Rate and predictors of surgical resection following radiotherapy for meningiomas: A Surveillance, Epidemiology, and End Results (SEER) database analysis

Rate and predictors of surgical resection following radiotherapy for meningiomas: A Surveillance, Epidemiology, and End Results (SEER) database analysis | 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 Rate and predictors of surgical resection following radiotherapy for meningiomas: A Surveillance, Epidemiology, and End Results (SEER) database analysis Kyle Tuohy, Sneh T Shah, David Bailey, Amanda Brisco, Sean Mahase, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8524166/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 Purpose Surgical resection for meningiomas, while curative, can be associated with potential morbidity. Radiotherapy (RT) provides comparable control in certain circumstances, however failure is often defined as radiologic progression. We evaluated salvage surgery following definitive radiotherapy for meningiomas as a primary measure of treatment failure. Methods A retrospective analysis was performed using the SEER database for all meninigioma patients treated with definitive radiation from 2000 to 2022. RT failure was defined as need for subsequent surgical resection. Demographic variables were collected and compared between groups using univariate and multivariate analyses. Survival data was collected and evaluated via Kaplan-Meyer curve. Results There were 6,776 patients included in the final analysis with 121 (1.78%) requiring microsurgical resection after RT. On univariate analysis, tumors > 30 mm and non-benign tumor behavior were associated with failure (p < 0.001). On multivariate analysis, tumor size (OR 2.359, 95% CI 1.563–3.561, p < 0.001) and non-benign behavior (OR 5.831, 95% CI 2.788–12.196, p < 0.001) remained predictors of treatment failure. The time from diagnosis to initial treatment was shorter for patients who later required surgical resection (99.75 vs 63.45 days, p < 0.001). There were no differences in survival between groups. Conclusion RT is an effective treatment for meningiomas, with only 1.78% of patients requiring salvage treatment. Factors associated with RT failure include larger tumor size and non-benign tumor behavior. Future prospective studies are needed to fully assess utilizing salvage surgery, as opposed to radiologic progression, as a primary measure of failure following RT. Meningioma radiotherapy stereotactic radiosurgery intensity modulated radiotherapy Figures Figure 1 Figure 2 Figure 3 Introduction Arising from arachnoid cap cells, meningiomas account for nearly one third of all intracranial tumors[1], with approximately 10% arising from the spinal dura.[2] The majority are benign, slow-growing tumors (WHO grade 1), but in rare cases may be more aggressive (WHO grade 2 or 3).[3]Surgery is the standard of care for symptomatic and/or enlarging lesion, as extent of resection is associated with improved outcomes[4], and gross total resection is definitive treatment for WHO grade 1 meningiomas. However, resecting tumors intimately associated with the skull base or near vital neurovascular structures is associated with higher morbidity.[5] Furthermore, patients who are not medically fit for general anesthesia or decline surgery require alternativetreatment modalities. Ionizing radiation, in the form of fractionated external beam radiotherapy (EBRT) or stereotactic radiosurgery (SRS) is a validated modality for intermediate and high risk meningiomas.[6] It is also a safe and effective modality for asymptomatic radiologically defined grade 1 meningiomas, lesions in difficult locations, or for patients unfit for or decline surgery.[7] The rate of local tumor control varies with grade and risk classification, but with primary EBRT ranges from 89-100% at 5-10 years, using total doses of 54-60 Gy.[8], [9] Similarly, SRS has shown rates of 5-year local control between 86-100%, using a single fraction of 12-18 Gy (depending on tumor grade) with fractionated SRS (fSRS) regimens increasingly utilized for larger lesions, or those near critical organs at risk.[10]Studies suggest comparable 5-year-overall survival among all modalities.[11] Most studies evaluating radiotherapy efficacy for meningiomas utilize progression free survival as the primary endpoint. While several guidelines exist for initial treatment of meningiomas, there is no established standard of care for salvage treatment of recurrent/progressive meningiomas. This study aims to evaluate factors associated with salvage resection following definitive radiotherapy for meningiomas. Methods The Surveillance, Epidemiology and End Results (SEER) database was queried for meningioma patients treated with radiation (beam or NOS) from 2000 to 2022. Patients with a diagnosis of meningioma were identified using the SEER*Stat software (Version 8.4.5) and “Incidence – SEER 17 Registries Custom Data (with additional treatment fields), Nov 2024 Sub (2000-2022 varying)” dataset. The database was queried using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology codes 9530–9539 for meningiomas, within the limits of known age and cases in the research database. Exclusion criteria included: patients who had surgery before radiation, “intraoperative radiation”, radiation “sequence unknown”, those with multiple intracranial tumors, and those with less than 3 months follow-up (Figure 1). Patient- and