14 2024. Consent to participate : Informed consent for retrospective data management was obtained for all subjects. 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Surg Neurol Int 14:419. 10.25259/SNI_875_2023 Collen C, Ampe B, Gevaert T, Moens M, Linthout N, De Ridder M, Verellen D, D’Haens J, Storme G (2011) Single Fraction Versus Fractionated Linac-Based Stereotactic Radiotherapy for Vestibular Schwannoma: A Single-Institution Experience. Int J Radiation Oncology*Biology*Physics 81:e503–e509. 10.1016/j.ijrobp.2011.04.066 Roland Goldbrunner M, Weller J, Regis M, Lund-Johansen P, Stavrinou D, Reuss DG, Evans F, Lefranc K, Sallabanda A, Falini P, Axon O, Sterkers L, Fariselli W, Wick (2020) Joerg-Christian Tonn, EANO guideline on the diagnosis and treatment of vestibular schwannoma, Neuro-Oncology , Volume 22, Issue 1, January Pages 31–45. https://doi.org/10.1093/neuonc/noz153 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 19 Jan, 2026 Reviews received at journal 14 Jan, 2026 Reviews received at journal 11 Jan, 2026 Reviews received at journal 10 Jan, 2026 Reviewers agreed at journal 07 Jan, 2026 Reviewers agreed at journal 07 Jan, 2026 Reviews received at journal 05 Jan, 2026 Reviewers agreed at journal 05 Jan, 2026 Reviewers agreed at journal 05 Jan, 2026 Reviewers invited by journal 04 Jan, 2026 Editor assigned by journal 17 Sep, 2025 Submission checks completed at journal 17 Sep, 2025 First submitted to journal 16 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7631342","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":569737591,"identity":"d2407fd5-8118-4fd8-92ef-88361c3e90ed","order_by":0,"name":"Filippo Friso","email":"","orcid":"","institution":"IRCCS Institute of Neurological Sciences of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Filippo","middleName":"","lastName":"Friso","suffix":""},{"id":569737593,"identity":"ff22dd33-4fd4-4f19-8c8e-b759dc201ff7","order_by":1,"name":"Noa Ben 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1","display":"","copyAsset":false,"role":"figure","size":97753,"visible":true,"origin":"","legend":"\u003cp\u003eBar chart showing the number of patients according to the Koos classification at two time points: prior to radiosurgery and prior to surgical intervention. A shift toward higher Koos grades at the time of surgery was evident.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7631342/v1/ad374484a41b0e62a32a33b5.png"},{"id":99622811,"identity":"08989a44-d250-4150-b23e-f238d511784c","added_by":"auto","created_at":"2026-01-06 14:33:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23665,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of Facial Nerve Function Following Salvage Microsurgery for Vestibular Schwannoma (House-Brackmann Grades I–VI).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7631342/v1/1af6e9bd3469599a8bd99534.png"},{"id":99804469,"identity":"1ba278b9-a2b4-48fd-abeb-b99914b8bba5","added_by":"auto","created_at":"2026-01-08 14:13:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":887822,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7631342/v1/a1e025af-04ba-4579-a912-f6c96aaf20ac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Salvage Microsurgery for Vestibular Schwannoma after failed Stereotactic Radiosurgery: A Multicentric Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVestibular schwannomas (VS), also known as acoustic neuromas, are benign tumors that arise from Schwann cells in the vestibular division of the eighth cranial nerve. These lesions represent the most prevalent neoplasm of the cerebellopontine angle (CPA) and typically present with progressive unilateral hearing loss, tinnitus, and imbalance, and less commonly with facial weakness or trigeminal dysfunction [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The widespread application of high-resolution MRI has contributed to an increased detection rate of small, often asymptomatic tumors, particularly in older adults [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorically, microsurgical resection was the primary treatment modality; however, the therapeutic landscape has evolved markedly with the advent and refinement of stereotactic radiosurgery (SRS) [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. SRS is now widely accepted as a first-line intervention for small- to medium-sized VS, typically those measuring\u0026thinsp;\u0026le;\u0026thinsp;2.5 to 3.0 cm in maximal extra-canalicular diameter\u0026mdash;owing to its high long-term tumor control rates (91\u0026ndash;98% at five years) and favorable safety profile in appropriately selected patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite its efficacy, treatment failure can occur in a subset of these patients. Reported failure rates range from 2.5% to 5%, with contributing factors including subtherapeutic marginal dosing, suboptimal isocenter distribution, and radioresistant tumor characteristics [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. When failure is identified, salvage options include repeated radiosurgery or microsurgical resection. While repeat SRS has shown high tumor control rates, it carries a substantial risk of cranial nerve deficits and hearing deterioration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Though definitive, microsurgical resection in the salvage setting is inherently more complex than primary surgery. Prior irradiation induces fibrosis, obliterates normal tissue planes, and increases adhesion to critical neurovascular structures, thereby increasing the risk of intraoperative morbidity [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These challenges require surgical expertise, advanced intraoperative monitoring, and individualized treatment strategies.