Long-Term Tumor Control Following Gamma Knife Radiosurgery for Parasagittal Meningiomas: A Single Institution Retrospective Analysis

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Shukla, Jeffrey I. Traylor, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6824067/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 Introduction: Parasagittal meningiomas present unique challenges due to their proximity to large draining veins and the superior sagittal sinus, limiting the ability to achieve gross total resection (GTR). There is limited literature regarding the long-term efficacy of Gamma Knife Radiosurgery (GKSRS) for tumor control in this progression-prone region. We evaluated the effectiveness of GKSRS in achieving tumor control for parasagittal meningiomas. Methods: A retrospective analysis was conducted at a single academic institution from 2015 to 2023, analyzing predictors of progression via univariable and multivariable Cox regression analyses. Results: 30 patients were included. The median age was 62.0 years (range: 33–86). 86.7% underwent surgical resection prior to GKSRS. At presentation, 14 patients (46.7%) had primary tumors, while 16 (53.3%) had recurrent tumors. The median tumor volume was 2.0 cm³, and median tumor diameter was 1.7 cm. The median follow-up period was 33.0 months; mortality rate at last follow-up was 16.7%. 24 patients (80%) were treated with 1 fraction, while 6 (20%) were treated with 5 fractions. The median total GKSRS dose was 1500.0 cGy. At last follow-up, 80% of patients exhibited local tumor control. Peritumoral edema was present in 1 (3.3%) patient prior to GKSRS, with no cases observed following treatment. Median progression-free survival (PFS) was 70.6 months. Kaplan–Meier analysis demonstrated that WHO grade I meningiomas had longer mean PFS compared to grade II or III tumors (78.5 vs. 32.4 months, p = 0.011). In univariable Cox regression, age was associated with significantly greater risk of progression (HR: 1.2, p = 0.028). This remained significant in multivariable analysis after adjusting for tumor volume and tumor type (primary vs. recurrent) (HR: 1.2, p = 0.036). Tumor volume, radiation dose, extent of resection, and tumor type were not significantly associated with progression in either analysis. Conclusion: Our study provides supporting evidence for the use of GKSRS in achieving long-term tumor control for parasagittal meningiomas, with a tumor control rate of 80.0% and median PFS of 70.6 months. While increased age at the time of radiation and WHO grade appeared to be associated with progression in our analysis, these findings should be interpreted cautiously given the limited sample size. Notably, only 1 case of post-GKSRS edema was observed. These findings reinforce the safety and efficacy of GKSRS for this progression-prone region, though further multi-institutional studies are warranted to validate our results. Gamma Knife Stereotactic Radiosurgery (GKSRS) Parasagittal Meningioma Tumor Control Radiosurgical Outcomes Fractionation Figures Figure 1 Figure 2 Introduction Meningiomas are the most common intracranial neoplasm in the United States, accounting for roughly one-third of all primary brain tumors. 1 – 3 The tumor is typically benign, and gross total resection (GTR) remains the gold standard for long-term control. 4 However, GTR may be impeded by factors such as tumor size, invasion of adjacent structures, and, notably, location. This is particularly true for the parasagittal region, where tumors frequently compress or invade the superior sagittal sinus (SSS), bridging veins, and the primary motor cortex. 5 – 8 Radical resection in these regions carries a high risk of venous infarction and postoperative neurological deficits. 9 As a result, subtotal resection (STR) is often performed, which increases the likelihood of tumor progression and the need for further intervention. 10 – 14 Gamma Knife Radiosurgery (GKSRS) has emerged as an effective treatment modality for intracranial meningiomas, particularly when GTR is not feasible. 15 , 16 In addition to being less invasive than surgical resection, previous studies have shown that GKSRS provides effective tumor control, especially for smaller, benign lesions across various locations. 17 – 19 Some reports suggest that progression free survival (PFS) rates following radiosurgery may be comparable to PFS following Simpson Grade I Resection. 19 , 20 Despite these promising outcomes, long-term outcome data on GKSRS for parasagittal meningiomas remain limited. More specifically, PFS and progression data is needed to assess the long-term viability of GKSRS and its role in managing these progression prone tumors. This study aims to assess the long-term efficacy of GKSRS in treating parasagittal meningiomas, and to identify factors associated with improved tumor control. We also provide extended follow-up data on key, long-term postoperative outcomes including progression rate, PFS, and mortality. By providing extended follow-up data, we aim to help define the role of GKSRS in the long-term treatment of parasagittal meningiomas. Methods Study Design We conducted a retrospective cohort study evaluating patients who underwent GKSRS for meningioma at a single, academic, tertiary care medical center between 2015 and 2023. The study was approved by the Institutional Review Board, with a waiver of informed consent granted due to minimal patient risk. Patient Identification and Inclusion Patients were identified through a comprehensive institutional database search using ICD-9, ICD-10, and CPT codes corresponding to meningioma diagnoses and GKSRS procedures. Eligible patients had a confirmed pathological diagnosis of meningioma and underwent GKSRS with available preoperative and postoperative clinical data. Exclusion criteria included patients with an alternative tumor diagnosis, lack of GKSRS, or incomplete medical records. After applying inclusion and exclusion criteria, 30 patients were included in the final analysis. Patient data was collected up until their last available follow up date, with the maximum being 93 months follow treatment. Data Collection Data were systematically extracted from electronic medical records and categorized into baseline, treatment, and post-treatment variables. Baseline variables included patient demographics (age in years, sex) and tumor characteristics such as diagnosis status (primary vs. recurrent), tumor World Health Organization (WHO) grade, anatomical location, maximum tumor diameter (cm), tumor volume (cm³), and history of prior surgical resection. For patients with previous surgery, the extent of resection was categorized as gross total resection (GTR) or subtotal resection (STR). Among patients who reported extent of resection follow surgery, 5 patients underwent GTR, while 17 underwent STR. Treatment variables encompassed the total number of radiation fractions administered and the median radiation dose delivered (cGy). Collected post-treatment variables included progression, overall follow-up duration, survival time, and mortality status. Progression was defined as increase in tumor diameter of 2 mm or more in any direction on imaging following GKSRS treatment. The occurrence of post-radiation imaging findings—such as peritumoral edema, necrosis, mass effect, and hydrocephalus—was also recorded. Statistical Analysis All statistical analyses were conducted using SPSS version 30.0. The Shapiro-Wilk test was used to assess the normality of continuous variables. Continuous variables were reported as medians (range) and compared using independent t-tests for normally distributed data or Mann-Whitney U tests for non-normally distributed data. Categorical variables were presented as frequencies with proportions (%) and analyzed using Chi-square or Fisher’s exact test, as appropriate. Univariable Cox regression analysis was performed to examine the association between various baseline and treatment variables and tumor progression following GKSRS. Multivariable Cox regression analysis was performed to determine if these relationships would remain significant even after controlling for key variables including tumor volume, extent of resection, total dosage, age, and tumor type. Hazard ratios (HR) were reported with 95% confidence intervals (CIs) and p-values, with statistical significance set at p < 0.05. A biostatistician (B.W.) reviewed all statistical methodologies to ensure robustness and appropriate interpretation of results. Results Patient Demographics, Treatment Characteristics, and Long-Term Outcomes A complete representation of patient demographics and tumor characteristics can be found in Table 1. A total of 30 patients who underwent GKSRS for a parasagittal meningioma were included in this study. 