Long-term Outcomes of Radical Resection vs. Combined Subtotal Resection and Gamma Knife Radiosurgery for Large Vestibular Schwannomas

Long-term Outcomes of Radical Resection vs. Combined Subtotal Resection and Gamma Knife Radiosurgery for Large Vestibular Schwannomas | 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 Long-term Outcomes of Radical Resection vs. Combined Subtotal Resection and Gamma Knife Radiosurgery for Large Vestibular Schwannomas Ryan Keswani, Yukihiro Goto, Ayako Shima, Hisao Hirai, Peter Adidharma, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6676378/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This study compares the long-term outcomes of radical resection versus subtotal removal followed by Gamma Knife (GK) radiosurgery for large vestibular schwannomas (VS), focusing on tumor control and neurological function preservation. Methods: A retrospective analysis of 87 patients with large VS (Koos grade III–IV) was conducted. Patients were divided into radical resection (Group R, n = 40) and subtotal removal followed by GK (Group C, n = 47). Tumor volume reduction, facial nerve function, hearing preservation, and other neurological outcomes were evaluated. Results: Group C had significantly larger tumor preoperatively (median: 10.8 cm³ vs. 7.9 cm³, p = 0.002). Despite this, facial nerve function was better preserved in Group C than in Group R (House-Brackmann > 3: 19% vs. 30%), and the incidence of non-serviceable hearing (> 50 dB) was less frequent in Group C (72% vs. 88%) immediately after surgery. Trigeminal dysesthesia improved in Group C (32–26%) but worsened in Group R (28–38%). Ataxia was more common in Group C (final: 19% vs. 3%, p < 0.001), likely due to larger tumor size. Tumor control was achieved in both groups, with a 95.7% reduction in Group R and a 69.5% reduction in Group C ( p < 0.0001). VP shunt placement was more frequent in Group C than in Group R (19% vs. 5%). Failure of tumor control was observed only in Group C, where 4% of patients required salvage surgery and 2% underwent additional Gamma Knife treatment. Conclusion: Subtotal removal with GK balances tumor control and neurological preservation in large VS. Despite larger tumors, this treatment approach demonstrated better long-term facial nerve and hearing outcomes than radical resection. cranial nerve preservation Gamma knife surgery long-term outcome microsurgery subtotal removal radical excision vestibular schwannoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The excision of large vestibular schwannomas (VS) presents significant surgical challenges [ 1 ]. Displacement of cranial nerves, involvement of vascular structures, and adhesions to the brainstem complicate the procedure, increasing the risk of neurological deficits. Despite advancements in microsurgical techniques, achieving radical tumor removal while preserving neurological function remains a formidable task. Previous study demonstrates that larger tumor size is associated with a higher risk of cranial nerve injury following surgery [ 2 , 7 ]. Gamma Knife surgery is predominantly recommended for small to medium-sized vestibular schwannomas due to its proven efficacy. Studies have shown that Gamma Knife surgery achieves superior outcomes compared to traditional surgical removal in terms of tumor control and cranial nerve preservation [ 1 , 10 , 11 , 12 ]. However, its use for large schwannomas is limited by the high irradiation dose required in a single session, which presents significant challenges [ 2 , 8 , 4 ]. For large vestibular schwannomas, a combination of subtotal removal followed by radiosurgery has emerged as a practical and effective treatment approach. This strategy balances the goals of safer removal and radiation efficacy while prioritizing the preservation of neurological function [ 1 ]. Nonetheless, studies directly comparing gross total removal with the combined strategy of subtotal excision followed by radiosurgery for managing vestibular schwannomas remain scarce [ 13 , 16 ]. This study aims to compare the efficacy and cranial nerve function preservation between radical excision and a combined approach of subtotal excision followed by Gamma Knife surgery for large vestibular schwannomas. Methods Patient Cohort We conducted a retrospective study comparing two treatment strategies for large vestibular schwannomas (VS): radical removal alone (group R) and a combined strategy of subtotal removal followed by Gamma Knife surgery (group C) at our institution. From 2004 to 2023, 443 patients were treated for vestibular schwannomas, of whom 118 had large tumors classified as larger than Koos Grade 3 [ 5 ], with contact to the brainstem surface. Of these, 40 patients were categorized into group R, and 47 patients were categorized into group C. Patients with neurofibromatosis type 2 were excluded from the study. Additionally, cases of subtotal removal without subsequent Gamma Knife treatment were excluded. The analysis was restricted to patients with a minimum follow-up period of one year (Fig. 1 ). Written informed consent was obtained from all participants prior to each procedure, and the study was approved by our hospital’s ethics committee. Microsurgical Procedures All patients were positioned laterally and underwent surgery using the standard retrosigmoid approach in most cases. For radical removal of large tumors, a trans-petrosal approach with drilling of the internal acoustic canal was utilized. A facial nerve stimulator (NIM™ 3.0, Medtronic, Minneapolis, USA) was employed to identify the location of the facial nerve. Continuous auditory brainstem response (ABR) monitoring was implemented to prevent hearing impairment in patients with serviceable hearing. After opening the dura mater, the tumor and surrounding neural structures were identified using anatomical landmarks and intraoperative monitoring. Tumors were then debulked using microsurgical instruments and an ultrasonic aspirator while prioritizing the preservation of cranial nerve function. Cases where gross total resection was achieved were categorized as Group R, while cases with subtotal tumor removal, followed by postoperative Gamma Knife treatment, were categorized as Group C. Radiosurgical Procedures In Group C, postoperative radiosurgery was administered. Patients underwent placement of a stereotactic frame (Leksell Model G, Elekta Instruments Inc.) under local anesthesia, with monitoring of vital signs during the procedure. Thin-slice MRI scans were obtained for treatment planning, with 2-mm slices using contrast-enhanced T1-weighted spoiled gradient recalled (SPGR) imaging. CT scans with bone window levels were also performed to detect and correct any MRI distortion and to ensure accurate target determination [ 4 , 8 ]. Dose planning was conducted using the GammaPlan system (Elekta, Stockholm, Sweden). The Gamma Knife Model C (Elekta, Stockholm, Sweden) was used for treatment until 2017, after which the Gamma Knife Perfection system (Elekta, Stockholm, Sweden) was utilized. Irradiation was typically delivered with a prescribed dose of 12 Gy at the 50% isodose line (maximum dose: 24 Gy). Assessment of Outcomes The neurological status of each patient was evaluated preoperatively and postoperatively, with follow-up conducted either at our clinic or their respective referral institutions. Assessments