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  • Case Report: Malignant neoplasia of the brain treated with CyberKnife radiation therapy

    Penny, a 5.5 year old female spayed Boxer, initially presented to her primary care veterinarian for rapidly progressive circling, ataxia, behavior changes and mental dullness. Due to the severity of neurologic signs, advanced imaging (MRI) was recommended. An MRI revealed an intra-axial mass in the right prosencephalon that was heterogeneous, hyperintense on T2 weighted images, hypointense on T1 weighted mages and peripherally contrast enhancing. This mass was in the area of the rostral internal capsule and right caudate nucleus. The mass measured 1.5 x 2.4 x 3.2 cm. There was a second 2 cm mass present in the white matter of the rostral left pyriform lobe with similar imaging characteristics. The 2 masses were equivocally connected by a thin bridge of tissue. Focal susceptibility artifacts in the center of the masses were noted, consistent with hemorrhage and a significant amount of perilesional edema was associated with both lesions. The top differential in this case was a malignant glioma. Other differentials include other types of neoplasia and granulomatous inflammation of  the brain. (Figure 1.)

    Figure1BoxerNeoFig2BoxerNeo

    Figure 1. On the left is a T1 weighted image post gadolinium contrast administration. The image on the right is a T2 weighted image showing the masses in the prosencephalon

    Penny was started on prednisone 0.5 mg/kg and mannitol 0.5 g/kg IV as needed. During hospitalization, mild focal seizures developed and treated with Levetiracetam 20 mg/kg and Phenobarbital 2 mg/kg as well as a Valium CRI. A radiation oncology consult was performed to discuss the biologic behavior of this tumor and treatment options. The concept of stereotactic radiation therapy in the form of Cyberknife was discussed with the owners. CyberKnife is a linear accelerator that is mounted on a robotic arm which has multiple degrees of freedom. This allows radiation to be delivered from up to 1200 different angles around a patient. Hundreds of small beams of radiation are targeted to the tumor using constant image guidance which relies on bony anatomy or the placement of fiducual markers, which are small radiopaque seeds. A large dose of radiation is delivered to the target, while a very low and clinically insignificant dose is delivered to surrounding, healthy tissue. CyberKnife relies on steep dose gradients between neoplastic and healthy tissue, which is why it is best utilized for cancers that are well-defined, macroscopic targets.

    Specifically for Penny, CyberKnife radiotherapy was chosen in order to deliver a larger dose of radiation in a much more rapid time frame. In addition, the precision with which the radiation is delivered eliminates much of the normal brain tissue that would be included in a field using conventional radiation therapy. Lastly, since CyberKnife radiotherapy also requires far fewer anesthetic episodes and given her altered neurologic state, fewer times under anesthesia was considered favorable (Figure 2).

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    Figure 2. CyberKnife treatment planning images. The top image is an axial orientation showing an MRI image of the brain tumor. The colored lines represent isodose lines, which show the various levels of radiation being received by the tumor and surrounding tissue. The thick yellow line is the prescription isodose line, which means that any tissue contained within this area is receiving the prescribed dose of radiation. The bottom image is a sagittal CT image showing a different orientation the treatment area. These treatment planning images show the concentrated dose of radiation within the tumor and the relatively small amount of radiation being received by surrounding brain tissue.

    Three treatments of CyberKnife were administered over a one-week period. Initially, her neurologic state deteriorated to the point that she was obtunded and not able to stand on her own. Over a 2-3 day period, in between her second and third treatments with radiation, Penny’s abnormal neurologic signs improved drastically so that she was able to ambulate on her own and could interact with her owners. She was discharged from the hospital 1 day after her third treatment with radiation. Her neurologic state continued to improve and she was able to run, play/ catch balls and have a normal quality of life.

    A repeat MRI was performed 2 weeks after the completion of Penny’s CyberKnife radiation therapy protocol. This time frame was chosen due to her rapid improvement in clinical signs and due to our interest in the changes radiation therapy may have induced in the tumor to bring about such drastic positive changes. The repeat MRI showed a slightly smaller tumor with evidence of decreased swelling of the surrounding brain, evidenced by improved visualization of the subarachnoid space. The mass showed an altered contrast enhancing pattern. There was also a visible improvement in the degree of mass effect within the brain as evidenced by a decreased midline shift (Figure 3).

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    Figure 3. Repeat MRI scan showing changes in the size of the masses, altered contrast enhancement, less midline shift and improved visualization of the subarachnoid space.

    Two months after the completion of Cyberknife, her owners noted a clinical decline in her neurologic status and alterative options were discussed. Differentials for this change are transient demyelination, tumor necrosis, or tumor progression. Transient demyelination is a temporary and reversible side effect that is typically managed with increased doses of steroids. Her owners elected against repeat advanced imaging and decided to pursue adjuvant chemotherapy with oral Lomustine.

    Historically, gliomas and other intra-axial neoplasia are rapidly progressive and may be associated with a worse prognosis than extra-axial neoplasia. Many veterinarians may not recommend treatment with radiation due to the assumed poor prognosis. Gliomas are invasive into the surrounding brain parenchyma and difficult to remove surgically. A paucity of information exists in the veterinary literature regarding treatment with conventional radiation therapy or stereotactic radiosurgery, and, to the author’s knowledge, there are no reports of the utilization of CyberKnife radiotherapy.1-4 This case report describes the use of CyberKnife to treat a malignant glioma in a dog after which a rapid improvement in neurologic status was noted. It is unknown whether the recent change in clinical status is truly disease related, however, further imaging was not performed. Further prospective studies are needed to establish the long-term benefit of this type of therapy.

    CyberKnife radiotherapy is offered locally in Malvern, PA at the Veterinary CyberKnife Cancer Center (VC3), which is directly adjacent to Hope Veterinary Specialists. VC3 is staffed by an on-site radiation oncologist, anesthesiologist, medical physicists and radiation therapist to ensure total care of referral patients. If you have a case that you think may be a candidate for CyberKnife therapy, please call VC3 at (844) 738-2927.

     

    References:
    1. Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.Journals: Vet Comp Oncol 0[0] 2014, C L Mariani; T A Schubert; R A House et a
    2. Radiosurgery using a stereotactic headframe system for irradiation of brain tumorsin dogs Journals: J Am Vet Med Assoc 219[11] December 2001: 1562-7, 1550, N V Lester; A L Hopkins; F J Bova et al
    3. Primary irradiation of canine intracranial masses.
    Journals: Vet Radiol Ultrasound 41[4] 2000 Jul-Aug: 377-80, E P Spugnini; D E Thrall; G S Price et al
    4. Hypofractionated radiation therapy of brain masses in dogs: a retrospective analysis of survival of 83 cases (1991-1996)
    Journals: J Vet Intern Med 13[5] 1999 Sep-Oct: 408-12, M J Brearley; N D Jeffery; S M Phillips; R Dennis

    **Funding for the second MRI scan was provided by Vet Imaging Partners, 2626 Van Buren Ave, Norristown, PA

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