17 patients (56.7%) were female, and the median patient age was 62.0 years (range: 33-86). 16 patients (53.3%) presented with recurrent tumors, while 14 (46.7%) had primary meningiomas. Notably, 24 (80.0%) patients had a prior surgical resection before receiving GKSRS. The median tumor diameter was 1.7 cm, and the median tumor volume was 2.0 cm 3 . Of the 30 patients, 18 (60.0%) had WHO grade I meningiomas, 11 (36.7%) had WHO grade II, and 1 (3.3%) had WHO grade III. For patients who underwent a single fraction, the total median prescribed dose was 1500.0 cGy, while patients who underwent 5 fractions received a total median prescribed dose of 2500.0 cGy. 24 out of our 30-patient cohort (80.0%) underwent single-fraction GKSRS, while 6 patients (20.0%) received 5 fractions. Peritumoral edema was present in 1 (3.3%) patient prior to GKSRS, with no cases observed following treatment. At a median follow-up of 33.0 months, the tumor control rate was 80.0%, with 6 patients (20.0%) experiencing progression in the field of radiation. Kaplan–Meier analysis demonstrated a median progression-free survival (PFS) of 70.6 months ( Figure 1 ). Among patients with recurrence, 4 (13.3%) underwent additional radiotherapy, while the remainder were managed with observation alone. The overall mortality rate at last follow-up included 5 patients (16.7%). Identifying Predictors of Progression Following Gamma Knife Radiosurgery Univariable Cox regression analysis was performed to identify predictors of tumor progression ( Table 2) . Increasing age at the time of GKSRS was significantly associated with higher risk of tumor progression (HR: 1.2, p=0.028). Although GTR was associated with a lower risk of tumor progression, the association did not reach statistical significance (HR: 4.6, p = 0.130). Interestingly, no significant correlation was observed between tumor volume (HR: 0.9, p=0.626), total radiation dose (HR: 1.0, p=0.113), or tumor type (primary vs. recurrent; HR: 1.4, p=0.677) and tumor progression in this cohort. Similarly, no statistically significant correlation was found between progression and GKSRS fractionation (HR: 3.5, p=0.290) or WHO Grade (HR: 4.4, p=0.143). Kaplan–Meier analysis stratified by WHO grade ( Figure 2 ) demonstrated significantly longer PFS in patients with WHO grade I meningiomas compared to those with grade II or III (78.5 months vs. 32.4 months, respectively; p = 0.011) Multivariate Analysis Age at the time of GKSRS remained associated with tumor progression in multivariable Cox regression analysis (HR = 1.2, p = 0.036) after adjusting for tumor volume and tumor type (primary vs. recurrent) ( Table 2 ). However, given the small sample size and limited number of progression events, these results should be interpreted with caution. Tumor volume and tumor type were not significantly associated with progression in the adjusted model. Discussion Summary of Key Findings Our single institution retrospective study provides evidence that GKSRS provides durable long-term tumor control for parasagittal meningiomas, with a tumor control rate of 80.0% at a median follow-up of 33.0 months and a median PFS of 70.6 months. Notably, univariable Cox analysis revealed that increased age at GKSRS was a significant predictor of tumor progression, while tumor volume, tumor type (primary vs. recurrent), extent of resection (GTR vs. STR), and total radiation dose were not associated with progression following radiation. Multivariable analysis confirmed that age was independently associated with tumor progression. However, these findings are limited by our small sample size and number of progression events and should be interpreted as preliminary. Despite the anatomical challenges of parasagittal meningiomas, our findings support GKSRS as a viable treatment option, both as primary therapy and as an adjunct following resection. While surgical resection remains the gold standard for parasagittal meningioma treatment, 4 our results support the role of GKSRS in achieving long-term tumor control. Comparison with Existing Literature Our findings support the efficacy of GKSRS in the treatment of parasagittal meningiomas. Limitations in the sample size of our study temper our ability to draw definitive comparisons, and our study may have been underpowered to detect more subtle associations. However, understanding the present study in the context of preexisting literature provides a clearer perspective on the effectiveness of the modality. Following GKSRS, tumor control rates are scarcely 100% due to the challenges posed by high-risk molecular features, tumor invasion beyond the treatment margins, and involvement of the dural sinuses, all technical limitations relevant to parasagittal meningiomas. 21 However, our PFS of 70.6 months and tumor control rate of 80.0% is lower than reported in prior studies also focusing on GKSRS in parasagittal meningiomas. For example, Ding et al. 22 reported a mean PFS of 104.2 months and tumor control rates as high as 92% at 3 years and 80% at 5 years following GKSRS. In a similar study that included 30 parasagittal meningiomas, Yu et al. 23 reported a tumor control rate of 79% and a median overall PFS of 73.4 months for all 130 meningioma cases in the study, regardless of location. Notably, the authors did identify parasagittal location as a predictor of treatment failure, highlighting the potential challenges associated with tumor control in this anatomical subgroup. Similarly, Azar et al. 24 presented tumor control rate of 91.8% in a cohort of 61 parasagittal meningiomas, with a 92% PFS rate at 3 years. Several factors could account for the differences in the clinical outcomes observed between our study and prior literature. While our study focuses solely on parasagittal meningiomas, most preexisting literature reports outcome data that includes meningiomas from other locations in their analysis. This variability may explain why some studies, such as Ding et al., report better control rates for parasagittal tumors, while others, like Yu et al., observe higher rates of progression in the same location. The discrepancy regarding progression between our findings and prior studies may also be reflected through factors such as pre-radiation extent of resection, whether the tumor had recurred prior to GKSRS, radiation dose, and tumor volume. For example, 60% of patients in our study underwent STR prior to GKSRS. We found that extent of resection in prior surgery was not predictive of progression following GKSRS treatment. This aligns with the findings of Yu et al., who reported that 66.2% of patients underwent STR prior to receiving post-operative GKSRS, with no significant association between STR and PFS. Azar et al. reported that 73.8% of patients had prior surgery before undergoing post-operative GKSRS, though they did not specify STR vs. GTR, and similarly found prior resection was not predictive of PFS. Beyond extent of resection, we also examined the impact of tumor progression prior to GKSRS and radiation dose. Although 53.3% of tumors were recurrent at the time of GKSRS in our study, whether the tumor had recurred before radiation was not found to be a significant predictor of tumor progression following radiosurgery. Yu et al. (35.4% recurrent) and Azar et al. (73.8% recurrent) mirrored our findings, also noting that recurrent status was not predictive of PFS following radiation. Similarly, our median radiation dose of 15 Gy was not associated with PFS, mirroring the findings of Ding et al. (15 Gy) and Yu et al. (13 Gy). Tumor volume followed a similar trend—our median volume of 2.0 cm³ was not predictive of outcomes, consistent with Ding et al. (3 cm³), while Yu et al. (8.6 mL) reported a significant association between larger volumes and worse prognosis. Ultimately, age and WHO grade emerged as the only variables to predict progression in our study. In both the univariable and multivariable analysis, older patients were more likely to experience progression following GKSRS. This finding aligns with results from Ding et al., who reported higher PFS in younger patients One possible explanation is that advanced age may be associated with an impaired response to radiation, with older patients exhibiting reduced vascular repair, slower clearance of tumor cells, and diminished immune response. 25 – 27 Additionally, the presence of comorbid conditions and variability in tumor molecular profile may play a role in reducing treatment efficacy. 