Treatment Outcomes of Canine Orbital Meningiomas in Seven Cases
ABSTRACT
Although intracranial and spinal cord meningioma prognoses have been reported, few studies have evaluated the outcomes and prognoses of orbital and optic nerve meningiomas in dogs. We aimed to evaluate the outcomes of canine orbital meningiomas. The seven dogs included were cytologically or histopathologically diagnosed with meningiomas. Four underwent first-line surgery; three received postoperative radiation therapy. The remaining three underwent first-line radiation therapy; however, 372 days after radiation therapy, one dog underwent surgery as the lesion progressed in size. Five dogs underwent surgical resection, had incomplete resections, and died during the observation period, with a median survival time of 943 days (range 668–1083 days). The two surviving dogs were followed up for 119 and 1083 days. Local recurrence was detected in three of the five dogs at 478, 660, and 814 days. The median progression-free survival was 569 days (range 262–814 days). Although keratoconjunctivitis (grade 2) was observed in one dog that underwent eye-sparing radiation therapy, no serious side effects were observed in the other dogs. Our results suggest that surgery and radiation therapy may play an important role in the treatment of orbital meningiomas and may offer longer survival than that of brain or spinal cord meningiomas.
Introduction
Meningiomas are tumors that originate from the arachnoid epithelium in arachnoid granules and most commonly occur intracranially or affect the spinal cord; occasionally, they may also occur in the orbital and optic nerve regions.1,2 Meningiomas, along with gliomas, are the most common intracranial tumors in humans.3 The majority of meningiomas in humans are benign and are classified as grades 1–3 according to the World Health Organization (WHO) classification, with prognosis depending on the grade.4 Meningiomas are not exclusive to humans and are often found in dogs. Meningiomas are the most common primary brain tumors in dogs, accounting for 45% of all primary brain tumors.5,6 Large-breed dogs are at a higher risk of developing intracranial meningiomas, with golden retrievers, boxers, miniature schnauzers, and rat terriers reported as predominant breeds.5−7 The age of onset is generally middle to old age, with the most common age of onset in dogs being 7 yr or older.5–7
The treatment often includes a combination of surgery and/or radiation therapy.5,8–10 One study reported that the median survival time (MST) for rostrotentorial meningiomas was 422 days after surgery alone.11 Other studies have reported an MST of 386 days for 101 dogs with intracranial meningiomas treated with surgery with or without chemotherapy and/or radiation therapy, with 1, 2, and 3 yr survival rates of 25, 15, and 10%, respectively.12
Radiation therapy may be administered for meningiomas arising in areas that are difficult to approach surgically or for local control after surgery. In a previous study, the MST for all brain tumors treated with radiation therapy was 351 days, with an MST of 444 days for extra-axial tumors suspected of being meningiomas.13 In addition, reports of meningiomas treated with surgery and radiation therapy reported MSTs of 16.3–16.5 mo, suggesting that the combination of surgery and radiation therapy may prolong survival.8,9,14
Meningiomas have been reported to not only occur intracranially but also affect the spinal cord.15,16 In a report of 16 dogs with meningiomas affecting the spinal cord, 14 dogs underwent surgery alone, and 2 dogs underwent surgery and radiation therapy, with an MST of 508 days.17 As with intracranial meningiomas, surgery and radiation therapy are considered effective treatments.16
Canine orbital meningioma is the most common tumor of the optic nerve, accounting for 3% of all meningiomas. Moreover, tumors that are primary in the orbit in dogs include osteosarcomas, mast cell tumors, histiocytic sarcomas, fibrosarcomas, and neurofibrosarcomas.18 Although the prognosis for orbital and optic nerve tumors is poor with conservative treatment, one study reported that orbital content resection (with or without chemotherapy or radiation therapy) resulted in more than 50% of patients being disease-free for more than 1 yr, with a 70% 1 yr survival rate.19 However, data on the treatment and prognosis of orbital meningiomas are limited.1,20 In Mauldin’s report of orbital meningiomas in 22 dogs, follow-up information was available for 17 dogs; however, survival was not described except for 3 dogs that were euthanized, and their prognosis and clinical behavior are still unknown.21
This study aimed to evaluate the prognosis and efficacy of surgery and radiation therapy for orbital meningiomas in dogs.
Materials and Methods
Cases
This was a retrospective study. Data from dogs diagnosed with meningiomas arising in the orbit and optic nerve region and treated with surgery alone, radiation therapy alone, or surgery and radiation therapy between March 2016 and July 2019 were obtained from the electronic medical record system. Informed consent was obtained from all the pet owners. All patients described in this study were clinically managed according to contemporary standards of care as described in JAAHA Instructions for Authors.
