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Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs
Abstract
Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.
... 15,16 The potential benefits of stereotactic radiotherapy for a variety of intracranial tumor types in dogs have previously been described, but pituitary tumors have accounted for very few stereotactic radiotherapy patients in the literature. [16][17][18][19][20][21][22] Stereotactic radiotherapy utilizes high radiation doses in 1-5 fractions, and normal tissues are typically spared by avoidance rather than fractionation. 23,24 Stereotactic radiotherapy delivers an ablative dose, and this type of administration is achievable by use of combined immobilization, image-guidance, and advanced computer radiation planning systems that create the highly conformal dose. ...
... In this stereotactic radiotherapy study, four dogs had pituitary masses and received a median dose of 16.25 Gy (range 15 -25 Gy), with a median survival of 118 days. 20 Stereotactic radiotherapy was also used in another study that included three dogs with pituitary masses; they received 24 Gy in three fractions of 8 Gy every other day, and they had survival times ranging from 255 to 342 days. 21 The goal of this study was to assess survival in a larger group of dogs receiving stereotactic radiotherapy for suspected pituitary tumors with two different stereotactic radiotherapy protocols on two different radiotherapy platforms. ...
... Stereotactic radiotherapy limits normal tissue dose, in part by use of advanced on-board imaging and reliable positioning for patients, and also by use of advanced planning systems.26,27,[36][37][38][39][40] To the authors' knowledge, there are only two peer-reviewed veterinary studies that describe stereotactic radiotherapy for very few canine pituitary cases.20,21 In one study, fourdogs received a median dose of 16.25 Gy and had a median survival of 118 days. ...
Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging‐diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009–2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226–410 days [range 1–2134 days]). Thirty‐two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221–427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2–626 days]). Twenty‐nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P = 0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.
... Although there are no published formal comparison studies, medical management, using anti-seizure medications and glucocorticoids, is associated with poor long-term survival for dogs with suspected meningioma [3,[8][9][10]. In contrast, direct anti-tumor treatment, mostly radiotherapy [11][12][13][14][15] or surgery [16][17][18][19] alone, but also both combined [8,20,21] appears to be efficacious. Summary synthesis of these series is difficult, because of differences in reporting and inclusion criteria, but suggests that both treatments generate similar survival outcomes [22]. ...
... Some of our secondary analyses provide results that seem unexpected, for instance that site of the lesion does not seem to be important (overall) in prognosis. There is some evidence that rostrotentorial lesions have a better prognosis [9,10], but this is not supported by our analysis, nor by some previous publications [12]. Furthermore, our analyses do not support an interaction between site and surgery (i.e., that there is a differential effect between radiotherapy and surgery in the different sites [as might be expected if caudal cranial fossa lesions are more difficult to operate]), although this conclusion is susceptible to type II error because of the low power of this type of exploratory analysis. ...
Background
The comparative effectiveness of radiotherapy and surgery for treating intracranial meningioma is unknown.
Objectives
To compare survival after treatment of suspected intracranial meningioma by either surgery or radiotherapy.
Animals
Two hundred eighty‐five companion dogs with suspected intracranial meningiomas presenting to 11 specialty clinics in three countries.
Methods
Parallel cohort comparison study on retrospective data. Dogs diagnosed with intracranial meningioma by board‐certified veterinary neurologists or radiologists and treated by radiotherapy or surgery were identified through medical record searches and presenting and survival data extracted. Lesion site was classified as rostro‐ or caudotentorial and size was measured on contrast magnetic resonance images. Outcome was all‐cause death. Analysis of survival by Cox proportional hazards, including selection for optimal multivariable model using lasso, counterfactual modeling including variables associated with treatment allocation and survival.
Results
One hundred sixty‐eight dogs received radiotherapy and 117 received surgery. All analyses indicated reduced survival associated with surgery compared to radiotherapy. There was a median survival after surgery of 297 (IQR: 99–768) days compared with 696 (IQR: 368–999) for dogs treated by radiation, associated with a univariable hazard ratio of 1.802 (95% CI: 1.357–2.394). Counterfactual modeling estimated a mean survival of 480 (95% CI: 395–564) days after surgery and 673 (95% CI: 565–782) days after radiotherapy, representing a decrease in survival of 29%. Location and size of the lesion were not associated with survival duration.
Conclusions and Clinical Importance
Dogs with suspected intracranial meningioma have substantially superior survival after radiotherapy compared to surgery.
... SRT involves fewer treatments, typically 1 to 3, called "fractions," with a larger amount of radiation applied at each administration as compared to the traditional or conventional RT, which typically involves multiple, smaller-dose fractions delivered 3 to 5 times weekly over 3 to 4 weeks. 17 Advantages of this noninvasive, single-dose to hypofractionated form of treatment of brain tumors in animals are that only a few episodes of general anesthesia are required and radiation exposure of normal brain tissue is substantially reduced, thereby avoiding complications associated with conventional RT. 18,19 The CyberKnife system is an RT device manufactured by Accuray Inc and is 1 type of SRT system that can facilitate SRT through a linear accelerator placed on a robotic arm, giving it many degrees of freedom. This freedom allows for increased accuracy in the delivered radiation to the area of interest and for the sparing of normal surrounding tissue. ...
... Historically, curative-intent RT treatments have been utilized in the treatment of both feline and canine intracranial tumors. 3,6,10,11,17,18,[23][24][25][26] However, there is a paucity of literature on feline patients diagnosed with intracranial meningiomas treated with SRT. In a 2003 paper by Troxel et al, 1 a total of 4 cats underwent RT for treatment of presumed intracranial meningiomas; however, the radiation protocol was only specified for 1 cat that received 3 doses weekly of 400 cGY for a total dose of 48 Gy. ...
OBJECTIVE
To report clinical features and outcomes of cats undergoing either stereotactic radiotherapy (SRT) or surgical excision for the treatment of intracranial meningioma.
ANIMALS
61 client-owned cats.
METHODS
Medical records were retrospectively reviewed of cats with intracranial meningiomas that were treated with surgical removal and/or SRT between 2005 and 2017. Signalment, clinical signs, duration of clinical signs, diagnostic imaging reports, histopathology reports, treatment protocol, complications, recurrence or progression, and survival time were obtained from the medical record and through follow-up phone calls.
RESULTS
Of the 61 patients, 46 had surgery, 14 had SRT, and 1 had surgery followed by SRT for initial treatment. Significantly more cats that underwent surgery had peritreatment complications compared to the SRT group ( P < .0001). Cats that received surgery initially had a significantly longer median survival time (MST) of 1,345 days compared to the MST of 339 days for the SRT cats ( P = .002). Fourteen (30%) cats in the surgery group and 4 cats in the SRT group (28%) had MRI- or CT-confirmed tumor regrowth or new tumor growth ( P = 1.00). Five cases that had SRT for subsequent recurrence had an MST of 700 days (range, 335 to 1,460 days) after the last treatment.
CLINICAL RELEVANCE
SRT proved to be a safe, alternative treatment option for feline patients with intracranial meningiomas; however, the survival times with surgery alone were significantly longer. SRT for the treatment of recurrence following initial surgery may show promising results.
... These clinical manifestations can be correlated to the imaging changes on follow up scans (5), and further explained on pathological examination of the brain adjacent or away from the targeted lesion. On necropsy studies, the treated regions show dose dependent changes ranging from minimal to complete avascular necrosis, extensive vacuolization in brain parenchyma along with rarefaction of the blood vessels (6)(7)(8)(9). An elegant study elucidating long-term radiation effects on normal brain tissue as a function of dose and time showed the possibility of neuroinflammation as the basis for the long-term side effects of radiation (10). ...
... The persistence of tumors after the treatment noted in the standard radiation treatment group, was similar to the tumor responses observed in the studies done in the past (6-8). The long-term treatment related changes seen in the standard radiation treatment group such as extensive vacuolization in brain parenchyma, encephalomalacia and rarefaction of vessels were similar to the findings reported in the literature (6)(7)(8)(9). ...
The main challenge in treating malignant brain neoplasms lies in eradicating the tumor while minimizing treatment-related damage. Conventional radiation treatments are associated with considerable side effects. Synchrotron generated micro-beam radiation (SMBRT) has shown to preserve brain architecture while killing tumor cells, however physical characteristics and limited facility access restrict its use. We have created a new clinical device which produces mini beams on a linear accelerator, to provide a new type of treatment called mini-beam radiation therapy (MBRT). The objective of this study is to compare the treatment outcomes of linear accelerator based MBRT versus standard radiation treatment (SRT), to evaluate the tumor response and the treatment-related changes in the normal brain with respect to each treatment type. Pet dogs with de-novo brain tumors were accrued for treatment. Dogs were randomized between standard fractionated stereotactic (9 Gy in 3 fractions) radiation treatment vs. a single fraction of MBRT (26 Gy mean dose). Dogs were monitored after treatment for clinical assessment and imaging. When the dogs were euthanized, a veterinary pathologist assessed the radiation changes and tumor response. We accrued 16 dogs, 8 dogs in each treatment arm. In the MBRT arm, 71% dogs achieved complete pathological remission. The radiation-related changes were all confined to the target region. Structural damage was not observed in the beam path outside of the target region. In contrast, none of the dogs in control group achieved remission and the treatment related damage was more extensive. Therapeutic superiority was observed with MBRT, including both tumor control and the normal structural preservation. The MBRT findings are suggestive of an immune related mechanism which is absent in standard treatment. These findings together with the widespread availability of clinical linear accelerators make MBRT a promising research topic to explore further treatment and clinical trial opportunities.
... These clinical manifestations can be correlated to the imaging changes on follow up scans (5), and further explained on pathological examination of the brain adjacent or away from the targeted lesion. On necropsy studies, the treated regions show dose dependent changes ranging from minimal to complete avascular necrosis, extensive vacuolization in brain parenchyma along with rarefaction of the blood vessels (6)(7)(8)(9). An elegant study elucidating long-term radiation effects on normal brain tissue as a function of dose and time showed the possibility of neuroinflammation as the basis for the long-term side effects of radiation (10). ...
... The persistence of tumors after the treatment noted in the standard radiation treatment group, was similar to the tumor responses observed in the studies done in the past (6-8). The long-term treatment related changes seen in the standard radiation treatment group such as extensive vacuolization in brain parenchyma, encephalomalacia and rarefaction of vessels were similar to the findings reported in the literature (6)(7)(8)(9). ...
... Regardless of grade, all canine meningiomas are capable of brain invasion, which can make surgical removal more challenging. Likewise, the incidence of atypical meningiomas in dogs is higher than their human counterparts, which may explain the difference in therapeutic response observed, as canine meningiomas tend to be more resistant to therapy (Sturges et al., 2008;Mariani et al., 2015;Suzuki et al., 1994). Canine meningiomas share many characteristic immunohistochemical patterns with their human counterpart, including those observed with vimentin and S100 labeling (Montoliu et al., 2006). ...
... In dogs, tumors located within the skullbase region or brainstem are not easily accessible, thus surgical resection is often associated with significant morbidity (Klopp et al., 2000;Niebauer et al., 1991). Hypofractionated radiation therapy and stereotactic radiosurgery offer alternative treatment options for canine meningioma with comparable median survival times of 10-17 months (Hu et al., 2015;Griffin et al., 2016;Mariani et al., 2015;Theon et al., 2000;Keyerleber et al., 2015;Bley et al., 2005). Likewise, adjuvant radiation therapy is typically reserved for atypical or anaplastic meningiomas in human patients (Apra et al., 2018). ...