\u003c/p\u003e \u003cp\u003eAlthough several retrospective studies and systematic reviews have enhanced the understanding of salvage surgery outcomes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], large high-quality multicenter data are limited. The present study sought to address this gap by presenting a comprehensive multicenter retrospective analysis of patients who underwent microsurgical resection after failed SRS for sporadic VS. Our objective was to characterize the clinical indications, operative challenges, and functional outcomes in this setting, focusing on facial nerve preservation and long-term tumor control.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis retrospective multicenter study was conducted at six European tertiary referral centers in Bologna (Italy), Modena (Italy), Verona (Italy), Milan (Italy), Warsaw (Poland), and Bern (Switzerland). This study covered a ten-year period from January 2012 to December 2022. Patient records were reviewed to identify cases of VS in which patients underwent salvage microsurgical resection after the failure of primary SRS.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eEligible participants included adult patients (\u0026gt;\u0026thinsp;18-year-old) with unilateral sporadic VS who received SRS as the initial treatment and subsequently underwent microsurgical resection. Salvage surgery was indicated either because of radiological evidence of tumor regrowth (defined as an increase of more than 20% in tumor volume on follow-up MRI compared to the earliest post-SRS scan), or because of the development of neurological symptoms such as trigeminal neuralgia, facial pain, or hydrocephalus, even in the absence of radiological progression.\u003c/p\u003e \u003cp\u003ePatients were excluded if they had undergone microsurgical resection prior to SRS, had a diagnosis of neurofibromatosis type 2 (NF2), showed malignant transformation of the tumor post-radiosurgery, or were treated with cerebrospinal fluid diversion alone without tumor removal.\u003c/p\u003e\n\u003ch3\u003eData Collection and Variables\u003c/h3\u003e\n\u003cp\u003eClinical and surgical data were retrospectively extracted from institutional databases. Demographic data included patient age and sex. Tumor characteristics, such as laterality and Koos classification [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], were recorded before radiosurgery and at the time of surgery for all the patients. Pretreatment and post-surgical hearing status was assessed according to the American Academy of Otolaryngology\u0026ndash;Head and Neck Surgery (AAO-HNS) classification [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Information regarding SRS included the type of device used (Gamma Knife, CyberKnife, or LINAC), radiation dose delivered to the tumor margin, and the time interval between radiosurgery and surgical intervention.\u003c/p\u003e \u003cp\u003eSurgical variables included the approach used, intraoperative findings, and extent of resection, which was evaluated based on postoperative imaging and classified into four categories. Gross Total Resection (GTR) was defined as complete radiographic removal of the tumor; Near-Total Resection (NTR) was characterized by a residual tumor volume of 2% or less; Subtotal Resection (STR) was defined as a residual volume greater than 2% but less than 5%; and Partial Resection (PR) indicated a residual volume of greater than 5%. Intraoperative findings were assessed based on the operative reports documented immediately after surgery, supplemented by a review of the corresponding intraoperative video recordings. Postoperative complications were also retrieved from patients\u0026rsquo; charts and follow-up visits. Facial nerve function was typically evaluated at discharge and at 3, 6, and 12 months postoperatively, with variable timing according to each Institution, using the House-Brackmann (HB) grading scale [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Radiological follow-up was conducted regularly at participating centers, with MRI surveillance extending up to 5 years after salvage surgery. Although precise imaging dates were not uniformly documented, most patients received long-term radiologic monitoring to assess tumor control.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe demographic, tumor, radiosurgery characteristics, and surgical outcomes of the study population are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003ePatient and Radiation Characteristics\u003c/h3\u003e\n\u003cp\u003eA total of 28 patients met the inclusion criteria, with 21 males (75%) and 7 females (25%), resulting in a male-to-female ratio of 3:1. The median age at the time of SRS was 48 years (range, 24\u0026ndash;70). Gamma Knife was the most commonly used modality, employed in 18 of 28 patients (64.3%), followed by CyberKnife in seven patients (25%), and LINAC in three patients (10.7%). The median dose to the tumor margin was 12 Gy (range 11\u0026ndash;14).