22 , 28 Kaplan–Meier analysis demonstrated that WHO grade I meningiomas were associated with longer PFS compared to grade II or III tumors (78.5 vs. 32.4 months, p = 0.011), suggesting that histopathologic grade influences long-term outcomes following GKSRS. This finding aligns with prior analyses of parasagittal meningiomas, such as Khanna et al., who reported shorter time to recurrence among high-grade tumors. 29 Overall, the variability in factors associated with tumor progression across our study and prior literature may reflect the influence of more complex variables. For example, differences in institutional practices—such as patient selection criteria, treatment protocols, and follow-up duration—may contribute to the heterogeneity in reported outcomes following GKSRS for parasagittal meningiomas. Another key outcome to consider is mortality. Our study reported a 16.7% overall mortality rate at last follow up, lower than the 22.5% reported in Ding et al. yet higher than the 8.2% reported in Azar et al. Although our study reported a lower overall mortality rate, the interpretation of this finding, similar to our findings regarding progression, remains complex. Another key distinction between our study and previous literature is the incidence of peritumoral edema following GKSRS, a well-documented concern in prior studies. For example, Sheehan et al. 30 noted that 40% of patients developed new or worsening edema after radiation, typically emerging around 36 months following treatment. Their analysis identified tumor volumes greater than 10 cm³ and higher radiation doses as significant predictors of edema following radiosurgery. Notably, our study did not observe substantial post-treatment edema, suggesting that GKSRS can be both safe and effective for appropriately selected patients. Our analysis found that 3.3% of patients had edema prior to GKSRS, while no patients developed edema following GKSRS. Importantly, 86.7% of our cohort underwent prior surgical resection, which Sheehan et al. suggested may reduce the risk of post-GKSRS edema. 30 Additionally, prior studies have linked greater maximum dose, tumor volume, and the presence of pre-treatment edema to an increased risk of edema following radiotherapy. 31 Given that only 3.3% of patients in our cohort had pre-existing edema, this may be partially responsible for the complete lack of edema observed postoperatively. Additionally, it is possible that the median tumor volume and dose in our cohort are smaller than those of other studies, further contributing to the lack of postoperative edema. 32 , 33 While further research is needed to clarify these differences, our results support the role of GKSRS in achieving tumor control while minimizing treatment-related complications. Clinical Implications Parasagittal meningiomas pose unique clinical challenges due to their proximity to the SSS, eloquent cortex, and critical venous structures, increasing the risk of venous infarction and postoperative neurological deficits with surgical resection. Our study suggests that GKSRS offers a less invasive alternative that may prevent tumor progression while avoiding the morbidity associated with aggressive resection. Our results also support the efficacy of single-session GKSRS rather than fractionated treatment. Most of our cohort (80%) underwent single-dose GKSRS and STR (60%) without developing significant complications, challenging the assumption that fractionation and GTR are necessary to reduce the risks of postoperative edema. While prior studies have observed similar outcomes between single-session and fractionated approaches, there is a lack of consensus in existing literature regarding the association between extent of resection and edema. 23 , 34 , 35 However, given our limited sample size and retrospective design, further studies are needed focusing on optimal dosing protocols and extent of resection in these patients. The present study supports the use of GKSRS as an effective, less invasive treatment option for achieving long-term tumor control of parasagittal meningiomas. The absence of significant edema coupled with the high proportion of STR and single-dose GKSRS in our cohort also challenges existing assumptions regarding which variables may be causative of this common post-GKSRS complication. Notably, factors such as patient age, WHO grade, and individual vascular anatomy may all influence outcomes following GKSRS, reinforcing the importance of careful patient selection. Given the significantly shorter PFS observed in patients with WHO grade II/III meningiomas in our cohort, these tumors may warrant closer surveillance and more frequent postoperative imaging to detect early progression. However, our observations should not be over-interpreted given the limited sample size and retrospective design. Patient-specific factors—particularly age, WHO grade, and vascular anatomy—should remain central to treatment decision-making. Future Directions and limitations Multi-institutional, prospective studies with larger cohorts of parasagittal meningioma patients are essential to validate our outcomes and identify both patient- and treatment-specific factors most predictive of recurrence following GKSRS. Future investigations should evaluate the role of prior surgical resection (e.g., gross total vs. subtotal resection), tumor volume thresholds specific to parasagittal lesions, and optimal radiation dosing strategies—including the potential benefits of hypofractionation—in improving long-term tumor control. Furthermore, the integration of machine learning-based predictive models tailored to parasagittal meningiomas may enhance individualized treatment planning by identifying patients at highest risk for recurrence or post-radiosurgical complications based on imaging, clinical, and dosimetric parameters. As a retrospective, single-institution analysis, selection bias and institutional practice patterns may limit the generalizability of our findings. Additionally, our study was limited by a median follow-up of approximately three years, leaving long-term post-treatment outcomes unexplored. Analyses investigating the effects of GKSRS over extended follow-up periods may provide a more detailed understanding of the long-term effects of the treatment modality. Given our limited sample size, the present study could not perform any subgroup analyses, specifically in comparing primary and recurrent meningiomas and single fraction versus fractionated treatment regimens. This limitation may be partly due to some patients receiving their GKSRS treatment at outside institutions and thus were not captured in our institutional dataset. Additionally, our analyzed sample was limited to patients with meningiomas located specifically in the parasagittal region, further narrowing our sample size. Finally, we did not assess post-GKSRS functional outcomes or quality of life, which are critical considerations to the success of radiation therapy for meningiomas. Conclusion Our study provides evidence in support of GKSRS for the treatment of parasagittal meningiomas, with age and WHO grade as the only significant predictors of progression. Tumor volume, tumor type (primary vs. recurrent before GKSRS), extent of resection, radiation dose, and fractionation (single vs. fractionated) were not predictive. The scarcity of post-GKSRS edema in our study suggests that, among our cohort, radiosurgery is both effective and safe, though further research is required to validate this finding. The variability between our findings compared to prior studies highlight the complexity of treating parasagittal meningiomas and indicate the need to investigate alternative factors that may impact tumor control outcomes. Declarations Author Contribution A.E., N.B., and I.S. drafted the manuscript and prepared Tables 1 and 2. I.S. and B.W. performed the statistical analyses and generated Figures 1 and 2. All authors reviewed the manuscript. 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Journal of Neurosurgery JNS . 01 Nov. https://doi.org/10.3171/2014.12.JNS142159 Milano MT, Sharma M, Soltys SG et al (2018) Radiation-Induced Edema After Single-Fraction or Multifraction Stereotactic Radiosurgery for Meningioma: A Critical Review. Int J Radiat Oncol Biol Phys Jun 1(2):344–357. 10.1016/j.ijrobp.2018.03.026 Kim IY, Kondziolka D, Niranjan A, Flickinger JC, Lunsford LD (May 2009) Gamma knife radiosurgery for intraventricular meningiomas. Acta Neurochir (Wien) 151(5):447–452 discussion 452. 