Clinical translation of novel therapeutics that improve the survival and quality of life of patients with neurological disease remains a challenge, with many investigational drug and device candidates failing in advanced stage clinical trials. Naturally occurring inherited and acquired neurological diseases, such as epilepsy, inborn errors of metabolism, brain tumors, spinal cord injury, and stroke occur frequently in companion animals, and many of these share epidemiologic, pathophysiologic and clinical features with their human counterparts. As companion animals have a relatively abbreviated lifespan and genetic background, are immunocompetent, share their environment with human caregivers, and can be clinically managed using techniques and tools similar to those used in humans, they have tremendous potential for increasing the predictive value of preclinical drug and device studies. Here, we review comparative features of spontaneous neurological diseases in companion animals with an emphasis on neuroimaging methods and features, illustrate their historical use in translational studies, and discuss inherent limitations associated with each disease model. Integration of companion animals with naturally occurring disease into preclinical studies can complement and expand the knowledge gained from studies in other animal models, accelerate or improve the manner in which research is translated to the human clinic, and ultimately generate discoveries that will benefit the health of humans and animals.
... Cohorts of dogs treated with RT as a sole treatment modality for presumptively diagnosed brain tumors indicate an average survival of ∼16 months, with reported overall MST ranging from 7 and 24 months when all treated intracranial masses are analyzed (157,160,171,177,(184)(185)(186)(187)(188)(189)(190)(191). Some RT studies reported that extra-axial tumors (meningiomas) have a more favorable prognosis than intra-axial (glial) tumors (157,187,191). ...
... Some RT studies reported that extra-axial tumors (meningiomas) have a more favorable prognosis than intra-axial (glial) tumors (157,187,191). MST associated with RT treatment of extra-axial masses, the majority of which were presumptively diagnosed meningiomas, range from 9 and 30 months, and MST reported for intra-axial masses range from 7.5 and 13 months (33,157,160,171,177,184,(186)(187)(188)(189)(190)(191). Given the variable outcomes associated with both RT and surgery, there is currently no clearly superior choice between these two modalities when either is used a sole treatment for canine meningiomas (154). ...
In the dog, primary intracranial neoplasia represents ~2–5% of all cancers and is especially common in certain breeds including English and French bulldogs and Boxers. The most common types of primary intracranial cancer in the dog are meningioma, glioma, and choroid plexus tumors, generally occurring in middle aged to older dogs. Much work has recently been done to understand the characteristic imaging and clinicopathologic features of these tumors. The gross and histologic landscape of these tumors in the dog compare favorably to their human counterparts with many similarities noted in histologic patterns, subtype, and grades. Data informing the underlying molecular abnormalities in the canine tumors have only begun to be unraveled, but reveal similar pathways are mutated between canine and human primary intracranial neoplasia. This review will provide an overview of the clinicopathologic features of the three most common forms of primary intracranial cancer in the dog, delve into the comparative aspects between the dog and human neoplasms, and provide an introduction to current standard of care while also highlighting novel, experimental treatments that may help bridge the gap between canine and human cancer therapies.
... Canine high-grade gliomas (HGGs), which develop de novo in an outbred, immunocompetent host, are increasingly being pursued as a therapeutic model for the human GBM [12][13][14][15][16][17]. Canine HGGs, as defined by the Comparative Brain Tumor Consortium of the National Cancer Institute, encompass grade III and IV canine astrocytomas and oligodendrogliomas [12]. ...
Purpose
Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high-grade glioma and human glioblastomas share many molecular similarities, including the accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford to target the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic glioma model. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma.
Methods
We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine.
Results
We established a flow cytometry gating strategy for identifying and isolating FOXP3⁺ Tregs in dogs. The canine CD4 + CD25high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines, and expression increased when exposed to Tregs but not CD4 + helper T-cells.
Conclusion
Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.
... Canine high-grade gliomas (HGGs) which develop de novo in an outbred, immunocompetent host, are increasingly pursued as a therapeutic model for human GBM [12][13][14][15][16][17]. Canine HGGs, as de ned by the Comparative Brain Tumor Consortium of the National Cancer Institute, encompass grade III and IV canine astrocytomas and oligodendrogliomas [12]. ...
Purpose
Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high grade glioma and human glioblastomas share many molecular similarities, including accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford targeting the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic model of glioma. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma.
Methods
We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine.
Results
We established a flow cytometry gating strategy for identification and isolation of FOXP3⁺ Tregs in dogs. The canine CD4 + CD25high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines and expression increased when exposed to Tregs but not to CD4 + helper T-cells.
Conclusion
Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.
... However, two dogs with invasive spinal NSTs managed aggressively only survived for 3 weeks and 3.5 months after diagnosis, and two palliatively treated dogs (one cranial NST and one peripheral spinal NST) each survived for a year or more. Among dogs with trigeminal NSTs treated with radiation therapy, survival times have been reported to be prolonged [6,25,47,49], but mean survival times were not significantly different in a series of dogs treated with radiation therapy compared to unirradiated dogs [17]. In dogs with spinal NSTs including some invading the canal, definitive treatments have also been suggested to prolong survival [14,29,48], especially if non-infiltrated margins are achieved for surgically managed cases [48]. ...
Nerve sheath tumors (NSTs) are well-recognized primary nervous system tumors, but there is relatively limited information in dogs including comparison of NSTs in different anatomical locations. This retrospective study describes the clinical features and outcomes in a group of dogs with NSTs affecting the cranial nerves or spinal nerves. Thirty dogs were included, 25 with a presumptive diagnosis and five confirmed by histopathologic analysis. Seven dogs also had cytology of tumor samples, which were supportive of the NST diagnosis in four. Eight dogs had cranial nerve-associated NSTs, with six involving the trigeminal nerve. Twenty-two dogs had spinal nerve-associated NSTs including 13 invading the spinal canal and nine peripheral to the spinal canal, with the majority affecting nerves or nerve roots of the brachial plexus. The prognosis was poor, with dogs being euthanized eventually because of disease progression. Among dogs alive 1 week after diagnosis, the median survival time was 4 months but ranged from 2 weeks to >2 years. While there was a broad overlap between NST locations, survival was generally longer for dogs without spinal canal or intracranial involvement. The results expand available information on NSTs in dogs but should be interpreted with caution given the small number of dogs with a definitive diagnosis. Further investigation is warranted to determine how tumor location, invasiveness, and treatments pursued impact outcome.
... Brachycephalic breeds including boxers, Boston terriers, bullmastiffs, and bulldogs are overrepresented, comprising nearly 60% of reported oligodendrogliomas [2]. Even with surgical resection and radiation therapy, the median survival time remains dreadfully short at 9-14 months [3][4][5]. Treatment resistance is likely multifactorial, as it is in human high-grade gliomas. For example, canine glioma tumor mutational rate is exceedingly low [6], providing protection from anti-tumor immune responses. ...
The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.
... Irradiation of the entire neuroaxis is recommended as adjuvant treatment of CPC in all humans older than three years [36,37], while in younger infants chemotherapy is favored due to a high risk of late neurological sequelae in this group of patients [10]. Large studies for irradiation of CPT in dogs are missing and available data for median survival times include other tumor types such as meningioma or glioma that are usually overrepresented in these studies compared to less common CPT [32,[38][39][40]. ...
Choroid plexus tumors are commonly described as intraventricular mass lesions and account for 7–10% of intracranial, primary tumors in dogs. A 3-year-old Shetland sheepdog was presented with a history of slowly progressive lethargy, vision impairment and cognitive deficits. On magnetic resonance imaging, a subdural fluid accumulation (SFA) overlying and compressing the left parietotemporal lobe as well as multifocal changes consisting of cyst-like lesions, supposed intra-axial brain lesions and mild, multifocal meningeal thickening and generalized contrast enhancement were identified. Cerebrospinal fluid (CSF) analysis showed a mononuclear pleocytosis with negative results for infectious agents. The dog was treated with prednisolone followed by burr hole craniotomy with puncture of the SFA, which macroscopically appeared to be CSF-like fluid. After initial improvement, the dog deteriorated despite continuation of prednisolone and cytarabine therapy and was euthanized four weeks after surgery. Histopathology was consistent with a disseminated, neuroinvasive choroid plexus carcinoma (CPC) that involved the entire neuroaxis including the meninges of the brain and spinal cord. Immunohistochemical examination showed a strong Kir7.1 and a heterogenous cytokeratin-immunoreactivity in neoplastic cells. In conclusion, a CPC should be considered as a possible cause of a SFA even in the absence of an intraventricular mass lesion.
... However, the cat presented 6 months later with reoccurrence of neurological signs and was euthanised 10 months after VPS placement due to rapid deterioration (4). In dogs, both RT and VPS placement have been described for the treatment of ventricular tumors, but direct comparison of survival times is difficult due to variations in detailed reports of tumor location and clinical condition (2,38). Our case presented a rapid improvement and 10 months after diagnosis, the cat was still neurologically normal and free of clinical signs. ...
A 14-year-old male neutered domestic short-hair cat was presented for a history of behavioral changes and episodes of urinary retention. Neurological examination was consistent with a multifocal intracranial neuroanatomical localization, with suspected right sided lateralisation and suspected raised intracranial pressure (ICP). Brain magnetic resonance imaging (MRI) revealed an intraventricular multilobulated well-defined T2W-hyperintense and T1W-isointense, markedly contrast enhancing mass lesion within the dorsal aspect of the III ventricle extending into the left lateral ventricle, causing hypertensive obstructive hydrocephalus. A ventriculoperitoneal shunt (VPS) was placed within the left lateral ventricle, followed by a radiation therapy (RT) course of 45 Gy total dose in 18 daily fractions. Six-months post-RT, computed tomography revealed mild reduction in mass size and resolution of the hydrocephalus. The patient was neurologically normal with no medical treatment. Raised ICP causes severe clinical signs, can lead to brain ischaemia and herniation, and significantly increases anesthetic risk during RT. Placement of a VPS in cats with hypertensive obstructive hydrocephalus may allow improvement of neurological signs due to raised ICP, and therefore making the patient a more stable candidate for anesthesia and radiation therapy.
... Glioma, meningioma, and metastatic tumor are all common intracranial tumors. Due to the difference in tumor morphology, size, and lesion location, different tumors have different treatment methods [3,4]. erefore, preoperative precise qualitative is important in the selection of tumor treatment methods, guiding the formulation of treatment plans and evaluating the prognosis of patients. ...
The study aimed to analyze the application of diffusion tensor imaging (DTI) in the surgery of benign and malignant intracranial tumors through improved fuzzy C-means (FCM). First, a method of combining the maximum and minimum distances was proposed to improve the FCM algorithm. Then, the optimized FCM was applied to the diffusion tensor imaging (DTI) diagnosis. The patients were rolled into the benign tumor group and the malignant tumor group, and relevant parameters were compared. Finally, the postoperative total resection rate and disability rate of the DTI experimental group and the traditional control (Ctrl) group were evaluated. It was found that the segmentation accuracy of the optimized FCM algorithm was higher than traditional one and the obtained corpus callosum edge contour was clearer. In 63 patients with intracranial space, there were obvious differences in pairwise comparison of meningioma and glioma, metastatic tumor’s apparent diffusion coefficient (ADC) value, relative apparent diffusion coefficient (r ADC) value, and relative anisotropy fraction (r FA) P
... This is a similar to possibly improved MST as compared to other published MSTs for dogs with intracranial tumors treated with SRT. 4,7,8,13 Discernible differences in outcome between different types of SRT have not been identified. Further studies, ideally headto-head, are needed to allow for comparison. ...
Background
Limited data exist about the use, efficacy, and prognostic factors influencing outcome when CyberKnife is used to treat dogs with intracranial neoplasia.
Objectives
To determine the prognosis and associated prognostic factors for dogs that were imaged, determined to have primary intracranial tumors, and treated with CyberKnife radiotherapy.
Animals
Fifty‐nine dogs treated with CyberKnife radiotherapy for primary intracranial tumors.