tumor-specific variables included: age group (0–19, 20–39, 40–59, 60–79, and 80+ years), sex (female, male), year of diagnosis, primary tumor site, and behavior (benign, borderline, malignant). Treatment characteristics included radiation (yes, no), chemotherapy (yes, no), tumor size (in average mm and 30 mm), rate of post-radiotherapy surgical resection, overall survival (OS, in months), and time from diagnosis to treatment (days). Statistical analysis was performed using SPSS Statistics, version 30.0. Frequencies were reported for categorical variables and means with standard deviations were reported for continuous variables. Categorical variables were analyzed using Fisher’s exact test and continuous variables through the Mann Whitney U test. Univariate analysis was performed for each variable regarding patient demographics, tumor characteristics, and treatment details. Variables with a significance of p<0.1 were included in the multivariate regression model. Survival distributions between patients who received radiotherapy (RT) only and those who required further treatment were compared using the Kaplan Meier method with the log-rank test and pooled over strata comparison. Results The final cohort entailed 6,776 meningioma patients that received definitive radiotherapy. Of these, 111 underwent a subsequent resection and 10 received surgery followed by adjuvant radiation. This leaves 98.22% of patients undergoing upfront radiotherapy who did not later require surgical removal. Tumor size was available in 5,596 patients.. The average size was 29.59 mm (SD 69.66) and 33.63 mm (SD 18.65) for the RT and failed RT groups, respectively (p < 0.001). When dichotomizing patients with tumors < 30 mm vs ≥30 mm, those who required surgical resection after radiotherapy were more likely to have tumors ≥30 mm (26.25% vs 47.92%; p < 0.001). Patients in this group were also more likely to have non-benign behaving tumors (1.37% vs 10.74%; p < 0.001). There was a difference in tumors coded as meninges, NOS (not otherwise specified) vs cerebral meninges, but no difference between cranial vs spinal meningiomas (Table 1 ). Table 1 Demographic data for each group with univariate analyses. Variable RT only RT then surgery p-value Age, n (%) 0–19 17 (0.26) 0 (0) 0.682 20–39 397 (5.97) 10 (8.26) 40–59 2455 (36.89) 48 (39.67) 60–79 3062 (46.01) 53 (43.8) 80+ 724 (10.88) 11 (9.09) Gender, n (%) M 1627 (24.45) 34 (28.1) 0.393 F 5028 (75.55) 87 (71.9) Race/ethnicity, n (%) Hispanic 870 (13.07) 18 (14.88) 0.660 American Indian/Alaska native 28 (0.42) 1 (0.83) Asian or Pacific islander 618 (9.29) 13 (10.73) Non-Hispanic Black 708 (10.64) 17 (14.05) Non-Hispanic White 78 (1.17) 1 (0.83) Non-Hispanic Unknown race 4353 (65.41) 71 (58.68) Tumor size Average (SD) 29.59 (69.66) 33.63 (18.65) < 0.001 < 30 mm, n (%) 4056 (73.75) 50 (52.08) =30 mm, n (%) 1444 (26.25) 46 (47.92) Behavior, n (%) Benign 6537 (98.23) 108 (89.26) < 0.001 Non-benign 118 (1.37) 13 (10.74) Location, n (%) Cerebral meninges 5849 (87.89) 110 (90.91) 0.028 Spinal meninges 63 (0.95) 3 (2.48) Meninges, NOS 675 (10.14) 5 (4.13) other 68 (1.02) 3 (2.48) Interval from diagnosis to treatment, mean (SD), in days 99.75 (103.56) 63.45 (84.58) < 0.001 Overall survival, mean (SD), in months 190 (187–193) 158 (141–175) 0.205 Among the 5,926 patients with time from diagnosis to first treatment available, those with a shorter interval were more likely to undergo subsequent surgery (99.75 vs 63.45 days, p < 0.001). There were no subjective trends or differences in failure rates based on treatment year (Fig. 2 ). Median survival was worse for borderline (151 months) and malignant (128 months) behavior compared to benign (median not reached). The OS for patient undergoing RT alone was generally higher for those with stable meningiomas(190 months;SD 187–193) than those who progressed (158 months;SD 141–175) (p = 0.205) (Table 3). On multivariate analysis, non-benign behavior (OR 6.05, 95% CI 2.84–12.87) and size ≥30 mm (OR 2.3, 95% CI 1.48–3.56) were associated higher likelihood of surgery following definitive RT (Table 2 ). Shorter time from diagnosis to treatment remained negatively associated with failure of upfront RT (OR 0.993, 95% CI 0.989–0.997). Table 2 Multivariate analysis of factors associated with the need for surgical resection after RT. Variable OR [95% CI] P-value Behavior Benign Reference Reference Non-benign 6.05 [2.84–12.87] < 0.001 Time from diagnosis to first treatment 0.993 [0.989–0.997] 30 mm 2.3 [1.48–3.56] < 0.001 Discussion EBRT and SRS meningiomas are validated options for definitive treatment of meningiomas. Most studies[ 12 ] define treatment failure as increased tumor size on surveillance imaging 11, 14–19 , however a more clinically relevant endpoint may be whether resection was required following radiotherapy. Kim et al. (2017)[ 13 ] looked at failure patterns in 771 meningioma patients treated with SRS. While 60 (7.78%) had radiologic evidence of growth, only 34 (4.4%) required resection. Wang et al. (2023) evaluated 137 patients who received conventionally fractionated radiotherapy, of which only 4 (3%) of 21 progressed tumors (15.33%) underwent resection. 14 A multicenter study by by Santacroce et al. encompassing 4,565 patients treated with SRS reported increased tumor volume in 281 lesions (7.5%), but similarly only 41 patients required additional treatment, of which 28 underwent microsurgery (0.74%). 