\u003c/p\u003e \u003cp\u003eThe Koos classification was documented both at the time of stereotactic radiosurgery and prior to salvage surgery in 22 patients, as summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Before radiosurgery, the majority of patients were classified as Koos grade III (n\u0026thinsp;=\u0026thinsp;7/22, 31.8%) or IV (n\u0026thinsp;=\u0026thinsp;9/22, 40.9%). At the time of salvage surgery, a higher proportion of high-grade tumors was observed, with 8 patients (29.6%) classified as grade III and 17 patients (63.0%) as grade IV. This shift suggests that tumor progression is a significant factor prompting surgical intervention.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Indication and Management\u003c/h2\u003e \u003cp\u003eThe median interval between radiosurgery and salvage microsurgery was 42 months (range 24\u0026ndash;120). The most frequent indication for surgery was asymptomatic tumor regrowth, which accounted for 17 patients (60.7%). Tumor regrowth with symptoms such as hydrocephalus or trigeminal neuralgia occurred in 10 patients (35.7%), and one patient underwent surgery due to symptomatic worsening in the absence of tumor growth (3.6%).\u003c/p\u003e \u003cp\u003eMicrosurgical resection was performed via the retrosigmoid approach in 24 patients (85.7%), translabyrinthine approach in 3 patients (10.7%), and transpromontorial approach in one patient (3.6%). Intraoperative findings revealed firm, poorly mobile tumors due to arachnoid adhesions or post-radiation changes, as observed in 67.9% of patients. Gross total resection was achieved in 15 patients (53.6%), near-total resection in eight patients (28.6%), subtotal resection in two patients (7.1%), and partial resection in three patients (10.7%).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgical Outcomes and Complications\u003c/h3\u003e\n\u003cp\u003ePostoperative complications were observed in 3 patients (10.7%). These included one case of meningitis, one case of cerebrospinal fluid leak, and one case of atrial fibrillation. Among the 14 patients with audiometric follow-up available post-revision surgery (50%), all were classified as AAO-HNS Class D, indicating non-serviceable hearing.\u003c/p\u003e \u003cp\u003eThe median duration of facial nerve follow-up was 64 months (range: 3\u0026ndash;120 months), based on data from 14 patients. Facial nerve function at discharge was grade I in two patients (7.1%), grade II in ten patients (35.7%), grade III in five patients (17.9%), grade IV in six patients (21.4%), grade V in three patients (10.7%), and grade VI in two patients (7.1%). At the 12-month follow-up, among the 16 patients with available data (57%), 10 (62.5%) had recovered to HB grade I, one (6.3%) to grade II, one (6.3%) to grade III, and four (25%) remained in HB grades V or VI. These trends are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of Study Cohort (N\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubgroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo. (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (75%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at radiosurgery, median (range), y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (24\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterval from radiosurgery to surgery, median (range), months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (24\u0026ndash;120)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary SRS modality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGamma Knife\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCyberKnife\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLINAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKoos grade at revision surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (63.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical approach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrosigmoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTranslabyrinthine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTranspromontorial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of surgical resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGross total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (46.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNear-total (\u0026le;\u0026thinsp;2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubtotal (\u0026gt;\u0026thinsp;2\u0026ndash;5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (28.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePartial (\u0026gt;\u0026thinsp;5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAny complication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSF leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multicenter retrospective study contributes to the expanding body of literature addressing the outcomes of salvage microsurgery for VS after failed SRS. As SRS continues to be widely adopted as a primary management strategy for small- to medium-sized VS, the frequency of salvage surgical interventions, although still relatively uncommon, may increase over time. In this evolving landscape, a deeper understanding of the indications, technical challenges, and outcomes of salvage procedures is warranted.