Methods
Retrospective medical record review of cases from January 2010 to June 2016. Data extracted from medical records included signalment, weight, seizure history, tumor location, tumor type (based on imaging), gross tumor volume, planned tumor volume, treatment dates, radiation dose, recurrence, date of death, and cause of death.
Results
The median progression‐free interval (PFI) was 347 days (range 47 to 1529 days), and the median survival time (MST) was 738 days (range 4 to 2079 days). Tumor location was significantly associated with PFI when comparing cerebrum (median PFI 357 days; range 47‐1529 days) versus cerebellum (median PFI 97 days; range 97‐168 days) versus brainstem (median PFI 266 days; range 30‐1484 days), P = .03. Additionally, the presumed tumor type was significantly associated with MST (P < .001).
Conclusions and Clinical Importance
Use of Cyberknife and SRT might improve MST, compared with RT, in dogs with intracranial neoplasia.
... Its objective is to induce tumour cell death or inhibit further cell division, while minimizing damage to any normal tissue surrounding or in the irradiated volume. The majority of studies on irradiation of brain neoplasms includes all types of tumours, most cases being meningiomas [9,[12][13][14][15][16][17][18][19][20] and only one recent case study is exclusively dedicated to gliomas [10]. ...
Background
Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners.
Results
The disease-specific MST was 698 days (95% CI: 598–1135). Survival at 1 and 2 years were respectively 74.2 ± 7.4% and 49.0 ± 9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed.
Conclusions
RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
... Its objective is to induce tumour cell death or inhibit further cell division, while minimizing damage to any normal tissue surrounding or in the irradiated volume. The majority of studies on irradiation of brain neoplasms includes all types of tumours, most cases being meningiomas [9,[12][13][14][15][16][17][18][19][20] and only one recent case study is exclusively dedicated to gliomas [10]. ...
Background : Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners.
Results: The disease-specific MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2±7.4% and 49.0±9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed.
Conclusions: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
... IMRT's greater conformity enables dose escalation within the target, such as with hypofractionated or stereotactic radiotherapy (SRT) 24 . Stereotactic radiation therapy has been increasingly utilized in veterinary medicine for the treatment of intracranial tumors [25][26][27] . Reported survival times have range between 13.3 -18.7 months 25-27 , with one publication noting an increase in acute delayed radiation side effects 26 . ...
Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three‐dimensional conformal radiotherapy, reports of definitive‐intent, IMRT for canine intracranial tumors are lacking. Intensity‐modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi‐institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty‐two dogs treated with fractionated, definitive‐intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45‐50 Gy (2.25‐2.5 Gy per fraction in 18‐20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3‐26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity‐modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.
... IMRT's greater conformity enables dose escalation within the target, such as with hypofractionated or stereotactic radiotherapy (SRT) 24 . Stereotactic radiation therapy has been increasingly utilized in veterinary medicine for the treatment of intracranial tumors [25][26][27] . Reported survival times have range between 13.3 -18.7 months 25-27 , with one publication noting an increase in acute delayed radiation side effects 26 . ...
No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive-intent, intensity-modulated radiation therapy in dogs with PC. Medical records review was performed, including 18 patients from 4 institutions undergoing definitive-intent IMRT to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco-regional lymph nodes at diagnosis. Seventeen patients received concurrent nonsteroidal anti-inflammatory drugs; 15/18 (83%) patients received maximally-tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48-54 Gy (median 50 Gy) delivered as daily doses of 2.5-2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1-2 diarrhea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture, and hindlimb edema) was observed in three patients. Median event-free survival following radiation therapy was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 days vs 220 days in symptomatic dogs, P = 0.042). Event-free survival was significantly longer in patients treated with MTD chemotherapy (241d vs 25d, P < 0.001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = 0.008). These findings suggest that definitive-intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity. This article is protected by copyright. All rights reserved.
... A SRT tem mostrado melhores resultados quando comparado com a radioterapia convencional em cães com tumores intracranianos (meningiomas, tumores hipofisário, tumores de nervo trigêmeo, gliomas, histiocítico, sarcomas e tumores de plexo coróide). O tempo médio de sobrevida dos animais submetidos a essa terapia chega a aproximadamente 399 dias (66). ...
O câncer é uma neoplasia que acomete seres humanos e animais, sendo responsável pelo maior número de mortalidade. A radioterapia é uma prática médica, que utiliza radiação ionizante para eliminar ou impedir a multiplicação das células cancerígenas. A radioterapia divide-se em duas modalidades, denominadas de braquiterapia e teleterapia. Essa última vem adquirindo espaço dentro da medicina veterinária, principalmente para tratamento de tumores de cabeça e pescoço. Contudo esse trabalho propôs copilar e descrever os principais casos de teleterapia aplicada em tumores de cabeça e pescoço em pequenos animais por meio da literatura. Após uma breve revisão de literatura elaborada nesse estudo, foi possível identificar as principais aplicações da teleterapia nos tumores de cabeça e pescoço em pequenos animais e destacar eficácia dessa modalidade terapêutica na sobrevida dos animais envolvidos.
... The most common CNS brain tumors in dogs are meningiomas (∼45-50%), gliomas (∼40-70%), and choroid plexus neoplasms (∼5-7%) (15)(16)(17)(18). Treatment options for dogs with brain cancer include surgery, radiation therapy, chemotherapy, or a combination of modalities (19)(20)(21)(22)(23). Since the tumor incidence, tumor histologies, and molecular genetic features of canine brain tumors are remarkably similar to their human counterparts, this positions dogs uniquely as translational models for human brain cancer biology and investigational therapeutic research (15,16,(24)(25)(26)(27). ...
Gliomas and meningiomas are the most common brain neoplasms affecting both humans and canines, and identifying druggable targets conserved across multiple brain cancer histologies and comparative species could broadly improve treatment outcomes. While satisfactory cure rates for low grade, non-invasive brain cancers are achievable with conventional therapies including surgery and radiation, the management of non-resectable or recurrent brain tumors remains problematic and necessitates the discovery of novel therapies that could be accelerated through a comparative approach, such as the inclusion of pet dogs with naturally-occurring brain cancers. Evidence supports procaspase-3 as a druggable brain cancer target with PAC-1, a pro-apoptotic, small molecule activator of procaspase-3 that crosses the blood-brain barrier. Procaspase-3 is frequently overexpressed in malignantly transformed tissues and provides a preferential target for inducing cancer cell apoptosis. While preliminary evidence supports procaspase-3 as a viable target in preclinical models, with PAC-1 demonstrating activity in rodent models and dogs with spontaneous brain tumors, the broader applicability of procaspase-3 as a target in human brain cancers, as well as the comparability of procaspase-3 expressions between differing species, requires further investigation. As such, a large-scale validation of procaspase-3 as a druggable target was undertaken across 651 human and canine brain tumors. Relative to normal brain tissues, procaspase-3 was overexpressed in histologically diverse cancerous brain tissues, supporting procaspase-3 as a broad and conserved therapeutic target. Additionally, procaspase-3 expressing glioma and meningioma cell lines were sensitive to the apoptotic effects of PAC-1 at biologically relevant exposures achievable in cancer patients. Importantly, the clinical relevance of procaspase-3 as a potential prognostic variable was demonstrated in human astrocytomas of variable histologic grades and associated clinical outcomes, whereby tumoral procaspase-3 expression was negatively correlated with survival; findings which suggest that PAC-1 might provide the greatest benefit for patients with the most guarded prognoses.
... The use of SRS is well tolerated in humans and may also result in shorter response times than conventional RT (Mehta et al., 2017). The same technique has recently been applied to dogs with pituitary tumors and showed promising results (Mariani et al., 2015;Zwingenberger et al., 2016). ...
Early‐delayed side effects (EDSEs) following treatment of canine intracranial meningiomas with 1–3‐fraction stereotactic radiation therapy (SRT) can cause worsening neurologic signs, and one potential method of mitigating this toxicity is reducing the dose per fraction. Twenty dogs with imaging‐diagnosed intracranial meningiomas and telephone follow‐up of at least 6 months received a protocol of 6 Gy × 5, daily (30 Gy). A ‘possible EDSE’ was defined as mental dullness, neurologic exacerbation of existing neurologic signs or new neurologic signs occurring within 1‐4 months of completing SRT, regardless of the response to steroids and even if an MRI was not performed. A ‘probable EDSE’ was defined as mental dullness, neurologic exacerbation of existing neurologic signs or new neurologic signs occurring within 1‐4 months of completing SRT. These signs were either reversible with the initiation or increased doses of prednisolone, or follow‐up MRI revealed no evidence of an alternate explanation. No dogs experienced acute radiotoxicity or clinical signs compatible with EDSEs. The protocol appears to result in limited acute radiotoxicity, and further evaluation of the frequency of long‐term toxicities and relative efficacy should be undertaken.
Background
To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid‐associated morbidity and may be unnecessary.
Objective
Determine whether long‐term corticosteroid dependency can be minimized by use of succinct prednisone tapering.
Animals
Fifty‐five pet dogs undergoing brain tumor irradiation.
Methods
Nineteen dogs were treated using a “rapid‐taper” protocol wherein corticosteroid dose reduction began 0 to 20 days after completing RT. Outcomes were compared with a retrospectively studied control group (“slow‐taper”; N = 36 dogs) in which corticosteroids were tapered more slowly according to individual clinician recommendations.
Results
Patient demographics were similar between groups. Mean time to lowest prednisone dose was 41 days postirradiation in the rapid‐taper group and 117 days in the slow‐taper group (P = .003). In the rapid‐taper group, 15 of 19 dogs (84%) were completely tapered off prednisone, vs 18 of 36 (50%) in the slow‐taper group (P = .04). Rates at which corticosteroids had to be reinstituted later were similar for the 2 groups (approximately 1 in 3 dogs). Adverse effect rates were similar for the 2 groups. Although no comparable questionnaire‐derived data were available for the “slow‐taper” group, overall and neurologic quality of life remained stable after RT in the rapid‐taper group.
Conclusions and Clinical Importance
For many dogs, lengthy courses of PO prednisone are avoidable after intracranial RT. Future efforts should aim to identify which dogs benefit most from accelerated prednisone tapering.
Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011–2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)‐diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33–1593 days). The survival time for two pathology‐diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short‐lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation‐specific complications are possible due to the small dataset and limited follow‐up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long‐term survivors are noted.
The aim of this retrospective, secondary analysis study was to quantify the dosimetric impact of the lack of interobserver agreement on gross tumor volume (GTV) delineation for canine meningioma. This study used a previously reported population of 13 dogs with GTVs contoured on CT alone and on registered CT-MR by 18 radiation oncologists. The "true" GTV was generated for each dog using a simultaneous truth and performance-level estimation algorithm, and "true" brain was defined as the whole brain minus true GTV. Treatment plans were generated for each dog and observer combination, using criteria applied to the observer's GTV and brain contours. Plans were then categorized as a pass (met all planning criteria for true GTV and true brain) or fail. A mixed-effects linear regression was performed to examine differences in metrics between CT and CT-MR plans and mixed-effects logistic regression was performed to examine differences in percentages of pass/fail between CT and CT-MRI plans. The mean percent coverage of true GTV by prescribed dose was higher for CT-MR plans than for CT plans (mean difference 5.9%; 95% CI, 3.7-8.0; P < 0.001). There was no difference in the mean volume of true brain receiving ≥24 Gy and in maximum true brain dose between CT plans and CT-MR plans (P ≥ 0.198). CT-MR plans were significantly more likely to pass the criteria for true GTV and true brain than CT plans (OR 1.75; 95% CI, 1.02-3.01; P = 0.044). This study demonstrated significant dosimetric impact when GTV contouring was performed on CT alone compared with CT-MR.
