Canine Intracranial Meningiomas Research Articles

Dynamic contrast enhanced high field magnetic resonance imaging for canine primary intracranial neoplasia.

Distinguishing meningiomas from other intracranial neoplasms is clinically relevant as the prognostic and therapeutic implications differ greatly and influence clinical decision making. Dynamic contrast-enhanced MRI (DCE-MRI) is an imaging technique that assists with characterisation of physiologic alterations such as blood flow and tissue vascular permeability. Quantitative pharmacokinetic analysis utilising DCE-MRI has not been studied in canine neuro-oncology. A retrospective study was performed in canine patients that underwent DCE-MRI with an imaging diagnosis of an intracranial meningioma and surgery for histopathological diagnosis. Kinetic parameters Ktrans and cerebral blood flow were measured and compared to assess whether differences could be identified between meningiomas and other intracranial neoplasms. Six dogs with meningiomas and 3 dogs with other intracranial neoplasms were included for statistical analysis. Cerebral blood flow values were found to be statistically higher within meningiomas compared to other intracranial neoplasms. Ktrans values were higher within meningiomas than in other types of intracranial tumours, however this difference did not reach statistical significance. Based on the results of this study cerebral blood flow measurement can be utilised to differentiate canine intracranial meningiomas from other similar appearing intracranial tumours.

Outcome After Radiation Therapy in Canine Intracranial Meningiomas or Gliomas

To characterize a group of dogs diagnosed with meningioma or glioma treated with radiation therapy and assess the clinical impact of diagnosis and radiation protocol on survival time. Canine patient records from a single veterinary referral hospital, between 2011 and 2015, were searched for intracranial tumour cases treated with radiation therapy, as a sole modality. Thirty-two dogs were included. Median survival times were 524 days [95% confidence interval (CI)=287-677] in total, 512 days (95% CI=101-682) for the glioma group and 536 days (95% CI=249-677) for the meningioma group. No significant difference in survival was detected when using a definitive or a palliative protocol (p=0.130), nor other prognostic factors were found. Our results highlight the efficacy of radiation therapy in the treatment of canine meningioma, as well as glioma, suggesting a change in the current perception of the response of glial tumours to radiation.

Atypical and malignant canine intracranial meningiomas may have lower apparent diffusion coefficient values than benign tumors.

Canine intracranial meningiomas can be graded based on histological classification as benign (grade I), atypical (grade II), and anaplastic or malignant (grade III). In people, grade II/III meningiomas behave more aggressively, have a higher potential for recurrence after surgical resection, and have lower apparent diffusion coefficient (ADC) values with diffusion weighted imaging (DWI). In this retrospective analytical cross-sectional study, 42 dogs had ADC values quantified in an attempt to differentiate tumor histologic grade. Our hypothesis was that ADC values would be significantly lower in grade II and III versus grade I meningiomas in dogs. On each ADC image, a polygonal region of interest (ROI) was hand-drawn along the lesion's periphery, excluding fluid-filled and hemorrhagic regions. Mean ADC value (ADCmean ) and minimum ADC value (ADCmin ) were calculated. Additionally, two smaller, ovoid ROI were drawn within the lesion with mean ADC calculated (ADCmean sR and ADCmin sR ). Normalized ADC values using white matter were also calculated (ADCn and ADCn sR ). Grades of each tumor were assigned based on histopathology review. Association between ADC parameters and histological grade was tested by means of two-sample t-tests. There were 14 grade I (33.3%), 25 grade II (59.5%), and three grade III (7.2%) meningiomas. ADCmean sR and ADCmin sR were significantly lower when comparing grade II/III to grade I (P<.05). Grade II tumors had significantly lower ADCmean , ADCmean sR , ADCmin sR , ADCn , and ADCn sR than grade I meningiomas. This preliminary study supports the potential of ADC values to help predict the histological grade of intracranial meningiomas in dogs.

Canine intracranial meningiomas: Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers

The haemostatic system influences angiogenesis, cell growth and metastasis in solid tumours. The aim of this study was to investigate tissue factor (TF) expression, fibrin/fibrinogen and D-dimer deposition, as well as the occurrence of intravascular thrombosis (IVT) in canine intracranial meningiomas using immunohistochemistry. All but three (26/29) meningiomas expressed TF. TF immunolabelling was significantly higher in high-grade (grades II and III) than in low-grade (grade I) meningiomas. Fibrin/fibrinogen and D-dimer deposits were detected in all meningiomas and staining scores were statistically different between different meningioma grades. IVT was detected in 19/29 specimens, but no statistical differences were observed between different malignancy grades. In conclusion, the haemostatic system may be involved in meningioma pathobiology and may be a potential therapeutic target for canine meningiomas, as also suggested for human meningiomas.

