Current Therapeutic Options

The prognosis for dogs with palliatively-treated brain tumors is poor. In one study of dogs with brain tumors definitively diagnosed at necropsy, the reported overall median survival was approximately 2 months after diagnosis via brain imaging.10 Surgical resection and fractionated radiotherapy are currently the principal methods used to treat canine and feline brain tumors, and these therapies are capable of improving both the quality and quantity of life in small animals. However, both surgery and radiotherapy can be associated with treatment-associated morbidity, and local treatment failures after these therapies remain a common cause of death or euthanasia.12–17 Surgical treatment has been best described for forebrain meningiomas, which is the most common primary brain tumor type in both dogs and cats.8,12–15 In dogs with meningiomas, the reported median survival after traditional surgical resection is approximately 7 months.12 In cats, the median survival after surgical resection of forebrain meningiomas is 24 months 13,14 Neurosurgical treatment that incorporates devices that improve intraoperative visualization, such as intracranial endoscopy, or facilitate tumor extirpation have been associated with median survivals ranging from 42 to 70 months.8,15 Transsphenoidal hypophysectomy has been demonstrated to be an effective surgical technique in dogs and cats with nonenlarged to moderately enlarged pituitary adenomas, with a reported 4-year survival rate of 68% in dogs.16 Currently available surgical techniques often preclude safe resection of intraparenchymal tumors that are infiltrating the surrounding brain or intimately associated with critical neuroanatomic structures. There is little information available regarding the efficacy of or indications for surgery in canine and feline brain tumors other than meningiomas and pituitary tumors.

Fractionated radiotherapy is beneficial in the treatment of brain tumors as a sole therapeutic modality or as an adjuvant after surgery.12–18 Studies investigating treatment of a variety of presumptively diagnosed brain tumors in dogs with fractionated radiotherapy reported median survivals that range from approximately 300 to 700 days.17,18 Dogs with meningiomas treated with 3-D conformal radiation therapy had an overall median survival of 577 days, and the median survival increased to nearly 30 months (ie, approximately 900 days) when dogs dying of causes other than meningioma were excluded.19 Systemically administered cytotoxic chemotherapeutics, including those agents capable of penetrating BBB, are largely ineffective as sole agents for the treatment of brain tumors. A recent study failed to demonstrate any difference in survival between dogs with brain tumors treated symptomatically with prednisone and anticonvulsant drugs compared with those that received symptomatic therapy and lomustine.20

There is increasing recognition of the epidemiologic, neuropathologic, molecular, and genetic homologies between canine and human brain tumors, which has driven the use of dogs with spontaneous brain tumors as a translational disease model.21–23 This review introduces contemporary therapeutic advancements for brain tumors and illustrates the role that tumor-bearing dogs have made to progressing the field of translational neuro-oncology. Because an exhaustive survey of brain tumor treatment is beyond the scope of this article, it focuses on SRS, CED, and immunotherapy (IT). These therapies hold great promise for the treatment of brain tumors and are being used clinically in dogs and cats.23–25 Reviews of boron neutron capture therapy, brachytherapy, high-intensity focused ultrasound (HiFU), gene therapy, laser interstitial thermal therapy, proton beam radiotherapy, oncolytic viruses, and pulsed electric fields are available elsewhere.7,26–34

These therapeutic approaches are not mutually exclusive. For example, because many molecularly targeted chemotherapeutics, gene-bearing vectors, and boron delivery agents are high-molecular-weight structures that cannot penetrate the BBB when administered systemically, they require delivery by a method that bypasses or disrupts the BBB, such as CED or HiFU.23,26,30 Distinct advantages are also realized when biologically directed treatments, primarily in the form of target-specific monoclonal antibodies, are conjugated to chemotherapeutics in efforts to sensitize tumors to external beam radiotherapy or radionuclides to allow for more selective tumor irradiation.35,36