Data Collection
Medical records were reviewed for signalment (sex, breed, age, and weight), physical examination, clinicopathological and imaging findings, surgical procedures, histopathological reports, postoperative chemotherapy, date and cause of death, and follow-up details. Whole-body computed tomography (CT) and MRI scans were performed at the initial visit for all the dogs to evaluate the site of tumor origin and for the possibility of secondary brain tumors metastasizing from other sites. The outcome data were obtained by communicating with the referring veterinarian through medical records or faxed questionnaires.
Statistical Analyses
Owing to the small sample size, quantitative descriptions are presented as median and range, and Kaplan-Meier survival curves were used to estimate MST and progression-free survival (PFS). Overall survival time was defined as the number of days from the date of surgery or radiation therapy initiation to the date of death from any cause. The survival time of the dogs alive at the end of the study was censored at the last follow-up date. PFS was defined as the number of days from the date of surgery or radiation therapy initiation to the date of documented tumor progression, death, or censoring. Owing to the small number of cases, prognostic factors were not analyzed. The end date of the study was defined as the last day of follow-up for the last dog.
Results
Cases
Seven dogs with meningiomas originating in the optic nerve region were included from the electronic medical records. The median age of the dogs was 11.0 yr (range 6–14 yr), and their median weight was 6.8 kg (range 3.0–21.2 kg). Two dogs were mixed-breed, and the remaining were Maltese, miniature dachshund, yorkshire terrier, toy poodle, and miniature schnauzer. The most common clinical manifestation was ocular protrusion, present in six of the seven dogs (85.7%). Other symptoms included keratoconjunctivitis in two dogs and pain and glaucoma in one dog each. No cases showed neurological symptoms at diagnosis. CT and MRI examinations were performed in all dogs at the time of the initial examination to identify the site of tumor origin and investigate the possibility of secondary brain tumors metastasizing from other sites. Of the seven cases included in the study, four were diagnosed with meningioma by cytology and histopathology, two by histopathology, and one by cytology. The mean largest tumor diameter of all dogs measured via MRI was 2.3 cm (range 2.0–3.3 cm). MRI imaging findings showed the tumor to be hypointense to isointense on contrast enhancement for T1-weighted images and isointense to hyperintense signal on T2-weighted images (Figures 1A, B).
Citation: Journal of the American Animal Hospital Association 61, 1; 10.5326/JAAHA-MS-7434
Treatment
Four dogs underwent orbital content resection as first-line treatment, and three of them underwent postoperative radiation therapy (Table 1). Orbital content resection in this study refers to the reduction in volume of orbital contents as much as possible after enucleation. The remaining three dogs underwent radiation therapy as first-line treatment, and 372 days after the completion of radiation therapy, one of them underwent surgery as the lesion progressed in size. All of the surgical resections were incomplete. None of the patients underwent chemotherapy. In this study, three-dimensional conformal radiation therapy with a linear acceleratora was used for radiation therapy. The treatment was planned by the treatment planning systemb. The radiation therapy protocol consisted of conventional fractionated irradiation three to five times per week in four dogs (15–16 fractions of 3 Gray [Gy]) and weekly hypofractionated irradiation in two dogs (5–7 fractions of 5–7 Gy). A total dose of 35–48 Gy was prescribed to the isocenter with the goal of definitive long-term local tumor control (median mean isocenter dose of 46.5 Gy). The gross tumor volume for patients with gross disease or residual disease following surgery was defined as all abnormal contrast enhancement in the orbital cavity. For cases in which surgery was performed, clinical target volume was defined as the area where the lesion was present on preoperative imaging studies. The median planning target volume (PTV) margin was 4.5 mm. Median mean dose to the eye contralateral to the lesion was 10 Gy; median mean dose to the brain was 12 Gy. The median mean dose to the eye on the side of the lesion in the three cases in which surgical removal was not performed was 37 Gy (Tables 2 and 3).
