Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma

Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma | 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 Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma In-Ho Jung, Kyung Won Chang, So Hee Park, Hyun Ho Jung, Jong Hee Chang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1417812/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Objective: Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. Methods: This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. Results: After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p=0.009) greater. When a 70% dose volume ≥1 cc was used, the possibility of ITN was 5.892-fold (p<0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months. Conclusions: When performing GKRS in meningioma, a 70% dose volume ≥1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS. radiosurgery gamma knife surgery meningioma intratumoral necrosis peritumoral edema pseudoprogression Figures Figure 1 Figure 2 Figure 3 Introduction Stereotactic radiosurgery is an established treatment and is as applicable to patients with meningioma as surgical resection is. It has the advantages of not requiring general anesthesia, being less invasive, and requiring a shorter hospital stay. Moreover, radiosurgery shows a sufficient local tumor control rate and an acceptable complication rate comparable to resection. 1 – 5 However, peritumoral cerebral edema has been reported as a side effect of stereotactic radiosurgery. 6 – 10 Traditionally, peritumoral edema (PTE) is considered to be caused by radiation-induced injury to the brain parenchyma. However, it is difficult to believe that brain parenchymal injury is caused by the low maximal dose applied to benign tumors, considering that a maximal dose of 130 Gy or more is applied during stereotactic radiosurgical thalamotomy to treat movement disorders. 11 – 13 Therefore, we investigated other mechanisms that might cause PTE to occur in the early postoperative stage. We have experienced many cases of PTE occurring after gamma knife radiosurgery (GKRS) for meningioma. PTE is often accompanied by intratumoral necrosis (ITN), and meningioma with ITN is often accompanied by a transient volume expansion. In this study, we evaluated our experiences statistically to determine whether ITN is a risk factor for PTE when GKRS is performed in patients with meningioma. In addition, we propose evidence of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. Methods The inclusion criteria are as follows; Patients who underwent GKRS for convexity meningioma between January 2019 and December 2020 and who had follow-up MRI to evaluate the perioperative tumor changes. Meningioma with falx, parasaggital, and skull base locations were excluded from this retrospective study. We evaluated risk factors for ITN and PTE by analyzing the demographics, tumor characteristics, and radiosurgical prescription parameters of the patients. In addition, the tumor volumes before GKRS, and postoperatively after 6 and 12 months, were measured to chart the natural course of the tumor after ITN. This study was conducted in accordance with the Declaration of Helsinki and was approved by Institutional Review Board of Severance hospital (4-2021-1190). The requirement to obtain written consent from the patients was waived because this was a retrospective study. Gamma knife radiosurgery On the day of treatment, each patient was affixed with the Leksell stereotactic frame G (Elekta Instruments AB; Stockholm, Sweden) and administered local anesthesia. After the stereotactic frame was fixed to the head, the patients underwent magnetic resonance imaging (MRI; 1.5 Tesla Philips Achieva). The MRI for GKRS included gadolinium-enhanced T1-weighted image with a slice thickness of 1.5 mm and T2-weighted image with a slice thickness of 2.5 mm. Radiosurgical planning was performed using Leksell Gamma Plan version 11.1.0, and the radiosurgery was performed using the Leksell Gamma Knife Perfexion Unit (Elekta AB, Elekta Company; Stockholm, Sweden). The prescription dose was 14 Gy with a median 50% isodose line. However, for large tumors that exceeded 10 cc, the prescription dose could be lowered to 13 Gy at the discretion of the neurosurgeon. As radiosurgical prescription parameters, the 50% marginal dose, coverage, selectivity, gradient index, and 70% dose volume were investigated. Coverage was defined as the fraction of the tumor volume within the prescribed isodose volume. Selectivity was defined as the fraction of the prescribed isodose volume within the tumor volume. The gradient index was defined as the volume ratio of half the prescribed isodose to the total prescription isodose. The 70% dose volume was defined as the tumor volume that received 70% of the maximal dose. Neuroimaging work-up All patients underwent MRI with gadolinium enhancement before the GKRS, and we determined the tumor characteristics based on this MRI. After GKRS, the patients were scheduled for clinical evaluation and postoperative MRI at 6 and 12 months. In addition, we performed an MRI exam whenever a patient showed neurological deterioration after GKRS. The tumor characteristics included the tumor volume, PTE, ITN, brain–tumor contact-surface index, and tumor/cerebellar peduncle T2-weighted imaging intensity (TCTI) ratio. As described by Hwang et al., 14 the brain–tumor contact-surface index was defined as the ratio of the tumor base length (dural side) and tumor dome length (parenchymal side) on an MRI slide that showed the maximum cross-sectional area of the tumor. To evaluate tumor consistency, TCTI ratios were calculated according to Smith et al. using T2-weighted MRIs. 15 – 18 The TCTI ratio was defined as the average intensity value in the tumor region of interest divided by the average intensity value in the ROI drawn within the cerebellar peduncle. ITN was defined as newly developed necrosis within a tumor, or aggravation of pre-existing necrosis, on T1-weighted images obtained after GKRS. PTE was defined as a newly developed high-signal change around a tumor, or aggravation of pre-existing PTE, on T2-weighted images obtained after GKRS. Statistical analysis All statistical analyses were performed using IBM SPSS Statistics (Version 25.0; IBM; Armonk, NY, USA). The risk factors for PTE and ITN were analyzed using logistic regression analysis. Analysis of variance (ANOVA) was performed to determine whether changes in tumor volume were statistically significant. P -values < 0.05 were considered statistically significant. Results Demographics and tumor characteristics Between January 2019 and December 2020, 127 patients underwent GKRS for convexity meningioma in our institution. Their mean age was 59.6 years. The average volume of the tumors was 1.7 cc. The details of the demographics and the tumor characteristics of the patients are presented in Table 1 . Table 1 Demographics and tumor characteristics Characteristics N = 127 Sex Female 108 (85.0%) Male 19 (15.0%) Age (years) 59.6 ± 10.3 Tumor volume, preoperative (cc) 1.7 ± 1.8 TCTI 1.4 ± 0.4 Brain-tumor contact-surface index 0.56 ± 0.13 Peritumoral edema, preoperative 3 (2.4%) TCTI = tumor/cerebellar peduncle T2-weighted imaging intensity Radiosurgical prescription parameters There were 125 (98.4%) patients who had 14 Gy prescribed as the 50% marginal dose. The mean coverage was 98.1 ± 2.7%, the mean selectivity was 70.7 ± 12.5%, and the mean gradient index was 2.76 ± 0.18. The average 70% dose volume was 0.9 ± 0.9 cc, and the average 70% dose ratio was 55.6 ± 8.5%. The radiosurgical prescription parameters are shown in Table 2 . Table 2 Radiosurgical prescription parameters Characteristics N = 127 50% Marginal dose (Gy) 14.0 125 (98.4%) 13.5 1 (0.8%) 13.0 1 (0.8%) Coverage (%) 98.1 ± 2.7 Selectivity (%) 70.7 ± 12.5 Gradient index 2.76 ± 0.18 70% dose volume (cc) 0.9 ± 0.9 70% dose ratio (%) 55.6 ± 8.5 Radiosurgical outcomes Following GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. The tumor volumes measured in the first follow-up MRI had decreased by 0.6% in the absence of ITN but increased by 24.5% in the presence of ITN. The details of the radiosurgical outcomes are shown in Table 3 . Table 3 Radiosurgical outcomes Variables N = 127 Intratumoral necrosis, postoperative 34 (26.8%) Tumor volume change (%) Intratumoral necrosis, Yes 24.5 ± 22.3 Intratumoral necrosis, No −0.6 ± 21.5 Peritumoral edema, postoperative 10 (7.9%) TCTI = tumor/cerebellar peduncle T2-weighted imaging intensity Risk factors for postoperative peritumoral edema To identify risk factors of postoperative PTE, univariable and multivariable logistic regression analyses were performed (Table 4 ). In the univariable logistic regression analysis, the variables whose p -values were < 0.100 included a preoperative tumor volume ≥ 3 cc (Odds ratio [OR]: 6.424, 95% confidence interval [CI]: 1.570–26.294; p = 0.010), preoperative PTE (OR: 29.000, 95% CI: 2.368–355.096; p = 0.008), postoperative ITN (OR: 33.120, 95% CI: 4.004–273.933; p = 0.001), selectivity ≥ 70% (OR: 6.485, 95% CI: 0.795–52.874; p = 0.081), and 70% dose volume ≥ 1 cc (OR: 4.350, 95% CI: 1.149–16.472; p = 0.030). Multivariate logistic regression analysis was performed using these five variables. The only variable showing a significant difference was the presence of postoperative ITN. When postoperative ITN occurred following GKRS, the incidence of postoperative PTE showed an 18.970-fold increase (95% CI: 2.111–170.497; p = 0.009). The model results had a Nagelkerke R-squared value of 0.419, which suggests that the model explained 41.9% of the variation in the outcome. The Hosmer–Lemeshow test of the goodness of fit suggested that the model was a good fit to the data, since p = 0.131 ( p > 0.05). Table 4 Univariable and multivariable logistic regression analyses for postoperative peritumoral edema Variables Univariable Multivariable OR (95% CI) p OR (95% CI) p Sex Female 1.000 (-) - Male 2.705 (0.634–11.553) 0.179 Age (years) 1.043 (0.976–1.115) 0.213 < 60 1.000 (-) ≥ 60 2.294 (0.566–9.304) 0.245 Tumor volume, preoperative (cc) < 3 1.000 (-) ≥ 3 6.424 (1.570–26.294) 0.010 4.221 (0.799–22.305) 0.090 TCTI < 1.5 1.000 (-) ≥ 1.5 2.343 (0.638–8.607) 0.200 Brain-tumor contact-surface index < 0.5 1.000 (-) ≥ 0.5 1.639 (0.331–8.116) 0.545 Peritumoral edema, preoperative 29.000 (2.368–355.096) 0.008 11.662 (0.814–167.022) 0.070 Intratumoral necrosis, postoperative 33.120 (4.004–273.933) 0.001 18.970 (2.111–170.497) 0.009 Coverage < 95% 1.000 (-) - ≥ 95% 1.125 (0.132–9.609) 0.914 Selectivity < 70% 1.000 (-) - 1.000 (-) - ≥ 70% 6.485 (0.795–52.874) 0.081 3.979 (0.309–51.249) 0.290 Gradient index < 2.70 1.000 (-) - ≥ 2.70 0.625 (0.171–2.280) 0.477 70% dose volume < 1cc 1.000 (-) - 1.000 (-) - ≥ 1cc 4.350 (1.149–16.472) 0.030 0.536 (0.059–4.828) 0.578 70% dose ratio < 50% 1.000 (-) - ≥ 50% 1.639 (0.331–8.116) 0.545 TCTI = tumor/cerebellar peduncle T2-weighted imaging intensity; OR = odds ratio; CI = confidence interval Risk factors for intratumoral necrosis To identify factors that could help predict postoperative ITN, univariable and multivariable logistic regression analyses were performed (Table 5 ). In the univariable logistic regression analysis, the variables whose p -value were < 0.100 were a preoperative tumor volume ≥ 3 cc (OR: 5.220, 95% CI: 1.695–16.073; p = 0.004), selectivity ≥ 70% (OR: 2.676, 95% CI: 1.097–6.527; p = 0.030), gradient index ≥ 2.7 (OR: 0.333, 95% CI: 0.148–0.749; p = 0.008), and 70% dose volume ≥ 1 cc (OR: 6.875, 95% CI: 2.881–16.406; p < 0.001). Multivariate logistic regression analysis was performed using these four variables. The only variable that showed a significant difference was having a 70% dose volume ≥ 1 cc. When the 70% dose volume was ≥ 1 cc, the incidence of ITN showed a 5.892-fold increase (95% CI: 2.420–14.349; p < 0.001). The model results had a Nagelkerke R-squared value of 0.242, which suggests that the model explained 24.2% of the variation in the outcome. The Hosmer–Lemeshow test of the goodness of fit suggested the model was a good fit to the data, since p = 0.947 ( p > 0.05). Table 5 Univariable and multivariable logistic regression analyses for intratumoral necrosis Variables Univariable Multivariable OR (95% CI) p OR (95% CI) p Sex Female 1.000 (-) - Male 2.294 (0.834–6.310) 0.108 Age (years) < 60 1.000 (-) - ≥ 60 1.460 (0.659–3.232) 0.351 Tumor volume, preoperative (cc) < 3 1.000 (-) - ≥ 3 5.220 (1.695–16.073) 0.004 1.118 (0.281–4.452) 0.874 TCTI < 1.5 1.000 (-) - ≥ 1.5 1.055 (0.455–2.449) 0.900 Coverage < 95% 1.000 (-) - ≥ 95% 1.386 (0.362–5.304) 0.633 Selectivity < 70% 1.000 (-) - 1.000 (-) - ≥ 70% 2.676 (1.097–6.527) 0.030 1.011 (0.969–1.056) 0.603 Gradient index < 2.70 1.000 (-) - 1.000 (-) - ≥ 2.70 0.333 (0.148–0.749) 0.008 0.454 (0.188–1.094) 0.078 70% dose volume < 1cc 1.000 (-) - 1.000 (-) - ≥ 1cc 6.875 (2.881–16.406) < 0.001 5.892 (2.420–14.349) < 0.001 70% dose ratio < 50% 1.000 (-) - ≥ 50% 0.531 (0.230–1.226) 0.138 TCTI = tumor/cerebellar peduncle T2-weighted imaging intensity; OR = odds ratio; CI = confidence interval In addition, a dural, arachnoid, or pial enhancement around the tumor was observed in 16 (47.1%) of the 34 patients with meningioma exhibiting ITN (Fig. 1 ). However, none of the cases of meningioma without ITN showed a meningeal enhancement. There was a significant difference between the two groups ( p < 0.001); therefore, we suggest that ITN might be associated with meningeal enhancement. Figure 1 shows the changes before and after GKRS for 4 cases of ITN without PTE and 2 cases of ITN with PTE. Tumor volume change after gamma knife radiosurgery As shown in Table 3 , the tumor volume was increased at the first follow-up in cases with ITN but not in cases without ITN. Based on the preoperative tumor volumes of the 34 meningiomas with ITN, the mean postoperative tumor volumes at 6 and 12 months were 128.5% and 94.6%, respectively. There were statistically significant differences between the preoperative tumor volume and the tumor volume at 6 months ( p < 0.001) and between the tumor volumes at 6 and 12 months ( p < 0.001) (Fig. 2 ). Of the 34 patients with ITN, 9 had PTE; 6 patients with PTE were asymptomatic, and only 3 patients with PTE showed neurological symptoms. In all patients, the symptoms and PTE improved at 6 months after conservative treatment. Discussion This study on the occurrence of ITN and PTE following GKRS treatment for meningioma had two important findings. First, the study elucidated the natural course of meningioma with ITN after GKRS and presented evidence of pseudoprogression. Although pseudoprogression after radiosurgery in vestibular schwannoma has been reported previously, 19 – 22 pseudoprogression after radiosurgery in meningioma is a novel finding. By 6 months after GKRS, the meningiomas with ITN had increased in volume by an average of 128.5% and were associated with meningeal enhancement and a risk of PTE. However, by 12 months after the GKRS, the ITN had disappeared, the volume had decreased to 94.6%, and the PTE and meningeal enhancement had improved (Fig. 2 ). Therefore, a volume expansion accompanied by ITN within 12 months after GKRS for meningioma is likely to be pseudoprogression, which can be treated conservatively rather than by immediate surgical resection. Second, our study found that the presence of ITN at 6 months after GKRS for meningioma was a risk factor for PTE, and that ITN was associated with a 70% dose volume. Previously, some articles have identified ITN as a risk factor for PTE. 9 , 23 Chen et al. presented two cases of meningioma after GKRS that were complicated with ITN and PTE. 9 Lee et al. argued that the maximum dose and target volume were significantly related to ITN, and that ITN and the maximum dose were significantly related to the development or aggravation of PTE. 23 In our study, we could not evaluate the effect of maximal dose on PTE, because most of the patients (98.4%) had the same prescription dose (14 Gy 50% marginal dose). However, our finding that ITN is significantly correlated to PTE is consistent with and confirms previous reports. Therefore, our study is the first large-scale study to verify that ITN is a significant risk factor for PTE. In addition, we identified that a 70% dose volume > 1 cc is a risk factor for ITN, which can subsequently lead to PTE (Fig. 3 ). Although vasogenic edema is a major component of PTE in meningioma, cytotoxic edema is known to contribute to PTE as well. 24 – 26 It is known that the presence of PTE is strongly correlated with the expression of vascular endothelial growth factor (VEGF) within a meningioma. 26 – 29 Some argue that there is also a significant correlation between matrix metalloproteinase 9 (MMP-9) and the presence of PTE. 30 , 31 Such a protein-based pathophysiology for PTE would necessitate a partial breakdown of the tumor–brain interface. 26 , 32 Based on our findings, we suggest that ITN triggered by GKRS may play a role in the breakdown. After GKRS for meningioma, PTE is a relatively common radiation-induced complication, and there have been many reports of PTE following GKRS. The incidence of symptomatic PTE after GKRS for meningioma has been reported as 5–11%, 33–37 whereas all PTE is 13–28%. 23,34,36−39 Our study showed a lower incidence of PTE than previously reported (2.4% for symptomatic PTE and 7.9% for all PTE). This low incidence of PTE is probably due to the nature of the tumors included in our study. It is already widely known that tumor volume and size are significant factors for PTE after GKRS for meningioma. 33–37,40−43 Although the tumor volume did not show statistical significance in our study, we do not deny that tumor volume is a significant factor for PTE after GKRS. Since the meningiomas included in our study were mostly small tumors (88.2% were < 3 cc), it is possible that the influence of tumor volume was underestimated. While some studies claim that tumor location is a risk factor for PTE, 42 , 44 others argue the opposite. 40 , 41 , 45 Meningiomas differ in growth patterns and tumor shape depending on location. The contact area between the tumor and the brain parenchyma varies depending on the tumor shape. Studies on meningioma show that the ratio of the dural base area to the brain parenchymal contact area affects the radiosurgical outcome. 14,37,46−50 Therefore, in this study, we limited the study subject to convexity meningioma in order to remove the tumor location as a confounding variable and focus on the radiosurgical prescription parameters that we could control. In our study, only 3 of 9 patients who had PTE with ITN showed neurological symptoms, and the symptoms disappeared after 6 months in all patients. Therefore, neurosurgeons should reassure their patients by providing sufficient explanations to patients with a high risk for PTE with ITN. We faced certain limitations during the course of this study. This study was limited by its retrospective study design. Despite being the largest study regarding the occurrence of ITN after GKRS for meningioma, our study was conducted using a small sample size. In our study, only follow-up MRIs at 6 and 12 months after GKRS were included in the study. Further studies might elucidate the longer-term natural course of meningioma with ITN through long-term follow-up. Conclusions When performing GKRS for meningioma, a 70% dose volume ≥ 1 cc is a risk factor for ITN. At 6 months after GKRS, meningioma with ITN is accompanied by a transient volume increase and PTE, which are characteristics of pseudoprogression. These characteristics improve at 12 months after GKRS. This study should help neurosurgeons plan and treat meningiomas using GKRS. Declarations This article has not been previously published in whole or in part or submitted elsewhere for review. Funding This research was funded by the Korea Medical Device Development Fund (KMDF_PR_20200901_0103) Conflicts of interest The authors have nothing to disclose. Acknowledgements The authors thank Ji Hyoun An, RN, MSN, and Gi Hong Kim, MS for their tremendous effort in Gamma knife center of Severance hospital. And the authors thank the Medical Illustration and Design team of the Medical Research Support Services of Yonsei University College of Medicine for providing excellent support with medical illustration. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki and was approved by Institutional Review Board of Severance hospital, waving the patient's written consent as a retrospective study (4-2021-1190). The requirement for obtaining patient's written consent was waived as this was a retrospective study. Data availability The datasets used and analyzed during the current study available from the corresponding author on reasonable request. References Ding, D., Xu, Z., McNeill, I. T., Yen, C. P. & Sheehan, J. P. Radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg 119 , 871–877, doi: 10.3171/2013.6.Jns13110 (2013). Kollová, A. et al. Gamma Knife surgery for benign meningioma. J Neurosurg 107 , 325–336, doi: 10.3171/jns-07/08/0325 (2007). Kondziolka, D. et al. Radiosurgery as definitive management of intracranial meningiomas. Neurosurgery 62 , 53–58; discussion 58–60, doi: 10.1227/01.Neu.0000311061.72626.0d (2008). Starke, R. M. et al. Gamma Knife surgery for skull base meningiomas: Clinical article. Journal of Neurosurgery JNS 116 , 588–597, doi: 10.3171/2011.11.Jns11530 (2012). Jang, C. K. et al. Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma. Brain Tumor Res Treat 3 , 103–107, doi: 10.14791/btrt.2015.3.2.103 (2015). Pan, H.-C. et al. Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery. Journal of neurosurgery 109 , 90–98 (2008). Shuto, T., Matsunaga, S., Suenaga, J., Inomori, S. & Fujino, H. Treatment strategy for metastatic brain tumors from renal cell carcinoma: selection of gamma knife surgery or craniotomy for control of growth and peritumoral edema. Journal of neuro-oncology 98 , 169–175 (2010). Sheehan, J. P. et al. Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. Journal of neurosurgery 123 , 1287–1293 (2015). Chen, C.-h. et al. Histopathology of radiation necrosis with severe peritumoral edema after Gamma knife radiosurgery for parasagittal meningioma. Stereotactic and functional neurosurgery 85 , 292–295 (2007). Nundkumar, N., Guthikonda, M. & Mittal, S. Peritumoral edema following Gamma Knife radiosurgery as the primary treatment for intraventricular meningiomas. Journal of Clinical Neuroscience 20 , 616–618 (2013). Kondziolka, D. et al. Gamma Knife thalamotomy for essential tremor. J Neurosurg 108 , 111–117, doi: 10.3171/jns/2008/108/01/0111 (2008). Khattab, M. H. et al. Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery. Int J Radiat Oncol Biol Phys 112 , 121–130, doi: 10.1016/j.ijrobp.2021.08.021 (2022). Ochiai, T. Gamma Knife Thalamotomy for a Medically Refractory Tremors: Longitudinal Evaluation of Clinical Effects and MRI Response Patterns. Acta Neurochir Suppl 128 , 127–132, doi: 10.1007/978-3-030-69217-9_14 (2021). Hwang, K. et al. Seizures After Stereotactic Radiosurgery for Benign Supratentorial Meningiomas: An Uncontrollable Type of Seizure? World Neurosurg 123 , e549-e556, doi: 10.1016/j.wneu.2018.11.211 (2019). Smith, K. A., Leever, J. D. & Chamoun, R. B. Predicting Consistency of Meningioma by Magnetic Resonance Imaging. J Neurol Surg B Skull Base 76 , 225–229 (2015). Smith, K. A., Leever, J. D., Hylton, P. D., Camarata, P. J. & Chamoun, R. B. Meningioma consistency prediction utilizing tumor to cerebellar peduncle intensity on T2-weighted magnetic resonance imaging sequences: TCTI ratio. Journal of Neurosurgery 126 , 242–248, doi: 10.3171/2016.1.JNS152329 (2017). Mastorakos, P. et al. Tumor to Cerebellar Peduncle T2-Weighted Imaging Intensity Ratio Fails to Predict Pituitary Adenoma Consistency. J Neurol Surg B Skull Base 80 , 252–257, doi: 10.1055/s-0038-1668516 (2019). Jung, I. H., Yoo, J., Roh, T. H., Park, H. H. & Hong, C. K. Importance of Sufficient Petrosectomy in an Anterior Petrosal Approach: Relightening of the Kawase Pyramid. World Neurosurg 153 , e11-e19, doi: 10.1016/j.wneu.2021.05.017 (2021). Breshears, J. D. et al. Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study. Neurosurgery 84 , 123–131, doi: 10.1093/neuros/nyy019 (2019). Kim, J. H. et al. Predictive Factors of Unfavorable Events After Gamma Knife Radiosurgery for Vestibular Schwannoma. World Neurosurg 107 , 175–184, doi: 10.1016/j.wneu.2017.07.139 (2017). Hayhurst, C. & Zadeh, G. Tumor pseudoprogression following radiosurgery for vestibular schwannoma. Neuro Oncol 14 , 87–92, doi: 10.1093/neuonc/nor171 (2012). Langenhuizen, P. et al. Prediction of transient tumor enlargement using MRI tumor texture after radiosurgery on vestibular schwannoma. Med Phys 47 , 1692–1701, doi: 10.1002/mp.14042 (2020). Lee, S. R., Yang, K. A., Kim, S. K. & Kim, S.-H. Radiation-Induced Intratumoral Necrosis and Peritumoral Edema after Gamma Knife Radiosurgery for Intracranial Meningiomas. J Korean Neurosurg Soc 52 , 98–102, doi: 10.3340/jkns.2012.52.2.98 (2012). Gurkanlar, D., Er, U., Sanli, M., Ozkan, M. & Sekerci, Z. Peritumoral brain edema in intracranial meningiomas. J Clin Neurosci 12 , 750–753, doi: 10.1016/j.jocn.2004.09.029 (2005). Yoshioka, H. et al. Peritumoral brain edema associated with meningioma: influence of vascular endothelial growth factor expression and vascular blood supply. Cancer 85 , 936–944, doi: 10.1002/(sici)1097-0142(19990215)85:43.0.co;2-j (1999). Reszec, J. et al. Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema. BioMed Research International 2015, 646853, doi: 10.1155/2015/646853 (2015). Nassehi, D. Intracranial meningiomas, the VEGF-A pathway, and peritumoral brain oedema. Dan Med J 60 , B4626 (2013). Hou, J., Kshettry, V. R., Selman, W. R. & Bambakidis, N. C. Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy. Neurosurg Focus 35 , E2, doi: 10.3171/2013.8.Focus13301 (2013). Markovic, M., Antunovic, V., Milenkovic, S. & Zivkovic, N. Prognostic value of peritumoral edema and angiogenesis in intracranial meningioma surgery. J buon 18 , 430–436 (2013). Paek, S. H. et al. The role of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in microcystic meningiomas. Oncol Rep 16 , 49–56 (2006). Jung, S. et al. Increased expression of intracystic matrix metalloproteinases in brain tumors: relationship to the pathogenesis of brain tumor-associated cysts and peritumoral edema. J Clin Neurosci 14 , 1192–1198, doi: 10.1016/j.jocn.2006.11.009 (2007). Ding, Y. S. et al. Expression of vascular endothelial growth factor in human meningiomas and peritumoral brain areas. Ann Clin Lab Sci 38 , 344–351 (2008). Conti, A. et al. Post-Treatment Edema after Meningioma Radiosurgery is a Predictable Complication. Cureus 8 , e605, doi: 10.7759/cureus.605 (2016). Hoe, Y. et al. Peritumoral Brain Edema after Stereotactic Radiosurgery for Asymptomatic Intracranial Meningiomas: Risks and Pattern of Evolution. J Korean Neurosurg Soc 58 , 379–384, doi: 10.3340/jkns.2015.58.4.379 (2015). Kuhn, E. N. et al. Is there a tumor volume threshold for postradiosurgical symptoms? A single-institution analysis. Neurosurgery 75 , 536–545; discussion 544 – 535; quiz 545, doi: 10.1227/neu.0000000000000519 (2014). Unger, K. R. et al. Risk factors for posttreatment edema in patients treated with stereotactic radiosurgery for meningiomas. Neurosurgery 70 , 639–645, doi: 10.1227/NEU.0b013e3182351ae7 (2012). Cai, R., Barnett, G. H., Novak, E., Chao, S. T. & Suh, J. H. Principal risk of peritumoral edema after stereotactic radiosurgery for intracranial meningioma is tumor-brain contact interface area. Neurosurgery 66 , 513–522, doi: 10.1227/01.Neu.0000365366.53337.88 (2010). Mansouri, A. et al. Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas. J Neurosurg 123 , 1294–1300, doi: 10.3171/2014.12.Jns141687 (2015). Park, S. H., Hwang, J. H. & Hwang, S. K. Change in plasma vascular endothelial growth factor after gamma knife radiosurgery for meningioma: a preliminary study. J Korean Neurosurg Soc 57 , 77–81, doi: 10.3340/jkns.2015.57.2.77 (2015). Girvigian, M. R., Chen, J. C., Rahimian, J., Miller, M. J. & Tome, M. Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy. Neurosurgery 62 , A19-27; discussion A27-18, doi: 10.1227/01.neu.0000325933.34154.cb (2008). Sheehan, J. P. et al. Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg 123 , 1287–1293, doi: 10.3171/2014.12.Jns142159 (2015). Sheehan, J. P. et al. Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study. J Neurooncol 125 , 317–324, doi: 10.1007/s11060-015-1911-1 (2015). Novotný, J., Jr., Kollová, A. & Liscák, R. Prediction of intracranial edema after radiosurgery of meningiomas. J Neurosurg 105 Suppl , 120–126, doi: 10.3171/sup.2006.105.7.120 (2006). Patil, C. G. et al. Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas. Neurosurgery 63 , 435–440; discussion 440 – 432, doi: 10.1227/01.Neu.0000325257.58684.92 (2008). Kondziolka, D., Flickinger, J. C. & Perez, B. Judicious resection and/or radiosurgery for parasagittal meningiomas: outcomes from a multicenter review. Gamma Knife Meningioma Study Group. Neurosurgery 43 , 405–413; discussion 413 – 404, doi: 10.1097/00006123-199809000-00001 (1998). Chang, J. H., Chang, J. W., Choi, J. Y., Park, Y. G. & Chung, S. S. Complications after gamma knife radiosurgery for benign meningiomas. J Neurol Neurosurg Psychiatry 74 , 226–230, doi: 10.1136/jnnp.74.2.226 (2003). Hasegawa, T. et al. Gamma knife surgery for convexity, parasagittal, and falcine meningiomas: Clinical article. Journal of Neurosurgery 114 , 1392–1398, doi: 10.3171/2010.11.JNS10112 (2011). Novotný Jr, J., Kollová, A. & Liscák, R. Prediction of intracranial edema after radiosurgery of meningiomas. Journal of neurosurgery 105 Suppl , 120–126, doi: 10.3171/sup.2006.105.7.120 (2006). Rogers, L. & Mehta, M. Role of radiation therapy in treating intracranial meningiomas. Neurosurgical focus 23 , doi: 10.3171/FOC-07/10/E4 (2007). Sheehan, J. P. et al. Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. Journal of Neurosurgery 123 , 1287–1293, doi: 10.3171/2014.12.JNS142159 (2015). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 23 Jun, 2022 Reviews received at journal 02 Jun, 2022 Reviewers agreed at journal 27 May, 2022 Reviewers invited by journal 27 May, 2022 Editor assigned by journal 27 May, 2022 Editor invited by journal 08 Mar, 2022 Submission checks completed at journal 08 Mar, 2022 First submitted to journal 04 Mar, 2022 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-1417812","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":89245851,"identity":"6b7bb158-132a-4461-9fbb-51c2a63cc38b","order_by":0,"name":"In-Ho Jung","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"In-Ho","middleName":"","lastName":"Jung","suffix":""},{"id":89245852,"identity":"1f86edac-b340-4bb1-aa59-2f0cfa891462","order_by":1,"name":"Kyung Won Chang","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kyung","middleName":"Won","lastName":"Chang","suffix":""},{"id":89245853,"identity":"f3368827-b471-4c35-b718-87f3254ae15b","order_by":2,"name":"So Hee Park","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"So","middleName":"Hee","lastName":"Park","suffix":""},{"id":89245854,"identity":"01a768ec-5db9-44b9-815f-75d6d303b3ad","order_by":3,"name":"Hyun Ho Jung","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hyun","middleName":"Ho","lastName":"Jung","suffix":""},{"id":89245855,"identity":"f4a7b639-2279-4335-8ab3-4613f6b132be","order_by":4,"name":"Jong Hee Chang","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jong","middleName":"Hee","lastName":"Chang","suffix":""},{"id":89245856,"identity":"d95a44c5-6851-4d1f-8ab4-6c9fce0adfea","order_by":5,"name":"Jin Woo Chang","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jin","middleName":"Woo","lastName":"Chang","suffix":""},{"id":89245857,"identity":"e2dc2aed-7247-4bbd-91f9-c171a67146b0","order_by":6,"name":"Won Seok Chang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBAC/hmJbRI/2+p47A8zH3zAwHCAsBaJG8nHJXvbDssxHGdLNiBKi0FEWvpsxrYDxgznedQkiNMikWMO0pLY2MzDVs3bdseegf3wA/xa5N+Y3WbcVpfYzMx77DZv27PEBp40A0K2mN2W3cac2MbMlwbUcjiBgSGHkMPyv1XzArX0MPOYFQO12DPwvyGgJSLHzJr3H7OxBFALM1ALY4MEAVskbuSYWfaeOyxnwMyWLDnn3GFgND3D7xf+GTlm4Kg04D988MObssP2/PzJD/BbgwyYeIAEG/HqgYDxB0nKR8EoGAWjYKQAAB9KSzAflVWcAAAAAElFTkSuQmCC","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Won","middleName":"Seok","lastName":"Chang","suffix":""}],"badges":[],"createdAt":"2022-03-04 06:29:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1417812/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1417812/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19127652,"identity":"8083d354-e3b5-4a19-b1aa-9c750fdd9576","added_by":"auto","created_at":"2022-03-11 15:31:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8050081,"visible":true,"origin":"","legend":"\u003cp\u003eChanges occurring before and after GKRS are shown for 4 cases of ITN without PTE (A-L) and 2 cases of ITN with PTE (M-X). All meningiomas with ITN after GKRS show pseudoprogression with a temporary volume expansion on the follow-up MRI at 6 months (B, E, H, K, N, Q, T, W). ITN may accompany meningeal enhancement (arrows) on T1-weighted images and PTE on T2-weighted images (dotted circles). On the follow-up MRI at 12 months, the ITN has disappeared, the volume is reduced, and the enhancement and PTE are improved. GKRS=gamma knife radiosurgery; ITN=intratumoral necrosis; PTE=peritumoral edema; MRI=magnetic resonance imaging.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1417812/v1/636dfcf6305bc66bd3dde092.jpg"},{"id":19128112,"identity":"4f1b5177-0afa-4431-baf3-3f4c02cfd7ee","added_by":"auto","created_at":"2022-03-11 15:34:41","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":984539,"visible":true,"origin":"","legend":"\u003cp\u003eAt 6 months after GKRS, the meningiomas with ITN have increased in volume by an average of 128.5%. And the tumors have a risk of PTE and meningeal enhancement (C). There is a statistically significant difference between the preoperative tumor volume and the tumor volume at 6 months (A, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). However, by 12 months after the GKRS, the ITN has disappeared, and the volume is decreased to 94.6%. The PTE and meningeal enhancement also have disappeared (D). There is a statistically significant difference between the tumor volumes at 6 and 12 months (A, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). GKRS=gamma knife radiosurgery; ITN=intratumoral necrosis; PTE=peritumoral edema.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1417812/v1/74ea5ee67a2e9e11f534cc17.jpg"},{"id":19127650,"identity":"a8a01d25-e1f5-488e-b85a-a5f07f81213a","added_by":"auto","created_at":"2022-03-11 15:31:41","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":224171,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the progression from a 70% dose volume to ITN to PTE. We identified a 70% dose volume \u0026gt;1 cc as a risk factor for ITN, and ITN as a risk factor for PTE. ITN=intratumoral necrosis; PTE=peritumoral edema.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1417812/v1/e90b4e99f64d81988f9605a1.jpg"},{"id":19128113,"identity":"43c93b98-6cd7-4b26-9198-f3c442718071","added_by":"auto","created_at":"2022-03-11 15:34:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":726635,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1417812/v1/153aa09d-8b51-4b2f-a7a4-7f3d9c24d38f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStereotactic radiosurgery is an established treatment and is as applicable to patients with meningioma as surgical resection is. It has the advantages of not requiring general anesthesia, being less invasive, and requiring a shorter hospital stay. Moreover, radiosurgery shows a sufficient local tumor control rate and an acceptable complication rate comparable to resection.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHowever, peritumoral cerebral edema has been reported as a side effect of stereotactic radiosurgery.\u003csup\u003e\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Traditionally, peritumoral edema (PTE) is considered to be caused by radiation-induced injury to the brain parenchyma. However, it is difficult to believe that brain parenchymal injury is caused by the low maximal dose applied to benign tumors, considering that a maximal dose of 130 Gy or more is applied during stereotactic radiosurgical thalamotomy to treat movement disorders.\u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Therefore, we investigated other mechanisms that might cause PTE to occur in the early postoperative stage.\u003c/p\u003e \u003cp\u003eWe have experienced many cases of PTE occurring after gamma knife radiosurgery (GKRS) for meningioma. PTE is often accompanied by intratumoral necrosis (ITN), and meningioma with ITN is often accompanied by a transient volume expansion. In this study, we evaluated our experiences statistically to determine whether ITN is a risk factor for PTE when GKRS is performed in patients with meningioma. In addition, we propose evidence of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe inclusion criteria are as follows; Patients who underwent GKRS for convexity meningioma between January 2019 and December 2020 and who had follow-up MRI to evaluate the perioperative tumor changes. Meningioma with falx, parasaggital, and skull base locations were excluded from this retrospective study. We evaluated risk factors for ITN and PTE by analyzing the demographics, tumor characteristics, and radiosurgical prescription parameters of the patients. In addition, the tumor volumes before GKRS, and postoperatively after 6 and 12 months, were measured to chart the natural course of the tumor after ITN. This study was conducted in accordance with the Declaration of Helsinki and was approved by Institutional Review Board of Severance hospital (4-2021-1190). The requirement to obtain written consent from the patients was waived because this was a retrospective study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eGamma knife radiosurgery\u003c/h2\u003e \u003cp\u003eOn the day of treatment, each patient was affixed with the Leksell stereotactic frame G (Elekta Instruments AB; Stockholm, Sweden) and administered local anesthesia. After the stereotactic frame was fixed to the head, the patients underwent magnetic resonance imaging (MRI; 1.5 Tesla Philips Achieva). The MRI for GKRS included gadolinium-enhanced T1-weighted image with a slice thickness of 1.5 mm and T2-weighted image with a slice thickness of 2.5 mm. Radiosurgical planning was performed using Leksell Gamma Plan version 11.1.0, and the radiosurgery was performed using the Leksell Gamma Knife Perfexion Unit (Elekta AB, Elekta Company; Stockholm, Sweden). The prescription dose was 14 Gy with a median 50% isodose line. However, for large tumors that exceeded 10 cc, the prescription dose could be lowered to 13 Gy at the discretion of the neurosurgeon.\u003c/p\u003e \u003cp\u003eAs radiosurgical prescription parameters, the 50% marginal dose, coverage, selectivity, gradient index, and 70% dose volume were investigated. Coverage was defined as the fraction of the tumor volume within the prescribed isodose volume. Selectivity was defined as the fraction of the prescribed isodose volume within the tumor volume. The gradient index was defined as the volume ratio of half the prescribed isodose to the total prescription isodose. The 70% dose volume was defined as the tumor volume that received 70% of the maximal dose.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eNeuroimaging work-up\u003c/h2\u003e \u003cp\u003eAll patients underwent MRI with gadolinium enhancement before the GKRS, and we determined the tumor characteristics based on this MRI. After GKRS, the patients were scheduled for clinical evaluation and postoperative MRI at 6 and 12 months. In addition, we performed an MRI exam whenever a patient showed neurological deterioration after GKRS. The tumor characteristics included the tumor volume, PTE, ITN, brain\u0026ndash;tumor contact-surface index, and tumor/cerebellar peduncle T2-weighted imaging intensity (TCTI) ratio. As described by Hwang et al.,\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e the brain\u0026ndash;tumor contact-surface index was defined as the ratio of the tumor base length (dural side) and tumor dome length (parenchymal side) on an MRI slide that showed the maximum cross-sectional area of the tumor. To evaluate tumor consistency, TCTI ratios were calculated according to Smith et al. using T2-weighted MRIs.