13 15–20 Unfortunately, two of the most recent retrospective cohorts over multiple decades did not discuss rates of post-RT surgical resection.[ 14 ], [ 15 ] Using a larger cohort than the aforementioned studies, we show that the failure rate of upfront radiotherapy to treat meningiomas, defined as patients undergoing subsequent surgical resection, was 1.78%. Factors associated with the need for secondary microsurgical resection were primarily size ≥ 3 cm and more aggressive behavior. A size cutoff of 3 cm was determined by previous studies that suggested that this size was associated with poor response to RT.[ 7 ], [ 16 ], [ 17 ] This is consistent with most studies that show improved tumor control at smaller volumes[ 18 ], [ 19 ], [ 20 ], [ 21 ] and benign behavior/histology.[ 7 ], [ 22 ], [ 23 ], [ 24 ] This is the impetus for fractionated SRS regimens to maintain a high biologically active dose while minimizing toxicity. While other studies associate progression following RT with older age[ 18 ], [ 25 ], [ 26 ] and male gender[ 23 ], [ 24 ], [ 27 ], these factors were not significant in our analysis. This may attributed to biases related to smaller retrospective cohorts in prior studies, or differences in the definition of treatment failure (lesion growth, compared to the need for post-RT surgical resection in our analysis). Patients with a shorter interval between diagnosis and treatment were more likely to require surgery after upfront RT. This association is less likely a causal relationship, and more likely a confounding variable as patients with larger tumors and/or more aggressively tumors are more likely to be symptomatic, thus necessitating expedited treatment. There were differences in tumor location between group, however it is unclear if there is any clinical significance to this. Location types such as Meninges, NOS and cerebral meninges are non-specific, thus limited meaningful associations based on tumor location. Intracrnaial and spinal menginiomas demonstrated similar failure rates. Although there were much fewer patients in the spine group (n = 66), these tumors are less well studied than their intracranial counterparts. Studies on benign spine tumors have shown feasibility and efficacy for SRS[ 28 ], [ 29 ], [ 30 ], but meningiomas were a subset of the overall cohort and not the primary tumor type. While both groups had similar overall survival,patients with non-benign tumors in both groups had lower median survival (Figs. 3 A-C). However, there was subsequently no difference in survival when comparing between RT vs failed RT groups (Fig. 3 D). The reason for similar survival rates between groups may be a function of good overall survival in meningiomas in general. There was also a low rate of non-benign tumors in our cohort (1.9%), limiting the power of this analysis. 35 At the very least, this data is reassuring that outcomes are not overtly worse with RT alone. The low rate of failure overall, as well as consistent rates each year, is reassuring that currently used regimens are successful. Nonetheless, additional studies should be performed to determine if regimens can be further optimized. Limitation Our analyses are subjected to limitations inherent to retrospective databases. We are constrained to the predetermined variables collected within the database, and therefore unable to evaluate certain factors of increasing significance to meningiomas, such as molecular alteration.[ 31 ], [ 32 ] We were unable to differentiate between RT types and dosages, nor could we analyze progression free survival, as these are not recorded in the SEER database. However, IMRT and SRS have been well-documented in the past decade, with efficacious dosing regimens that have been clearly described[ 33 ] and are comparable in outcome.[ 11 ] This analysis was performed on the premise that patients in failure group underwent resection because they failed initial RT, as opposed to a planned sequence of preoperative radiation then surgery. However, there is no accepted guideline for preoperative radiotherapy prior to surgery, nor is it common in clinical practice. There will be a subset of patients deemed not surgical candidates regardless of tumor progression. Additionally, there is no data on the specific patient-related factors or surgeon preferences that led to a given treatment, and thus there may be considerable practice variability in selecting pre-treatment modality. Furthermore, reirradiation has become a rapidly evolving field in neuro-oncology[ 34 ], and although questions remain as to the ideal patient population and dose optimization, potential efficacy has been shown in WHO grade 2 and 3 meningiomas.[ 35 ], [ 36 ], [ 37 ] Conclusion The failure rate, defined as salvage surgery, following definitive radiotherapy formeningiomas is low( 1.78%). Further studies are warranted to consider surgery as the primary measure of radiation therapy failure. Statements and 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, data collection and analysis were performed by Kyle Tuohy and Sneh Shah. The first draft of the manuscript was written by Kyle Tuohy and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval: The SEER database contains de-identified retrospective data and is therefore exempt from Institutional Review Board oversight. References Q. T. Ostrom et al. , “CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012–2016,” Neuro Oncol , vol. 21, no. Supplement_5, pp. v1–v100, Nov. 2019, doi: 10.1093/neuonc/noz150. N. Kumar, W. L. B. Tan, W. Wei, and B. A. 