Introduction

Primary brain tumors occur with a reported incidence of 2.2% in cats, and meningioma is the most reported primary brain tumor in cats,^1–6 accounting for 56% to 58% of all intracranial tumors.^1,7 Cats with meningiomas are significantly older than cats with other types of intracranial tumors,^1,8,9 and no sex predilection has been consistently demonstrated.

Feline meningiomas are considered benign, slow-growing, and mostly solitary tumors that are typically well circumscribed and delineated from the surrounding brain tissue.^10,11 Median survival times following surgical excision of meningiomas range from 693 to 1,125 days (22.8 to 37 months),^1,9,12,13 with a 2-year survival rate of 50%.¹³ Due to these characteristics, the recommendations for treatment of intracranial meningiomas in cats is primarily surgery. However, surgery is not without risks and complications, and occasionally the location and size of the tumor, or patient comorbidities, may preclude surgery as a treatment option.¹⁴ Morbidity associated with brain surgery can be quite high, and reported complications include hemorrhage, anemia, central blindness, acute renal failure, pneumocephalus, increased intracranial pressure, seizures, brain herniation, infections, and aspiration pneumonia.^10–13,15 An immediate postoperative mortality rate of 6% to 19% has been described in cats.^9,12,13 Recurrence following surgical excision ranges from 12% to 21.4%.^1,12,13 The median postoperative time to recurrence in 6 cats was noted to be 285 days (range, 123 to 683 days).¹

Radiation therapy has become a mainstay of treatment for intracranial neoplasia in both humans and animals as both a primary and adjunctive treatment.³ Stereotactic radiotherapy (SRT) delivers a curative dose of radiation from numerous different angles to focus the radiation while sparing the surrounding normal tissue from damage.¹⁶ The large number of beams allows for highly conformal target treatment with a steep dose gradient, while the nonintersecting arcs minimize exposure of normal overlying tissue, allowing a larger single treatment dose and, therefore, a lower total dose to be applied. 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. To our knowledge, no literature regarding SRT involving 1 to 3 high-dose fractions or the use of a CyberKnife system for the specific treatment of feline meningiomas is available and no prior studies have evaluated whether SRT alone significantly prolongs survival time. The purpose of this retrospective study was to report clinical features, outcomes, and survival times of cats undergoing either SRT or surgical excision for the treatment of intracranial meningioma.

Methods

Statistical analysis

Continuous data were described using median and IQR due to nonnormal distributions. Frequencies and percentages were used to describe categorical data. Associations between treatment used and categorical variables were assessed using Fisher exact tests. Kruskal-Wallis tests were used to test between differences in continuous variables on the basis of the treatment used. Kaplan-Meier methodology was used to draw survival curves for time to progression or recurrence and survival time (Figure 1). Cats were censored in the time to recurrence or progression analysis if there was no documentation of progression or recurrence before data collection for study, loss to follow-up, or death. In the survival time analysis, cats were censored if alive at last follow-up or if lost to follow-up. Log rank tests were used to compare survival distributions between treatment groups.

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Kaplan-Meier curve to show survival probability (A) and recurrence probability (B) in 61 cats with cranial meningiomas by treatment type.

Citation: Journal of the American Veterinary Medical Association 262, 1; 10.2460/javma.23.02.0083

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Statistical significance was set at P = .05, and the statistical analysis was performed using a commercially available software package (SAS software version 9.4; SAS Institute Inc).