\u003csup\u003e\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The TCTI ratio was defined as the average intensity value in the tumor region of interest divided by the average intensity value in the ROI drawn within the cerebellar peduncle.\u003c/p\u003e \u003cp\u003eITN was defined as newly developed necrosis within a tumor, or aggravation of pre-existing necrosis, on T1-weighted images obtained after GKRS. PTE was defined as a newly developed high-signal change around a tumor, or aggravation of pre-existing PTE, on T2-weighted images obtained after GKRS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics (Version 25.0; IBM; Armonk, NY, USA). The risk factors for PTE and ITN were analyzed using logistic regression analysis. Analysis of variance (ANOVA) was performed to determine whether changes in tumor volume were statistically significant. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDemographics and tumor characteristics\u003c/h2\u003e \u003cp\u003eBetween January 2019 and December 2020, 127 patients underwent GKRS for convexity meningioma in our institution. Their mean age was 59.6 years. The average volume of the tumors was 1.7 cc. The details of the demographics and the tumor characteristics of the patients are presented in 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\u003eDemographics and tumor characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;127\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e108 (85.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor volume, preoperative\u003c/b\u003e (cc)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCTI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBrain-tumor contact-surface index\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeritumoral edema, preoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eTCTI\u0026thinsp;=\u0026thinsp;tumor/cerebellar peduncle T2-weighted imaging intensity\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRadiosurgical prescription parameters\u003c/h2\u003e \u003cp\u003eThere were 125 (98.4%) patients who had 14 Gy prescribed as the 50% marginal dose. The mean coverage was 98.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7%, the mean selectivity was 70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5%, and the mean gradient index was 2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18. The average 70% dose volume was 0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 cc, and the average 70% dose ratio was 55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5%. The radiosurgical prescription parameters are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\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\u003eRadiosurgical prescription parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;127\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003e50% Marginal dose\u003c/b\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125 (98.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoverage\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelectivity\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGradient index\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e70% dose volume\u003c/b\u003e (cc)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e70% dose ratio\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eRadiosurgical outcomes\u003c/h2\u003e \u003cp\u003eFollowing GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. The tumor volumes measured in the first follow-up MRI had decreased by 0.6% in the absence of ITN but increased by 24.5% in the presence of ITN. The details of the radiosurgical outcomes are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRadiosurgical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;127\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntratumoral necrosis, postoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (26.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor volume change\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntratumoral necrosis, Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntratumoral necrosis, No\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;21.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeritumoral edema, postoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eTCTI\u0026thinsp;=\u0026thinsp;tumor/cerebellar peduncle T2-weighted imaging intensity\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eRisk factors for postoperative peritumoral edema\u003c/h2\u003e \u003cp\u003eTo identify risk factors of postoperative PTE, univariable and multivariable logistic regression analyses were performed (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In the univariable logistic regression analysis, the variables whose \u003cem\u003ep\u003c/em\u003e-values were \u0026lt;\u0026thinsp;0.100 included a preoperative tumor volume\u0026thinsp;\u0026ge;\u0026thinsp;3 cc (Odds ratio [OR]: 6.424, 95% confidence interval [CI]: 1.570\u0026ndash;26.294; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010), preoperative PTE (OR: 29.000, 95% CI: 2.368\u0026ndash;355.096; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), postoperative ITN (OR: 33.120, 95% CI: 4.004\u0026ndash;273.933; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), selectivity\u0026thinsp;\u0026ge;\u0026thinsp;70% (OR: 6.485, 95% CI: 0.795\u0026ndash;52.874; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.081), and 70% dose volume\u0026thinsp;\u0026ge;\u0026thinsp;1 cc (OR: 4.350, 95% CI: 1.149\u0026ndash;16.472; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030). Multivariate logistic regression analysis was performed using these five variables. The only variable showing a significant difference was the presence of postoperative ITN. When postoperative ITN occurred following GKRS, the incidence of postoperative PTE showed an 18.970-fold increase (95% CI: 2.111\u0026ndash;170.497; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009). The model results had a Nagelkerke R-squared value of 0.419, which suggests that the model explained 41.9% of the variation in the outcome. The Hosmer\u0026ndash;Lemeshow test of the goodness of fit suggested that the model was a good fit to the data, since \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.131 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable and multivariable logistic regression analyses for postoperative peritumoral edema\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.705 (0.634\u0026ndash;11.553)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.043 (0.976\u0026ndash;1.115)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.294 (0.566\u0026ndash;9.304)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor volume, preoperative\u003c/b\u003e (cc)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.424 (1.570\u0026ndash;26.294)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.221 (0.799\u0026ndash;22.305)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCTI\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.343 (0.638\u0026ndash;8.607)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBrain-tumor contact-surface index\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.639 (0.331\u0026ndash;8.116)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeritumoral edema, preoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.000 (2.368\u0026ndash;355.096)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.662 (0.814\u0026ndash;167.022)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntratumoral necrosis, postoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.120 (4.004\u0026ndash;273.933)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.970 (2.111\u0026ndash;170.497)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoverage\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.125 (0.132\u0026ndash;9.609)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelectivity\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.485 (0.795\u0026ndash;52.874)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.081\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.979 (0.309\u0026ndash;51.249)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGradient index\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.625 (0.171\u0026ndash;2.280)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e70% dose volume\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.350 (1.149\u0026ndash;16.472)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.536 (0.059\u0026ndash;4.828)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.578\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e70% dose ratio\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.639 (0.331\u0026ndash;8.116)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTCTI\u0026thinsp;=\u0026thinsp;tumor/cerebellar peduncle T2-weighted imaging intensity; OR\u0026thinsp;=\u0026thinsp;odds ratio; CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRisk factors for intratumoral necrosis\u003c/h2\u003e \u003cp\u003eTo identify factors that could help predict postoperative ITN, univariable and multivariable logistic regression analyses were performed (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). In the univariable logistic regression analysis, the variables whose \u003cem\u003ep\u003c/em\u003e-value were \u0026lt;\u0026thinsp;0.100 were a preoperative tumor volume\u0026thinsp;\u0026ge;\u0026thinsp;3 cc (OR: 5.220, 95% CI: 1.695\u0026ndash;16.073; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), selectivity\u0026thinsp;\u0026ge;\u0026thinsp;70% (OR: 2.676, 95% CI: 1.097\u0026ndash;6.527; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030), gradient index\u0026thinsp;\u0026ge;\u0026thinsp;2.7 (OR: 0.333, 95% CI: 0.148\u0026ndash;0.749; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), and 