Conventionally, radiation therapy (RT) has involved the delivery of large total doses of radiation, broken up, and given in many small daily dose “fractions”. Stereotactic radiosurgery (SRS) represents a departure from the paradigms of conventional RT. In SRS, the entire course of radiation therapy is condensed into a single treatment session. In today's world, most veterinary radiation oncologists would consider a standard (or conventional) course of definitive‐intent RT to deliver a total dose of 40‐54 Gy in 10‐20 daily fractions. In veterinary neuro‐oncology, SRS, and Stereotactic radiotherapy (SRT) have been associated with clinical outcomes that are broadly similar to those reported for conventional full‐course definitive‐intent RT. Such is the case when SRS and SRT are applied as treatments for canine intracranial meningiomas; treatment is generally well‐tolerated, and the median overall survival times are 18‐24 months. Similarly, postoperative SRS is infrequently used in human neuro‐oncology.
Hypophysectomy is the removal of the pituitary gland. Transsphenoidal hypophysectomy (TSH) is the removal of the pituitary gland via the sphenoid bone. Nonfunctional sellar masses in the dog and cat have been treated medically with a corticosteroid to control brain edema. Case selection for hypophysectomy in veterinary medicine is dependent on clinical signs, endocrine testing, tumor size, and concurrent co‐morbidities in a given patient. Postoperative management of these patients includes monitoring of vital signs, neurological status, fluid intake and output, serum electrolyte concentrations, palate incision site, and tear production. The optic chiasm and optic nerves are parasellar structures that can be damaged while performing TSH and lead to blindness. Long‐term follow up is necessary for optimal success post‐TSH. Because TSH causes diabetes insipidus, hypothyroidism, and hypoadrenocorticism, specific parameters will need to be monitored regularly post‐surgery.
Background
Intraventricular tumors are rare, optimal treatment is not defined. Symptomatic patients often exhibit life‐threatening hydrocephalus. With several months time‐to‐effect after radiotherapy (RT), increased intracranial pressure is concerning. This increase in pressure can be overcome by ventriculoperitoneal shunting (VPS).
Objectives
Retrospective evaluation of outcome and complications in dogs and cats with intracranial tumors treated with either RT or VPS/RT.
Animals
Twelve client‐owned cats and dogs.
Methods
Dogs and cats with symptomatic intraventricular tumors treated with definitive‐intent RT or VPS/RT were included in a retrospective, descriptive case series. Complications, tumor volume evolution, time‐to‐progression, and survival time were determined.
Results
Twelve animals were included: 1 cat and 5 dogs treated with single‐modality RT and 4 cats and 2 dogs treated with VPS/RT. Neurological worsening seen in 4/6 animals during single‐modality RT and 2/6 died during RT (suspected brain herniation). All dogs with VPS normalized clinically by the end of RT or earlier. Complications occurred in 4/6 animals, all but 1 were successfully managed surgically. Imaging follow‐up in 8 animals surviving RT showed a marked decrease in tumor volume. Median survival time was 162 days (95% confidence interval [CI]: 16; infinity) for animals treated with RT and 1103 days (95%CI: 752; infinity) for animals treated with VPS/RT. Median time‐to‐progression was 71 days (95%CI: 7; infinity) and 895 days (95%CI: 704; infinity) for each group, respectively. Two dogs died because of intraventricular metastasis 427 and 461 days after single‐modality RT.
Conclusions and Clinical Importance
Ventriculoperitoneal shunting led to rapid normalization of neurological signs and RT had a measurable effect on tumor volume. Combination of VPS/RT seems to be beneficial.
Pituitary tumors are recognized clinically either because the dog has clinical signs of hyperadrenocorticism or is having neurological signs. Several studies have found that the vast majority of dogs will have a return to normal or nearnormal neurologic status during or within several months after radiation treatment. Dogs with functional adrenal tumors require medical management perioperatively to help reduce the likelihood of complications. The majority of cats have a benign thyroid tumor described as multinodular adenomatous goiter, adenomatous hyperplasia, or adenoma. In dogs with a thyroid adenocarcinoma in the normal location, the thyroid gland appears abnormal in size, shape, or amount of uptake on scintigraphy compared with the normal gland, whereas in dogs with masses of non‐thyroid origin, the thyroid glands appear normal. The most common endocrine tumor of the pancreas in small animals is insulinoma, but it remains an uncommon tumor in dogs, rare in cats and common in ferrets.
This chapter covers the common surgical procedures for biopsy and resection of tumors of the nervous system (including skull and vertebrae), surgical decision‐making, and important procedural limitations, and describes patient evaluation and neuroimaging techniques. Unlike intracranial masses, calvarial masses are typically amenable to biopsy. Fine needle aspirates, needle biopsies, or minor surgical biopsies may have a role in the diagnosis of calvarial masses prior to a more invasive surgical resection or excision procedure. The chapter discusses pre‐surgical diagnostic workup and post‐operative care for brain tumors, and spinal cord tumors. It presents adjuvant therapies (e.g. stereotactic radiosurgery, fractionated radiation therapy, chemotherapy, immunotherapy) that pertain to specific tumor histologic types briefly as part of the overall clinical management of patients with nervous system tumors. Nerve sheath tumors arise from nerve roots and may compress the spinal cord as they grow proximally into the nerve root entry zones because of their close proximity.
The ideal treatment for intracranial histiocytic sarcoma (HS) remains unclear. Herein, we report a case of intracranial HS that was successfully treated using prednisolone and radiation therapy. The patient was a 9-year-old spayed female Pembroke Welsh Corgi that presented with epileptic seizures. Magnetic resonance imaging revealed a contrast-enhancing mass adjacent to the right piriform lobe. Prednisolone administration (1 mg/kg/day) decreased the lesion size. Additional palliative radiation therapy (total dose, 37 Gy) resulted in complete disappearance of the lesion. However, on day 164, the dog’s neurological signs deteriorated, and she was euthanized. Necropsy revealed an intracranial metastasis of HS via the cerebrospinal fluid without any extracranial metastasis. Nonetheless, combined prednisolone and radiation therapy might be effective in treating intracranial HS.
Background
Glioma-associated microglia/macrophage (GAM) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAM are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment, nor TGF Beta (TGFB) signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Spontaneously occurring canine gliomas share many features with human glioma and provide a complementary translational animal model for further study. Given the importance of GAM and TGFB in human glioma, the aims of this study were to further define the GAM-associated molecular profile and the relevance of TGFB signaling in canine glioma that may serve as the basis for future translational studies.
Methods
GAM morphometry, levels of GAM-associated molecules, and the canonical TGFB signaling axis were compared in archived samples of canine astrocytomas versus normal canine brain. Further, the effect of TGFB on the malignant phenotype of canine astrocytoma cells was evaluated.
Results
GAMs diffusely infiltrated canine astrocytomas. GAM density was increased in high-grade tumors that correlated with a pro-tumorigenic molecular signature and up-regulation of the canonical TGFB signaling axis. Moreover, TGFB1 enhanced migration of canine astrocytoma cells in vitro.
Conclusions
Canine astrocytomas share a similar GAM-associated immune landscape with human adult glioma. Our data also support a contributing role for TGFB1 signaling in the malignant phenotype of canine astrocytoma. These data further support naturally occurring canine glioma as a valid model for investigation of GAM-associated therapeutic strategies for human malignant glioma.
There is a lack of information regarding interobserver agreement on canine meningioma gross tumor volume (GTV) delineation, and on the impact of MRI on this agreement. The objectives of this retrospective, secondary analysis, observer agreement study were to describe agreement between veterinary radiation oncologists on GTV for canine intracranial meningioma, and to compare interobserver agreement between delineation based on CT alone and delineation based on fused CT-MRI. Eighteen radiation oncologists delineated GTV for 13 dogs with an imaging diagnosis of meningioma on pre- and postcontrast CT, pre- and postcontrast T1-weighted magnetic resonance, and T2-weighted magnetic resonance images. Dice similarity coefficient (DSC), concordance index (CI), and center of volume (COV) were used to quantify interobserver agreement. Multilevel mixed models were used to examine the difference in volume, DSC, CI and COV 3D distance between CT and CT-MR imaging. The mean volume for GTV contours delineated using fused CT-MRI was larger than when CT alone was used for delineation (mean difference CT-MR - CT = 0.89 cm3, 95% CI 0.66 to 1.12, P < .001). Interobserver agreement on GTV was improved when MRI was used; the mean DSC and CI were higher, and the mean COV 3D distance was lower, when fused CT-MRI was used than when CT alone was used (P < .001 for all differences). Based on our results, fused CT-MRI is recommended for radiation therapy planning of canine intracranial meningioma.
Background: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners.
Results: The disease-specific MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2±7.4% and 49.0±9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed.
Conclusions: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
Background: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumors. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumor imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners.
Results: The MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2±7.4% and 49.0±9.8%. Initial clinical signs were related to survival, as well as tumor characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed.
Conclusions: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumor control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI descriptions (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
Canine pituitary tumors are increasingly treated with stereotactic radiotherapy (SRT). Here, we report clinical outcomes in dogs treated with single‐fraction SRT; we also explore technical aspects of SRT treatment planning. A single‐institution retrospective study was performed, including any dog with a pituitary mass (PM) that was treated using a standardized single fraction (16 Gy) SRT protocol between 2014 and 2017. Via medical records review, 13 cases were identified. Nine dogs neurologically improved after SRT. Four dogs experienced MRI‐documented tumor volume reduction. Nine dogs experienced neurologic decline 1.5‐18 months after SRT and were euthanized. The median overall survival time was 357 days, with 15% alive 18 months after SRT. To better understand whether SRT target delineation is predictably altered by use of MRI in addition to CT, two radiation oncologists (RO) retrospectively re‐evaluated all imaging studies used for SRT planning in these 13 cases. Gross tumor volume (GTV) was contoured on co‐registered CT and MRIs for each case. In 7 cases, CT alone was deemed inadequate for GTV contouring by at least 1 RO. T1 post contrast MRI was considered the ideal image for GTV contouring in 11 cases. Contouring on MRI yielded larger GTV than CT for 11 cases. Interobserver variability existed in each case and was greater for MRI. In summary, use of co‐registered CT and MRI images is generally considered advantageous for PM delineation when using SRT. Notably, survival times reported herein are shorter than what has previously been reported for PM treated with finely fractionated full‐course RT protocols.
This article is protected by copyright. All rights reserved.
Background
Hypertensive or obstructive hydrocephalus is a common complication in dogs with tumors affecting the third ventricle for which few therapeutic options are available.
Objectives
To describe signalment, neurological status, and pre‐ and postsurgical findings, complications and survival time in 4 dogs with obstructive hydrocephalus caused by third ventricle tumors that were palliatively treated using ventriculoperitoneal shunting (VPS).
Animals
Four client‐owned dogs with obstructive hydrocephalus caused by tumors affecting the third ventricle.
Methods
Medical records were reviewed for dogs diagnosed with third ventricular tumors. Inclusion criteria were complete medical record, advanced diagnostic imaging for review, and VPS as sole surgical treatment.
Results
At the time of diagnosis, all patients displayed acute onset and rapidly progressive diffuse intracranial clinical signs. On advanced imaging, all dogs had a homogeneously enhancing mass occupying or collapsing the third ventricle as well as obstructive hydrocephalus. All of the dogs underwent VPS of the most dilated lateral ventricle. In 2 of the patients, intracranial hypertension followed by normotension after VPS placement was confirmed intraoperatively by means of direct intracranial pressure monitoring. Excellent clinical improvement was observed in all dogs immediately after surgery. Three patients required a second VPS in the contralateral lateral ventricle 3, 7 and 11 months after the first surgery, all of them with renewed improvement in clinical signs.
Conclusion and Clinical Importance
Ventriculoperitoneal shunting is a rapid and effective treatment for patients with obstructive (hypertensive) hydrocephalus caused by tumors located within the third ventricle.