included hearing function, facial nerve function, trigeminal symptoms, diplopia, lower cranial nerve symptoms, ataxia, and long tract signs. Hearing function was deemed non-serviceable when thresholds exceeded 50 db. Facial weakness was considered significant if the House-Brackmann (HB) grade was worse than grade 3. The Karnofsky Performance Status (KPS) score was also recorded for each patient. Tumor size was monitored through periodic MRI examinations, with imaging outcomes evaluated using the latest available MRI reviewed by neurosurgeons at our institution. Tumor volume was calculated by measuring the three axes (X, Y, and Z) on MRI. Statistical Analysis Statistical analyses were performed using the R statistical environment (version 4.4.1). Patient and surgical characteristics were summarized descriptively. Normality was assessed using the Shapiro-Wilk test. Group comparisons were conducted using the chi-square test, Mann-Whitney U test, t-test, or paired t-test, as appropriate (α = 0.05). Kaplan-Meier analysis, performed with the survival package (version 3.5-5), was used to evaluate the probability of remaining free from significant facial weakness and non-serviceable hearing loss. In the facial weakness analysis, an event was defined as the occurrence of HB grade > 3. In the hearing loss analysis, an event was defined as hearing loss > 50 db. Results Patient Characteristics Between January 2004 and December 2023, 443 patients with vestibular schwannomas were treated at our institutions (Fig. 1 ). Of these, 283 patients underwent Gamma Knife (GK) treatment alone, while 160 underwent surgical removal with or without GK. Among the surgical cases, 42 patients had Koos grade I or II tumors, and 118 patients had Koos grade III or IV tumors. From these 118 patients, 87 were included in the final analysis after excluding those with neurofibromatosis type 2 (n = 8), follow-up periods of less than one year (n = 18), and subtotal tumor removal without subsequent GK (n = 5). The treatments were divided into two groups: radical removal alone (Group R, n = 40) and a combined approach of subtotal removal followed by Gamma Knife (Group C, n = 47). The median age was 53 years (range: 30–71) in Group R and 54 years (range: 24–89) in Group C. Female patients accounted for 58% of Group R and 64% of Group C. The median follow-up period was 38 months (range: 16–98) in Group R and 42 months (range: 12–127) in Group C. The retrosigmoid approach was employed in 83% of Group R cases and 85% of Group C cases, while the remaining cases underwent a trans-petrosal approach. Internal auditory canal drilling was performed in 35% of Group R cases and 26% of Group C cases. There were no statistically significant differences in patient characteristics or operative approaches between the two groups. Tumor Volume Changes Preoperative tumor volumes showed significant variation between the groups (Fig. 3 ). Group R had a median tumor volume of 7.9 cm³ (range: 1.6–33.6 cm³), while Group C had a median preoperative volume of 10.8 cm³ (range: 3.5–70.9 cm³). Postoperatively, Group R achieved a median tumor volume reduction of 89.9%, resulting in a residual volume of 0.3 cm³ (range: 0–7.9 cm³). In comparison, Group C experienced a median reduction of 57.7%, with a residual volume of 3.1 cm³ (range: 2.3–24.0 cm³). At the final follow-up, tumor control was successfully maintained in both groups. Group R reported a median residual volume of 0.4 cm³, reflecting a 95.7% total reduction, while Group C reported a median residual volume of 2.8 cm³, representing a 69.5% total reduction (P < 0.0001). Tumor volumes demonstrated statistically significant differences between the groups at all stages of treatment. Larger tumors were more commonly categorized into Group C, reflecting the use of a combined subtotal removal and Gamma Knife approach for these cases. Radical removal was predominantly performed on smaller tumors compared to the combined treatment strategy. All patients in Group R maintained complete tumor control with no significant recurrence (tumor control rate = 100%). In contrast, tumor control failure was observed in Group C, where 2 patients (4%) required salvage surgery and 1 patient (2%) underwent additional Gamma Knife treatment, resulting in an overall tumor control rate of 94%. Hearing Preservation Preoperatively, non-serviceable hearing disturbance (> 50db) was present in 68% of patients in Group R and 66% in Group C. Immediately after surgery, these rates increased to 88% and 72%, respectively, and further deteriorated to 95% and 94% at the final follow-up (Table 1). Kaplan-Meier analysis showed no statistically significant difference between the groups in the probability of remaining free from non-serviceable hearing disturbance (Fig. 4 ). Facial Nerve Function Preoperative facial weakness (HB > 3) was present in 10% of patients in Group R and 15% in Group C. Postoperatively, these rates worsened to 30% and 19%, respectively. Although Group R exhibited worse facial nerve outcomes, the difference between the groups was not statistically significant. Facial nerve function showed improvement in the long term. At the final follow-up, facial weakness was present in 18% of Group R and 13% of Group C patients (Table 1). While Kaplan-Meier analysis showed no statistically significant difference in the probability of remaining free from facial weakness, Group C consistently demonstrated a higher preservation rate than Group R throughout the 120-month follow-up period (Fig. 5 ). Trigeminal Dysesthesia Preoperative trigeminal dysesthesia was more common in Group C (32%) than in Group R (28%), likely due to the larger tumor sizes in Group C. In Group R, symptoms worsened to 38% postoperatively due to the radical surgical manipulations and remained unchanged in the long term. In contrast, patients in Group C experienced an initial improvement, as tumors near the trigeminal nerve root were left untouched. The incidence decreased to 30% immediately after surgery and further improved to 26% at the final follow-up. Statistical analysis showed no significant differences between the groups. Ataxia Patients in Group C exhibited significantly worse cerebellar ataxia at all time points compared to those in Group R. Preoperatively, ataxia was observed in 10% of patients in Group R and 34% of patients in Group C. Postoperatively, the incidence decreased to 3% in Group R but remained at 21% in Group C. At the final follow-up, ataxia was present in 3% of Group R and 19% of Group C. These findings were consistent with the larger tumor volumes observed in Group C at all time points. Other Neurological Status Lower cranial nerve deficits were rare in both groups, with an incidence of 2–5% and no statistically significant difference. Hemiparesis was not observed in Group R at any time point, whereas it was present in 4% of patients in Group C, though the difference was not statistically significant. Functional performance, measured by the Karnofsky Performance Status (KPS), remained stable in both groups, with median scores of 90 maintained from the preoperative assessment to the final follow-up evaluation. Subsequent Intervention VP shunt placement was more frequently required in Group C (19%) compared to Group R (5%), though the difference was not statistically significant. No patients in Group