70% dose volume\u0026thinsp;\u0026ge;\u0026thinsp;1 cc (OR: 6.875, 95% CI: 2.881\u0026ndash;16.406; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate logistic regression analysis was performed using these four variables. The only variable that showed a significant difference was having a 70% dose volume\u0026thinsp;\u0026ge;\u0026thinsp;1 cc. When the 70% dose volume was \u0026ge;\u0026thinsp;1 cc, the incidence of ITN showed a 5.892-fold increase (95% CI: 2.420\u0026ndash;14.349; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The model results had a Nagelkerke R-squared value of 0.242, which suggests that the model explained 24.2% of the variation in the outcome. The Hosmer\u0026ndash;Lemeshow test of the goodness of fit suggested the model was a good fit to the data, since \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.947 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable and multivariable logistic regression analyses for intratumoral necrosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.294 (0.834\u0026ndash;6.310)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.460 (0.659\u0026ndash;3.232)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor volume, preoperative\u003c/b\u003e (cc)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.220 (1.695\u0026ndash;16.073)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.118 (0.281\u0026ndash;4.452)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCTI\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.055 (0.455\u0026ndash;2.449)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoverage\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.386 (0.362\u0026ndash;5.304)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelectivity\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.676 (1.097\u0026ndash;6.527)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.011 (0.969\u0026ndash;1.056)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGradient index\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.333 (0.148\u0026ndash;0.749)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.454 (0.188\u0026ndash;1.094)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e70% dose volume\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.875 (2.881\u0026ndash;16.406)\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 \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.892 (2.420\u0026ndash;14.349)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003cb\u003e70% dose ratio\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.000 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.531 (0.230\u0026ndash;1.226)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTCTI\u0026thinsp;=\u0026thinsp;tumor/cerebellar peduncle T2-weighted imaging intensity; OR\u0026thinsp;=\u0026thinsp;odds ratio; CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, a dural, arachnoid, or pial enhancement around the tumor was observed in 16 (47.1%) of the 34 patients with meningioma exhibiting ITN (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, none of the cases of meningioma without ITN showed a meningeal enhancement. There was a significant difference between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); therefore, we suggest that ITN might be associated with meningeal enhancement. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the changes before and after GKRS for 4 cases of ITN without PTE and 2 cases of ITN with PTE.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTumor volume change after gamma knife radiosurgery\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the tumor volume was increased at the first follow-up in cases with ITN but not in cases without ITN. Based on the preoperative tumor volumes of the 34 meningiomas with ITN, the mean postoperative tumor volumes at 6 and 12 months were 128.5% and 94.6%, respectively. There were statistically significant differences between the preoperative tumor volume and the tumor volume at 6 months (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and between the tumor volumes at 6 and 12 months (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the 34 patients with ITN, 9 had PTE; 6 patients with PTE were asymptomatic, and only 3 patients with PTE showed neurological symptoms. In all patients, the symptoms and PTE improved at 6 months after conservative treatment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study on the occurrence of ITN and PTE following GKRS treatment for meningioma had two important findings. First, the study elucidated the natural course of meningioma with ITN after GKRS and presented evidence of pseudoprogression. Although pseudoprogression after radiosurgery in vestibular schwannoma has been reported previously,\u003csup\u003e\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e pseudoprogression after radiosurgery in meningioma is a novel finding. By 6 months after GKRS, the meningiomas with ITN had increased in volume by an average of 128.5% and were associated with meningeal enhancement and a risk of PTE. However, by 12 months after the GKRS, the ITN had disappeared, the volume had decreased to 94.6%, and the PTE and meningeal enhancement had improved (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Therefore, a volume expansion accompanied by ITN within 12 months after GKRS for meningioma is likely to be pseudoprogression, which can be treated conservatively rather than by immediate surgical resection.\u003c/p\u003e \u003cp\u003eSecond, our study found that the presence of ITN at 6 months after GKRS for meningioma was a risk factor for PTE, and that ITN was associated with a 70% dose volume. Previously, some articles have identified ITN as a risk factor for PTE.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Chen et al. presented two cases of meningioma after GKRS that were complicated with ITN and PTE.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Lee et al. argued that the maximum dose and target volume were significantly related to ITN, and that ITN and the maximum dose were significantly related to the development or aggravation of PTE.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e In our study, we could not evaluate the effect of maximal dose on PTE, because most of the patients (98.4%) had the same prescription dose (14 Gy 50% marginal dose). However, our finding that ITN is significantly correlated to PTE is consistent with and confirms previous reports. Therefore, our study is the first large-scale study to verify that ITN is a significant risk factor for PTE.\u003c/p\u003e \u003cp\u003eIn addition, we identified that a 70% dose volume\u0026thinsp;\u0026gt;\u0026thinsp;1 cc is a risk factor for ITN, which can subsequently lead to PTE (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Although vasogenic edema is a major component of PTE in meningioma, cytotoxic edema is known to contribute to PTE as well.\u003csup\u003e\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e It is known that the presence of PTE is strongly correlated with the expression of vascular endothelial growth factor (VEGF) within a meningioma.\u003csup\u003e\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Some argue that there is also a significant correlation between matrix metalloproteinase 9 (MMP-9) and the presence of PTE.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Such a protein-based pathophysiology for PTE would necessitate a partial breakdown of the tumor\u0026ndash;brain interface.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Based on our findings, we suggest that ITN triggered by GKRS may play a role in the breakdown.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter GKRS for meningioma, PTE is a relatively common radiation-induced complication, and there have been many reports of PTE following GKRS. The incidence of symptomatic PTE after GKRS for meningioma has been reported as 5\u0026ndash;11%,\u003csup\u003e33\u0026ndash;37\u003c/sup\u003e whereas all PTE is 13\u0026ndash;28%.\u003csup\u003e23,34,36\u0026minus;39\u003c/sup\u003e Our study showed a lower incidence of PTE than previously reported (2.4% for symptomatic PTE and 7.9% for all PTE). This low incidence of PTE is probably due to the nature of the tumors included in our study. It is already widely known that tumor volume and size are significant factors for PTE after GKRS for meningioma.\u003csup\u003e33\u0026ndash;37,40\u0026minus;43\u003c/sup\u003e Although the tumor volume did not show statistical significance in our study, we do not deny that tumor volume is a significant factor for PTE after GKRS. Since the meningiomas included in our study were mostly small tumors (88.2% were \u0026lt;\u0026thinsp;3 cc), it is possible that the influence of tumor volume was underestimated.\u003c/p\u003e \u003cp\u003eWhile some studies claim that tumor location is a risk factor for PTE,\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e others argue the opposite.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e Meningiomas differ in growth patterns and tumor shape depending on location. The contact area between the tumor and the brain parenchyma varies depending on the tumor shape. Studies on meningioma show that the ratio of the dural base area to the brain parenchymal contact area affects the radiosurgical outcome.\u003csup\u003e14,37,46\u0026minus;50\u003c/sup\u003e Therefore, in this study, we limited the study subject to convexity meningioma in order to remove the tumor location as a confounding variable and focus on the radiosurgical prescription parameters that we could control.\u003c/p\u003e \u003cp\u003eIn our study, only 3 of 9 patients who had PTE with ITN showed neurological symptoms, and the symptoms disappeared after 6 months in all patients. Therefore, neurosurgeons should reassure their patients by providing sufficient explanations to patients with a high risk for PTE with ITN.