Stereotactic radiation therapy (SRT) has emerged as a convenient definitive treatment modality in veterinary medicine, but few studies exist evaluating outcome with treatment for canine nasal tumors, and no studies report the treatment of one single tumor histotype. This retrospective, observational study evaluates toxicity, response, and survival in 17 dogs with nasal carcinomas treated with SRT. Dogs received a median of 3000 centigray in three fractions via 6‐MV linear accelerator. Eighty‐eight percent of patients (n = 15) demonstrated clinical benefit. Of dogs with repeated CT imaging (n = 10), 60% (n = 6) achieved a partial response and 10% (n = 1) achieved a complete response. Median progression‐free survival (PFS) was 359 days. Median survival time (MST) was 563 days. Among dogs evaluable for acute toxicity, 50% (n = 10) developed low grade toxicity (grade 1, n = 4; grade 2, n = 1). No patients developed grade 3 toxicity. 16 dogs (87%) evaluable over the long term developed signs consistent with possible late toxicity. The majority of late toxicities were mild (alopecia, hyperpigmentation, and leukotrichia n = 10; ocular discharge and keratoconjunctivitis sicca n = 5). Thirty‐seven percent of patients (n = 6) developed seven possible grade 3 late toxicities (blindness, n = 3; fistula, n = 1; seizures, n = 3), which were difficult to distinguish from progressive disease in most patients. Of the prognostic factors evaluated (demographics, tumor stage, dosimetric data, epistaxis, facial deformity, clinical response, image‐based response, nonsteroidal anti‐inflammatory drugs, and chemotherapy), only clinical response was a positive prognostic factor on MST (P < .00). No factors were found to be significantly associated with PFS.
The use of conventional multifractionated radiotherapy for the treatment of glial tumors is well documented in the literature. Recently, stereotactic radiotherapy (SRT) has become more widely available allowing for hypofractionated protocols; however, its usefulness in the treatment of canine intracranial gliomas is largely undetermined. We conducted a retrospective analysis, including 21 dogs diagnosed with presumptive intracranial gliomas treated with one or more courses of 3 fractions of 8-10 Gy CyberKnife SRT. The objective of this study was to evaluate the efficacy, safety and prognostic factors associated with the use of SRT for the treatment of canine intracranial gliomas. Overall MST for all dogs was 636 days (d). Dogs treated with one course of the described SRT protocol had a MST of 258 d while those treated with >1 course had a MST of 865 d (P = 0.0077 log rank, 0.0139 Wilcoxon). Dogs treated with one course of SRT who received adjuvant chemotherapy had a MST of >658 d and lived significantly longer than those who did not receive chemotherapy (MST, 230 d) (P = 0.0414 log rank, 0.0453 Wilcoxon). The most common adverse event included presumptive transient demyelination in 3/21 dogs, which was treated successfully with corticosteroids in all patients. This study provides evidence that SRT is effective in prolonging survival in dogs with intracranial gliomas, and may provide similar results to conventional fractionated protocols, while decreasing the number of hospital visits and anesthetic episodes. Additionally, it appears that patients can be safely treated with multiple rounds of SRT resulting in improved survival times. This article is protected by copyright. All rights reserved.
Sources of residual setup error after image guidance include image localization accuracy, errors associated with image registration, and inability of some treatment couches to correct submillimeter translational errors and/or pitch and roll errors. The purpose of this experimental study was to measure setup error after image‐guided correction of the canine intracranial region, using a 4°‐of‐freedom couch capable of 1 mm translational moves. Six cadaver dogs were positioned 45 times as for clinical treatment using a vacuum deformable body cushion, a customizable head cushion, a thermoplastic mask and an indexed maxillary plate with a dental mold. The location of five fiducial markers in the skull bones was compared between the reference position and after Megavoltage (MV), Kilovoltage (kV) and Cone‐Beam Computed Tomography (CBCT)‐guided correction using orthogonal kV images. The mean three‐dimensional distance vectors after MV, kV and CBCT‐guided correction were 1.7 mm, 1.5 mm and 2.2 mm, respectively. All values were significantly different (P < 0.01). The 95th percentiles of the three‐dimensional distance vectors after online MV, kV and CBCT‐guided correction were 2.8 mm, 2.6 mm and 3.6 mm, respectively. Residual setup error in the clinical scenario examined was on the order of millimeters and should be considered when choosing PTV margins for image‐guided radiation therapy of the canine intracranial region. This article is protected by copyright. All rights reserved.
In this prospective, exploratory study, we evaluated the positioning accuracy in a group of 15 dogs undergoing fractionated stereotactic radiotherapy for tumors affecting the head, using a modified human maxillary fixation device (Elekta Fraxion™ system). Positioning was assessed using on‐board volumetric imaging, with a six‐degrees‐of‐freedom image registration technique. Prior to treatment delivery, CBCT images were obtained and patient alignment was corrected, in both translational and rotational planes, using a six‐degrees‐of‐freedom robotic patient positioning system (HexaPOD Evo RT System). The maximum angular inter‐fraction motions observed were 6.1° (yaw), 10.9° (pitch), and 4.5° (roll). The mean systematic translational errors were 4.7, 2.6, and 2.3 mm, mean random translational errors were 3.0, 2.2, and 2.5 mm, and mean overall translational errors were 2.4, 0.7, and 2.3 mm in the cranial‐caudal, lateral, and dorsal‐ventral directions, respectively. The mean systematic rotational errors were 1.17°, 0.77°, and 1.43°, the mean rotational random errors were 1.65°, 1.46°, and 1.34° and the mean overall rotational errors were 0.56°, 0.22°, and 0.29° in the yaw, pitch, and roll directions, respectively. The mean error of the three‐dimensional vector was 6.9 mm with a standard deviation of 3.8 mm. Ninety‐five percent of the three‐dimensional vectors were <14.8 mm. This study demonstrates that this maxillary fixation device relies on six‐degrees‐of‐freedom registration and an ability to apply corrections using a six‐degrees‐of‐freedom couch for accurate patient positioning and tumor targeting. Its use in conformal radiation therapy in dogs is not recommended.
Magnetic resonance images of twenty-five dogs with histopathologically confirmed primary brain tumors were evaluated. A lesion was visible in each dog. Meningiomas were extra-axial lesions that enhanced markedly withj gadolinium-DTPA. Glimas were Characteized by intra-axial location, significant mass effect and surrounding edema, and variable enhancement patterns. Choroid plexus tumors and pituitary tumors were differentiated by their location and marked enbancement. Prediction of general typeof tumor was correct in 24 of 25 dogs.
Management of patients with recurrent glioblastoma (GB) comprises a therapeutic challenge in neurooncology owing to the aggressive nature of the disease with poor local control despite a combined modality treatment. The majority of cases recur within the high-dose radiotherapy field limiting the use of conventional techniques for re-irradiation due to potential toxicity. Stereotactic radiosurgery (SRS) offers a viable noninvasive therapeutic option in palliative treatment of recurrent GB as a sophisticated modality with improved setup accuracy allowing the administration of high-dose, precise radiotherapy. The aim of the study was to, we report our experience with single-dose linear accelerator (LINAC) based SRS in the management of patients with recurrent GB.
Between 1998 and 2010 a total of 19 patients with recurrent GB were treated using single-dose LINAC-based SRS. The median age was 47 (23-65) years at primary diagnosis. Karnofsky Performance Score was > or = 70 for all the patients. The median planning target volume (PTV) was 13 (7-19) cc. The median marginal dose was 16 (10-19) Gy prescribed to the 80%-95% isodose line encompassing the planning target volume. The median follow-up time was 13 (2-59) months.
The median survival was 21 months and 9.3 months from the initial GB diagnosis and from SRS, respectively. The median progression-free survival from SRS was 5.7 months. All the patients tolerated radiosurgical treatment well without any Common Toxicity Criteria (CTC) grade > 2 acute side effects.
Single-dose LINAC-based SRS is a safe and well- tolerated palliative therapeutic option in the management of patients with recurrent GB.
The optimal management of subtotally resected or recurrent malignant meningiomas remains controversial. We evaluated the efficacy of linear accelerator (LINAC) radiosurgery for atypical and anaplastic meningiomas after incomplete resection or treatment of recurrences.
Between August 1990 and December 2003, 16 patients with 28 meningiomas WHO II and III were treated by stereotactic LINAC radiosurgery at our institution. The median radiological follow-up was 60.3 months, respectively (range: 7.2-173.9 months). Fourteen tumors in nine patients were classified as WHO II and 14 tumors in seven patients as WHO III. The median surface dose was 14 Gy (range: 10-15 Gy) with a median tumor volume of 4.8 ml (range: 0.51-51.4 ml).
Clinical condition improved in four patients, remained unchanged in nine and deteriorated in one. Tumor shrinkage was seen in eight of 28 meningiomas and a stable disease in 12. Eight of 28 meningiomas showed local tumor progression. The overall tumor control rate (TCR) was 84%, 70%, 70% after 3, 5, 10 years. According to grading the corresponding TCR after 3, 5, 10 years was 91%, 81%, 81% for grade II and 77%, 60%, 60% for grade III meningiomas. Overall progression-free survival (PFS) was 74%, 67%, 58% after 3, 5, 10 years. According to grading the PFS after 3, 5, 10 years was 88%, 75%, 75% for grade II meningiomas and 57%, 57%, 43% for grade III meningiomas.
Our results show the efficacy and safety of LINAC radiosurgery for incompletely resected or recurrent malignant meningiomas with a relatively high local tumor control and low morbidity.
Trans-sphenoidal neurosurgery is the gold standard treatment for pituitary adenomas, but it can be contraindicated or ineffective. Stereotactic radiosurgery is a procedure aimed at controlling hormone hypersecretion and tumor size of pituitary adenomas. This Review discusses the long-term efficacy and adverse effects of stereotactic radiosurgery with the Gamma Knife((R)) in secreting and nonsecreting pituitary adenomas. Long-term data confirm the antisecretory efficacy of the procedure (about 50% remission in hypersecreting tumors) but also a previously unknown low risk of recurrence (2-10% of cases). The time to remission is estimated to range from 12 to 60 months. The antitumoral efficacy of this treatment against nonsecreting tumors is observed in about 90% of cases. Hypopituitarism is the main adverse effect, observed in 20-40% of cases. Comparisons with conventional fractionated radiotherapy reveal a lower rate of remission with Gamma Knife((R)) radiosurgery, counterbalanced by a more rapid efficacy and a lower rate of hypopituitarism. Short-term follow-up results on stereotactic fractionated radiotherapy suggest a risk of hypopituitarism similar to the one observed with radiosurgery. Therefore, stereotactic radiosurgery is probably still useful to treat some cases of pituitary adenoma, despite the fact that antisecretory drugs, particularly for acromegaly and prolactinomas, are becoming more effective and are well tolerated, thus increasing the probability of success with nonsurgical therapy.
Question
Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities?
Target population
These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect.
Recommendations
SRS plus WBRT vs. WBRT alone
Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS ≥ 70.
Level 2 Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1–4 metastatic brain tumors who have a KPS ≥ 70.
Level 3 Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2–3 metastatic brain tumors.
Level 4 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70.
SRS plus WBRT vs. SRS alone
Level 2 Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time.
Surgical Resection plus WBRT vs. SRS ± WBRT
Level 2 Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3: Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible.
SRS alone vs. WBRT alone
Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.
Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.