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Lin et al. , “Radiologic Response and Disease Control of Recurrent Intracranial Meningiomas Treated With Reirradiation,” International Journal of Radiation Oncology*Biology*Physics , vol. 102, no. 1, pp. 194–203, 2018, doi: https://doi.org/10.1016/j.ijrobp.2018.05.011. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8524166","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":571520005,"identity":"d52eb05b-f42f-451b-8adb-9b7c8b9b4c07","order_by":0,"name":"Kyle Tuohy","email":"","orcid":"","institution":"Penn State Hershey Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kyle","middleName":"","lastName":"Tuohy","suffix":""},{"id":571520006,"identity":"525cda6a-a0de-4c6c-afda-4ff22dc7ca0f","order_by":1,"name":"Sneh T Shah","email":"","orcid":"","institution":"Penn State College of 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Center","correspondingAuthor":true,"prefix":"","firstName":"Gregory","middleName":"","lastName":"Arnone","suffix":""}],"badges":[],"createdAt":"2026-01-05 18:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8524166/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8524166/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100012616,"identity":"5ad174c1-51b1-4107-90e1-6abf976689e4","added_by":"auto","created_at":"2026-01-12 06:16:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":563819,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFINAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/27140fa473aee0f66785c2ff.docx"},{"id":100361383,"identity":"223df74e-57bc-4046-bb3c-952cb6d471bb","added_by":"auto","created_at":"2026-01-16 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07:46:40","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":84385,"visible":true,"origin":"","legend":"","description":"","filename":"46bec36901e44c08a42b42b515afc71d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/261647130c2d5dbbee62184e.xml"},{"id":100012624,"identity":"5789c105-f941-4453-a2ba-8aee5b52df84","added_by":"auto","created_at":"2026-01-12 06:16:08","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":95093,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/7946b5b09a34239c2afa13ab.html"},{"id":100361523,"identity":"1553b59c-589c-4ee2-b2ea-d33065798775","added_by":"auto","created_at":"2026-01-16 07:45:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":137123,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram for determination of final patient cohort\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/6a2149d7d8c650768720d296.png"},{"id":100012614,"identity":"7d031fe5-1d29-40a9-a8fe-04274e5f432d","added_by":"auto","created_at":"2026-01-12 06:16:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42497,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients receiving RT alone vs post-RT surgical resection by year. Percentage of patient who failed RT listed above each year\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/0eb9078b0f7f64f05086af67.png"},{"id":100012615,"identity":"6a0a45b3-8e42-4934-8bc2-b5894861e0de","added_by":"auto","created_at":"2026-01-12 06:16:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":123795,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier curves for overall survival. All patients by tumor behavior (A); patients receiving RT only (B); Patients who required surgery after RT (C); by outcome group, RT vs failed RT (D)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/b23d668b2545d14dc12c47e0.png"},{"id":100929965,"identity":"21b380c9-6098-459a-b9f4-8427c05075c2","added_by":"auto","created_at":"2026-01-23 00:39:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":721721,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8524166/v1/ee46e751-d18d-41f5-ab50-d411ed8894c3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rate and predictors of surgical resection following radiotherapy for meningiomas: A Surveillance, Epidemiology, and End Results (SEER) database analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eArising from arachnoid cap cells, meningiomas account for nearly one third of all intracranial tumors[1], with approximately 10% arising from the spinal dura.[2] The majority are benign, slow-growing tumors (WHO grade 1), but in rare cases may be more aggressive (WHO grade 2 or 3).[3]Surgery is the standard of care for symptomatic and/or enlarging lesion, as extent of resection is associated with improved outcomes[4], and gross total resection is definitive treatment for WHO grade 1 meningiomas. However, resecting tumors intimately associated with the skull base or near vital neurovascular structures is associated with higher morbidity.[5] Furthermore, patients who are not medically fit for general anesthesia or decline surgery require alternativetreatment modalities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIonizing radiation, in the form of fractionated external beam radiotherapy (EBRT) or stereotactic radiosurgery (SRS) is a validated modality for intermediate and high risk meningiomas.[6] It is also a safe and effective modality for asymptomatic radiologically defined grade 1 meningiomas, lesions in difficult locations, or for patients unfit for or decline surgery.