Background and purposeDisruption of the tumor-brain barrier in meningioma plays a critical role in the development of peritumoral brain edema (PTBE). We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation in patients with intracranial meningioma. OPEN ACCESS Citation: Lee R-H, Kim JM, Cheong JH, Ryu JI, Kim YS, Han M-H (2020) Significance of skull osteoporosis to the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma. PLoS ONE 15(2): e0226312. https://doi.org/10.

28Background and purpose: Disruption of the tumor-brain barrier in meningioma plays a 29 critical role in the development of peritumoral brain edema (PTBE). We hypothesized that 30 osteoporotic conditions may be associated with PTBE occurrence after radiation in patients 31 with intracranial meningioma. 32 Methods: We measured Hounsfield units (HU) of the frontal skull on simulation brain CT in 33 patients who underwent linear accelerator (LINAC)-based radiation treatment for intracranial 34 meningioma. Receiver operating characteristic curve analysis was performed to determine the 35 optimal cut-off values for several predictive factors. The cumulative hazard for PTBE was 36 estimated and classified according to these factors. Hazard ratios were then estimated to 37 identify independent predictive factors associated with the development of PTBE after 38 radiation in intracranial meningioma patients.39Results: A total of 83 intracranial meningiomas in 76 patients who received LINAC-based 40 radiation treatment in our hospital over an approximate 5-year period were included for the 41 study. We found mean frontal skull HU ≤630.625 and gross tumor volume >7.194 cc to be 42 independent predictors of PTBE after radiation treatment in patients with meningioma (hazard 43 ratio, 8.38; P=0.021; hazard ratio, 5.78; P=0.034, respectively). In addition, patients who were 44 ≥65 years showed a marginally significant association with PTBE. 45 Conclusions:Our study suggests that possible osteoporotic conditions, large tumor volume, 46 and older age may be associated with PTBE occurrence after LINAC-based radiation 47 treatment for intracranial meningioma. In the future we anticipate that these findings may 48 enhance the understanding of the underlying mechanisms of PTBE after radiation in 3 49 meningioma patients. Meningiomas are the most common extra-axial primary intracranial benign tumors and account 75 for 13-26% of all primary intracranial tumors [1]. Although microsurgical tumor resection is 76 the treatment of choice for symptomatic meningiomas, gross total resection of meningiomas is 77 not always possible due to various conditions such as tumor size, location, adjacent 78 neurovascular structures, or the patient's medical status. Radiation therapy is used as a 79 treatment for meningiomas when the remnant tumor is present after surgery or when surgical 80 resection is not an option [2]. Radiotherapy for meningioma is accepted as a safe treatment 81 modality. Approximately 5% to 40% of patients experience treatment-related complications 82[3]. It was reported that symptomatic brain edema occurs in 37.5% of patients with parasagittal 83 meningiomas after gamma knife radiosurgery [4]. 84Disruption of the tumor-brain barrier in meningioma plays a critical role in the development 85 of peritumoral brain edema (PTBE) [5]. A previous study regarding microscopic anatomy of 86 the brain-meningioma interface reported the presence of arachnoid trabeculae at the brain-87 meningioma contact interface [6]. We previously demonst...