Meningiomas located in the region of the base of skull are difficult to access. Complex combined surgical approaches are more likely to achieve complete tumor removal, but frequently at a cost of treatment related high morbidity. Local control following subtotal excision of benign meningiomas can be improved with conventional fractionated external beam radiation therapy with a reported 5-year progression-free survival up to 95%. New radiation techniques, including stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), and intensity-modulated radiotherapy (IMRT) have been developed as a more accurate technique of irradiation with more precise tumor localization, and consequently a reduction in the volume of normal brain irradiated to high radiation doses. SRS achieves a high tumour control rate in the range of 85-97% at 5 years, although it should be recommended only for tumors less than 3 cm away more than 3 mm from the optic pathway because of high risk of long-term neurological deficits. Fractionated RT delivered as FSRT, IMRT and protons is useful for larger and irregularly or complex-shaped skull base meningiomas close to critical structures not suitable for single-fraction SRS. The reported results indicate a high tumour control rate in the range of 85-100% at 5 years with a low risk of significant incidence of long-term toxicity. Because of the long natural history of benign meningiomas, larger series and longer follow-up are necessary to compare results and toxicity of different techniques.
The purpose of this study was to describe our clinical experience using optically-guided linear accelerator (linac)-based frameless stereotactic radiosurgery (SRS) for the treatment of brain metastases. Sixty-five patients (204 lesions) were treated between 2005 and 2008 with frameless SRS using an optically-guided bite-block system. Patients had a median of 2 lesions (range, 1-13). Prescription dose ranged from 14 to 22 Gy (median, 18 Gy) and was given in a single fraction. Clinical and radiographic evaluation occurred every 2-4 months following treatment. At a median follow-up of 6.2 months, actuarial survival at 12 months was 40% [95% confidence interval (CI), 28-52). Of 135 lesions that were evaluable for local control (LC), 119 lesions (88%) did not show evidence of progression. Actuarial 12 month LC was 76% (95% CI, 66-86). Tumors <or=2 cm in size had a better 12 month LC rate (81% vs. 36%, P = 0.017) than those >2 cm. Adverse events occurred in three patients (5%). Optically-guided linac-based frameless SRS can produce clinical outcomes that compare favorably to frame-based techniques. As this technique is convenient to use and allows for the uncomplicated delivery of hypofractionated radiotherapy, frameless SRS will likely have an increasingly important role in the management of brain metastases.
This study reviews the long-term clinical results of stereotactic radiosurgery in the treatment of pituitary adenoma patients.
We reviewed the outcomes of 298 patients who underwent Gamma Knife radiosurgery for recurrent or residual pituitary adenomas. These results are compared to other contemporary radiosurgical series.
Pituitary tumors are well-suited for radiosurgery, since radiation can be focused on a well circumscribed region, while adjacent neural structures in the suprasellar and parasellar regions are spared. The overall rate of volume reduction following stereotactic radiosurgery is 85% for non-secretory adenomas that are followed for more than 1-year. The rates of hormonal normalization in patients with hypersecretory adenomas can vary considerably, and tends to be higher in patients with Cushing's Disease and acromegaly (remission rate of approximately 53% and 54%, respectively) when compared with patients who have prolactinomas (24% remission) and Nelson's syndrome (29%) remission. Advances in dose delivery and modulation of adenoma cells at the time of radiosurgery may further improve results.
Although the effectiveness of radiosurgery varies considerably depending on the adenoma histopathology, volume, and radiation dose, most studies indicate that radiosurgery when combined with microsurgery is effective in controlling pituitary adenoma growth and hormone hypersecretion. Long-term follow-up is essential to determine the rate of endocrinopathy, visual dysfunction, hormonal recurrence, and adenoma volume control.
A retrospective study of 86 dogs with brain tumors was undertaken. Sixty-nine dogs had histologic confirmation of tumor type, whereas the remaining 17 dogs had CT evidence of a brain tumor. All dogs had neurologic abnormalities. Seven dogs received no treatment, 38 dogs received only symptomatic treatment, and 41 dogs received some form of definitive treatment, in addition to medical management. Types of definitive treatment included surgery, cobalt-60 radiation, whole-body hyperthermia, 125I implants, and chemotherapy, alone or in combination. The factor that was most associated with survival duration was mode of therapy. Those dogs who were treated with cobalt-60 radiation, with or without other combinations of therapy, lived significantly longer than dogs who received surgery (+/- 125I implants), or dogs who received symptomatic treatment (P = 0.01 and P less than 0.001, respectively). After statistic adjustment for treatment, multiplicity of brain involvement (solitary vs. multiple) provided prognostic information with respect to survival (P = 0.001), with dogs who had a solitary site of involvement having a better prognosis. After further adjustment, initial neurologic dysfunction (mild/moderate vs. severe) showed significance as prognostic variable (P = 0.005). Both the mild and moderate groups had a more favorable prognosis compared with dogs who had severe initial neurologic impairment. The median survival time for the 86 dogs was 1.0 month (range: 1 day-42.4 mo). Median survival times of dogs receiving: 1) no therapy or only symptomatic therapy, 2) surgery (+/- 125I), or 3) cobalt-60 radiation (+/- hyperthermia, +/- surgery) were 0.2, 0.9, and 4.9 months, respectively.
The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible.
From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm.
Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047).
SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.
Over a reporting period of 5 years, craniotomy was performed in 26 dogs and 5 cats with various intracranial lesions. X-ray computed tomography was performed in all animals prior to surgery. Twenty dogs and all cats had intracranial neoplasms; of these, 14 were meningioma, and 11 represented a wide variety of brain tumors and skeletal tumors. Three dogs were treated surgically for traumatic, open-skull fractures with cerebral damage, and 3 underwent biopsy to evaluate chronic inflammatory brain disease. The overall median survival time was 212 days, the 1-year survival rate was 39%, and the 2-year survival rate was 20%. Dogs and cats with meningioma survived a mean 198 and 485 days, respectively, with 1-year survival rates of 30% for dogs and 50% for cats. The overall median survival time for animals with tumors other than meningeal intracranial neoplasms was 414 days, with a 1-year survival rate of 40%. The death of 19% of all animals could be related to the combination of advanced brain disease and surgery. Because fatality seldom occurred as a direct result of surgery, morbidity and mortality associated with craniotomy in pet animals can be seen as acceptably low. In 29 of 34 craniotomies, dura mater defects were left unsutured and no adverse effects were seen.
Methods of stereotactic radiosurgery are reviewed and compared with respect to technical factors and published clinical results. Heavy-ion beams, the Leksell cobalt-60 gamma knife, and the conventional linear accelerator (linac) are compared with respect to dosimetry, radiobiology, treatment planning, cost, staffing requirements, and ease of use. Clinical results on the efficacy of treatment of arteriovenous malformations are tabulated, and other applications of radiosurgery are described. It is concluded that although there are dosimetric and radiobiological advantages to charged-particle beams that may ultimately prove critical in the application of radiosurgery to large (> 30 mm) lesions, these advantages have not yet demonstrated clinical effect. On the other hand, equally excellent clinical results are obtained for small lesions with photon beams--the gamma knife and the linac. There are only minor differences between gamma and x-ray beam dose distributions for small, spherical-shaped targets. Mechanical precision is superior for the gamma knife as compared with the linac. The superior mechanical precision is of limited importance for most clinical targets, because inaccuracy of cranial target localization based on radiological imaging is greater than the typical linac imprecision of +/- 1 mm. Treatment planning for the linac is not standardized, but existing systems are based on well-known algorithms. The linac allows flexible, ready access to individualized beam control, without intrinsic field size limitations. Thus, it is more readily possible to achieve homogeneous dose distributions for nonspherical targets with one or more dimensions greater than 25 mm, as compared with that achieved with the gamma unit.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper records preliminary results achieved in 10 dogs with histologically confirmed intracranial tumours treated by a variety of methods. One case was treated by surgical excision alone, three cases by surgical excision and external beam radiotherapy, one by surgical excision followed by cytotoxic chemotherapy (lomustine), two by radiotherapy alone, two by chemotherapy alone, and a combination of all modalities was used in one case. Palliation of clinical signs was acheived to varying degrees in all but one case and the quality of life was much improved in nine out of 10 animals. Survival times following first treatment varied from 10 days to 16 months. One dog is still alive with no deficits at 12 months following first treatment (surgery). These results and those reported else-where are discussed.
ABSTRACTA prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary-dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at
Distinguishing radiation necrosis (RN) from tumor recurrence after stereotactic radiosurgery (SRS) for brain metastases is challenging. This study assesses the sensitivity (SN) and specificity (SP) of an MRI-based parameter, the "lesion quotient" (LQ), in characterizing tumor progression from RN. Records of patients treated with SRS for brain metastases between 01/01/1999 and 12/31/2009 and with histopathologic analysis of a subsequent contrast enhancing enlarging lesion at the treated site at a single institution were examined. The LQ, the ratio of maximal nodular cross sectional area on T2-weighted imaging to the corresponding maximal cross sectional area of T1-contrast enhancement, was calculated by a neuroradiologist blinded to the histopathological outcome. Cutoffs of <0.3, 0.3-0.6, and >0.6 have been previously suggested to have correlated with RN, mixed findings and tumor recurrence, respectively. These cutoff values were evaluated for SN, SP, positive predictive value (PPV) and negative predictive value (NPV). Logistic regression analysis evaluated for associated clinical factors. For the 51 patients evaluated, the SN, SP, PPV and NPV for identifying RN (LQ < 0.3) were 8, 91, 25 and 73 %, respectively. For the combination of recurrent tumor and RN (LQ 0.3-0.6) the SN, SP, PPV and NPV were 0, 64, 0 and 83 %. The SN, SP, PPV and NPV of the LQ for recurrent tumor (LQ > 0.6) were 59, 41, 62 and 39 %, respectively. Standard MRI techniques do not reliably discriminate between tumor progression and RN after treatment with SRS for brain metastases. Additional imaging modalities are warranted to aid in distinguishing between these diagnoses.
Atypical meningiomas have poor local control with emerging literature indicating the use of radiosurgery in treatment. The purpose of this study was to evaluate clinical outcomes including local control and failure pattern after Gamma Knife radiosurgery (GKRS) and factors that may affect these outcomes. Between 1999 and 2008, 24 patients were treated with GKRS as either primary or salvage treatment for pathologically proven atypical meningiomas. Treatment failures were determined by serial magnetic resonance imaging. A median marginal dose of 14 Gy was used (range 10.5-18 Gy). Overall local control rates at 1, 2, and 5 years were 75, 51, and 44%, respectively. With median follow-up time of 42.5 months, 14 of 24 patients experienced a treatment failure at time of last follow-up. Eight recurrences were in-field, four were marginal failures, and two were distant failures. Wilcoxon analysis revealed that the conformality index (CI) was a significant predictor of local recurrence (P = 0.04). CI did not predict for distant recurrences (P = 0.16). On multivariate analysis evaluating factors predicting progression free survival, dose >14 Gy was found to be statistically significant (P = 0.01). There appears to be a dose response using GKRS beyond 14 Gy but given the suboptimal local control rates in this study, higher doses may still be needed to obtain better local control.
The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown.
To estimate sensitivity, specificity, and inter-rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs.
One hundred and twenty-one client-owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44).
Retrospective, multi-institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter-rater agreement were calculated to estimate diagnostic performance.
MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter-rater agreement was very good for overall detection of structural brain lesions (κ = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (κ = 0.299, 95% CI = 0, 0.761, P = .21).
MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.
Skull base meningiomas are challenging tumors owing in part to their close proximity to important neurovascular structures. Complete microsurgical resection can be associated with significant morbidity, and recurrence rates are not inconsequential. In this study, the authors evaluate the outcomes of skull base meningiomas treated with Gamma Knife surgery (GKS) both as an adjunct to microsurgery and as a primary treatment modality.
The authors performed a retrospective review of a prospectively compiled database detailing the outcomes in 255 patients with skull base meningiomas treated at the University of Virginia from 1989 to 2006. All patients had a minimum follow-up of 24 months. The group comprised 54 male and 201 female patients, with a median age of 55 years (range 19-85 years). One hundred nine patients were treated with upfront radiosurgery, and 146 patients were treated with GKS following resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.