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eIndications and Timing for Salvage Intervention\u003c/h2\u003e \u003cp\u003eIn our cohort, radiological tumor progression, with or without associated symptoms, was the predominant indication for salvage microsurgery (60.7%). These findings are in concordance with the most recent systematic review and meta-analysis by Ribeiro et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and are further supported by earlier studies [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe median interval between SRS and surgical intervention was 42 months, reflecting the clinical preference for delayed surgery in the absence of acute neurological deterioration, consistent with evolving clinical standards [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This preference for deferred intervention is grounded in the evolving understanding of post-radiation tumor behavior and its impact on surgical morbidity. Within the first 6\u0026ndash;18 months, transient tumor swelling, often referred to as pseudoprogression, is a well-documented phenomenon [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This phase is characterized by treatment-related edema, inflammation, and early fibrosis, which can mimic true progression both radiologically and symptomatically. Crucially, surgical intervention during this period is associated with increased operative risk owing to obscured anatomical planes and heightened vulnerability of adjacent neurovascular structures. As such, delayed surgery\u0026mdash;ideally beyond 24 to 36 months\u0026mdash;has become the preferred strategy in patients without urgent clinical deterioration, offering improved operative conditions and a lower-risk profile [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eConsiderations on Pre-Radiosurgery Tumor Volume\u003c/h2\u003e \u003cp\u003eA noteworthy characteristic of our salvage cohort is the substantial tumor volume present at the time of initial SRS. Among the patients with available pre-treatment data, a significant majority were classified with Koos grade III or IV tumors before receiving radiation. Of the 22 patients for whom this data was available, the majority were classified as either Koos grade III (7 patients) or Koos grade IV (9 patients) at the time of their primary SRS treatment. This means that 16 of these 22 patients (approximately 73%) already had large tumors with significant mass effect prior to receiving radiation. This finding is particularly relevant given that the literature supports SRS as a first-line intervention primarily for small- to medium-sized vestibular schwannomas, typically those measuring\u0026thinsp;\u0026le;\u0026thinsp;2.5 to 3.0 cm, where its safety profile and efficacy are most favorable [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. While this study was not designed to identify risk factors for SRS failure, the prevalence of large tumors in this cohort of treatment failures warrants consideration. It underscores the importance of careful patient selection for primary SRS and suggests that applying this modality to larger tumors may carry a higher risk of requiring future salvage microsurgery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eOperative Challenges and Functional Outcomes\u003c/h2\u003e \u003cp\u003eThe intraoperative findings in our cohort highlight the inherent complexity of salvage microsurgery for previously irradiated VS. Radiation-induced alterations, most notably fibrosis and arachnoid adhesions, were encountered in 67.9% of cases. These phenomena have been well documented in the literature and are known to obscure surgical planes, increase operative time, and elevate the risk of cranial nerve injury [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Salvage procedures require meticulous dissection techniques, comprehensive intraoperative monitoring, and experience with distorted microsurgical anatomy.\u003c/p\u003e \u003cp\u003eAn important adjunct to these observations was the documented progression in the Koos classification between radiosurgery and surgery. Among the 22 patients with complete data, 27.3% were initially classified as Koos grades I\u0026ndash;II, whereas only 7.4% remained at grade II at the time of surgical intervention. The proportion of Koos grade IV tumors increased substantially from 40.9% to 63.0%. This progression likely reflects not only true volumetric growth, but also increased brainstem involvement and mass effect, factors that critically influence surgical approach and morbidity.\u003c/p\u003e \u003cp\u003eThe Koos classification has traditionally served as a radiological staging tool and guide for treatment selection [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, in the salvage setting, the Koos grade may underrepresent the intraoperative complexity posed by radiation-induced anatomical distortion [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In our experience, several tumors initially graded as Koos II demonstrated surgical characteristics typical of grade IV lesions, including dense adhesions to the brainstem and facial nerve, loss of arachnoidal planes, and friable tumor consistency. These findings suggest that static imaging-based classifications may not reliably reflect the surgical risk in previously irradiated patients and that appropriate counselling with the patient on this topic is crucial.