[7] The rate of local tumor control varies with grade and risk classification, but with primary EBRT ranges from 89-100% at 5-10 years, using total doses of 54-60 Gy.[8], [9] Similarly, SRS has shown rates of 5-year local control between 86-100%, using a single fraction of 12-18 Gy (depending on tumor grade) with fractionated SRS (fSRS) regimens increasingly utilized for larger lesions, or those near critical organs at risk.[10]Studies suggest comparable 5-year-overall survival among all modalities.[11]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMost studies evaluating radiotherapy efficacy for meningiomas utilize progression free survival as the primary endpoint. While several guidelines exist for initial treatment of meningiomas, there is no established standard of care for salvage treatment of recurrent/progressive meningiomas. \u0026nbsp;This study aims to evaluate factors associated with salvage resection following definitive radiotherapy for meningiomas.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe Surveillance, Epidemiology and End Results (SEER) database was queried for meningioma patients treated with radiation (beam or NOS) from 2000 to 2022. Patients with a diagnosis of meningioma were identified using the SEER*Stat software (Version 8.4.5) and “Incidence – SEER 17 Registries Custom Data (with additional treatment fields), Nov 2024 Sub (2000-2022 varying)” dataset. The database was queried using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology codes 9530–9539 for meningiomas, within the limits of known age and cases in the research database. Exclusion criteria included: patients who had surgery before radiation, “intraoperative radiation”, radiation “sequence unknown”, those with multiple intracranial tumors, and those with less than 3 months follow-up (Figure 1).\u003c/p\u003e\n\u003cp\u003ePatient- and tumor-specific variables included: age group (0–19, 20–39, 40–59, 60–79, and 80+ years), sex (female, male), year of diagnosis, primary tumor site, and behavior (benign, borderline, malignant). Treatment characteristics included radiation (yes, no), chemotherapy (yes, no), tumor size (in average mm and \u0026lt;/\u0026gt; 30 mm), rate of post-radiotherapy surgical resection, overall survival (OS, in months), and time from diagnosis to treatment (days).\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS Statistics, version 30.0. Frequencies were reported for categorical variables and means with standard deviations were reported for continuous variables. Categorical variables were analyzed using Fisher’s exact test and continuous variables through the Mann Whitney U test. Univariate analysis was performed for each variable regarding patient demographics, tumor characteristics, and treatment details. Variables with a significance of p\u0026lt;0.1 were included in the multivariate regression model. Survival distributions between patients who received radiotherapy (RT) only and those who required further treatment were compared using the Kaplan Meier method with the log-rank test and pooled over strata comparison.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe final cohort entailed 6,776 meningioma patients that received definitive radiotherapy. Of these, 111 underwent a subsequent resection and 10 received surgery followed by adjuvant radiation. This leaves 98.22% of patients undergoing upfront radiotherapy who did not later require surgical removal.\u003c/p\u003e \u003cp\u003eTumor size was available in 5,596 patients.. The average size was 29.59 mm (SD 69.66) and 33.63 mm (SD 18.65) for the RT and failed RT groups, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). When dichotomizing patients with tumors\u0026thinsp;\u0026lt;\u0026thinsp;30 mm vs \u0026ge;30 mm, those who required surgical resection after radiotherapy were more likely to have tumors \u0026ge;30 mm (26.25% vs 47.92%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients in this group were also more likely to have non-benign behaving tumors (1.37% vs 10.74%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was a difference in tumors coded as meninges, NOS (not otherwise specified) vs cerebral meninges, but no difference between cranial vs spinal meningiomas (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003eDemographic data for each group with univariate analyses.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRT only\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRT then surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e397 (5.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (8.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2455 (36.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (39.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026ndash;79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3062 (46.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (43.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e80+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e724 (10.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1627 (24.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5028 (75.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (71.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace/ethnicity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e870 (13.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (14.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.660\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmerican Indian/Alaska native\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (0.