Development Of Peritumoral Edema Research Articles

Risk Factors Associated with Development of Peritumoral Edema Following Stereotactic Radiosurgery and Radiotherapy for Intracranial Meningioma

Peritumoral edema (PTE) is a potential adverse effect following radiotherapy for intracranial meningioma. The purpose of this study is to identify which baseline factors may increase risk for PTE. A retrospective chart review was conducted of 431 patients who underwent primary radiotherapy to 480 radiographically-defined intracranial meningiomas between January 2008 and December 2021 within an integrated health care system. Patients with prior surgical management were excluded. Patients were treated with frameless LINAC-based image-guided single fraction stereotactic radiosurgery (SRS) (32.9%), 5 fraction SRS (FSRS) (30.8%), or fractionated stereotactic radiotherapy (FSRT) (36.3%). Pre- and post-radiotherapy MRI studies were reviewed to evaluate for PTE following treatment. An event was defined as new or worsening PTE compared to pre-radiotherapy imaging or development of new symptoms post-radiotherapy. Univariate and stepwise logistics regression analyses were performed to compare the risk of PTE between groups. Median follow-up was 85.8 months (IQR: 49.4-125.4). Median patient age was 66 years (IQR: 56-73). Patients treated with SRS (median age: 61 years) were younger than those treated with FSRS/FSRT (median age: 68 years) (p<0.001). Lesions treated with SRS (median volume: 1.33cc) were smaller than those treated with FSRS/FSRT (median volume: 6.36cc) (p<0.001). For all-comers, 68 (14.2%) lesions developed any PTE, and 27 (5.6%) developed symptomatic PTE (SPTE). Of these, 4 patients developed symptoms post-treatment without radiographic evidence of new or worsening PTE. Incidence of PTE/SPTE by site was as follows: base of skull (BOS): 10.3%/6.1%, convexity: 22.7%/7.6%, falcine: 17.6%/4.1%, parasagittal: 27.8%/8.3%, posterior fossa/tentorium 7.0%/0.0%. Incidence of PTE/SPTE by technique was as follows: SRS: 6.3%/3.8%, FSRS: 20.9%/7.4%, FSRT: 15.5%/5.7%. On univariate analysis, age >65 (OR = 2.17 (95% CI: 1.26-3.77) p = 0.006), tumor volume (OR = 1.05 (1.02-1.08), p = 0.003), pre-treatment PTE (OR = 6.82 (95% CI: 3.59-12.94) p<0.001), and convexity/falcine/parasagittal (CFPS) location (OR = 2.52 (95% CI: 1.49-4.23) p<0.001) were associated with increased incidence of PTE. On multivariate analysis, age >65 (OR = 1.91 (95% CI: 1.05-3.45) p<0.03), tumor volume (OR = 1.04 (95% CI: 1.00-1.08) p = 0.03), pre-treatment PTE (OR = 4.64 (95% CI: 2.33-9.24) p<0.001), and CFPS location (OR = 2.53 (95% CI: 1.41-4.52) p = 0.002) were associated with increased incidence of PTE. Two patients with PTE underwent resection for local failure which revealed atypical meningioma. Age >65, larger tumor volume, presence of pre-treatment PTE, and CFPS location were associated with increased incidence of PTE following radiotherapy. Patients with these risk factors should be counseled regarding post-treatment effects. Infrequently, PTE following treatment may be an indicator of higher-grade meningioma.

Expression of MMP-2 and MMP-9 in Benign Canine Rostrotentorial Meningiomas Is Not Correlated to the Extent of Peritumoral Edema

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved with extracellular matrix degradation. They have been considered to be important for tumor growth and development of peritumoral edema. This retrospective study investigated the expression of MMP subtypes 9 and 2 in canine intracranial meningiomas and their association with peritumoral edema. Twenty-two cases of histologically confirmed grade I meningiomas based on human World Health Organization classification were enrolled. Tumor volume and peritumoral edema were measured by magnetic resonance imaging volumetry. The intratumoral MMP expression was semiquantitatively assessed by immunoreactivity scores and compared with the imaging data. MMP-9 was expressed in all the samples (22/22), whereas proMMP-2 was expressed in 21 of 22 meningiomas, and a/proMMP-2 was expressed in 9 of 22. The immunoreactivity scores were not statistically linked to the severity of peritumoral edema. None of the evaluated MMP expression parameters were statistically linked to the edema index. Although both edema index and MMP-9 expression were highest in meningiomas of the olfactory and frontal region, only the latter mounted up to statistical significance (P = .002) if compared with parafalx and convexity meningiomas of the parietal lobe. In summary, MMP-2 and MMP-9 expression by tumor cells, evaluated through immunohistochemistry, is not predictive of the formation of peritumoral edema in canine rostrotentorial meningiomas.

