History: An 8-year-old male castrated Labrador Retriever was presumptively diagnosed with osteosarcoma of the left distal radius. His presenting clinical signs included acute grade 3 lameness and a bony mass associated with the distal radius. Radiographs taken at that time revealed an aggressive lesion of the distal radial metaphysis with moth-eaten lysis and a mixed periosteal reaction, which varied from smooth to palisading to more amorphous. There was a short zone of transition and mild overlying soft tissue swelling. (see figure 1). Initial staging tests were performed: CBC and serum chemistry were within normal limits and thoracic radiographs (three-view) did not reveal evidence of pulmonary metastasis. His owners were given curative-intent (amputation and chemotherapy) and palliative intent (radiation therapy) options. They elected to pursue a palliative approach consisting of radiation therapy in the form of CyberKnife stereotactic radiosurgery (SRS) with the goal of improving comfort and quality of life. CyberKnife stereotactic radiosurgery/ radiation therapy entails precise administration of radiation therapy via a robotic delivery system with submillimeter accuracy, resulting in the ability to deliver a definitive-intent radiation therapy protocol in 1-3 treatments. Adjuvant treatment in the form of pamidronate, a bisphosphonate drug used to decrease bone resorption by inhibiting osteoclast activity was administered prior to radiation therapy (Protocol: 1mg.kg IV over 2 hours q 4 weeks)1. The patient received a single fraction of 25 Gy delivered to the distal radius, which was preceded by a dose of pamidronate the day before.
Following discharge, the patient received 4 additional more treatments of pamidronate and experienced a complete remission of his discomfort, however, the bony deformity remained at his distal radius based upon repeat imaging. Thoracic and limb radiographs of the left front limb 8 months after CyberKnife treatment and then again 12 months after treatment (see figures 2 and 3). At the time this case report was being written, the patient is 13 months post-CyberKnife treatment with some minimal bony changes/ remodeling of the distal radius and no evidence of distant metastatic disease based upon serial radiographs.
Comparison of the radiographs by a board-certified radiologist yielded the following report: Monostic aggressive lesion of the distal radius consistent with a primary bone tumor-osteosarcoma most likely. Between the Aug 2014 and Aug 2015 there is mild to moderate progression of the periosteal reaction without a significant progression of lysis.
Reduction in bone pain as a result of irradiation is theorized to result from multiple mechanisms: by direct killing of tumor cells and inflammatory cells and by reducing bone destruction by osteoclasts. Prostaglandins produced by neoplastic cells as well as tumor-associated macrophages may also stimulate nociceptors and increase the pain response23. Radiation may mitigate this response thereby improving patient comfort.
Two published studies on SRS treatment of osteosarcomas have been published in dogs. The first reported published in 2004 on 11 dogs that received 20-30 Gy of radiation in a single treatment. The overall medial survival time in this study was 363 days with a 36% pathologic fracture rate5. The second study was published in 2014 and evaluated dogs that received a single SRS treatment but either had a fracture prior to SRS or developed one on the months following radiation treatment. Fractures were addressed either with internal fixation, external fixation or plating. All dogs also received chemotherapy with a protocol containing doxorubicin (30 mg/m2) and carboplatin (300 mg/m2) or single agent doxorubicin. Distant metastatic spread was documented in 5 dogs (lungs n=4; rib n=1). Survival time ranged from 364-897 days with one dog lost to follow up at 8 months. In this study, histopathology of their lesions was performed after SRS, and demonstrated extensive necrosis and proliferation of fibrous connective tissue. Interestingly, no evidence of neoplastic cells was found6.
Alternatives to stereotactic radiosurgery include the previously mentioned standard of care, amputation + chemotherapy, or treatment with conventional fractionated radiation therapy. Amputation followed by chemotherapy typically yields survival times of 235-540 days. Several chemotherapy protocols have been evaluated with none demonstrating superiority8-22.
Using conventional hypofractionated radiation therapy, or “palliative radiation therapy”, typically 2-4 fractions (treatments) of radiation are given once a week for 2-4 weeks. It has been documented that, on average, 76-96% of dogs will experience pain relief after 11-15 days from the start of a radiation protocol. The typical duration of pain relief is 60-120 days and average survival time is 120-180 days2-4.
This case demonstrates that treatment with stereotactic radiosurgery with CyberKnife yielded similar results to amputation + chemotherapy. This modality of treatment may be preferred by owners of dogs that are not good candidates for amputation due to concurrent orthopedic disease or because of owners’ wishes. One potential drawback of SRS treatment of osteosarcoma lesions, however, is the ongoing risk of pathologic fracture, which likely peaks approximately 6 months after irradiation but then decreases as new bone is formed7.
Further studies are needed to evaluate the rate of metastatic disease development after treatment of OSA with SRS or CyberKnife. Currently most palliative RT protocols do not include chemotherapy as most dogs succumb to intractable pain prior to the development of metastatic disease, however, with the ability of stereotactic radiosurgery to control pain for a significantly longer period of time, the addition of chemotherapy to control metastatic disease may be warranted. Limitations of the current case report include a lack of a definitive histopathologic diagnosis.
Figure 1. The left front limb in August 2014
Figure 2. The left front limb in April 2015
Figure 3. The left front limb in August 2015