R required salvage surgery or additional Gamma Knife treatment, whereas in Group C, salvage surgery was necessary in 4% of patients, and additional Gamma Knife treatment was performed in 2% of patients. Discussion The management of large vestibular schwannomas presents a complex challenge, requiring a balance between achieving maximal tumor resection and preserving neurological function. Historically, radical resection has been the preferred approach; however, subtotal resection followed by radiosurgery has emerged as a viable alternative. Comparative studies between surgical excision and Gamma Knife (GK) treatment for large vestibular schwannomas remain limited. While surgical excision offers more effective long-term volume control, most previous studies suggest that hearing and facial nerve function are better preserved in patients undergoing GK treatment (Table 2) [ 10 , 11 , 13 , 3 , 18 , 16 , 17 ]. Furthermore, recent large-cohort studies reinforce this trend, indicating that GK treatment is increasingly favored for managing large vestibular schwannomas [ 18 , 16 , 15 ]. While some evidence suggests that the combined strategy may result in lower cranial nerve complications [ 4 , 16 ], long-term outcome data from large-scale comparative studies are still needed. Iwai et al. demonstrated that this strategy effectively preserves cranial nerve function, particularly for large vestibular schwannomas where complete resection might carry higher risks [ 4 ]. This study highlights the advantages of the combined approach compared to radical resection, particularly in terms of facial nerve and hearing preservation, despite the significantly larger tumor sizes in patients treated with the combined approach. A significant difference in tumor size was observed between the groups, which likely influenced treatment decisions. Given the challenges associated with resecting large tumors, subtotal removal followed by GK was favored for cases where radical excision posed a high risk of neurological deficits. This aligns with recent trends emphasizing functional preservation while maintaining adequate tumor control [ 4 , 16 , 17 ]. This study demonstrated more favorable long-term preservation of facial nerve function and hearing with the combined approach, despite patients having larger tumors. Postoperatively, facial weakness was more common in patients who underwent radical removal compared to those treated with the combined approach. These results support the hypothesis that subtotal resection minimizes direct nerve trauma while subsequent GK treatment effectively controls residual tumor growth without excessive radiation exposure [ 4 , 14 , 18 ]. As expected, larger tumor volumes were significantly associated with worse ataxia ( p < 0.001), likely due to increased brainstem compression [ 7 , 17 ]. However, trigeminal dysesthesia followed a different pattern. Despite the larger tumor sizes in the combined group, trigeminal symptoms improved postoperatively (from 32–26%), whereas they worsened in the radical resection group (from 28–38%). This suggests that subtotal resection effectively alleviated trigeminal compression while minimizing excessive manipulation of the nerve root, thereby contributing to functional preservation [ 16 , 18 ]. While both groups achieved satisfactory long-term tumor control, they demonstrated a comparable need for VP shunt placement. The overall rates of salvage surgery and additional GK in the combined group remained low, indicating that subtotal removal combined with GK remains an effective strategy for durable tumor management [ 4 , 8 ]. The 69.5% overall tumor volume reduction in the combined group, despite the initially larger tumor size, further underscores the efficacy of this approach [ 14 ]. These findings align with an evolving paradigm shift in VS treatment. The combined approach provides a reasonable compromise between achieving tumor control and minimizing morbidity. For large vestibular schwannomas, subtotal removal followed by GK should be considered the preferred strategy, particularly when preserving cranial nerve function is a priority. Conversely, radical resection may still be warranted for smaller tumors where gross total resection can be safely achieved without compromising neurological function [ 9 , 13 ]. Limitations and Future Directions This study is limited by its retrospective nature and the inherent selection bias in treatment allocation. Larger, prospective, multi-institutional studies are needed to further validate these findings. Additionally, future research should explore the long-term quality-of-life implications of each approach, given the growing emphasis on patient-centered outcomes in neurosurgical decision-making. Conclusion This study supports the growing preference for subtotal resection combined with GK for large vestibular schwannomas. Despite the larger tumor sizes in patients treated with the combined approach, better long-term preservation of facial nerve function and hearing was demonstrated compared to radical resection. These findings reinforce the need for a tailored approach in VS management, prioritizing neurological preservation without compromising tumor control. Declarations Funding No funding was received for this research. Conflict of Interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. Informed consent Informed consent was obtained from all individual participants included in the study. Author Contribution Conceptualization: Ryan Keswani, Takuro InoueFormal Analysis: Ryan Keswani, Peter AdidharmaInvestigation: Ryan Keswani, Takuro Inoue, Yukihiro Goto, Ayako Shima, Hisao HiraiMethodology: Ryan Keswani, Takuro Inoue, Peter AdidharmaProject Administration: Ryan Keswani, Takuro InoueWriting – Original Draft: Ryan KeswaniWriting – Review & Editing: Ryan Keswani, Takuro Inoue References Dhayalan D, Tveiten ØV, Finnkirk M, Storstein A, Hufthammer KO, Goplen FK, Lund-Johansen M (2023) V-REX Trial investigators. Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial. JAMA 330(5):421–431 Dumot C, Pikis S, Mantziaris G, Xu Z, Anand RK, Nabeel AM et al (2022) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study. J Neurooncol 160(1):201–208 Golfinos JG, Hill TC, Rokosh R, Choudhry O, Shinseki M, Mansouri A, Friedmann DR, Thomas Roland J Jr, Kondziolka D (2016) A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas. J Neurosurg 125(6):1472–1482 Iwai Y, Ishibashi K, Watanabe Y, Uemura G, Yamanaka K (2015) Functional Preservation After Planned Partial Resection Followed by Gamma Knife Radiosurgery for Large Vestibular Schwannomas. World Neurosurg 84(2):292–300 Koos WT, Day JD, Matula C, Levy DI (1998) Neurotopographic considerations in the microsurgical treatment of small acoustic neurinomas. J Neurosurg 88(3):506–512 Lak AM, Khan YS (2024) Cerebellopontine Angle Cancer. [Updated 2023 Jun 26]. StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL). Jan-. Mindermann T, Schlegel I (2013) Grading of vestibular schwannomas and corresponding tumor volumes: ramifications for radiosurgery. Acta Neurochir (Wien) 155(1):71–74 Pikis S, Mantziaris G, Kormath Anand R, Nabeel AM, Sheehan D et al (2022) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study. J Neurosurg 138(2):405–412 Pollock BE (2008) Vestibular schwannoma management: an evidence-based comparison of stereotactic