\u003c/p\u003e \u003cp\u003eWe faced certain limitations during the course of this study. This study was limited by its retrospective study design. Despite being the largest study regarding the occurrence of ITN after GKRS for meningioma, our study was conducted using a small sample size. In our study, only follow-up MRIs at 6 and 12 months after GKRS were included in the study. Further studies might elucidate the longer-term natural course of meningioma with ITN through long-term follow-up.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWhen performing GKRS for meningioma, a 70% dose volume\u0026thinsp;\u0026ge;\u0026thinsp;1 cc is a risk factor for ITN. At 6 months after GKRS, meningioma with ITN is accompanied by a transient volume increase and PTE, which are characteristics of pseudoprogression. These characteristics improve at 12 months after GKRS. This study should help neurosurgeons plan and treat meningiomas using GKRS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis article has not been previously published in whole or in part or submitted elsewhere for review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Korea Medical Device Development Fund (KMDF_PR_20200901_0103)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have nothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Ji Hyoun An, RN, MSN, and Gi Hong Kim, MS for their tremendous effort in Gamma knife center of Severance hospital. And the authors thank the Medical Illustration and Design team of the Medical Research Support Services of Yonsei University College of Medicine for providing excellent support with medical illustration.\u003c/p\u003e\n\u003cp\u003eEthical approval: This study was conducted in accordance with the Declaration of Helsinki and was approved by Institutional Review Board of Severance hospital, waving the patient\u0026apos;s written consent as a retrospective study (4-2021-1190). The requirement for obtaining patient\u0026apos;s written consent was waived as this was a retrospective study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDing, D., Xu, Z., McNeill, I. T., Yen, C. P. \u0026amp; Sheehan, J. P. Radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg \u003cb\u003e119\u003c/b\u003e, 871\u0026ndash;877, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2013.6.Jns13110\u003c/span\u003e\u003c/span\u003e (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKollov\u0026aacute;, A. \u003cem\u003eet al.\u003c/em\u003e Gamma Knife surgery for benign meningioma. J Neurosurg \u003cb\u003e107\u003c/b\u003e, 325\u0026ndash;336, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/jns-07/08/0325\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKondziolka, D. \u003cem\u003eet al.\u003c/em\u003e Radiosurgery as definitive management of intracranial meningiomas. \u003cem\u003eNeurosurgery\u003c/em\u003e \u003cb\u003e62\u003c/b\u003e, 53\u0026ndash;58; discussion 58\u0026ndash;60, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.Neu.0000311061.72626.0d\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStarke, R. M. \u003cem\u003eet al.\u003c/em\u003e Gamma Knife surgery for skull base meningiomas: Clinical article. Journal of Neurosurgery JNS \u003cb\u003e116\u003c/b\u003e, 588\u0026ndash;597, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2011.11.Jns11530\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang, C. K. \u003cem\u003eet al.\u003c/em\u003e Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma. Brain Tumor Res Treat \u003cb\u003e3\u003c/b\u003e, 103\u0026ndash;107, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.14791/btrt.2015.3.2.103\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePan, H.-C. \u003cem\u003eet al.\u003c/em\u003e Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery. Journal of neurosurgery \u003cb\u003e109\u003c/b\u003e, 90\u0026ndash;98 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShuto, T., Matsunaga, S., Suenaga, J., Inomori, S. \u0026amp; Fujino, H. Treatment strategy for metastatic brain tumors from renal cell carcinoma: selection of gamma knife surgery or craniotomy for control of growth and peritumoral edema. \u003cem\u003eJournal of neuro-oncology\u003c/em\u003e \u003cb\u003e98\u003c/b\u003e, 169\u0026ndash;175 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan, J. P. \u003cem\u003eet al.\u003c/em\u003e Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. Journal of neurosurgery \u003cb\u003e123\u003c/b\u003e, 1287\u0026ndash;1293 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen, C.-h. \u003cem\u003eet al.\u003c/em\u003e Histopathology of radiation necrosis with severe peritumoral edema after Gamma knife radiosurgery for parasagittal meningioma. Stereotactic and functional neurosurgery \u003cb\u003e85\u003c/b\u003e, 292\u0026ndash;295 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNundkumar, N., Guthikonda, M. \u0026amp; Mittal, S. Peritumoral edema following Gamma Knife radiosurgery as the primary treatment for intraventricular meningiomas. Journal of Clinical Neuroscience \u003cb\u003e20\u003c/b\u003e, 616\u0026ndash;618 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKondziolka, D. \u003cem\u003eet al.\u003c/em\u003e Gamma Knife thalamotomy for essential tremor. J Neurosurg \u003cb\u003e108\u003c/b\u003e, 111\u0026ndash;117, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/jns/2008/108/01/0111\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhattab, M. H. \u003cem\u003eet al.\u003c/em\u003e Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery. Int J Radiat Oncol Biol Phys \u003cb\u003e112\u003c/b\u003e, 121\u0026ndash;130, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijrobp.2021.08.021\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOchiai, T. Gamma Knife Thalamotomy for a Medically Refractory Tremors: Longitudinal Evaluation of Clinical Effects and MRI Response Patterns. Acta Neurochir Suppl \u003cb\u003e128\u003c/b\u003e, 127\u0026ndash;132, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-030-69217-9_14\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHwang, K. \u003cem\u003eet al.\u003c/em\u003e Seizures After Stereotactic Radiosurgery for Benign Supratentorial Meningiomas: An Uncontrollable Type of Seizure? World Neurosurg \u003cb\u003e123\u003c/b\u003e, e549-e556, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2018.11.211\u003c/span\u003e\u003c/span\u003e (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith, K. A., Leever, J. D. \u0026amp; Chamoun, R. B. Predicting Consistency of Meningioma by Magnetic Resonance Imaging. J Neurol Surg B Skull Base \u003cb\u003e76\u003c/b\u003e, 225\u0026ndash;229 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith, K. A., Leever, J. D., Hylton, P. D., Camarata, P. J. \u0026amp; Chamoun, R. B. Meningioma consistency prediction utilizing tumor to cerebellar peduncle intensity on T2-weighted magnetic resonance imaging sequences: TCTI ratio. Journal of Neurosurgery \u003cb\u003e126\u003c/b\u003e, 242\u0026ndash;248, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2016.1.JNS152329\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMastorakos, P. \u003cem\u003eet al.\u003c/em\u003e Tumor to Cerebellar Peduncle T2-Weighted Imaging Intensity Ratio Fails to Predict Pituitary Adenoma Consistency. J Neurol Surg B Skull Base \u003cb\u003e80\u003c/b\u003e, 252\u0026ndash;257, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1055/s-0038-1668516\u003c/span\u003e\u003c/span\u003e (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung, I. H., Yoo, J., Roh, T. H., Park, H. H. \u0026amp; Hong, C. K. Importance of Sufficient Petrosectomy in an Anterior Petrosal Approach: Relightening of the Kawase Pyramid. World Neurosurg \u003cb\u003e153\u003c/b\u003e, e11-e19, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2021.05.017\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBreshears, J. D. \u003cem\u003eet al.\u003c/em\u003e Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study. Neurosurgery \u003cb\u003e84\u003c/b\u003e, 123\u0026ndash;131, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/neuros/nyy019\u003c/span\u003e\u003c/span\u003e (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, J. H. \u003cem\u003eet al.\u003c/em\u003e Predictive Factors of Unfavorable Events After Gamma Knife Radiosurgery for Vestibular Schwannoma. World Neurosurg \u003cb\u003e107\u003c/b\u003e, 175\u0026ndash;184, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2017.07.139\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayhurst, C. \u0026amp; Zadeh, G. Tumor pseudoprogression following radiosurgery for vestibular schwannoma. Neuro Oncol \u003cb\u003e14\u003c/b\u003e, 87\u0026ndash;92, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/neuonc/nor171\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLangenhuizen, P. \u003cem\u003eet al.\u003c/em\u003e Prediction of transient tumor enlargement using MRI tumor texture after radiosurgery on vestibular schwannoma. Med Phys \u003cb\u003e47\u003c/b\u003e, 1692\u0026ndash;1701, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/mp.14042\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, S. R., Yang, K. A., Kim, S. K. \u0026amp; Kim, S.-H. Radiation-Induced Intratumoral Necrosis and Peritumoral Edema after Gamma Knife Radiosurgery for Intracranial Meningiomas. J Korean Neurosurg Soc \u003cb\u003e52\u003c/b\u003e, 98\u0026ndash;102, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3340/jkns.2012.52.2.98\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurkanlar, D., Er, U., Sanli, M., Ozkan, M. \u0026amp; Sekerci, Z. Peritumoral brain edema in intracranial meningiomas. J Clin Neurosci \u003cb\u003e12\u003c/b\u003e, 750\u0026ndash;753, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jocn.2004.09.029\u003c/span\u003e\u003c/span\u003e (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshioka, H. \u003cem\u003eet al.\u003c/em\u003e Peritumoral brain edema associated with meningioma: influence of vascular endothelial growth factor expression and vascular blood supply. Cancer \u003cb\u003e85\u003c/b\u003e, 936\u0026ndash;944, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/(sici)1097-0142(19990215)85:4\u0026lt;936::aid-cncr23\u0026gt;3.0.co;2-j\u003c/span\u003e\u003c/span\u003e (1999).