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian or Pacific islander\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e618 (9.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (10.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e708 (10.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (14.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (1.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Unknown race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4353 (65.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (58.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.59 (69.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.63 (18.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;30 mm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4056 (73.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (52.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=30 mm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1444 (26.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (47.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBehavior, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6537 (98.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (89.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-benign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (10.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral meninges\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5849 (87.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (90.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpinal meninges\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeninges, NOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e675 (10.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterval from diagnosis to treatment, mean (SD), in days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.75 (103.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.45 (84.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall survival, mean (SD), in months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (187\u0026ndash;193)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158 (141\u0026ndash;175)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the 5,926 patients with time from diagnosis to first treatment available, those with a shorter interval were more likely to undergo subsequent surgery (99.75 vs 63.45 days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no subjective trends or differences in failure rates based on treatment year (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMedian survival was worse for borderline (151 months) and malignant (128 months) behavior compared to benign (median not reached). The OS for patient undergoing RT alone was generally higher for those with stable meningiomas(190 months;SD 187\u0026ndash;193) than those who progressed (158 months;SD 141\u0026ndash;175) (p\u0026thinsp;=\u0026thinsp;0.205) (Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eOn multivariate analysis, non-benign behavior (OR 6.05, 95% CI 2.84\u0026ndash;12.87) and size \u0026ge;30 mm (OR 2.3, 95% CI 1.48\u0026ndash;3.56) were associated higher likelihood of surgery following definitive RT (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Shorter time from diagnosis to treatment remained negatively associated with failure of upfront RT (OR 0.993, 95% CI 0.989\u0026ndash;0.997).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of factors associated with the need for surgical resection after RT.\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\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBehavior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-benign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.05 [2.84\u0026ndash;12.87]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from diagnosis to first treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.993 [0.989\u0026ndash;0.997]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size\u0026thinsp;\u0026gt;\u0026thinsp;30 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3 [1.48\u0026ndash;3.56]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\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\u003eEBRT and SRS meningiomas are validated options for definitive treatment of meningiomas. Most studies[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] define treatment failure as increased tumor size on surveillance imaging\u003csup\u003e11, 14\u0026ndash;19\u003c/sup\u003e, however a more clinically relevant endpoint may be whether resection was required following radiotherapy. Kim et al. (2017)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] looked at failure patterns in 771 meningioma patients treated with SRS. While 60 (7.78%) had radiologic evidence of growth, only 34 (4.4%) required resection. Wang et al. (2023) evaluated 137 patients who received conventionally fractionated radiotherapy, of which only 4 (3%) of 21 progressed tumors (15.33%) underwent resection.\u003csup\u003e14\u003c/sup\u003eA multicenter study by by Santacroce et al. encompassing 4,565 patients treated with SRS reported increased tumor volume in 281 lesions (7.5%), but similarly only 41 patients required additional treatment, of which 28 underwent microsurgery (0.74%).