radiosurgery and microsurgical resection. Prog Neurol Surg 21:222–227 Pollock BE, Driscoll CL, Foote RL, Link MJ, Gorman DA, Bauch CD et al (2006) Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotactic radiosurgery. Neurosurgery 59(1):77–85 Pollock BE, Lunsford LD, Kondziolka D, Flickinger JC, Bissonette DJ, Kelsey SF, Jannetta PJ (1995) Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 36(1):215–224 Schnurman Z, Gurewitz J, Smouha E, McMenomey SO, Roland JT Jr, Golfinos JG, Kondziolka D (2022) Matched Comparison of Hearing Outcomes in Patients With Vestibular Schwannoma Treated With Stereotactic Radiosurgery or Observation. Neurosurgery 91(4):641–647 Shirato H, Sakamoto T, Sawamura Y, Kagei K, Isu T, Kato T et al (1999) Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma. Int J Radiat Oncol Biol Phys 44(3):545–550 Stastna D, Urgosik D, Chytka T, Liscak R (2021) Large vestibular schwannomas: long-term outcomes after stereotactic radiosurgery. Neuro Endocrinol Lett 41(6):329–338 Szymoniuk M, Kochański M, Wilk K, Miazga D, Kanonik O, Dryla A, Kamieniak P (2024) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a systematic review and meta-analysis. Acta Neurochir (Wien) 166(1):101 Tatagiba M, Wang SS, Rizk A, Ebner F, van Eck ATCJ, Naros G, Horstmann G (2023) A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome. Neurooncol Adv 5(1):vdad146 Wang SS, Rizk A, Ebner FH, van Eck A, Naros G, Horstmann G, Tatagiba M (2024) Cystic vestibular schwannoma - a subgroup analysis from a comparative study between radiosurgery and microsurgery. Neurosurg Rev 47(1):291 Yakkala VK, Mammi M, Lamba N, Kandikatla R, Paliwal B, Elshibiny H, Corrales CE, Smith TR, Mekary RA (2022) Audiovestibular symptoms and facial nerve function comparing microsurgery versus SRS for vestibular schwannomas: a systematic review and meta-analysis. Acta Neurochir (Wien) 164(12):3221–3233 Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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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-6676378","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458312919,"identity":"bba889ac-c3bb-45e9-acc0-ee2f1c2d8423","order_by":0,"name":"Ryan Keswani","email":"","orcid":"","institution":"National Brain Centre","correspondingAuthor":false,"prefix":"","firstName":"Ryan","middleName":"","lastName":"Keswani","suffix":""},{"id":458312920,"identity":"efa04397-267f-4f89-85b7-3884bd568f84","order_by":1,"name":"Yukihiro Goto","email":"","orcid":"","institution":"Koto Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yukihiro","middleName":"","lastName":"Goto","suffix":""},{"id":458312921,"identity":"7541f293-ca73-4ab3-bcb8-84b90a3cd592","order_by":2,"name":"Ayako Shima","email":"","orcid":"","institution":"Koto Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ayako","middleName":"","lastName":"Shima","suffix":""},{"id":458312922,"identity":"a34e24b6-c8e5-434f-8d35-f6b0537b0906","order_by":3,"name":"Hisao Hirai","email":"","orcid":"","institution":"Koto Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hisao","middleName":"","lastName":"Hirai","suffix":""},{"id":458312923,"identity":"6d703bd4-47fe-4453-ae06-01295303d693","order_by":4,"name":"Peter Adidharma","email":"","orcid":"","institution":"The Newcastle upon Tyne Hospitals NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Adidharma","suffix":""},{"id":458312924,"identity":"554e3db2-f98c-4938-93e4-beda9a9caea4","order_by":5,"name":"Takuro Inoue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYFACNhBRI8cPohIKiNDAA9FyzFiyAaTFgHgtzIkbDoBoYrTYsx9Lk66oYEvcfH514ocHBgzy/GIHCNjCk3ZM8swZGeNtN95ulgA6zHDm7ARCDktvk2xsY5PdduPsBpCWBIPbhLTwPwdpYWbcPOPs5h/EaZEAOgyoRXEDf+82Im258SzZsuHMMWOJG7zbLBIMJAj7hb0/zfBmQwUwKvvPbr75o8JGnl+agBYEkACrlCBWOQjwHyBF9SgYBaNgFIwkAAB11UHynOJzJQAAAABJRU5ErkJggg==","orcid":"","institution":"Koto Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Takuro","middleName":"","lastName":"Inoue","suffix":""}],"badges":[],"createdAt":"2025-05-16 02:23:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6676378/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6676378/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83352277,"identity":"400966fb-42d0-4185-a8c9-149e0bead060","added_by":"auto","created_at":"2025-05-23 14:23:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":550540,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParticipant flow diagram\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGK, Gamma knife; NF2, Neurofibromatosis type 2\u003c/p\u003e","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/4c90d41c1b1dd9fdecc9ac21.jpg"},{"id":83353276,"identity":"aeecbf94-aa7b-4915-94f9-2c491fbf6fc5","added_by":"auto","created_at":"2025-05-23 14:31:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":600944,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative cases of each group (a: group R, b: group C)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea1\u003c/strong\u003e A 66-year-old woman presented with dizziness, diagnosed with a right-sided vestibular schwannoma (Koos grade 4). Preoperative hearing on the affected side was 17.5 dB.\u003cbr\u003e\n \u003cstrong\u003ea2\u003c/strong\u003e Total tumor removal was achieved by sacrificing the vestibular nerve and drilling out the internal auditory canal. Postoperative complications included hearing loss and facial palsy graded at House-Brackmann II.\u003cbr\u003e\n \u003cstrong\u003ea3\u003c/strong\u003e At the 4-year follow-up, no tumor recurrence was observed, and the facial palsy had fully resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb1\u003c/strong\u003e A 46-year-old man presented with tinnitus and hearing impairment (32 dB) due to a right-sided vestibular schwannoma (Koos grade 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb2\u003c/strong\u003e He underwent subtotal tumor removal, followed by Gamma Knife radiosurgery three months postoperatively. His hearing declined to 62 dB postoperatively, and he developed facial palsy graded as House-Brackmann II.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb3\u003c/strong\u003e The patient experienced temporary tumor enlargement following Gamma Knife treatment. However, the tumor remained stable in size at the final follow-up, six years postoperatively, with no neurological deterioration observed during this period.