Radiation-Induced Intratumoral Necrosis and Peritumoral Edema after Gamma Knife Radiosurgery for Intracranial Meningiomas

ObjectiveTo study the clinical significance and relevant factors of radiation-induced intratumoral necrosis (RIN) and peritumoral edema (PTE) after Gamma knife radiosurgery (GKRS) for intracranial meningiomas.MethodsWe retrospectively analyzed the data of 64 patients who underwent GKRS for intracranial meningioma. The mean lesion volume was 4.9 cc (range, 0.3-20), and the mean prescription dose of 13.4 Gy (range, 11-18) was delivered to the mean 49.9% (range, 45-50) isodose line. RIN was defined as newly developed or enlarged intratumoral necrosis after GKRS.ResultsRIN and new development or aggravation of PTE were observed in 21 (32.8%) and 18 (28.1%) cases of meningioma, respectively during the median follow-up duration of 19.9±1.0 months. Among various factors, maximum dose (>25 Gy) and target volume (>4.5 cc) were significantly related to RIN, and RIN and maximum dose (>24 Gy) were significantly related to the development or aggravation of PTE. In 21 meningiomas with development of RIN after GKRS, there was no significant change of the tumor volume itself between the times of GKRS and RIN. However, the PTE volume increased significantly compared to that at the time of GKRS (p=0.013). The median interval to RIN after GKRS was 6.5±0.4 months and the median interval to new or aggravated PTE was 7.0±0.7 months.ConclusionA close observation is required for meningiomas treated with a maximum dose >24 Gy and showing RIN after GKRS, since following or accompanying PTE may deteriorate neurological conditions especially when the location involves adjacent critical structures.

Tumoral micro-blood vessels and vascular microenvironment in human astrocytic tumors. A transmission electron microscopy study

The development of peritumoral edema is thought to be due to extravasation of plasma water and macromolecules through a defective blood-brain barrier (BBB), but the exact mechanism by which occurs is poorly understood. The aim of this study was analyze at submicroscopic level the morphological changes in both micro-blood vessels and vascular microenvironment of astrocytic tumors in an attempt of understanding the pathological aspects that may help in the future researches for the design of future therapeutic strategies. Biopsies of 25 patients with pathological diagnosis of astrocytic tumors were examined with the transmission electron microscope. Both open and close tight junctions were observed in the micro-blood vessels, inclusive in a same tumor. Cytoskeletal disorganization associated with disintegrated perijunctional actin filaments were seen. The paracellular space showed enlargement and commonly occupied by fluid proteinaceous, endothelial cells display oncotic and ischemic changes, basal lamina reveals enlargement, edema, vacuolization and collagen fibers disposed in irregular array. Pericytes exhibited edema and phagocytoced material, astrocytic perivascular-feet showed signs of oncosis and necrosis, co-option vessels totally surrounding by neoplastic cells also were seen. The ultrastructural abnormalities observed in both junctional complexes and vascular microenvironment suggest a multi-factorial pathobiology process, probably hypoxia intratumoral, calcium overload in endothelial cells, and degradative effects of metalloproteinases over the basal membrane appear as determinant factors that leading to structural modifications of junctional complexes, therefore, treatment with both HIF-1alpha and metalloproteinases inhibitors possibly can contribute with the pharmacological handling of the peritumoral edema associated with astrocytic tumors.

Expression of vascular permeability factor in glioblastoma specimens: correlation with tumor vascular endothelial surface and peritumoral edema.

Keeping in mind that the expression of vascular permeability factor (VPF) in astrocytic tumors has been related to tumor angiogenesis and peritumoral edema (PE), the aim of this study is to investigate the correlation between degree of VPF expression by tumor cells, and degree of PE and vascular endothelial surface (VES) in glioblastoma. Tumor tissue and neuroimaging data were studied in a series of 38 patients with glioblastoma. For each tumor, immunohistochemical and morphometric studies were performed in order to obtain a score of VPF expression, and a VES score, expressed as the CD-34 immunostained endothelial surface per each 1000 tumor cells. These parameters were related to the degree of PE. The results show that in glioblastomas there exist a clear correlation between the tumor-cell expression of VPF and VES, but we failed to obtain a significant correlation between degree of PE and degree of VES, or between degree of VPF expression and degree of PE. Our present results suggest that in glioblastomas, tumor angiogenesis is clearly related to the expression of VPF by tumor cells, but factors other than intratumoralpresence of VPF may contribute to the development of PE.

MRI of high-grade glial tumors: correlation between the degree of contrast enhancement and the volume of surrounding edema.

Contrast enhancement of malignant gliomas and the development of peritumoral edema are thought to be due to a breakdown of the blood-brain barrier (BBB). The degree to which these two factors are related to each other or to the degree of damage to the BBB is unknown. Our purpose was to quantitatively correlate the degree of enhancement with Gd-DTPA of anaplastic gliomas and glioblastoma multiforme with the volume of surrounding edema. In 14 patients, quantitative measurements of the volume of peritumoral edema and the degree of contrast enhancement were made. A high degree of correlation was found (r = 0.86, P < 0.01). These results can be viewed as indirect, radiological evidence that edema production is quantitatively related to the degree of breakdown of the BBB as determined by gadolinium enhancement. These results imply that the origin of the edema is in the area of breakdown of the BBB.