Minimal interleukin expression in canine intracranial meningiomas

MENINGIOMAS are a common CNS neoplasm in both humans and dogs. The propagation of meningiomas has been linked with several inflammatory interleukins; human meningioma cells have been identified to synthesise...

Stereotactic radiation therapy for treatment of canine intracranial meningiomas.

The objective of this study is to determine the rate of toxicity, median survival time (MST) and prognostic factors in dogs with presumed intracranial meningiomas that were treated with stereotactic radiation therapy (SRT). Patient demographics, neurological history, details of SRT plans and response to treatment (including toxicity and survival times) were examined for potential prognostic factors. Overall MST (MST) due to death for any cause was 561 days. There was a mild to moderate exacerbation of neurological symptoms 3-16 weeks following SRT treatments in 11/30 (36.7%) of dogs. This presumed adverse event was treated with corticosteroids, and improvement was seen in most of these dogs. Death within 6 months of treatment as a result of worsening neurologic signs was seen in 4/30 (13.3%) of dogs. Volume of normal brain that received full dose at a prescription of 8Gy × 3 fractions was predictive of death due to neurological problems within this 6-month period.

Three‐dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three-dimensional conformal radiation therapy (3D-CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross-sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272-829 days; range = 30-1942 days) when all deaths were considered and 906 days (interquartile range = 336-912 days; range = 10 -1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D-CRT may be a viable alternative to surgery.

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.

Characterization of Immune Cell Infiltration Into Canine Intracranial Meningiomas

Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (αD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3(+) T cells. Large numbers of CD18(+) microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d(+). Scattered macrophages at the tumor-brain interface were TLR4(+) and TLR9(+). Rare CD79a(+) B cells were noted in only a small subset of tumors. Lesser numbers of lymphocytes that were CD11d(+), CD45RA(+), or FoxP3(+) were noted in a number of the meningiomas. Although the function of these cells is not yet clear, work in other species suggests that evaluation of this immune cell infiltrate may provide important prognostic information and may be useful in the design of novel therapies.

Cyclooxygenase‐2 (COX‐2) expression in canine intracranial meningiomas

Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.

Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas. Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome. Seventy client-owned dogs with WHO grade I intracranial meningiomas. Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures. Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival. MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

Vascular Endothelial Growth Factor Expression in Canine Intracranial Meningiomas and Association with Patient Survival

Background: Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and vascular permeability. In human patients with meningiomas, increased VEGF expression is predictive of postsurgical recurrence. The objectives of this study were to evaluate VEGF expression in canine intracranial meningiomas and to determine whether an association between VEGF expression and patient survival existed. Methodology: Tumor tissue from 17 dogs with histologically confirmed intracranial meningiomas was obtained surgically. All dogs then were treated with radiotherapy. Immunohistochemistry was performed on 5‐μm sections of paraffin‐embedded tumor tissue with rabbit anti‐human VEGF polyclonal antibody. The extent, intensity, and distribution of VEGF staining for each section were assessed with light microscopy by means of a semiquantitative scale. Survival was analyzed by the Kaplan‐Meier procedure. Survival rates among groups were compared by log‐rank tests with the significance set at P≤.05. Findings: VEGF expression was detected in all tumors, with &gt;50% of cells staining positively in tissues from 15/17 dogs. Shorter survival times were associated with greater VEGF expression (P= .01). Conclusions: VEGF expression can be measured in canine intracranial meningiomas and may be associated with poor outcome. Significance: The extent of VEGF expression in canine intracranial meningiomas may be used as a prognostic marker and suggests a potential future target for therapy.

Vascular Endothelial Growth Factor Expression in Canine Intracranial Meningiomas and Association with Patient Survival

Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and vascular permeability. In human patients with meningiomas, increased VEGF expression is predictive of postsurgical recurrence. The objectives of this study were to evaluate VEGF expression in canine intracranial meningiomas and to determine whether an association between VEGF expression and patient survival existed. Tumor tissue from 17 dogs with histologically confirmed intracranial meningiomas was obtained surgically. All dogs then were treated with radiotherapy. Immunohistochemistry was performed on 5-microm sections of paraffin-embedded tumor tissue with rabbit anti-human VEGF polyclonal antibody. The extent, intensity, and distribution of VEGF staining for each section were assessed with light microscopy by means of a semiquantitative scale. Survival was analyzed by the Kaplan-Meier procedure. Survival rates among groups were compared by log-rank tests with the significance set at P < or = .05. VEGF expression was detected in all tumors, with >50% of cells staining positively in tissues from 15/17 dogs. Shorter survival times were associated with greater VEGF expression (P = .01). VEGF expression can be measured in canine intracranial meningiomas and may be associated with poor outcome. The extent of VEGF expression in canine intracranial meningiomas may be used as a prognostic marker and suggests a potential future target for therapy.