Results

Discussion

Historically, curative-intent RT treatments have been utilized in the treatment of both feline and canine intracranial tumors.^{3,6,10,11,17,18,23–26} 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. This cat survived 240 days and was euthanized for an unrelated neoplasm.¹ Sessums and Mariani¹⁰ reported treating 2 cats with MRI-diagnosed cerebral meningiomas using a linear accelerator–based SRT unit; however, the case series is unpublished and data cannot be gathered from this review. Eleven client-owned cats with MRI-diagnosed pituitary tumors were treated with modified linear accelerator–based radiosurgery receiving 1 to 3 treatments.¹⁹ Improvement in clinical signs was noted in 63.6% of treated cats, and there were no confirmed acute or late adverse radiation effects.¹⁹ In the largest and most recent study evaluating the outcome of cats with intracranial tumors treated with RT, 21 cats were treated with various definitive-intent daily fractionated protocols, from 3 to 20 fractions.⁶ The single case that received 3 fractions was diagnosed with a choroid plexus tumor and was censored at 588 days post-treatment.⁶ Eleven cats were diagnosed with meningioma and received anywhere from 10 to 20 fractions of between 40 and 45 Gy (total dose), with an average overall survival time of 315 days (range, 50 to 963 days).⁶ Three cats were alive at the time of data evaluation (overall survival range, 121 to 225 days), 1 cat was reirradiated resulting in an additional progression-free interval of 223 days, and 3 cats died from tumor- or treatment-related causes.⁶

In this paper, we reported the outcome of either surgery or SRT for the treatment of intracranial meningiomas in a subset of feline patients. As previously noted, the MST for surgically treated intracranial meningiomas in cats is 693 to 1,125 days (22.8 to 37 months)^1,9,12,13 with a 2-year survival rate of 50%¹³ in the literature. In this study, cats that had initial surgery were found to have an MST of 1,345 days, which is equivalent to 44 months. Median survival time for cats in the SRT group was 339 days, equivalent to 11 months. The difference in MST between the surgery group and the SRT group did reach statistical significance (P = .002; Figure 1). The MST for the SRT group is below the documented MST for surgical treatment; however, it is close to the value noted in the single case that received 3 fractions of SRT and lived for 240 days described by Troxel.¹ Historically, RT has been utilized in lesions not easily accessible by surgical approaches in human and veterinary medicine. No known literature is available that evaluates the relationship between the intracranial location of feline meningiomas and prognosis and rate of recurrence; however, in a 2009 paper by Klopp et al³⁰ discussing endoscopic-assisted meningioma removal in dogs, the MST for dogs with forebrain meningiomas was significantly longer when compared with the dogs with caudal brain/brain stem meningiomas (P = .05). In that paper, the MST for forebrain meningiomas was 2,104 days compared with 702 days for caudal brain meningiomas.²⁷ Forterre et al¹⁵ found that for tumors in less-accessible locations, such as tentorially located meningiomas, survival time was found to decrease to 19 months (578 days) postoperatively in feline patients. Lesion localization between the 2 groups in the current paper nearly reached significance (P = .07; Table 1) with the only 3 lesions located in the brain stem in the SRT group. Location of the tumor may have contributed to the lower MST found in the SRT group.

A single cat in the SRT group and 5 cats in the surgery group were noted to have 2 or more masses located within the brain at the time of diagnosis. In addition to single meningioma, there is also a high incidence of multiple meningiomas in cats noted in the literature.²⁸ In a 2003 paper¹ retrospectively reviewing feline intracranial neoplasms, 17.2% were found to have multiple meningiomas at the time of diagnosis. A 2007 paper²⁸ evaluating multiple meningiomas in cats that underwent surgery suggests that the postoperative outcome does not seem to be influenced by the number of meningiomas present. This paper evaluated only 4 cats, all of which had surgery to remove the masses, and they all were administered hydroxyurea postoperatively in an attempt to diminish tumor regrowth.²⁸ While the number of cases diagnosed with multiple tumors in this paper was low, the effect this finding had on the outcome of both treatment groups was not explicitly evaluated and therefore cannot be disregarded. Significantly more cats in the surgery group had peritreatment complications compared to the SRT group (P < .0001). The most common peritreatment complication in the surgery group was anemia (54%), and 1 case developed seizures following surgery and arrested. A paper¹³ that evaluated 42 cats that underwent surgery for their intracranial meningiomas reported 31% of cases were anemic postoperatively (range, 10% to 25%) and 19% died or were euthanized in the immediate postoperative period. Intracranial hemorrhage can be significant during surgery and can continue after recovery from anesthesia, thus leading to anemia. Due to the retrospective nature of the current study, specifics relating to intraoperative hemorrhage and technique for hemostasis were not consistently documented. Whereas the available literature reports a 6% to 19% mortality rate in the immediate postoperative period, this paper only had a single perioperative death. Much of the available information regarding surgical treatment for feline intracranial meningiomas is from studies performed decades ago. Perhaps the risk of mortality with surgery may be lower than originally reported now that newer surgical approaches and improved technique have been utilized. The most recent paper⁹ discussing surgical treatment in 121 cats reported an immediate postoperative mortality rate of 6%. A single cat in the SRT group was noted to have peritreatment complications, which included hyperthermia and tachypnea, both of which resolved. In this study, SRT treatment, delivered by the CyberKnife system, required anywhere from 1 to 3 anesthetic events compared to the single event for surgery. According to a 2007 paper by Bley et al,²⁹ repeated propofol-associated anesthesia does not lead to clinically relevant hematologic changes or adverse events in cats undergoing short-duration radiotherapy.