Meningiomas were centered over the cerebellopontine angle in 43 patients (17%), the clivus in 40 (16%), the petroclival region in 28 (11%), the petrous region in 6 (2%), and the parasellar region in 138 (54%). The median duration of follow-up was 6.5 years (range 2-18 years). The mean preradiosurgery tumor volume was 5.0 cm(3) (range 0.3-54.8 cm(3)). At most recent follow-up, 220 patients (86%) displayed either no change or a decrease in tumor volume, and 35 (14%) displayed an increase in volume. Actuarial progression-free survival at 3, 5, and 10 years was 99%, 96%, and 79%, respectively. In Cox multivariate analysis, pre-GKS covariates associated with tumor progression included age greater then 65 years (HR 3.41, 95% CI 1.63-7.13, p = 0.001) and decreasing dose to tumor margin (HR 0.90, 95% CI 0.80-1.00, p = 0.05). At most recent clinical follow-up, 230 patients (90%) demonstrated no change or improvement in their neurological condition and the condition of 25 patients had deteriorated (10%). In multivariate analysis, the factors predictive of new or worsening symptoms were increasing duration of follow-up (OR 1.01, 95% CI 1.00-1.02, p = 0.015), tumor progression (OR 2.91, 95% CI 1.60-5.31, p < 0.001), decreasing maximum dose (OR 0.90, 95% CI 0.84-0.97, p = 0.007), and petrous or clival location versus parasellar, petroclival, and cerebellopontine angle location (OR 3.47, 95% CI 1.23-9.74, p = 0.018).
Stereotactic radiosurgery offers a high rate of tumor control and neurological preservation in patients with skull base meningiomas. After radiosurgery, better outcomes were observed for those receiving an optimal radiosurgery dose and harboring tumors located in a cerebellopontine angle, parasellar, or petroclival location.
A stereotactic brain biopsy system that is magnetic resonance (MR) imaging-guided has not been validated in dogs. Our purpose was to determine the mean needle placement error in the caudate nucleus, thalamus, and midbrain of a canine cadaver brain using the modified Brainsight stereotactic system. Relocatable reference markers (fiducial markers) were attached to the cadaver head using a dental bite block. A T1-weighted gradient echo three-dimensional (3D) sequence was acquired using set parameters. Fiducial markers were used to register the head to the acquired MR images in reference to a 3D position sensor. This allowed the planning of trajectory path to brain targets in real time. Coordinates (X, Y, Z) were established for each target and 0.5 microl of diluted gadolinium was injected at each target using a 26-gauge needle to create a lesion. The center of the gadolinium deposition was identified on the postoperative MR images and coordinates (X', Y', Z') were established. The precision of this system in bringing the needle to target (needle placement error) was calculated. Seventeen sites were targeted in the brain. The mean needle placement error for all target sites was 1.79 +/- 0.87 mm. The upper bound of error for this stereotactic system was 3.31 mm. There was no statistically significant relationship between needle placement error and target depth (P = 0.23). The ease of use and precision of this stereotactic system support its development for clinical use in dogs with brain lesions > 3.31 mm.
Meningiomas are the second most common primary tumor of the brain. Surgical resection is the preferred treatment for easily accessible tumors that can be safely removed. However, many tumors arise deep within the skull base making complete surgical resection difficult or impossible. Stereotactic radiosurgery is a highly effective alternative to surgical resection that has been used as a primary therapy for benign meningiomas as well as an adjuvant treatment for residual or recurrent tumors. The 5-year tumor control rates for stereotactic radiosurgery are equivalent to gross-total resection with lower morbidity than surgery, especially for skull base lesions. Additionally, adjuvant treatment of subtotally resected tumors results in tumor control rates equivalent to gross-total resection. Stereotactic radiosurgery has been used extensively for the treatment of small and medium sized skull base meningiomas. This technique has also been applied to large meningiomas and superficial tumors such as convexity and parasagittal meningiomas. However, multiple studies demonstrate that tumor control is decreased for superficial lesions and with increasing tumor size. In addition, radiation toxicity increases with increasing tumor size and superficial location. Based on a thorough review of the literature, stereotactic radiosurgery should be considered the primary treatment for skull base meningiomas with high surgical risk and in cases of superficial meningiomas where surgery is contraindicated.
A study was undertaken to define the variables associated with tumor control and survival after single-session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas.
Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm(3) ; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow-up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22).
Tumor grade correlated with disease-specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression-free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm(3) were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation-related complications at a median of 6 months after radiosurgery.
Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas.
Although histologic examination following stereotactic or surgical brain biopsy is required for definitive antemortem diagnosis of intracranial neoplasms, these tumors are often associated with magnetic resonance (MR) imaging features that warrant a presumptive or prioritized differential diagnosis. The MR imaging features of common canine central nervous system (CNS), adenohypophyseal, and metastatic intracranial neoplasms are reviewed. Characterization of neoplasms by histologic type and biological grade is based on the 2007 World Health Organization classification system for CNS tumors in humans.
Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial. We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy. The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91-100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation to >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84-100% but disappointing hearing preservation rates of 33-42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures. As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.
Meningiomas represent a common intracranial tumor in the adult population. Although extirpation to achieve a gross total resection or at least decrease mass effect has been the mainstay of treatment, stereotactic radiosurgery has come to play an increasingly important role in the management of patients with meningiomas. Radiosurgery utilizes highly focused, beams of ionizing radiation to inactivate tumor cells. Image guidance and a steep dose fall off are critical features of this approach. The radiobiology of radiosurgery differs in certain advantageous ways from conventional radiotherapy. Radiosurgery initially was utilized to treat recurrent or residual skull base meningiomas. As success was observed in this setting, radiosurgery has gradually expanded its role so as to treat convexity meningiomas; it is also used as an upfront treatment for patients for whom clinical and neuro-imaging findings are consistent with a meningioma. Most large series demonstrate tumor control rates for patients with grade I meningiomas in excess of 85%. Neurological function is generally preserved or improved for patients with meningiomas. However, complications can occur. Longitudinal follow-up including neurologic and radiologic assessment is required. Single and multisession stereotactic radiosurgery will likely play an expanded role in the treatment of patients with meningiomas.
One hundred and seventeen patients with cavernous sinus meningiomas had LINAC radiosurgery at our institution in the period 1993-2007. Six cases were lost and 9 had less than 1 year follow up. The remaining 102 patients were prospectively followed up at 1 y intervals with clinical, neuro-ophthalmological and MRI examinations. Patients' age ranged between 31 and 86 years (mean 57). Seventy percent were females. The mean tumor volume was 7 cc. Thirty-three patients had previous microsurgery. Tumors were defined with high resolution MRI obtained 1-2 days before treatment and fused to stereotactic CT. Treatment was mostly delivered through a minimultileaf collimator and multiple dynamic arcs. The minimal dose to the tumor margin was 12-17.5 Gy (mean 13.5) encompassed by the 80% isodose shell. Radiation dose to the optic apparatus was kept below 10 Gy. Follow up ranged from 12 to 180 months (mean 67 months). Tumor control (lack of growth) was 98% (58% of the tumors reduced their volumes). Sixty-four patients presented with cranial nerve deficit. Thirty-nine percent improved or resolved following radiosurgery. Cranial neuropathy had significantly higher resolution rates when radiosurgery was performed early (<1 year) after its appearance (53% as opposed to 26%) even in patients with deficits post surgery. Complications were seen in five patients (1 with deafferentation pain, 1 with facial hypesthesia, 1 with visual loss and 2 with partial VI neuropathy). Radiosurgery had a high control rate for meningiomas of the cavernous sinus with few and mild complications. Cranial neuropathy can be solved by treatment, particularly those of recent onset.
Magnetic resonance (MR) images of 40 dogs with histologically confirmed primary and secondary intracranial tumours were reviewed. Forty-one tumours were diagnosed by means of MR imaging (MRI). MRI findings allowed diagnosis of a neoplastic lesion in 37/41 cases. Based on MRI features, differentiation between neoplastic and non-neoplastic lesions was possible in 24/27 (89%) primary brain tumours and in 13/14 (92%) secondary brain tumours. Diagnosis of tumour type based on MRI features was correct in 19/27 (70%) primary tumours and in 13/14 secondary tumours. The results of this study show that MRI is a good diagnostic imaging modality to detect neoplastic lesions and to diagnose tumour type in dogs. However, as some neoplasms show equivocal MRI features the technique has limitations in the detection of some intracranial tumours and in predicting tumour type.
The placebo effect is a well-recognized phenomenon in human medicine; in contrast, little information exists on the effect of placebo administration in veterinary patients.
Nonpharmacologic therapeutic effects play a role in response rates identified in canine epilepsy trials.
Thirty-four dogs with epilepsy.
Meta-analysis of the 3 known prospective, placebo-controlled canine epilepsy trials. The number of seizures per week was compiled for each dog throughout their participation in the trial. Log-linear models were developed to evaluate seizure frequency during treatment and placebo relative to baseline.
Twenty-two of 28 (79%) dogs in the study that received placebo demonstrated a decrease in seizure frequency compared with baseline, and 8 (29%) could be considered responders, with a 50% or greater reduction in seizures. For the 3 trials evaluated, the average reduction in seizures during placebo administration relative to baseline was 26% (P = .0018), 29% (P = .17), and 46% (P = .01).
A positive response to placebo administration, manifesting as a decrease in seizure frequency, can be observed in epileptic dogs. This is of importance when evaluating open label studies in dogs that aim to assess efficacy of antiepileptic drugs, as the reported results might be overstated. Findings from this study highlight the need for more placebo-controlled trials in veterinary medicine.
To investigate the correlation between volume of brain irradiated by stereotactic radiosurgery (SRS) and the incidence of symptomatic and asymptomatic brain radionecrosis (RN).
A retrospective analysis was performed of patients treated with single-fraction SRS for brain metastases at our institution. Patients with at least 6-month imaging follow-up were included and diagnosed with RN according to a combination of criteria, including appearance on serial imaging and histology. Univariate and multivariate analyses were performed to determine the predictive value of multiple variables, including volume of brain receiving a specific dose (V8 Gy-V18 Gy).
Sixty-three patients were reviewed, with a total of 173 lesions. Most patients (63%) had received previous whole-brain irradiation. Mean prescribed SRS dose was 18 Gy. Symptomatic RN was observed in 10% and asymptomatic RN in 4% of lesions treated. Multivariate regression analysis showed V8 Gy-V16 Gy to be most predictive of symptomatic RN (p < 0.0001). Threshold volumes for significant rise in RN rates occurred between the 75th and 90th percentiles, with a midpoint volume of 10.45 cm(3) for V10 Gy and 7.85 cm(3) for V12 Gy.
Analysis of patient and treatment variables revealed V8 Gy-V16 Gy to be the best predictors for RN using linear accelerator-based single-fraction SRS for brain metastases. We propose that patients with V10 Gy >10.5 cm(3) or V12 Gy >7.9 cm(3) be considered for hypofractionated rather than single-fraction treatment, to minimize the risk of symptomatic RN.
Stereotactic radiosurgery is a frequently performed procedure for patients with benign intracranial tumors. Benign tumors are good candidates for radiosurgery because they are generally non-invasive, are well visualized by magnetic resonance imaging, and their slow rate of proliferation makes conventional radiation dose fractionation unnecessary. Stereotactic radiosurgery is now an important part of both neurosurgical and radiation oncology training. This chapter will review the indications and results of radiosurgery for patients with intracranial meningiomas, vestibular schwannomas, and pituitary adenomas having single-fraction radiosurgery at the Mayo Clinic since 1990.
The benefits of endoscopic assistance to remove intracranial tumors in small animals are not described.
To evaluate the effectiveness of endoscopic-assisted intracranial tumor removal in dogs and cats.