\u003csup\u003e13 15\u0026ndash;20\u003c/sup\u003e Unfortunately, two of the most recent retrospective cohorts over multiple decades did not discuss rates of post-RT surgical resection.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eUsing a larger cohort than the aforementioned studies, we show that the failure rate of upfront radiotherapy to treat meningiomas, defined as patients undergoing subsequent surgical resection, was 1.78%. Factors associated with the need for secondary microsurgical resection were primarily size\u0026thinsp;\u0026ge;\u0026thinsp;3 cm and more aggressive behavior. A size cutoff of 3 cm was determined by previous studies that suggested that this size was associated with poor response to RT.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] This is consistent with most studies that show improved tumor control at smaller volumes[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and benign behavior/histology.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] This is the impetus for fractionated SRS regimens to maintain a high biologically active dose while minimizing toxicity. While other studies associate progression following RT with older age[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and male gender[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], these factors were not significant in our analysis. This may attributed to biases related to smaller retrospective cohorts in prior studies, or differences in the definition of treatment failure (lesion growth, compared to the need for post-RT surgical resection in our analysis).\u003c/p\u003e \u003cp\u003ePatients with a shorter interval between diagnosis and treatment were more likely to require surgery after upfront RT. This association is less likely a causal relationship, and more likely a confounding variable as patients with larger tumors and/or more aggressively tumors are more likely to be symptomatic, thus necessitating expedited treatment.\u003c/p\u003e \u003cp\u003eThere were differences in tumor location between group, however it is unclear if there is any clinical significance to this. Location types such as Meninges, NOS and cerebral meninges are non-specific, thus limited meaningful associations based on tumor location. Intracrnaial and spinal menginiomas demonstrated similar failure rates. Although there were much fewer patients in the spine group (n\u0026thinsp;=\u0026thinsp;66), these tumors are less well studied than their intracranial counterparts. Studies on benign spine tumors have shown feasibility and efficacy for SRS[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], but meningiomas were a subset of the overall cohort and not the primary tumor type.\u003c/p\u003e \u003cp\u003eWhile both groups had similar overall survival,patients with non-benign tumors in both groups had lower median survival (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-C). However, there was subsequently no difference in survival when comparing between RT vs failed RT groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). The reason for similar survival rates between groups may be a function of good overall survival in meningiomas in general. There was also a low rate of non-benign tumors in our cohort (1.9%), limiting the power of this analysis.\u003csup\u003e35\u003c/sup\u003e At the very least, this data is reassuring that outcomes are not overtly worse with RT alone. The low rate of failure overall, as well as consistent rates each year, is reassuring that currently used regimens are successful. Nonetheless, additional studies should be performed to determine if regimens can be further optimized.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eLimitation\u003c/p\u003e \u003cp\u003eOur analyses are subjected to limitations inherent to retrospective databases. We are constrained to the predetermined variables collected within the database, and therefore unable to evaluate certain factors of increasing significance to meningiomas, such as molecular alteration.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] We were unable to differentiate between RT types and dosages, nor could we analyze progression free survival, as these are not recorded in the SEER database. However, IMRT and SRS have been well-documented in the past decade, with efficacious dosing regimens that have been clearly described[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and are comparable in outcome.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] This analysis was performed on the premise that patients in failure group underwent resection because they failed initial RT, as opposed to a planned sequence of preoperative radiation then surgery. However, there is no accepted guideline for preoperative radiotherapy prior to surgery, nor is it common in clinical practice.\u003c/p\u003e \u003cp\u003eThere will be a subset of patients deemed not surgical candidates regardless of tumor progression. Additionally, there is no data on the specific patient-related factors or surgeon preferences that led to a given treatment, and thus there may be considerable practice variability in selecting pre-treatment modality. Furthermore, reirradiation has become a rapidly evolving field in neuro-oncology[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], and although questions remain as to the ideal patient population and dose optimization, potential efficacy has been shown in WHO grade 2 and 3 meningiomas.