\u003c/p\u003e \u003cp\u003eThe clinical implications of this mismatch are reflected in the surgical outcomes. In our series, GTR was achieved in only 46.6% of cases, which is considerably lower than the rates reported for non-irradiated Koos I\u0026ndash;III tumors, where GTR typically exceeds 70% [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Accordingly, STR and NTR were deliberately pursued in anatomically unfavorable cases, particularly where tumor adherence to critical neurovascular structures was evident. This approach is increasingly supported in the literature, where long-term control has been demonstrated even in the absence of GTR [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFacial nerve outcomes were encouraging; although only 7.1% of patients had House-Brackmann (HB) grade I function at discharge, this improved to 62.5% at 12 months. These data are consistent with those of other studies, highlighting the potential for delayed facial nerve recovery after salvage surgery [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs expected, none of the patients in our cohort retained serviceable hearing following surgery, and all patients were classified as AAO-HNS class D postoperatively. This outcome is expected in the salvage context, where prior cochlear radiation exposure and the nature of the surgical approach limit the possibility of functional cochlear preservation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In this context, hearing preservation should not be considered a realistic goal of salvage surgery.\u003c/p\u003e \u003cp\u003eOur complication rate was relatively low (10.7%) and included only one case each of meningitis, cerebrospinal fluid leak, and atrial fibrillation. This compares favorably with published reports [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and likely reflects careful patient selection and experience in high-volume centers. Importantly, no procedure-related mortality occurred, consistent with the experience of other high-volume centers and underscoring the safety of salvage MS when performed by experienced teams with appropriate patient selection criteria [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLong-term follow-up was available in most patients, with median FN monitoring of 64 months and radiological surveillance often extending beyond five years post-surgery. The durable functional outcomes reported here underscore the value of prolonged monitoring, particularly in patients undergoing complex salvage procedures after stereotactic radiosurgery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study had several limitations due to its retrospective design. The relatively small sample size, although reflective of the rarity of salvage microsurgery after failed SRS, did not permit formal statistical analysis and limited the scope of the inferential interpretation. Additionally, heterogeneity in surgical techniques, perioperative management, and follow-up duration across participating centers may introduce variability that affects the generalizability of the findings.\u003c/p\u003e \u003cp\u003eFunctional outcomes, particularly those related to long-term facial nerve recovery, were assessed based on clinical documentation and follow-up availability, which may be subject to institutional differences in reporting and retrospective nature of the study. The present rate of data attrition could potentially influence the reported outcomes; therefore, the findings on functional recovery should be interpreted with appropriate caution as they may not be generalizable to the entire cohort. The absence of a control group (e.g., patients undergoing primary microsurgery or repeat SRS) also limits comparative assessment. Future prospective studies with standardized outcome measures and larger multicenter cohorts are essential to validate and expand these findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSalvage microsurgery represents a viable and safe therapeutic option for managing VS following failed SRS. The timing of surgical intervention is critical to optimizing outcomes. Favorable results in this cohort may reflect both the high-volume expertise of participating centers and a shared institutional preference for delayed intervention. Although technically more demanding than primary resection, acceptable morbidity and good functional outcomes can be achieved when function-preserving strategies are employed.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e:\u0026nbsp;The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e: All authors contributed to the study conception and design. Material preparation and data collection were performed by Filippo Friso, Alfredo Decio Fabbri, Federico Calvaruso, Virginia Dallari, Franco Federico Bochicchio, Emanuele La Corte, Kazimierz Niemczyk, Adrian Drożdż, Lukas Anschuetz, Giacomo Pavesi, Barbara Masotto, and Francesco DiMeco. Data analysis and first draft writing was performed by Noa Ben Dor. All authors commented on previous versions of the manuscript. Supervision was provided by Giulia Molinari, Livio Presutti, Paolo Ferroli, Francesco DiMeco, and Alfredo Conti. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e:\u0026nbsp;The dataset analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Comitato Etico di Area Vasta Emilia Centro (IRCCS Azienda Ospedaliero\u0026ndash;Universitaria di Bologna, Policlinico di Sant\u0026rsquo;Orsola). Approval Code: 436/2023/Oss/AOUBo; date of approval: February 14 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eInformed consent for retrospective data management was obtained for all subjects.