10.1007/s00701-009-0273-x Nakaya K, Chernov M, Kasuya H et al (2009) Risk factors for regrowth of intracranial meningiomas after gamma knife radiosurgery: importance of the histopathological grade and MIB-1 index. Minim Invasive Neurosurg Oct 52(5–6):216–221. 10.1055/s-0029-1243244 Huang SH, Wang CC, Wei KC et al (2020) Treatment of intracranial meningioma with single-session and fractionated radiosurgery: a propensity score matching study. Sci Rep Oct 28(1):18500. 10.1038/s41598-020-75559-8 Ding D, Xu Z, McNeill IT, Yen CP, Sheehan JP (2013) Radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg Oct 119(4):871–877. 10.3171/2013.6.Jns13110 Tables Table 1: Patient Demographics, Treatment Characteristics, and Long-Term Outcomes Variable Total Cohort Number of Patients 30 Age (years) 62.0 (33-86) Sex Distribution Female 17 (56.7) Male 13 (43.3) Primary vs. Recurrent Tumor Primary 14 (46.7) Recurrent 16 (53.3) Surgery Prior to GKSRS 26 (86.7) GTR* 6 (20.0) STR* 18 (60.0) Tumor Diameter (cm) 1.7 (0.9-11.2) Tumor Volume (cm 3 ) 2.0 (0.4-16.6) WHO Grade I 18 (60.0) II 11 (36.7) III 1 (3.3) Intraoperative Characteristics Fractions 1 24 (80.0) 5 6 (20.0) Dose (cGy) 1500.0 (500-1600) Postoperative Outcomes Progression 6 (20.0) Follow-up Time (months) 33.0 (4-93) PFS (months) (median (95% CI)) 70.6 (70.2-71.0) Mortality 5 (16.7) *80.0% of the total cohort underwent surgical resection prior to radiation Continuous variables are reported as median (range) while categorical variables are reported as proportions. Abbreviations: cm: centimeters GKSRS: Gamma Knife Radiosurgery WHO: World Health Organization GTR: Gross Total Resection STR: Subtotal Resection SE: Standard Error mm: millimeters CI: Confidence Interval cGy: centigray Table 2: Univariable and Multivariable Cox Regression Analyses of Predictors of Progression Following Gamma Knife Radiosurgery Univariable Cox Regression HR (95% CI) p-value Age at GKSRS (years) 1.2 (1.0 to 1.3) 0.028* Tumor Volume (cm 3 ) 0.9 (0.6 to 1.4) 0.626 Tumor Type (Primary [0] vs Recurrent [1]) 1.4 (0.3 to 7.2) 0.677 Extent of Resection (STR [0] vs. GTR [1]) 4.4 (0.6 to 31.5) 0.143 Total Radiation Dose (cGy) 1.0 (1.0 to 1.004) 0.113 GKSRS Fractionation (Single [0] vs. Fractionated [1]) 3.5 (0.3 to 36.5) 0.290 Multivariable Cox Regression HR (95% CI) p-value Age at GKSRS (years) 1.2 (1.0 to 1.4) 0.036* Tumor Volume (cm 3 ) 0.9 (0.7 to 1.2) 0.432 Tumor Type (Primary [0] vs Recurrent [1]) 0.5 (0.06 to 4.5) 0.565 *Indicates significance at p < 0.05 Abbreviations: CI: Confidence Interval mm: millimeters GKSRS: Gamma Knife Radiosurgery GTR: Gross Total Resection STR: Subtotal Resection WHO: World Health Organization Additional Declarations No competing interests reported. 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Shukla","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ishav","middleName":"Y.","lastName":"Shukla","suffix":""},{"id":468101684,"identity":"3984822c-dc7f-4e9f-a2b2-78dfecebcb1c","order_by":3,"name":"Jeffrey I. Traylor","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jeffrey","middleName":"I.","lastName":"Traylor","suffix":""},{"id":468101685,"identity":"deea5705-a8be-4762-aa03-f6315513b01c","order_by":4,"name":"Bingchun Wan","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Bingchun","middleName":"","lastName":"Wan","suffix":""},{"id":468101686,"identity":"16ea37ea-be4e-4362-8fdc-9da62dc8298a","order_by":5,"name":"Robert D. Timmerman","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"D.","lastName":"Timmerman","suffix":""},{"id":468101687,"identity":"66f13f5b-7423-4bd3-85f2-ccee0eca9041","order_by":6,"name":"Michael Dohopolski","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Dohopolski","suffix":""},{"id":468101688,"identity":"0a3627c7-45f3-4c05-bed8-d2e895e90be8","order_by":7,"name":"Jill De Vis","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jill","middleName":"","lastName":"De Vis","suffix":""},{"id":468101689,"identity":"97b4a70e-c905-4415-b793-6b6e2cf69abf","order_by":8,"name":"Toral Patel","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Toral","middleName":"","lastName":"Patel","suffix":""},{"id":468101690,"identity":"9c026df9-6bd4-45be-a00e-2ec3f7a6afb8","order_by":9,"name":"Ankur Patel","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ankur","middleName":"","lastName":"Patel","suffix":""},{"id":468101691,"identity":"b0d2e223-792f-4875-b820-0f9d209e94f6","order_by":10,"name":"Samuel L. Barnett","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"L.","lastName":"Barnett","suffix":""},{"id":468101692,"identity":"3495f4c1-68b1-4107-8b27-31bfc251e14a","order_by":11,"name":"Zabi Wardak","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zabi","middleName":"","lastName":"Wardak","suffix":""},{"id":468101693,"identity":"fc538f37-1d28-43e0-9095-cb4dcfebc78e","order_by":12,"name":"Tu Dan","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tu","middleName":"","lastName":"Dan","suffix":""},{"id":468101694,"identity":"4c37b540-f821-49f4-9e28-e31c9f7502ce","order_by":13,"name":"Matthew Z. Sun","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"Z.","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2025-06-05 01:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6824067/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6824067/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84305092,"identity":"fcf694ef-96ec-4724-bceb-95a874ec5bba","added_by":"auto","created_at":"2025-06-10 11:23:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":67725,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival\u003c/p\u003e","description":"","filename":"Figure118.png","url":"https://assets-eu.researchsquare.com/files/rs-6824067/v1/d1f280d12d8e8b091b1cc50b.png"},{"id":84305089,"identity":"44b8bccc-26e5-41da-ab5a-80406b319191","added_by":"auto","created_at":"2025-06-10 11:23:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":105711,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival Stratified by WHO Grade\u003c/p\u003e","description":"","filename":"Figure219.png","url":"https://assets-eu.researchsquare.com/files/rs-6824067/v1/d756e4ce414376879bb14f6d.png"},{"id":85072016,"identity":"dad32d4f-282c-41aa-a102-241f18966b47","added_by":"auto","created_at":"2025-06-20 15:46:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":809306,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6824067/v1/c020115d-4a89-4e29-ba33-38fd2631eb86.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-Term Tumor Control Following Gamma Knife Radiosurgery for Parasagittal Meningiomas: A Single Institution Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMeningiomas are the most common intracranial neoplasm in the United States, accounting for roughly one-third of all primary brain tumors.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The tumor is typically benign, and gross total resection (GTR) remains the gold standard for long-term control.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e However, GTR may be impeded by factors such as tumor size, invasion of adjacent structures, and, notably, location. This is particularly true for the parasagittal region, where tumors frequently compress or invade the superior sagittal sinus (SSS), bridging veins, and the primary motor cortex.\u003csup\u003e\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Radical resection in these regions carries a high risk of venous infarction and postoperative neurological deficits.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e As a result, subtotal resection (STR) is often performed, which increases the likelihood of tumor progression and the need for further intervention.\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGamma Knife Radiosurgery (GKSRS) has emerged as an effective treatment modality for intracranial meningiomas, particularly when GTR is not feasible.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e In addition to being less invasive than surgical resection, previous studies have shown that GKSRS provides effective tumor control, especially for smaller, benign lesions across various locations.\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Some reports suggest that progression free survival (PFS) rates following radiosurgery may be comparable to PFS following Simpson Grade I Resection.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Despite these promising outcomes, long-term outcome data on GKSRS for parasagittal meningiomas remain limited. More specifically, PFS and progression data is needed to assess the long-term viability of GKSRS and its role in managing these progression prone tumors.