Thirty-three dogs and 6 cats with intracranial tumors.
Retrospective study. CBC, serum chemistry profile, coagulation testing, blood typing, and systemic tumor staging, which included 3-view thoracic radiographs and abdominal ultrasound examination, were performed to detect other significant underlying disease in preparation of the animal for surgery. Magnetic resonance imaging was used in 37/39 cases to image the brain tumor. Surgical approach was dictated by the location of the tumor. Histopathologic examination of the tumor tissue was performed in all cases. Animals were followed throughout their postoperative course for complications and survival times. Statistical analysis (Kaplan-Meier curves) was performed to obtain median survival times in dogs with meningiomas.
Use of an endoscope resulted in visualization of residual tumor and potentially more complete removal of the brain tumors. There were no clinically important complications associated with the use of the endoscope. Median survival time was 2,104 days for dogs with forebrain meningiomas surgically removed with endoscopic assistance and 702 days for dogs with caudal brain meningiomas.
These results demonstrate that the use of an endoscope to assist in brain tumor removal is apparently safe and might result in improved survival times.
This report describes computed tomography (CT)-guided stereotactic brain biopsy using the Kopf stereotactic system, a commercially available patient restraint system which does not require additional modification for use in small animals. The accuracy of biopsy needle placement was determined by injecting dilute iohexol into cadaver brains and comparing the three-dimensional coordinates of the desired target location to the actual needle tract observed on postcontrast CT images. Overall mean error in needle placement in a dorsoventral trajectory was 0.9 +/- 0.9 mm (n = 80 injections) for dogs and 1.0 +/- 1.1 mm (n = 30 injections) for cats. The overall mean error in needle placement via an oblique trajectory in five dogs was 1.7 +/- 1.6 mm (n = 12 injections). These results suggest that this system can be used to successfully place a biopsy needle into the brain to obtain biopsies from small lesions.
Over a reporting period of 5 years, craniotomy was performed in 26 dogs and 5 cats with various intracranial lesions. X-ray computed tomography was performed in all animals prior to surgery. Twenty dogs and all cats had intracranial neoplasms; of these, 14 were meningioma, and 11 represented a wide variety of brain tumors and skeletal tumors. Three dogs were treated surgically for traumatic, open-skull fractures with cerebral damage, and 3 underwent biopsy to evaluate chronic inflammatory brain disease. The overall medium survival time was 212 days, the 1-year survival rate was 39%, and the 2-year survival rate was 20%. Dogs and cats with meningioma survived a mean 198 and 485 days, respectively, with 1-year survival rates of 30% for dogs and 50% for cats. The overall median survival time for animals with tumors other than meningeal intracranial neoplasms was 414 days, with a 1-year survival rate of 40%. The death of 19% of all animals could be related to the combination of advanced brain disease and surgery. Because fatality seldom occurred as a direct result of surgery, morbidity and mortality associated with craniotomy in pet animals can be seen as acceptably low. In 29 of 34 craniotomies, dura mater defects were left unsutured and no adverse effects were seen.
Olfactory bulb lesions were diagnosed in four dogs presented for generalized seizure disorders. Surgery was performed on each dog using a transfrontal craniotomy. A free fascial-fat graft was used to cover the dural defect resulting from surgery. No major complications were observed during the immediate postoperative period. The histopathologic diagnosis in each case was meningioma. Generalized seizures recurred in all dogs, and three dogs were euthanized for this reason from 9 to 29 weeks postoperatively. One dog was euthanized 12 weeks after surgery due to pancreatitis and pneumonia. Necropsy showed that two dogs had recurrent olfactory bulb meningiomas, one dog had a meningioma of the opposite olfactory bulb, and one dog was tumor free.
Fifty histologically identified primary brain tumors in the dog were analyzed by computed tomography to establish criteria for identifying tumor types by computed tomography characteristics. Meningiomas could be distinguished from tumors within the brain parenchyma because they usually were broad-based, peripherally located masses that were enhanced homogeneously with contrast material. Among parenchymal tumors, astrocytomas were not distinguished easily from oligodendrogliomas because both tumors had similar features of ring-like and nonuniform enhancement, and poorly defined tumor margins. Choroid plexus tumors were seen as well-defined, hyperdense masses that had marked, uniform contrast enhancement. Pituitary tumors were distinguished readily by their location, minimal peritumoral edema, uniform contrast enhancement, and well-defined margins. Distinguishing features of other less frequently seen tumors (ependymoma, primitive neuroectodermal tumor, glioma, and neoplastic reticulosis) were not identified.
Intracranial meningiomas were identified in 28 dogs based on histologic examination of tissue. The average age of the dogs was 11 years, and 83% (20/24) were 10 years old or older. German shepherd and mixed breed were most common (31% each, 8/26). Grossly, meningiomas were oval, dome-shaped and flattened masses adherent to the dura and compressing the brain. Forty-eight percent (15/26) of the tumors affected the dorsal surface of the brain, and two thirds of these were located in the anterior half. Histologically, tumor types were transitional (13), meningotheliomatous (11), angioblastic (three), and fibroblastic (one). There was direct invasion of the brain in 27% (6/22) although we observed neurologic signs and pathologic changes in 88% (23/26) and 90% (18/20) of the dogs, respectively. Intracranial meningioma can be compared and contrasted with this tumor in man and cats.
Brain tumors in 4 dogs were treated with external beam, megavoltage radiation. X-ray computed tomography was used to localize and characterize brain tumors and to assess treatment response. Total radiation doses were 3,000 or 3,600 rad, given in 5 or 6 fractions over 14 to 19 days. Complete tumor regression, as determined from computed tomography scans, improvement in clinical signs, and reduction in medication, were documented in all irradiated dogs. The median survival time for irradiated dogs was 322 days, which was significantly (P less than 0.05) longer than the median survival time of 56 days in 8 dogs with brain tumors treated symptomatically. The one-year survival rate for the irradiated dogs, after correcting for deaths from intercurrent disease, was 100%. It was concluded that canine brain tumors may be treated effectively by use of megavoltage radiation.
This article evaluates the responses of 14 dogs with brain masses using orthovoltage irradiation for definitive treatment. Dogs were anesthetized for computed tomography (CT) examination, formation of head immobilization and positioning devices, radiation treatment simulation, and treatments. Total doses of 39 Gy (9 dogs) or 45 Gy (5 dogs) to the tumor were administered over 25 to 41 days. Two or three portals (parallel opposed lateral with or without a dorsal field) were used. Treatment volumes included the tumor and peritumoral edema, as determined by CT scan, and a 1-cm margin. Histopathologic diagnoses were available in 9 of 14 dogs. There were 4 meningiomas, 1 lymphosarcoma, 1 pituitary adenoma, 1 metastatic anaplastic carcinoma, 1 anaplastic oligodendroglioma and 1 dog with granulomatous meningoencephalitis. At the end of radiation therapy, 10 dogs could be evaluated for progression of clinical signs: 3 dogs deteriorated or failed to improve, and 7 dogs improved. At the time of analysis, all dogs were dead. Mean and median survival times, measured from the beginning of radiation, were 345 and 489 days, respectively. This was compared with mean survival times of 30 to 81 days reported in the literature for dogs with brain tumors that did not receive treatment. The median survival time of 9 dogs treated with 39 Gy was 153 days, versus 519 days for 5 dogs that received 45 Gy. It appears that radiation therapy prolongs survival times for dogs with brain masses. Although megavoltage therapy would be optimal, orthovoltage radiation can be applied in total doses of 45 Gy in 3.75 Gy fractions over 28 days without adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuroradiation oncology is a subdiscipline that is rapidly developing in veterinary practice. This article reviews the literature and emphasizes the positive results that are being achieved with better techniques and higher doses.
Since the infancy of radiology and radiation therapy, reactions to radiation have been noted and followed, and attempts have been made to minimize these reactions. We have turned to radiobiologists to explain these reactions and to radiation oncologists to prevent or decrease the normal tissue effects of radiation therapy. Radiation toxicities are divided into early (acute) and late (chronic) reactions; however, it is important to note that severe toxicities are rare and occur typically in less than 5% of veterinary radiation therapy patients.
Brain tumors occur commonly in small animals. The clinical history and physical examination findings can strongly suggest their presence. Specifically, an older dog with onset of seizures and behavioral changes, or an older cat with behavioural changes and weakness, should be further evaluated for the presence of a brain tumor. A thorough neurological examination should be performed to localize the lesion(s). Groups of neurological signs will suggest the tumor to be cerebral, cerebellar, or brainstem. Cerebral tumors without brainstem signs carry the best prognosis, especially for cats. Patients suspected of having brain tumors should be imaged with computed tomography, or magnetic resonance imaging. Initial medical therapy includes anticonvulsants and glucocorticosteroids. Cerebral tumors not located on the floor of the calvarium can be successfully excised. These and other tumors can also be treated with radiation therapy.
The authors review the main contributions of the international literature concerning the role of hyperfractionation (HF), accelerated fractionation (AF), and accelerated hyperfractionation (AHF) of the dose in radiation therapy (RT) of central nervous system tumors. Basic rationales, clinical results, acute/late toxicity, and current prospectives are summarized in three sections focusing on malignant gliomas, pediatric brainstem tumors, and brain metastases. In supratentorial malignant gliomas the superiority of AHF (0.89 Gy x 3 fractions/day; total dose 61.4 Gy) over conventional fractionation ((CF) total dose 58 Gy) was demonstrated by a randomized trial. However, the gain in median survival time was less than 6 months. No other randomized trials support the preferential choice of non-CF schedules outside clinical trials. Ongoing trials are exploring the role of AHF in combination with chemotherapy, hypoxic cell and radiosensitizing agents. As for pediatric brainstem tumors, there are no data to support the routine use of HF that should be preferably used in an investigative setting. As late sequelae have been reported in the few long-term survivors, patients should be carefully selected. Regarding brain metastases AF RT and AHF RT, with their faster treatment course, may represent a convenient alternative to CF RT for the palliation of brain metastases. In carefully selected patients with solitary brain metastases non-CF RT may be part of aggressive treatment approaches.
To develop and test a system for high precision fractionated stereotactic radiotherapy that separates immobilization and localization devices.
Patient localization is achieved through detection and digital registration of an independent bite plate system. The bite plate is made and linked to a set of six infrared light emitting diodes (IRLEDs). These IRLEDs are detected by an infrared camera system that identifies the position of each IRLED within 0.1 to 0.15 mm. Calibration of the camera system defines isocenter and translational X, Y, and Z axes of the stereotactic radiosurgery subsystem and thereby digitally defines the virtual treatment room space in a computer linked to the camera system. Positions of the bite plate's IRLEDs are processed digitally using a computer algorithm so that positional differences between an actual bite plate position and a desired position can be resolved within 0.1 mm of translation (X, Y, and Z distance) and 0.1 degree of rotation. Furthermore, bite plate misalignment can be displayed digitally in real time with translational (x, y, and z) and rotational (roll, pitch, and yaw) parameters for an actual bite plate position. Immobilization is achieved by a custom head mold and thermal plastic mask linked by hook-and-loop fastener tape. The head holder system permits rotational and translational movements for daily treatment positioning based on the bite plate localization system. Initial testing of the localization system was performed on 20 patients treated with radiosurgery. The system was used to treat 11 patients with fractionated stereotactic radiotherapy.
Assessment of bite plate localization in radiosurgery patients revealed that the patient's bite plate could be positioned and repositioned within 0.5 +/- 0.3 mm (standard deviation). After adjustments, the first 11 patients were treated with the bite plate repositioning error reduced to 0.2 +/- 0.1 mm.
High precision stereotactic radiotherapy can be delivered using separate localization and immobilization systems. Treatment setup and delivery can be accomplished in 15 min or less. Advantages compared with standard systems require further study.