\u003c/p\u003e","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/0f82a27901945467848cc193.jpg"},{"id":83354081,"identity":"5523e92a-fb5b-4c20-8ccb-9c81423029d0","added_by":"auto","created_at":"2025-05-23 14:39:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":309298,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMean tumor volume change of each group\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/589e605d5f0fddb07d98cab9.jpg"},{"id":83351928,"identity":"cea0e07d-209c-4275-a12d-604b0cdc6521","added_by":"auto","created_at":"2025-05-23 14:15:09","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":280350,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProbability of Remaining Free from Hearing Disturbance\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig.4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/6c2fe2c82628372619513660.jpg"},{"id":83353273,"identity":"6a22c4c4-3290-4adb-8f82-6fef2c774024","added_by":"auto","created_at":"2025-05-23 14:31:09","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":293077,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProbability of Remaining Free from Facial Weakness\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig.5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/3681ff9c0e2e0d3a82e48ede.jpg"},{"id":83639988,"identity":"acfe065c-1bea-4969-8a4b-30b71bdb1d65","added_by":"auto","created_at":"2025-05-30 03:02:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2706000,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/98437a8d-3388-4597-9a4f-3202dd21c969.pdf"},{"id":83351921,"identity":"7bf53a1a-a27e-47de-9864-7f9dad42ef63","added_by":"auto","created_at":"2025-05-23 14:15:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19469,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/95debebbcddd342caa36613f.docx"},{"id":83351926,"identity":"a0adaa6c-6443-4105-b59c-a0878ccedbee","added_by":"auto","created_at":"2025-05-23 14:15:09","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18042,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6676378/v1/bed05cdff7bfc6143a9841fa.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term Outcomes of Radical Resection vs. Combined Subtotal Resection and Gamma Knife Radiosurgery for Large Vestibular Schwannomas","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe excision of large vestibular schwannomas (VS) presents significant surgical challenges [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Displacement of cranial nerves, involvement of vascular structures, and adhesions to the brainstem complicate the procedure, increasing the risk of neurological deficits. Despite advancements in microsurgical techniques, achieving radical tumor removal while preserving neurological function remains a formidable task. Previous study demonstrates that larger tumor size is associated with a higher risk of cranial nerve injury following surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGamma Knife surgery is predominantly recommended for small to medium-sized vestibular schwannomas due to its proven efficacy. Studies have shown that Gamma Knife surgery achieves superior outcomes compared to traditional surgical removal in terms of tumor control and cranial nerve preservation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, its use for large schwannomas is limited by the high irradiation dose required in a single session, which presents significant challenges [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor large vestibular schwannomas, a combination of subtotal removal followed by radiosurgery has emerged as a practical and effective treatment approach. This strategy balances the goals of safer removal and radiation efficacy while prioritizing the preservation of neurological function [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Nonetheless, studies directly comparing gross total removal with the combined strategy of subtotal excision followed by radiosurgery for managing vestibular schwannomas remain scarce [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to compare the efficacy and cranial nerve function preservation between radical excision and a combined approach of subtotal excision followed by Gamma Knife surgery for large vestibular schwannomas.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Cohort\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective study comparing two treatment strategies for large vestibular schwannomas (VS): radical removal alone (group R) and a combined strategy of subtotal removal followed by Gamma Knife surgery (group C) at our institution. From 2004 to 2023, 443 patients were treated for vestibular schwannomas, of whom 118 had large tumors classified as larger than Koos Grade 3 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], with contact to the brainstem surface. Of these, 40 patients were categorized into group R, and 47 patients were categorized into group C. Patients with neurofibromatosis type 2 were excluded from the study. Additionally, cases of subtotal removal without subsequent Gamma Knife treatment were excluded. The analysis was restricted to patients with a minimum follow-up period of one year (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Written informed consent was obtained from all participants prior to each procedure, and the study was approved by our hospital\u0026rsquo;s ethics committee.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMicrosurgical Procedures\u003c/h3\u003e\n\u003cp\u003eAll patients were positioned laterally and underwent surgery using the standard retrosigmoid approach in most cases. For radical removal of large tumors, a trans-petrosal approach with drilling of the internal acoustic canal was utilized. A facial nerve stimulator (NIM\u0026trade; 3.0, Medtronic, Minneapolis, USA) was employed to identify the location of the facial nerve. Continuous auditory brainstem response (ABR) monitoring was implemented to prevent hearing impairment in patients with serviceable hearing.\u003c/p\u003e \u003cp\u003eAfter opening the dura mater, the tumor and surrounding neural structures were identified using anatomical landmarks and intraoperative monitoring. Tumors were then debulked using microsurgical instruments and an ultrasonic aspirator while prioritizing the preservation of cranial nerve function. Cases where gross total resection was achieved were categorized as Group R, while cases with subtotal tumor removal, followed by postoperative Gamma Knife treatment, were categorized as Group C.\u003c/p\u003e\n\u003ch3\u003eRadiosurgical Procedures\u003c/h3\u003e\n\u003cp\u003eIn Group C, postoperative radiosurgery was administered. Patients underwent placement of a stereotactic frame (Leksell Model G, Elekta Instruments Inc.) under local anesthesia, with monitoring of vital signs during the procedure. Thin-slice MRI scans were obtained for treatment planning, with 2-mm slices using contrast-enhanced T1-weighted spoiled gradient recalled (SPGR) imaging. CT scans with bone window levels were also performed to detect and correct any MRI distortion and to ensure accurate target determination [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDose planning was conducted using the GammaPlan system (Elekta, Stockholm, Sweden). The Gamma Knife Model C (Elekta, Stockholm, Sweden) was used for treatment until 2017, after which the Gamma Knife Perfection system (Elekta, Stockholm, Sweden) was utilized. Irradiation was typically delivered with a prescribed dose of 12 Gy at the 50% isodose line (maximum dose: 24 Gy).\u003c/p\u003e\n\u003ch3\u003eAssessment of Outcomes\u003c/h3\u003e\n\u003cp\u003eThe neurological status of each patient was evaluated preoperatively and postoperatively, with follow-up conducted either at our clinic or their respective referral institutions. Assessments included hearing function, facial nerve function, trigeminal symptoms, diplopia, lower cranial nerve symptoms, ataxia, and long tract signs. Hearing function was deemed non-serviceable when thresholds exceeded 50 db. Facial weakness was considered significant if the House-Brackmann (HB) grade was worse than grade 3. The Karnofsky Performance Status (KPS) score was also recorded for each patient.