\u003c/p\u003e \u003cp\u003eThis study aims to assess the long-term efficacy of GKSRS in treating parasagittal meningiomas, and to identify factors associated with improved tumor control. We also provide extended follow-up data on key, long-term postoperative outcomes including progression rate, PFS, and mortality. By providing extended follow-up data, we aim to help define the role of GKSRS in the long-term treatment of parasagittal meningiomas.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003e We conducted a retrospective cohort study evaluating patients who underwent GKSRS for meningioma at a single, academic, tertiary care medical center between 2015 and 2023. The study was approved by the Institutional Review Board, with a waiver of informed consent granted due to minimal patient risk.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Identification and Inclusion\u003c/h3\u003e\n\u003cp\u003ePatients were identified through a comprehensive institutional database search using ICD-9, ICD-10, and CPT codes corresponding to meningioma diagnoses and GKSRS procedures. Eligible patients had a confirmed pathological diagnosis of meningioma and underwent GKSRS with available preoperative and postoperative clinical data. Exclusion criteria included patients with an alternative tumor diagnosis, lack of GKSRS, or incomplete medical records. After applying inclusion and exclusion criteria, 30 patients were included in the final analysis. Patient data was collected up until their last available follow up date, with the maximum being 93 months follow treatment.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eData were systematically extracted from electronic medical records and categorized into baseline, treatment, and post-treatment variables. Baseline variables included patient demographics (age in years, sex) and tumor characteristics such as diagnosis status (primary vs. recurrent), tumor World Health Organization (WHO) grade, anatomical location, maximum tumor diameter (cm), tumor volume (cm\u0026sup3;), and history of prior surgical resection. For patients with previous surgery, the extent of resection was categorized as gross total resection (GTR) or subtotal resection (STR). Among patients who reported extent of resection follow surgery, 5 patients underwent GTR, while 17 underwent STR. Treatment variables encompassed the total number of radiation fractions administered and the median radiation dose delivered (cGy). Collected post-treatment variables included progression, overall follow-up duration, survival time, and mortality status. Progression was defined as increase in tumor diameter of 2 mm or more in any direction on imaging following GKSRS treatment. The occurrence of post-radiation imaging findings\u0026mdash;such as peritumoral edema, necrosis, mass effect, and hydrocephalus\u0026mdash;was also recorded.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were conducted using SPSS version 30.0. The Shapiro-Wilk test was used to assess the normality of continuous variables. Continuous variables were reported as medians (range) and compared using independent t-tests for normally distributed data or Mann-Whitney U tests for non-normally distributed data. Categorical variables were presented as frequencies with proportions (%) and analyzed using Chi-square or Fisher\u0026rsquo;s exact test, as appropriate. Univariable Cox regression analysis was performed to examine the association between various baseline and treatment variables and tumor progression following GKSRS. Multivariable Cox regression analysis was performed to determine if these relationships would remain significant even after controlling for key variables including tumor volume, extent of resection, total dosage, age, and tumor type. Hazard ratios (HR) were reported with 95% confidence intervals (CIs) and p-values, with statistical significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. A biostatistician (B.W.) reviewed all statistical methodologies to ensure robustness and appropriate interpretation of results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003ePatient Demographics, Treatment Characteristics, and Long-Term Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA complete representation of patient demographics and tumor characteristics can be found in \u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eA total of 30 patients who underwent GKSRS for a parasagittal meningioma were included in this study. 17 patients (56.7%) were female, and the median patient age was 62.0 years (range: 33-86). 16 patients (53.3%) presented with recurrent tumors, while 14 (46.7%) had primary meningiomas. Notably, 24 (80.0%) patients had a prior surgical resection before receiving GKSRS. The median tumor diameter was 1.7 cm, and the median tumor volume was 2.0 cm\u003csup\u003e3\u003c/sup\u003e. Of the 30 patients, 18 (60.0%) had WHO grade I meningiomas, 11 (36.7%) had WHO grade II, and 1 (3.3%) had WHO grade III.\u0026nbsp;For patients who underwent a single fraction, the total median prescribed dose was 1500.0 cGy, while patients who underwent 5 fractions received a total median prescribed dose of 2500.0 cGy. 24 out of our 30-patient cohort (80.0%) underwent single-fraction GKSRS, while 6 patients (20.0%) received 5 fractions. Peritumoral edema was present in 1 (3.3%) patient prior to GKSRS, with no cases observed following treatment. At a median follow-up of 33.0 months, the tumor control rate was 80.0%, with 6 patients (20.0%) experiencing progression in the field of radiation. Kaplan\u0026ndash;Meier analysis demonstrated a median progression-free survival (PFS) of 70.6 months (\u003cstrong\u003eFigure 1\u003c/strong\u003e). Among patients with recurrence, 4 (13.3%) underwent additional radiotherapy, while the remainder were managed with observation alone. The overall mortality rate at last follow-up included 5 patients (16.7%).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIdentifying Predictors of Progression Following Gamma Knife Radiosurgery\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUnivariable Cox regression analysis was performed to identify predictors of tumor progression (\u003cstrong\u003eTable 2)\u003c/strong\u003e. Increasing age at the time of GKSRS was significantly associated with higher risk of tumor progression (HR: 1.2, p=0.028). Although GTR was associated with a lower risk of tumor progression, the association did not reach statistical significance (HR: 4.6, p = 0.130). Interestingly, no significant correlation was observed between tumor volume (HR: 0.9, p=0.626), total radiation dose (HR: 1.0, p=0.113), or tumor type (primary vs. recurrent; HR: 1.4, p=0.677) and tumor progression in this cohort. Similarly, no statistically significant correlation was found between progression and GKSRS fractionation (HR: 3.5, p=0.290) or WHO Grade (HR: 4.4, p=0.143). Kaplan\u0026ndash;Meier analysis stratified by WHO grade (\u003cstrong\u003eFigure 2\u003c/strong\u003e) demonstrated significantly longer PFS in patients with WHO grade I meningiomas compared to those with grade II or III (78.5 months vs. 32.4 months, respectively; p = 0.011)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMultivariate Analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAge at the time of GKSRS remained associated with tumor progression in multivariable Cox regression analysis (HR = 1.2, p = 0.036) after adjusting for tumor volume and tumor type (primary vs. recurrent) (\u003cstrong\u003eTable 2\u003c/strong\u003e). However, given the small sample size and limited number of progression events, these results should be interpreted with caution. Tumor volume and tumor type were not significantly associated with progression in the adjusted model.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSummary of Key Findings\u003c/h2\u003e \u003cp\u003eOur single institution retrospective study provides evidence that GKSRS provides durable long-term tumor control for parasagittal meningiomas, with a tumor control rate of 80.0% at a median follow-up of 33.0 months and a median PFS of 70.6 months. Notably, univariable Cox analysis revealed that increased age at GKSRS was a significant predictor of tumor progression, while tumor volume, tumor type (primary vs. recurrent), extent of resection (GTR vs. STR), and total radiation dose were not associated with progression following radiation. Multivariable analysis confirmed that age was independently associated with tumor progression. However, these findings are limited by our small sample size and number of progression events and should be interpreted as preliminary. Despite the anatomical challenges of parasagittal meningiomas, our findings support GKSRS as a viable treatment option, both as primary therapy and as an adjunct following resection. While surgical resection remains the gold standard for parasagittal meningioma treatment,\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e our results support the role of GKSRS in achieving long-term tumor control.