[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe failure rate, defined as salvage surgery, following definitive radiotherapy formeningiomas is low( 1.78%). Further studies are warranted to consider surgery as the primary measure of radiation therapy failure.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003eFunding: \u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Kyle Tuohy and Sneh Shah. The first draft of the manuscript was written by Kyle Tuohy and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eData availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval: The SEER database contains de-identified retrospective data and is therefore exempt from Institutional Review Board oversight.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eQ. T. Ostrom \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012\u0026ndash;2016,\u0026rdquo; \u003cem\u003eNeuro Oncol\u003c/em\u003e, vol. 21, no. Supplement_5, pp. v1\u0026ndash;v100, Nov. 2019, doi: 10.1093/neuonc/noz150.\u003c/li\u003e\n\u003cli\u003eN. Kumar, W. L. B. Tan, W. Wei, and B. A. 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Andratschke \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus on re-irradiation: definition, reporting, and clinical decision making,\u0026rdquo; \u003cem\u003eLancet Oncol\u003c/em\u003e, vol. 23, no. 10, pp. e469\u0026ndash;e478, Oct. 2022, doi: 10.1016/S1470-2045(22)00447-8.\u003c/li\u003e\n\u003cli\u003eD. Scartoni \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Proton therapy re-irradiation provides promising clinical results in recurrent brain meningioma,\u0026rdquo; \u003cem\u003eActa Oncol (Madr)\u003c/em\u003e, vol. 62, no. 9, pp. 1096\u0026ndash;1101, Sep. 2023, doi: 10.1080/0284186X.2023.2241994.\u003c/li\u003e\n\u003cli\u003eR. A. El Shafie \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma,\u0026rdquo; \u003cem\u003eRadiation Oncology\u003c/em\u003e, vol. 13, no. 1, p. 86, 2018, doi: 10.1186/s13014-018-1026-x.\u003c/li\u003e\n\u003cli\u003eA. J. Lin \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Radiologic Response and Disease Control of Recurrent Intracranial Meningiomas Treated With Reirradiation,\u0026rdquo; \u003cem\u003eInternational Journal of Radiation Oncology*Biology*Physics\u003c/em\u003e, vol. 102, no. 1, pp. 194\u0026ndash;203, 2018, doi: https://doi.org/10.1016/j.ijrobp.2018.05.011.\u003c/li\u003e\n\u003c/ol\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":"Meningioma, radiotherapy, stereotactic radiosurgery, intensity modulated radiotherapy","lastPublishedDoi":"10.21203/rs.3.rs-8524166/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8524166/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSurgical resection for meningiomas, while curative, can be associated with potential morbidity. Radiotherapy (RT) provides comparable control in certain circumstances, however failure is often defined as radiologic progression. We evaluated salvage surgery following definitive radiotherapy for meningiomas as a primary measure of treatment failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA retrospective analysis was performed using the SEER database for all meninigioma patients treated with definitive radiation from 2000 to 2022. RT failure was defined as need for subsequent surgical resection. Demographic variables were collected and compared between groups using univariate and multivariate analyses. Survival data was collected and evaluated via Kaplan-Meyer curve.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere were 6,776 patients included in the final analysis with 121 (1.78%) requiring microsurgical resection after RT. On univariate analysis, tumors\u0026thinsp;\u0026gt;\u0026thinsp;30 mm and non-benign tumor behavior were associated with failure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). On multivariate analysis, tumor size (OR 2.359, 95% CI 1.563\u0026ndash;3.561, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and non-benign behavior (OR 5.831, 95% CI 2.788\u0026ndash;12.196, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) remained predictors of treatment failure. The time from diagnosis to initial treatment was shorter for patients who later required surgical resection (99.75 vs 63.45 days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no differences in survival between groups.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eRT is an effective treatment for meningiomas, with only 1.78% of patients requiring salvage treatment. Factors associated with RT failure include larger tumor size and non-benign tumor behavior. Future prospective studies are needed to fully assess utilizing salvage surgery, as opposed to radiologic progression, as a primary measure of failure following RT.\u003c/p\u003e","manuscriptTitle":"Rate and predictors of surgical resection following radiotherapy for meningiomas: A Surveillance, Epidemiology, and End Results (SEER) database analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:16:01","doi":"10.21203/rs.3.rs-8524166/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":"a43d2d48-0ec4-41bf-9aee-6871cf5efa28","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-23T00:38:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 06:16:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8524166","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8524166","identity":"rs-8524166","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}