\u003c/p\u003e \u003cp\u003eTumor size was monitored through periodic MRI examinations, with imaging outcomes evaluated using the latest available MRI reviewed by neurosurgeons at our institution. Tumor volume was calculated by measuring the three axes (X, Y, and Z) on MRI.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using the R statistical environment (version 4.4.1). Patient and surgical characteristics were summarized descriptively. Normality was assessed using the Shapiro-Wilk test. Group comparisons were conducted using the chi-square test, Mann-Whitney U test, t-test, or paired t-test, as appropriate (α\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eKaplan-Meier analysis, performed with the survival package (version 3.5-5), was used to evaluate the probability of remaining free from significant facial weakness and non-serviceable hearing loss. In the facial weakness analysis, an event was defined as the occurrence of HB grade\u0026thinsp;\u0026gt;\u0026thinsp;3. In the hearing loss analysis, an event was defined as hearing loss\u0026thinsp;\u0026gt;\u0026thinsp;50 db.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eBetween January 2004 and December 2023, 443 patients with vestibular schwannomas were treated at our institutions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 283 patients underwent Gamma Knife (GK) treatment alone, while 160 underwent surgical removal with or without GK. Among the surgical cases, 42 patients had Koos grade I or II tumors, and 118 patients had Koos grade III or IV tumors. From these 118 patients, 87 were included in the final analysis after excluding those with neurofibromatosis type 2 (n\u0026thinsp;=\u0026thinsp;8), follow-up periods of less than one year (n\u0026thinsp;=\u0026thinsp;18), and subtotal tumor removal without subsequent GK (n\u0026thinsp;=\u0026thinsp;5). The treatments were divided into two groups: radical removal alone (Group R, n\u0026thinsp;=\u0026thinsp;40) and a combined approach of subtotal removal followed by Gamma Knife (Group C, n\u0026thinsp;=\u0026thinsp;47).\u003c/p\u003e \u003cp\u003eThe median age was 53 years (range: 30\u0026ndash;71) in Group R and 54 years (range: 24\u0026ndash;89) in Group C. Female patients accounted for 58% of Group R and 64% of Group C. The median follow-up period was 38 months (range: 16\u0026ndash;98) in Group R and 42 months (range: 12\u0026ndash;127) in Group C. The retrosigmoid approach was employed in 83% of Group R cases and 85% of Group C cases, while the remaining cases underwent a trans-petrosal approach. Internal auditory canal drilling was performed in 35% of Group R cases and 26% of Group C cases. There were no statistically significant differences in patient characteristics or operative approaches between the two groups.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTumor Volume Changes\u003c/h3\u003e\n\u003cp\u003ePreoperative tumor volumes showed significant variation between the groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Group R had a median tumor volume of 7.9 cm\u0026sup3; (range: 1.6\u0026ndash;33.6 cm\u0026sup3;), while Group C had a median preoperative volume of 10.8 cm\u0026sup3; (range: 3.5\u0026ndash;70.9 cm\u0026sup3;). Postoperatively, Group R achieved a median tumor volume reduction of 89.9%, resulting in a residual volume of 0.3 cm\u0026sup3; (range: 0\u0026ndash;7.9 cm\u0026sup3;). In comparison, Group C experienced a median reduction of 57.7%, with a residual volume of 3.1 cm\u0026sup3; (range: 2.3\u0026ndash;24.0 cm\u0026sup3;).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAt the final follow-up, tumor control was successfully maintained in both groups. Group R reported a median residual volume of 0.4 cm\u0026sup3;, reflecting a 95.7% total reduction, while Group C reported a median residual volume of 2.8 cm\u0026sup3;, representing a 69.5% total reduction (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Tumor volumes demonstrated statistically significant differences between the groups at all stages of treatment. Larger tumors were more commonly categorized into Group C, reflecting the use of a combined subtotal removal and Gamma Knife approach for these cases. Radical removal was predominantly performed on smaller tumors compared to the combined treatment strategy. All patients in Group R maintained complete tumor control with no significant recurrence (tumor control rate\u0026thinsp;=\u0026thinsp;100%). In contrast, tumor control failure was observed in Group C, where 2 patients (4%) required salvage surgery and 1 patient (2%) underwent additional Gamma Knife treatment, resulting in an overall tumor control rate of 94%.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eHearing Preservation\u003c/h2\u003e \u003cp\u003ePreoperatively, non-serviceable hearing disturbance (\u0026gt;\u0026thinsp;50db) was present in 68% of patients in Group R and 66% in Group C. Immediately after surgery, these rates increased to 88% and 72%, respectively, and further deteriorated to 95% and 94% at the final follow-up (Table\u0026nbsp;1). Kaplan-Meier analysis showed no statistically significant difference between the groups in the probability of remaining free from non-serviceable hearing disturbance (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eFacial Nerve Function\u003c/h2\u003e \u003cp\u003ePreoperative facial weakness (HB\u0026thinsp;\u0026gt;\u0026thinsp;3) was present in 10% of patients in Group R and 15% in Group C. Postoperatively, these rates worsened to 30% and 19%, respectively. Although Group R exhibited worse facial nerve outcomes, the difference between the groups was not statistically significant. Facial nerve function showed improvement in the long term. At the final follow-up, facial weakness was present in 18% of Group R and 13% of Group C patients (Table\u0026nbsp;1). While Kaplan-Meier analysis showed no statistically significant difference in the probability of remaining free from facial weakness, Group C consistently demonstrated a higher preservation rate than Group R throughout the 120-month follow-up period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTrigeminal Dysesthesia\u003c/h2\u003e \u003cp\u003ePreoperative trigeminal dysesthesia was more common in Group C (32%) than in Group R (28%), likely due to the larger tumor sizes in Group C. In Group R, symptoms worsened to 38% postoperatively due to the radical surgical manipulations and remained unchanged in the long term. In contrast, patients in Group C experienced an initial improvement, as tumors near the trigeminal nerve root were left untouched. The incidence decreased to 30% immediately after surgery and further improved to 26% at the final follow-up. Statistical analysis showed no significant differences between the groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAtaxia\u003c/h2\u003e \u003cp\u003ePatients in Group C exhibited significantly worse cerebellar ataxia at all time points compared to those in Group R. Preoperatively, ataxia was observed in 10% of patients in Group R and 34% of patients in Group C. Postoperatively, the incidence decreased to 3% in Group R but remained at 21% in Group C. At the final follow-up, ataxia was present in 3% of Group R and 19% of Group C. These findings were consistent with the larger tumor volumes observed in Group C at all time points.