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eComparison with Existing Literature\u003c/h2\u003e \u003cp\u003eOur findings support the efficacy of GKSRS in the treatment of parasagittal meningiomas. Limitations in the sample size of our study temper our ability to draw definitive comparisons, and our study may have been underpowered to detect more subtle associations. However, understanding the present study in the context of preexisting literature provides a clearer perspective on the effectiveness of the modality. Following GKSRS, tumor control rates are scarcely 100% due to the challenges posed by high-risk molecular features, tumor invasion beyond the treatment margins, and involvement of the dural sinuses, all technical limitations relevant to parasagittal meningiomas.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e However, our PFS of 70.6 months and tumor control rate of 80.0% is lower than reported in prior studies also focusing on GKSRS in parasagittal meningiomas. For example, Ding et al.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e reported a mean PFS of 104.2 months and tumor control rates as high as 92% at 3 years and 80% at 5 years following GKSRS. In a similar study that included 30 parasagittal meningiomas, Yu et al.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e reported a tumor control rate of 79% and a median overall PFS of 73.4 months for all 130 meningioma cases in the study, regardless of location. Notably, the authors did identify parasagittal location as a predictor of treatment failure, highlighting the potential challenges associated with tumor control in this anatomical subgroup. Similarly, Azar et al.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e presented tumor control rate of 91.8% in a cohort of 61 parasagittal meningiomas, with a 92% PFS rate at 3 years.\u003c/p\u003e \u003cp\u003eSeveral factors could account for the differences in the clinical outcomes observed between our study and prior literature. While our study focuses solely on parasagittal meningiomas, most preexisting literature reports outcome data that includes meningiomas from other locations in their analysis. This variability may explain why some studies, such as Ding et al., report better control rates for parasagittal tumors, while others, like Yu et al., observe higher rates of progression in the same location. The discrepancy regarding progression between our findings and prior studies may also be reflected through factors such as pre-radiation extent of resection, whether the tumor had recurred prior to GKSRS, radiation dose, and tumor volume.\u003c/p\u003e \u003cp\u003eFor example, 60% of patients in our study underwent STR prior to GKSRS. We found that extent of resection in prior surgery was not predictive of progression following GKSRS treatment. This aligns with the findings of Yu et al., who reported that 66.2% of patients underwent STR prior to receiving post-operative GKSRS, with no significant association between STR and PFS. Azar et al. reported that 73.8% of patients had prior surgery before undergoing post-operative GKSRS, though they did not specify STR vs. GTR, and similarly found prior resection was not predictive of PFS.\u003c/p\u003e \u003cp\u003eBeyond extent of resection, we also examined the impact of tumor progression prior to GKSRS and radiation dose. Although 53.3% of tumors were recurrent at the time of GKSRS in our study, whether the tumor had recurred before radiation was not found to be a significant predictor of tumor progression following radiosurgery. Yu et al. (35.4% recurrent) and Azar et al. (73.8% recurrent) mirrored our findings, also noting that recurrent status was not predictive of PFS following radiation. Similarly, our median radiation dose of 15 Gy was not associated with PFS, mirroring the findings of Ding et al. (15 Gy) and Yu et al. (13 Gy). Tumor volume followed a similar trend\u0026mdash;our median volume of 2.0 cm\u0026sup3; was not predictive of outcomes, consistent with Ding et al. (3 cm\u0026sup3;), while Yu et al. (8.6 mL) reported a significant association between larger volumes and worse prognosis.\u003c/p\u003e \u003cp\u003eUltimately, age and WHO grade emerged as the only variables to predict progression in our study. In both the univariable and multivariable analysis, older patients were more likely to experience progression following GKSRS. This finding aligns with results from Ding et al., who reported higher PFS in younger patients One possible explanation is that advanced age may be associated with an impaired response to radiation, with older patients exhibiting reduced vascular repair, slower clearance of tumor cells, and diminished immune response.\u003csup\u003e\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Additionally, the presence of comorbid conditions and variability in tumor molecular profile may play a role in reducing treatment efficacy.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Kaplan\u0026ndash;Meier analysis demonstrated that WHO grade I meningiomas were associated with longer PFS compared to grade II or III tumors (78.5 vs. 32.4 months, p\u0026thinsp;=\u0026thinsp;0.011), suggesting that histopathologic grade influences long-term outcomes following GKSRS. This finding aligns with prior analyses of parasagittal meningiomas, such as Khanna et al., who reported shorter time to recurrence among high-grade tumors.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOverall, the variability in factors associated with tumor progression across our study and prior literature may reflect the influence of more complex variables. For example, differences in institutional practices\u0026mdash;such as patient selection criteria, treatment protocols, and follow-up duration\u0026mdash;may contribute to the heterogeneity in reported outcomes following GKSRS for parasagittal meningiomas. Another key outcome to consider is mortality. Our study reported a 16.7% overall mortality rate at last follow up, lower than the 22.5% reported in Ding et al. yet higher than the 8.2% reported in Azar et al. Although our study reported a lower overall mortality rate, the interpretation of this finding, similar to our findings regarding progression, remains complex.\u003c/p\u003e \u003cp\u003eAnother key distinction between our study and previous literature is the incidence of peritumoral edema following GKSRS, a well-documented concern in prior studies. For example, Sheehan et al.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e noted that 40% of patients developed new or worsening edema after radiation, typically emerging around 36 months following treatment. Their analysis identified tumor volumes greater than 10 cm\u0026sup3; and higher radiation doses as significant predictors of edema following radiosurgery. Notably, our study did not observe substantial post-treatment edema, suggesting that GKSRS can be both safe and effective for appropriately selected patients. Our analysis found that 3.3% of patients had edema prior to GKSRS, while no patients developed edema following GKSRS. Importantly, 86.7% of our cohort underwent prior surgical resection, which Sheehan et al. suggested may reduce the risk of post-GKSRS edema.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Additionally, prior studies have linked greater maximum dose, tumor volume, and the presence of pre-treatment edema to an increased risk of edema following radiotherapy.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Given that only 3.3% of patients in our cohort had pre-existing edema, this may be partially responsible for the complete lack of edema observed postoperatively. Additionally, it is possible that the median tumor volume and dose in our cohort are smaller than those of other studies, further contributing to the lack of postoperative edema.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e While further research is needed to clarify these differences, our results support the role of GKSRS in achieving tumor control while minimizing treatment-related complications.