Four (28.6%) cats in the SRT group and 14 (30.4%) cats in the surgery group had CT- or MRI-confirmed recurrence following initial surgery. According to the literature, a 14% to 21.4% recurrence rate has been noted for surgical treatment^1,12,13 and the 1 case that received SRT for an intracranial meningioma did not have documented recurrence.¹ Lack of repeat advanced imaging to confirm tumor growth in previous reports may have contributed to a lower than actual tumor recurrence in cats with intracranial meningioma. To the authors’ knowledge, the recurrence rate following initial SRT treatment for feline intracranial meningioma is not available. The median time to recurrence for cats receiving surgery as the primary treatment was 1,183 days compared to 315 days in the SRT treatment group (P = .009; Figure 1). The MST for the 5 of 7 cases that had SRT for subsequent recurrence was 700 days (range, 335 to 1,461 days; 11 to 48 months) after the last treatment, with 2 cases lost to follow-up. We were unable to compare the significance of overall survival times of patients that had SRT as an adjuvant treatment for recurrence of meningioma. This lack of significance could be a result of a type 2 error given the small patient population.

This study had several limitations. A definitive histologic diagnosis was obtained in all of the surgically treated cases; however, a presumptive diagnosis was made in the cats treated with SRT. The accuracy of advanced imaging, using CT or MRI, for diagnosis of primary brain tumors in cats, however, has been long established. In a 2004 study by Troxel et al,²⁰ MRI features of feline intracranial neoplasia were retrospectively reviewed and 96% of tumors were correctly identified as meningioma on the basis of MRI characteristics alone. MRI is the imaging modality of choice for the detection of brain tumors in humans and allows for superior resolution of intracranial lesions compared to CT.³⁰ Six cats were noted to have multiple tumors: 5 in the surgery group and 1 in the SRT group. The effect of multiple tumors on patients included in the study was not investigated; therefore, the influence in the overall clinical picture and survival cannot be elucidated. Additional limitations of this study include its retrospective nature, small case numbers (only 15 patients underwent SRT initially), and lack of follow-up imaging for all patients to determine the impact of SRT on the size of the tumor, determine the progression-free interval, and rule out the possibility of development of secondary delayed radiation effects.

In summary, SRT proved to be a safe, alternative treatment for feline patients with intracranial meningiomas that may have reasons to not undergo surgery, such as nonresectable tumors, comorbidities making surgery not an ideal option, or owners who decline surgery. While the MST for the surgery group was significantly longer, at 1,345 days (44 months), the SRT group lived for almost a year, at 339 days (11 months) post-treatment. Due to the low numbers that received SRT for subsequent recurrence, the evaluation of prolonged survival time and benefit was not able to be determined. Future studies with larger case populations evaluating cats with meningiomas treated with SRT alone, as an adjuvant to surgery, or as a treatment for recurrence would be needed to better highlight where SRT might be the most beneficial in the treatment of intracranial meningiomas in cats.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have nothing to disclose.