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eOther Neurological Status\u003c/h2\u003e \u003cp\u003eLower cranial nerve deficits were rare in both groups, with an incidence of 2\u0026ndash;5% and no statistically significant difference. Hemiparesis was not observed in Group R at any time point, whereas it was present in 4% of patients in Group C, though the difference was not statistically significant. Functional performance, measured by the Karnofsky Performance Status (KPS), remained stable in both groups, with median scores of 90 maintained from the preoperative assessment to the final follow-up evaluation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eSubsequent Intervention\u003c/h2\u003e \u003cp\u003eVP shunt placement was more frequently required in Group C (19%) compared to Group R (5%), though the difference was not statistically significant. No patients in Group R required salvage surgery or additional Gamma Knife treatment, whereas in Group C, salvage surgery was necessary in 4% of patients, and additional Gamma Knife treatment was performed in 2% of patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe management of large vestibular schwannomas presents a complex challenge, requiring a balance between achieving maximal tumor resection and preserving neurological function. Historically, radical resection has been the preferred approach; however, subtotal resection followed by radiosurgery has emerged as a viable alternative. Comparative studies between surgical excision and Gamma Knife (GK) treatment for large vestibular schwannomas remain limited. While surgical excision offers more effective long-term volume control, most previous studies suggest that hearing and facial nerve function are better preserved in patients undergoing GK treatment (Table\u0026nbsp;2) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Furthermore, recent large-cohort studies reinforce this trend, indicating that GK treatment is increasingly favored for managing large vestibular schwannomas [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile some evidence suggests that the combined strategy may result in lower cranial nerve complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], long-term outcome data from large-scale comparative studies are still needed. Iwai et al. demonstrated that this strategy effectively preserves cranial nerve function, particularly for large vestibular schwannomas where complete resection might carry higher risks [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This study highlights the advantages of the combined approach compared to radical resection, particularly in terms of facial nerve and hearing preservation, despite the significantly larger tumor sizes in patients treated with the combined approach.\u003c/p\u003e \u003cp\u003eA significant difference in tumor size was observed between the groups, which likely influenced treatment decisions. Given the challenges associated with resecting large tumors, subtotal removal followed by GK was favored for cases where radical excision posed a high risk of neurological deficits. This aligns with recent trends emphasizing functional preservation while maintaining adequate tumor control [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study demonstrated more favorable long-term preservation of facial nerve function and hearing with the combined approach, despite patients having larger tumors. Postoperatively, facial weakness was more common in patients who underwent radical removal compared to those treated with the combined approach. These results support the hypothesis that subtotal resection minimizes direct nerve trauma while subsequent GK treatment effectively controls residual tumor growth without excessive radiation exposure [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs expected, larger tumor volumes were significantly associated with worse ataxia (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), likely due to increased brainstem compression [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, trigeminal dysesthesia followed a different pattern. Despite the larger tumor sizes in the combined group, trigeminal symptoms improved postoperatively (from 32\u0026ndash;26%), whereas they worsened in the radical resection group (from 28\u0026ndash;38%). This suggests that subtotal resection effectively alleviated trigeminal compression while minimizing excessive manipulation of the nerve root, thereby contributing to functional preservation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile both groups achieved satisfactory long-term tumor control, they demonstrated a comparable need for VP shunt placement. The overall rates of salvage surgery and additional GK in the combined group remained low, indicating that subtotal removal combined with GK remains an effective strategy for durable tumor management [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The 69.5% overall tumor volume reduction in the combined group, despite the initially larger tumor size, further underscores the efficacy of this approach [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese findings align with an evolving paradigm shift in VS treatment. The combined approach provides a reasonable compromise between achieving tumor control and minimizing morbidity. For large vestibular schwannomas, subtotal removal followed by GK should be considered the preferred strategy, particularly when preserving cranial nerve function is a priority. Conversely, radical resection may still be warranted for smaller tumors where gross total resection can be safely achieved without compromising neurological function [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and Future Directions\u003c/h2\u003e \u003cp\u003eThis study is limited by its retrospective nature and the inherent selection bias in treatment allocation. Larger, prospective, multi-institutional studies are needed to further validate these findings. Additionally, future research should explore the long-term quality-of-life implications of each approach, given the growing emphasis on patient-centered outcomes in neurosurgical decision-making.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study supports the growing preference for subtotal resection combined with GK for large vestibular schwannomas. Despite the larger tumor sizes in patients treated with the combined approach, better long-term preservation of facial nerve function and hearing was demonstrated compared to radical resection. These findings reinforce the need for a tailored approach in VS management, prioritizing neurological preservation without compromising tumor control.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers\u0026apos; bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Ryan Keswani, Takuro InoueFormal Analysis: Ryan Keswani, Peter AdidharmaInvestigation: Ryan Keswani, Takuro Inoue, Yukihiro Goto, Ayako Shima, Hisao HiraiMethodology: Ryan Keswani, Takuro Inoue, Peter AdidharmaProject Administration: Ryan Keswani, Takuro InoueWriting \u0026ndash; Original Draft: Ryan KeswaniWriting \u0026ndash; Review \u0026amp; Editing: Ryan Keswani, Takuro Inoue\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDhayalan D, Tveiten \u0026Oslash;V, Finnkirk M, Storstein A, Hufthammer KO, Goplen FK, Lund-Johansen M (2023) V-REX Trial investigators. Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial. JAMA 330(5):421\u0026ndash;431\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDumot C, Pikis S, Mantziaris G, Xu Z, Anand RK, Nabeel AM et al (2022) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study. J Neurooncol 160(1):201\u0026ndash;208\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGolfinos JG, Hill TC, Rokosh R, Choudhry O, Shinseki M, Mansouri A, Friedmann DR, Thomas Roland J Jr, Kondziolka D (2016) A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas. J Neurosurg 125(6):1472\u0026ndash;1482\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwai Y, Ishibashi K, Watanabe Y, Uemura G, Yamanaka K (2015) Functional Preservation After Planned Partial Resection Followed by Gamma Knife Radiosurgery for Large Vestibular Schwannomas. World Neurosurg 84(2):292\u0026ndash;300\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoos WT, Day JD, Matula C, Levy DI (1998) Neurotopographic considerations in the microsurgical treatment of small acoustic neurinomas. J Neurosurg 88(3):506\u0026ndash;512\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLak AM, Khan YS (2024) Cerebellopontine Angle Cancer. [Updated 2023 Jun 26]. StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL). Jan-.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMindermann T, Schlegel I (2013) Grading of vestibular schwannomas and corresponding tumor volumes: ramifications for radiosurgery. Acta Neurochir (Wien) 155(1):71\u0026ndash;74\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePikis S, Mantziaris G, Kormath Anand R, Nabeel AM, Sheehan D et al (2022) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study. J Neurosurg 138(2):405\u0026ndash;412\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePollock BE (2008) Vestibular schwannoma management: an evidence-based comparison of stereotactic radiosurgery and microsurgical resection. Prog Neurol Surg 21:222\u0026ndash;227\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePollock BE, Driscoll CL, Foote RL, Link MJ, Gorman DA, Bauch CD et al (2006) Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotactic radiosurgery. Neurosurgery 59(1):77\u0026ndash;85\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePollock BE, Lunsford LD, Kondziolka D, Flickinger JC, Bissonette DJ, Kelsey SF, Jannetta PJ (1995) Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 36(1):215\u0026ndash;224\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchnurman Z, Gurewitz J, Smouha E, McMenomey SO, Roland JT Jr, Golfinos JG, Kondziolka D (2022) Matched Comparison of Hearing Outcomes in Patients With Vestibular Schwannoma Treated With Stereotactic Radiosurgery or Observation. Neurosurgery 91(4):641\u0026ndash;647\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShirato H, Sakamoto T, Sawamura Y, Kagei K, Isu T, Kato T et al (1999) Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma. Int J Radiat Oncol Biol Phys 44(3):545\u0026ndash;550\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStastna D, Urgosik D, Chytka T, Liscak R (2021) Large vestibular schwannomas: long-term outcomes after stereotactic radiosurgery. Neuro Endocrinol Lett 41(6):329\u0026ndash;338\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzymoniuk M, Kochański M, Wilk K, Miazga D, Kanonik O, Dryla A, Kamieniak P (2024) Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a systematic review and meta-analysis. Acta Neurochir (Wien) 166(1):101\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTatagiba M, Wang SS, Rizk A, Ebner F, van Eck ATCJ, Naros G, Horstmann G (2023) A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome. Neurooncol Adv 5(1):vdad146\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang SS, Rizk A, Ebner FH, van Eck A, Naros G, Horstmann G, Tatagiba M (2024) Cystic vestibular schwannoma - a subgroup analysis from a comparative study between radiosurgery and microsurgery. Neurosurg Rev 47(1):291\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYakkala VK, Mammi M, Lamba N, Kandikatla R, Paliwal B, Elshibiny H, Corrales CE, Smith TR, Mekary RA (2022) Audiovestibular symptoms and facial nerve function comparing microsurgery versus SRS for vestibular schwannomas: a systematic review and meta-analysis. Acta Neurochir (Wien) 164(12):3221\u0026ndash;3233\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cranial nerve preservation, Gamma knife surgery, long-term outcome, microsurgery, subtotal removal, radical excision, vestibular schwannoma","lastPublishedDoi":"10.21203/rs.3.rs-6676378/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6676378/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eThis study compares the long-term outcomes of radical resection versus subtotal removal followed by Gamma Knife (GK) radiosurgery for large vestibular schwannomas (VS), focusing on tumor control and neurological function preservation.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective analysis of 87 patients with large VS (Koos grade III\u0026ndash;IV) was conducted. Patients were divided into radical resection (Group R, n\u0026thinsp;=\u0026thinsp;40) and subtotal removal followed by GK (Group C, n\u0026thinsp;=\u0026thinsp;47). Tumor volume reduction, facial nerve function, hearing preservation, and other neurological outcomes were evaluated.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eGroup C had significantly larger tumor preoperatively (median: 10.8 cm\u0026sup3; vs. 7.9 cm\u0026sup3;, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). Despite this, facial nerve function was better preserved in Group C than in Group R (House-Brackmann\u0026thinsp;\u0026gt;\u0026thinsp;3: 19% vs. 30%), and the incidence of non-serviceable hearing (\u0026gt;\u0026thinsp;50 dB) was less frequent in Group C (72% vs. 88%) immediately after surgery. Trigeminal dysesthesia improved in Group C (32\u0026ndash;26%) but worsened in Group R (28\u0026ndash;38%). Ataxia was more common in Group C (final: 19% vs. 3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), likely due to larger tumor size. Tumor control was achieved in both groups, with a 95.7% reduction in Group R and a 69.5% reduction in Group C (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). VP shunt placement was more frequent in Group C than in Group R (19% vs. 5%). Failure of tumor control was observed only in Group C, where 4% of patients required salvage surgery and 2% underwent additional Gamma Knife treatment.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eSubtotal removal with GK balances tumor control and neurological preservation in large VS. Despite larger tumors, this treatment approach demonstrated better long-term facial nerve and hearing outcomes than radical resection.\u003c/p\u003e","manuscriptTitle":"Long-term Outcomes of Radical Resection vs. Combined Subtotal Resection and Gamma Knife Radiosurgery for Large Vestibular Schwannomas","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-23 14:15:04","doi":"10.21203/rs.3.rs-6676378/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"abfe7241-1c98-4cdb-a462-6775bca3df57","owner":[],"postedDate":"May 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-30T02:53:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-23 14:15:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6676378","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6676378","identity":"rs-6676378","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}