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eClinical Implications\u003c/h2\u003e \u003cp\u003eParasagittal meningiomas pose unique clinical challenges due to their proximity to the SSS, eloquent cortex, and critical venous structures, increasing the risk of venous infarction and postoperative neurological deficits with surgical resection. Our study suggests that GKSRS offers a less invasive alternative that may prevent tumor progression while avoiding the morbidity associated with aggressive resection.\u003c/p\u003e \u003cp\u003eOur results also support the efficacy of single-session GKSRS rather than fractionated treatment. Most of our cohort (80%) underwent single-dose GKSRS and STR (60%) without developing significant complications, challenging the assumption that fractionation and GTR are necessary to reduce the risks of postoperative edema. While prior studies have observed similar outcomes between single-session and fractionated approaches, there is a lack of consensus in existing literature regarding the association between extent of resection and edema.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e However, given our limited sample size and retrospective design, further studies are needed focusing on optimal dosing protocols and extent of resection in these patients.\u003c/p\u003e \u003cp\u003eThe present study supports the use of GKSRS as an effective, less invasive treatment option for achieving long-term tumor control of parasagittal meningiomas. The absence of significant edema coupled with the high proportion of STR and single-dose GKSRS in our cohort also challenges existing assumptions regarding which variables may be causative of this common post-GKSRS complication. Notably, factors such as patient age, WHO grade, and individual vascular anatomy may all influence outcomes following GKSRS, reinforcing the importance of careful patient selection. Given the significantly shorter PFS observed in patients with WHO grade II/III meningiomas in our cohort, these tumors may warrant closer surveillance and more frequent postoperative imaging to detect early progression. However, our observations should not be over-interpreted given the limited sample size and retrospective design. Patient-specific factors\u0026mdash;particularly age, WHO grade, and vascular anatomy\u0026mdash;should remain central to treatment decision-making.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eFuture Directions and limitations\u003c/h2\u003e \u003cp\u003eMulti-institutional, prospective studies with larger cohorts of parasagittal meningioma patients are essential to validate our outcomes and identify both patient- and treatment-specific factors most predictive of recurrence following GKSRS. Future investigations should evaluate the role of prior surgical resection (e.g., gross total vs. subtotal resection), tumor volume thresholds specific to parasagittal lesions, and optimal radiation dosing strategies\u0026mdash;including the potential benefits of hypofractionation\u0026mdash;in improving long-term tumor control. Furthermore, the integration of machine learning-based predictive models tailored to parasagittal meningiomas may enhance individualized treatment planning by identifying patients at highest risk for recurrence or post-radiosurgical complications based on imaging, clinical, and dosimetric parameters.\u003c/p\u003e \u003cp\u003eAs a retrospective, single-institution analysis, selection bias and institutional practice patterns may limit the generalizability of our findings. Additionally, our study was limited by a median follow-up of approximately three years, leaving long-term post-treatment outcomes unexplored. Analyses investigating the effects of GKSRS over extended follow-up periods may provide a more detailed understanding of the long-term effects of the treatment modality. Given our limited sample size, the present study could not perform any subgroup analyses, specifically in comparing primary and recurrent meningiomas and single fraction versus fractionated treatment regimens. This limitation may be partly due to some patients receiving their GKSRS treatment at outside institutions and thus were not captured in our institutional dataset. Additionally, our analyzed sample was limited to patients with meningiomas located specifically in the parasagittal region, further narrowing our sample size. Finally, we did not assess post-GKSRS functional outcomes or quality of life, which are critical considerations to the success of radiation therapy for meningiomas.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study provides evidence in support of GKSRS for the treatment of parasagittal meningiomas, with age and WHO grade as the only significant predictors of progression. Tumor volume, tumor type (primary vs. recurrent before GKSRS), extent of resection, radiation dose, and fractionation (single vs. fractionated) were not predictive. The scarcity of post-GKSRS edema in our study suggests that, among our cohort, radiosurgery is both effective and safe, though further research is required to validate this finding. The variability between our findings compared to prior studies highlight the complexity of treating parasagittal meningiomas and indicate the need to investigate alternative factors that may impact tumor control outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.E., N.B., and I.S. drafted the manuscript and prepared Tables 1 and 2. I.S. and B.W. performed the statistical analyses and generated Figures 1 and 2. All authors reviewed the manuscript. J.T., R.T., M.D., J.V., T.P., A.P., S.B., Z.W., T.D., and M.S. provided oncologic care to the patients included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOstrom QT, Gittleman H, Fulop J et al (2015) CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008\u0026ndash;2012. Neurooncology 17(suppl4):iv1\u0026ndash;iv62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/neuonc/nov189\u003c/span\u003e\u003cspan address=\"10.1093/neuonc/nov189\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRogers L, Barani I, Chamberlain M et al (2015) Meningiomas: knowledge base, treatment outcomes, and uncertainties. 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Acta Neurochir (Wien) Dec 165(12):4175\u0026ndash;4182. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00701-023-05848-4\u003c/span\u003e\u003cspan address=\"10.1007/s00701-023-05848-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan JP, Lee C-C, Xu Z, Przybylowski CJ, Melmer PD, Schlesinger D (2015) 2015;123(5):1287\u0026ndash;1293 Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. \u003cem\u003eJournal of Neurosurgery JNS\u003c/em\u003e. 01 Nov. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3171/2014.12.JNS142159\u003c/span\u003e\u003cspan address=\"10.3171/2014.12.JNS142159\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMilano MT, Sharma M, Soltys SG et al (2018) Radiation-Induced Edema After Single-Fraction or Multifraction Stereotactic Radiosurgery for Meningioma: A Critical Review. 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Minim Invasive Neurosurg Oct 52(5\u0026ndash;6):216\u0026ndash;221. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1055/s-0029-1243244\u003c/span\u003e\u003cspan address=\"10.1055/s-0029-1243244\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang SH, Wang CC, Wei KC et al (2020) Treatment of intracranial meningioma with single-session and fractionated radiosurgery: a propensity score matching study. Sci Rep Oct 28(1):18500. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-020-75559-8\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-75559-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing D, Xu Z, McNeill IT, Yen CP, Sheehan JP (2013) Radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg Oct 119(4):871\u0026ndash;877. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2013.6.Jns13110\u003c/span\u003e\u003cspan address=\"10.3171/2013.6.Jns13110\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003ePatient Demographics, Treatment Characteristics, and Long-Term Outcomes\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eNumber of Patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e62.0 (33-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003eSex Distribution\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e17 (56.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e13 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003ePrimary vs. Recurrent Tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e14 (46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eRecurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e16 (53.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eSurgery Prior to GKSRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26 (86.