Outcomes
Follow-up was mainly evaluated by CT scan findings. Follow-up intervals varied from case to case, ranging from 1 mo to 1 yr from the start of treatment. The response evaluation criteria in solid tumors were used to determine response to treatment. Five of the seven dogs had died by the end of the study period. The follow-up periods for the two surviving dogs were 119 and 1083 days. Two of the five dogs died of neurological symptoms, likely caused by intracranially invasive optic nerve meningiomas, and one died of cardiac hemangiosarcoma. The MST was 943 days (range 668–1083 days; Figure 2). The median PFS was 569 days (range 262–814 days; Figure 3). One of the three dogs treated with radiation therapy as the first-line therapy had partial remission 77 days after the completion of radiation therapy, and two had stable disease. One dog revealed an enlargement of the tumor after radiation therapy was completed, and the time from the completion of radiation therapy to enlargement was 372 days. Based on toxicity criteria of the veterinary radiation therapy oncology group acute radiation-induced toxicity criteria, conjunctivitis with grade 2 was observed in one of the three dogs that underwent eye-sparing radiation therapy.22 However, there were no serious radiation side effects in the other patients. One of the dogs treated with surgery and radiation therapy had multiple nodular lesions in the lungs 625 days after the initiation of treatment, but no biopsy was performed; hence, the details are unknown. In other cases, there was no evidence of distant metastasis.
Citation: Journal of the American Animal Hospital Association 61, 1; 10.5326/JAAHA-MS-7434
Citation: Journal of the American Animal Hospital Association 61, 1; 10.5326/JAAHA-MS-7434
Discussion
To the best of our knowledge, this is the first study to evaluate surgery, radiation therapy, and survival in dogs with orbital meningiomas. The MST with surgery and radiation therapy was 943 days. Mauldin’s study reported the median follow-up period as 1.7 yr, suggesting the possibility of relatively long-term survival.23 These results suggest that canine orbital meningiomas have a better prognosis than meningiomas arising in the brain or affecting the spinal cord. There are three possible reasons for the superior prognosis compared with that for meningiomas in other areas, such as intracranial tumors. First, enlargement in areas with limited volume, such as intracranial areas, may be more likely to cause fatal events. Second, orbital meningiomas tend to be of lower grade than meningiomas at other sites. WHO grades of intracranial meningiomas have been reported as grade 1, grade 2, and grade 3 with 56, 43, and 1% frequency, respectively.7 All five of the cases included in this study for which a grade classification was possible were WHO grade 1. Third, although all cases in this study were incompletely resected, orbital meningiomas may be easier to resect and more susceptible to reducing the tumor volume than meningiomas at other sites. Aggressive treatment may result in a disease-free period comparable with that of other orbital tumors. In human orbital meningiomas, follow-up with no treatment or radiation therapy is recommended when the disease is asymptomatic, whereas a combination of surgical resection and radiation therapy is recommended when the disease is symptomatic.23,24 Conventionally fractionated radiation therapy has been widely used over the past several decades as an effective treatment for human orbital meningiomas; recently, the efficacy of stereotactic radiation therapy has been reported.25–27 Although the most common clinical manifestation of orbital meningiomas in humans is painless, slowly progressive vision loss, the most common clinical manifestation in this study was ocular protrusion, which is likely to be diagnosed in a more advanced state in dogs than in humans. Although the small number of cases precludes the comparison of outcomes by treatment, all surgically treated dogs had incomplete resections. In light of the aforementioned reports, radiation therapy as an adjuvant treatment may be recommended.
In the present study, none of the patients experienced severe side effects from radiation, and radiation therapy was well tolerated. In humans, either observation or radiation therapy is recommended for asymptomatic orbital meningiomas.24 It may be difficult to detect orbital meningiomas in dogs at an early asymptomatic stage; however, if they are detected early, radiation therapy alone may be recommended.
The limitations of this study largely arise from the retrospective nature of the study design and the population size. Typically, studies should include prospective case acquisition with larger patient numbers, standardized treatment plans, and diagnostic evaluation, all with a single variable to determine significance. A research goal that can be increasingly difficult to achieve with the nature of retrospective studies is the infrequency of orbital meningiomas.
Conclusion
This study suggests that surgery and/or radiation therapy may result in favorable prognoses for dogs with orbital meningiomas. Therefore, surgery and/or radiation therapy are recommended for dogs with orbital meningiomas. Further studies with larger sample sizes are needed to evaluate the prognostic factors and compare treatments.
Transverse magnetic resonance images of an orbital meningioma. (A) T2-weighted images. (B) Postcontrast T1-weighted images.
Kaplan-Meier curve of the overall survival time of seven dogs with orbital meningioma. The median survival time is 943 days (range 668–1083 days).
Kaplan-Meier curve of the progression-free survival time of seven dogs with orbital meningioma. The median progression-free survival time is 569 days (range 262–814 days).
Contributor Notes