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReszec, J. \u003cem\u003eet al.\u003c/em\u003e Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema. \u003cem\u003eBioMed Research International\u003c/em\u003e 2015, 646853, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2015/646853\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNassehi, D. Intracranial meningiomas, the VEGF-A pathway, and peritumoral brain oedema. Dan Med J \u003cb\u003e60\u003c/b\u003e, B4626 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou, J., Kshettry, V. R., Selman, W. R. \u0026amp; Bambakidis, N. C. Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy. Neurosurg Focus \u003cb\u003e35\u003c/b\u003e, E2, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2013.8.Focus13301\u003c/span\u003e\u003c/span\u003e (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkovic, M., Antunovic, V., Milenkovic, S. \u0026amp; Zivkovic, N. Prognostic value of peritumoral edema and angiogenesis in intracranial meningioma surgery. J buon \u003cb\u003e18\u003c/b\u003e, 430\u0026ndash;436 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaek, S. H. \u003cem\u003eet al.\u003c/em\u003e The role of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in microcystic meningiomas. Oncol Rep \u003cb\u003e16\u003c/b\u003e, 49\u0026ndash;56 (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung, S. \u003cem\u003eet al.\u003c/em\u003e Increased expression of intracystic matrix metalloproteinases in brain tumors: relationship to the pathogenesis of brain tumor-associated cysts and peritumoral edema. J Clin Neurosci \u003cb\u003e14\u003c/b\u003e, 1192\u0026ndash;1198, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jocn.2006.11.009\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing, Y. S. \u003cem\u003eet al.\u003c/em\u003e Expression of vascular endothelial growth factor in human meningiomas and peritumoral brain areas. Ann Clin Lab Sci \u003cb\u003e38\u003c/b\u003e, 344\u0026ndash;351 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConti, A. \u003cem\u003eet al.\u003c/em\u003e Post-Treatment Edema after Meningioma Radiosurgery is a Predictable Complication. Cureus \u003cb\u003e8\u003c/b\u003e, e605, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.605\u003c/span\u003e\u003c/span\u003e (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoe, Y. \u003cem\u003eet al.\u003c/em\u003e Peritumoral Brain Edema after Stereotactic Radiosurgery for Asymptomatic Intracranial Meningiomas: Risks and Pattern of Evolution. J Korean Neurosurg Soc \u003cb\u003e58\u003c/b\u003e, 379\u0026ndash;384, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3340/jkns.2015.58.4.379\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuhn, E. N. \u003cem\u003eet al.\u003c/em\u003e Is there a tumor volume threshold for postradiosurgical symptoms? A single-institution analysis. Neurosurgery \u003cb\u003e75\u003c/b\u003e, 536\u0026ndash;545; discussion 544 \u0026ndash; 535; quiz 545, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/neu.0000000000000519\u003c/span\u003e\u003c/span\u003e (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnger, K. R. \u003cem\u003eet al.\u003c/em\u003e Risk factors for posttreatment edema in patients treated with stereotactic radiosurgery for meningiomas. Neurosurgery \u003cb\u003e70\u003c/b\u003e, 639\u0026ndash;645, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/NEU.0b013e3182351ae7\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCai, R., Barnett, G. H., Novak, E., Chao, S. T. \u0026amp; Suh, J. H. Principal risk of peritumoral edema after stereotactic radiosurgery for intracranial meningioma is tumor-brain contact interface area. Neurosurgery \u003cb\u003e66\u003c/b\u003e, 513\u0026ndash;522, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.Neu.0000365366.53337.88\u003c/span\u003e\u003c/span\u003e (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMansouri, A. \u003cem\u003eet al.\u003c/em\u003e Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas. J Neurosurg \u003cb\u003e123\u003c/b\u003e, 1294\u0026ndash;1300, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2014.12.Jns141687\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark, S. H., Hwang, J. H. \u0026amp; Hwang, S. K. Change in plasma vascular endothelial growth factor after gamma knife radiosurgery for meningioma: a preliminary study. J Korean Neurosurg Soc \u003cb\u003e57\u003c/b\u003e, 77\u0026ndash;81, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3340/jkns.2015.57.2.77\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGirvigian, M. R., Chen, J. C., Rahimian, J., Miller, M. J. \u0026amp; Tome, M. Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy. Neurosurgery \u003cb\u003e62\u003c/b\u003e, A19-27; discussion A27-18, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.neu.0000325933.34154.cb\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan, J. P. \u003cem\u003eet al.\u003c/em\u003e Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. J Neurosurg \u003cb\u003e123\u003c/b\u003e, 1287\u0026ndash;1293, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2014.12.Jns142159\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan, J. P. \u003cem\u003eet al.\u003c/em\u003e Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study. J Neurooncol \u003cb\u003e125\u003c/b\u003e, 317\u0026ndash;324, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11060-015-1911-1\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovotn\u0026yacute;, J., Jr., Kollov\u0026aacute;, A. \u0026amp; Lisc\u0026aacute;k, R. Prediction of intracranial edema after radiosurgery of meningiomas. J Neurosurg \u003cb\u003e105 Suppl\u003c/b\u003e, 120\u0026ndash;126, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/sup.2006.105.7.120\u003c/span\u003e\u003c/span\u003e (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatil, C. G. \u003cem\u003eet al.\u003c/em\u003e Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas. Neurosurgery \u003cb\u003e63\u003c/b\u003e, 435\u0026ndash;440; discussion 440 \u0026ndash; 432, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.Neu.0000325257.58684.92\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKondziolka, D., Flickinger, J. C. \u0026amp; Perez, B. Judicious resection and/or radiosurgery for parasagittal meningiomas: outcomes from a multicenter review. Gamma Knife Meningioma Study Group. Neurosurgery \u003cb\u003e43\u003c/b\u003e, 405\u0026ndash;413; discussion 413 \u0026ndash; 404, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00006123-199809000-00001\u003c/span\u003e\u003c/span\u003e (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang, J. H., Chang, J. W., Choi, J. Y., Park, Y. G. \u0026amp; Chung, S. S. Complications after gamma knife radiosurgery for benign meningiomas. J Neurol Neurosurg Psychiatry \u003cb\u003e74\u003c/b\u003e, 226\u0026ndash;230, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/jnnp.74.2.226\u003c/span\u003e\u003c/span\u003e (2003).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasegawa, T. \u003cem\u003eet al.\u003c/em\u003e Gamma knife surgery for convexity, parasagittal, and falcine meningiomas: Clinical article. Journal of Neurosurgery \u003cb\u003e114\u003c/b\u003e, 1392\u0026ndash;1398, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2010.11.JNS10112\u003c/span\u003e\u003c/span\u003e (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovotn\u0026yacute; Jr, J., Kollov\u0026aacute;, A. \u0026amp; Lisc\u0026aacute;k, R. Prediction of intracranial edema after radiosurgery of meningiomas. Journal of neurosurgery \u003cb\u003e105 Suppl\u003c/b\u003e, 120\u0026ndash;126, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/sup.2006.105.7.120\u003c/span\u003e\u003c/span\u003e (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRogers, L. \u0026amp; Mehta, M. Role of radiation therapy in treating intracranial meningiomas. Neurosurgical focus \u003cb\u003e23\u003c/b\u003e, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/FOC-07/10/E4\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan, J. P. \u003cem\u003eet al.\u003c/em\u003e Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas. Journal of Neurosurgery \u003cb\u003e123\u003c/b\u003e, 1287\u0026ndash;1293, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2014.12.JNS142159\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"radiosurgery, gamma knife surgery, meningioma, intratumoral necrosis, peritumoral edema, pseudoprogression","lastPublishedDoi":"10.21203/rs.3.rs-1417812/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1417812/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p=0.009) greater. When a 70% dose volume ≥1 cc was used, the possibility of ITN was 5.892-fold (p\u0026lt;0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e When performing GKRS in meningioma, a 70% dose volume ≥1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS.\u003c/p\u003e","manuscriptTitle":"Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-11 15:31:39","doi":"10.21203/rs.3.rs-1417812/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-06-23T06:55:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-06-02T13:50:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1e0ca447-1165-4fef-95ae-a518f596f2e9","date":"2022-05-27T21:09:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-05-27T21:06:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-05-27T20:34:08+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-03-08T17:55:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-03-08T17:45:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2022-03-04T06:14:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e781664-0619-4f86-a185-199908f97f60","owner":[],"postedDate":"March 11th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-08-01T08:29:22+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-11 15:31:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1417812","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1417812","identity":"rs-1417812","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}