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eGTR*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e6 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eSTR*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e18 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eTumor Diameter (cm)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.7 (0.9-11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eTumor Volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2.0 (0.4-16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003eWHO Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e18 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e11 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraoperative Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003eFractions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e24 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e6 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eDose (cGy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1500.0 (500-1600)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 431px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eProgression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e6 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eFollow-up Time (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e33.0 (4-93)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003ePFS (months) (median (95% CI))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e70.6 (70.2-71.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003eMortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e5 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*80.0% of the total cohort underwent surgical resection prior to radiation\u003c/p\u003e\n\u003cp\u003eContinuous variables are reported as median (range) while categorical variables are reported as proportions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ecm: centimeters\u003c/p\u003e\n\u003cp\u003eGKSRS: Gamma Knife Radiosurgery\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\u003c/p\u003e\n\u003cp\u003eGTR: Gross Total Resection\u003c/p\u003e\n\u003cp\u003eSTR: Subtotal Resection\u003c/p\u003e\n\u003cp\u003eSE: Standard Error\u003c/p\u003e\n\u003cp\u003emm: millimeters\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e\n\u003cp\u003ecGy: centigray\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003eUnivariable and Multivariable Cox Regression Analyses of Predictors of Progression Following Gamma Knife Radiosurgery\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"684\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Cox\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRegression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eAge at GKSRS (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e1.2 (1.0 to 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.028*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eTumor Volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e0.9 (0.6 to 1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.626\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eTumor Type (Primary [0] vs Recurrent [1])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e1.4 (0.3 to 7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eExtent of Resection (STR [0] vs. GTR [1])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e4.4 (0.6 to 31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eTotal Radiation Dose (cGy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e1.0 (1.0 to 1.004)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eGKSRS Fractionation (Single [0] vs. Fractionated [1])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e3.5 (0.3 to 36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.290\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Cox\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRegression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eAge at GKSRS (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e1.2 (1.0 to 1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eTumor Volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e0.9 (0.7 to 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.432\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 366px;\"\u003e\n \u003cp\u003eTumor Type (Primary [0] vs Recurrent [1])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 182px;\"\u003e\n \u003cp\u003e0.5 (0.06 to 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Indicates significance at p \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e\n\u003cp\u003emm: millimeters\u003c/p\u003e\n\u003cp\u003eGKSRS: Gamma Knife Radiosurgery\u003c/p\u003e\n\u003cp\u003eGTR: Gross Total Resection\u003c/p\u003e\n\u003cp\u003eSTR: Subtotal Resection\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\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":"Gamma Knife Stereotactic Radiosurgery (GKSRS), Parasagittal Meningioma, Tumor Control, Radiosurgical Outcomes, Fractionation","lastPublishedDoi":"10.21203/rs.3.rs-6824067/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6824067/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction:\u003c/p\u003e\n\u003cp\u003eParasagittal meningiomas present unique challenges due to their proximity to large draining veins and the superior sagittal sinus, limiting the ability to achieve gross total resection (GTR). There is limited literature regarding the long-term efficacy of Gamma Knife Radiosurgery (GKSRS) for tumor control in this progression-prone region. We evaluated the effectiveness of GKSRS in achieving tumor control for parasagittal meningiomas.\u003c/p\u003e\n\u003cp\u003eMethods:\u003c/p\u003e\n\u003cp\u003eA retrospective analysis was conducted at a single academic institution from 2015 to 2023, analyzing predictors of progression via univariable and multivariable Cox regression analyses.\u003c/p\u003e\n\u003cp\u003eResults:\u003c/p\u003e\n\u003cp\u003e30 patients were included. The median age was 62.0 years (range: 33–86). 86.7% underwent surgical resection prior to GKSRS. At presentation, 14 patients (46.7%) had primary tumors, while 16 (53.3%) had recurrent tumors. The median tumor volume was 2.0 cm³, and median tumor diameter was 1.7 cm. The median follow-up period was 33.0 months; mortality rate at last follow-up was 16.7%. 24 patients (80%) were treated with 1 fraction, while 6 (20%) were treated with 5 fractions. The median total GKSRS dose was 1500.0 cGy. At last follow-up, 80% of patients exhibited local tumor control. Peritumoral edema was present in 1 (3.3%) patient prior to GKSRS, with no cases observed following treatment. Median progression-free survival (PFS) was 70.6 months. Kaplan–Meier analysis demonstrated that WHO grade I meningiomas had longer mean PFS compared to grade II or III tumors (78.5 vs. 32.4 months, p = 0.011). In univariable Cox regression, age was associated with significantly greater risk of progression (HR: 1.2, p = 0.028). This remained significant in multivariable analysis after adjusting for tumor volume and tumor type (primary vs. recurrent) (HR: 1.2, p = 0.036). Tumor volume, radiation dose, extent of resection, and tumor type were not significantly associated with progression in either analysis.\u003c/p\u003e\n\u003cp\u003eConclusion:\u003c/p\u003e\n\u003cp\u003eOur study provides supporting evidence for the use of GKSRS in achieving long-term tumor control for parasagittal meningiomas, with a tumor control rate of 80.0% and median PFS of 70.6 months. While increased age at the time of radiation and WHO grade appeared to be associated with progression in our analysis, these findings should be interpreted cautiously given the limited sample size. Notably, only 1 case of post-GKSRS edema was observed. These findings reinforce the safety and efficacy of GKSRS for this progression-prone region, though further multi-institutional studies are warranted to validate our results.\u003c/p\u003e","manuscriptTitle":"Long-Term Tumor Control Following Gamma Knife Radiosurgery for Parasagittal Meningiomas: A Single Institution Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-10 11:23:16","doi":"10.21203/rs.3.rs-6824067/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":"e91abbfd-c7b0-4171-8912-43f6b73de0cc","owner":[],"postedDate":"June 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-20T15:38:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-10 11:23:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6824067","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6824067","identity":"rs-6824067","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}