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCarlson ML, Link MJ, Vestibular Schwannomas (2021) N Engl J Med 384:1335\u0026ndash;1348. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra2020394\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra2020394\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarinelli JP, Beeler CJ, Carlson ML, Caye-Thomasen P, Spear SA, Erbele ID (2022) Global Incidence of Sporadic Vestibular Schwannoma: A Systematic Review. 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Int J Radiation Oncology*Biology*Physics 81:e503\u0026ndash;e509. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijrobp.2011.04.066\u003c/span\u003e\u003cspan address=\"10.1016/j.ijrobp.2011.04.066\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoland Goldbrunner M, Weller J, Regis M, Lund-Johansen P, Stavrinou D, Reuss DG, Evans F, Lefranc K, Sallabanda A, Falini P, Axon O, Sterkers L, Fariselli W, Wick (2020) Joerg-Christian Tonn, EANO guideline on the diagnosis and treatment of vestibular schwannoma, \u003cem\u003eNeuro-Oncology\u003c/em\u003e, Volume 22, Issue 1, January Pages 31\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/neuonc/noz153\u003c/span\u003e\u003cspan address=\"10.1093/neuonc/noz153\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Vestibular Schwannoma, Acoustic Neuroma, Recurrence, Stereotactic Radiosurgery, Radiation Therapy, Salvage Microsurgery, Oncology","lastPublishedDoi":"10.21203/rs.3.rs-7631342/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7631342/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the clinical indications, technical characteristics, and outcomes of salvage microsurgery in patients with sporadic vestibular schwannomas (VS) primarily treated with Stereotactic radiosurgery (SRS).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective multicenter study included 28 patients who underwent salvage microsurgery between 2012 and 2022 at six European tertiary referral centers. Data on demographics, tumor characteristics, surgical approach, extent of resection, and functional outcomes were collected, with a focus on facial nerve preservation and postoperative complications.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTumor progression, with or without symptoms, was the predominant indication for surgery (60.7% of cases). The median interval between SRS and surgery was 42 months (range 24\u0026ndash;120). Intraoperative findings revealed altered tumor consistency and limited mobility due to arachnoid adhesions or fibrosis in 19 patients (67.9%). Gross total resection was achieved in 53.6% of the cases, with near-total resection in 28.6% of the cases. No patient retained serviceable hearing, but postoperative facial nerve function improved over time, with 62.5% achieving House-Brackmann grade I at 12 months. The complication rate was 10.7%, with no procedure-related mortality observed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSalvage microsurgery represents a viable and safe therapeutic option for managing VS following failed SRS. The timing of surgical intervention may be critical to optimizing outcomes. Favorable results in this cohort may reflect both the high-volume expertise of participating centers and a shared institutional preference for delayed intervention. Although technically more demanding than primary resection, acceptable morbidity and good functional outcomes can be achieved when function-preserving strategies are employed.\u003c/p\u003e","manuscriptTitle":"Salvage Microsurgery for Vestibular Schwannoma after failed Stereotactic Radiosurgery: A Multicentric Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-06 14:33:24","doi":"10.21203/rs.3.rs-7631342/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-20T04:34:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-14T20:15:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-11T23:19:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-10T12:07:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227234235696177302512334590385148986007","date":"2026-01-07T20:37:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162933272557053734240895879922490491375","date":"2026-01-07T06:06:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-05T07:02:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179644173722168471313801438167365713666","date":"2026-01-05T05:33:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"284268411110735783046922031155901458312","date":"2026-01-05T05:31:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-05T04:35:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-17T10:53:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-17T08:21:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neuro-Oncology","date":"2025-09-16T13:59:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d3b5fec6-dfe6-47f8-b6ec-0181711de1fa","owner":[],"postedDate":"January 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T10:10:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-06 14:33:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7631342","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7631342","identity":"rs-7631342","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}