Canine Osteosarcoma, Is There a Cure?
J. Kirpensteijn, DVM, PhD, Diplomate ECVS & ACVS
Chief, Soft Tissue Surgery Section, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University
Utrecht, The Netherlands
Osteosarcoma (OS) is the most common bone tumour in dogs and is characterized by a highly invasive and metastatic behaviour. This tumour frequently affects middle-aged, large breed dogs (less than 5% occur in breeds smaller than 12 kg) and arises in 75% of cases in the metaphyseal area of bones of the appendicular skeleton. The median age of dogs with OSA is 6-7 years. Males are more commonly affected than females. A cause for OSA is unknown although many etiologies have been stipulated (radiation, microtrauma, genetics, implants, nutrition).
OSA is a malignant spindle-cell tumour characterized by direct formation of bone or osteoid tissue by tumour cells. OSA is an aggressive tumour with a locally invasive behaviour and a high rate of metastasis and can be subdivided in chondroblastic, osteoblastic, fibroblastic, telangiectatic, and mixed type tumours. Common locations for OSA include the distal radius, proximal humerus, distal femur, proximal tibia, distal tibia, proximal femur, ulna and scapula. The remainder of OSA (25%) occur in the axial skeleton (mandible, maxilla, vertebrae and ribs). Multicentric OSA is rare (< 10% of cases). Pulmonary metastases are present in more than 90% of the patients at time of initial diagnosis. The prognosis for dogs with OSA without therapy is poor, less than 5% will survive longer than one year after diagnosis. Histologic tumour grading has proven to be a significant prognosticator in canine OS.
History, clinical signs, and differential diagnosis
Dogs with OSA are often presented with an acute or chronic lameness and a visible swelling at the affected site. Often the lameness is backdated by the owner to a minor traumatic incident and pain can be elicited upon palpation. Muscle atrophy, a history of progressively decreased weight bearing, and pathologic fractures may be present. Differential diagnoses include other primary bone tumours (fibrosarcoma, chondrosarcoma, etc.), metastatic tumours, bone cysts and bacterial or fungal osteomyelitis.
The presumptive diagnosis of a bone tumour is easily obtained by regional radiography. Radiographic changes include a mixed pattern of osteolysis and bony proliferation and either change can predominate. Macroscopic pulmonary metastases (> 5 mm) are evident in 10% of cases at initial radiographic examination. Metastatic nodules have the 'canon-ball' appearance and are often located in the periphery. The definite diagnosis is obtained by bone biopsy and histologic examination. The biopsy can be performed using a Jamshidi biopsy needle or Michele bone trephine. Two biopsy specimens, one obtained from the centre and one from the tumour-normal tissue transition zone, will allow proper diagnosis in 92% of cases. Additionally, scintigraphy may be used to diagnose multicentric or metastatic OSA. However, scintigraphy will not differentiate benign (non-tumorous) from malignant lesions, and should be followed by radiography of regions with increased uptake. CT- and MRI-scans can be used to estimate the extent of bony and surrounding soft tissue involvement.
Figure 1. Typical appearance of a malignant bone tumour
Successful treatment of canine osteosarcoma includes local tumour control as well as the treatment of systemic tumour spread. Local marginal resection as sole treatment will result in high recurrence rates, dysfunction of the leg and undiminished metastatic spread of tumour and should be avoided if adjunctive therapy is not available. Amputation alone provides good primary local tumour control, but otherwise does not prolong survival time. A median survival time of 19 weeks is seen after amputation. Ninety percent of these dogs will die within a year because of the development of distant metastases. After amputation, recovery from surgery and adaptation to three legs is fast. Most dogs, even the larger breeds, function extremely well three-legged and most owners are satisfied with the animal's quality of life.
Amputation in combination with chemotherapy enhances survival in canine osteosarcoma because it decreases the occurrence of metastases. The best-known chemotherapeutic agent, cisplatin, has been shown to significantly prolong the disease-free intervals and survival times in dogs, and remains the drug of choice. Cisplatin is administered intravenously at 60-70 mg/m2 for 4-6 doses, at three week intervals. Cisplatin is associated with the risk of severe side-effects (nephrotoxicity, gastrointestinal toxicity, myelosuppression, and ototoxicity) if given as a sole agent. Median survival intervals of dogs treated with cisplatin chemotherapy and resection of the primary tumour is significantly higher than dogs without chemotherapy. A one-year survival percentage of 45-55% has been reported. The median survival interval of dogs treated with chemotherapy before resection of the primary tumour compared to postoperative chemotherapy were not significantly different. Also, the route of administration (IV vs IA) did not influence survival. Dogs that receive more than three doses of cisplatin will survive longer than dogs that receive two or less. Currently, it is recommended to give at least four doses of cisplatin.
Other agents, used for canine osteosarcoma, that have shown a beneficial effect include doxorubicin, liposome encapsulated muramyl tripeptides (liposome/MTP) and carboplatin. Doxorubicin has been shown to prolong survival in combination with cisplatin and as single agent. Dogs treated for osteosarcoma with liposome/MTP survived significantly longer than those treated with placebos. Carboplatin, a second generation platinum compound, does not induce nephrotoxicity and can be given as a 15-minute bolus injection without saline diuresis. Carboplatin significantly increased survival times compared to dogs with amputation alone and was comparable to cisplatin chemotherapy. Carboplatin is given intravenously on an every 21-day schedule at 300 mg/m2.
Instead of amputation, local control may also be obtained by limb-sparing procedures. The goal of limb-sparing is to obtain local tumour control, while providing a pain-free and functional leg. The procedure usually involves (marginal) local surgical excision of the tumour in combination with chemotherapy or radiation therapy. Common locations amenable for performing limb-sparing are the distal radius, proximal humerus, scapula and ulna. OSA of the distal radius and proximal humerus are removed by marginal resection, replaced by an allograft and affixed to the host bone using a bone plate. Arthrodesis of the adjacent joint is often necessary. Recovery after surgery is often fast with dogs bearing weight within a week. Eighty percent of dogs return to normal function after limb-sparing procedures in 6-8 weeks. OSA of the ulna and scapula may be resected without the use of an allograft. Ulnectomies distal to the elbow joint and partial scapulectomies are extremely well tolerated. Complications associated with limb-sparing procedures include infection, recurrence and implant failure. The incidence of local tumour recurrence after limb-sparing varies between 25-50%. Methods to prevent local recurrence include preoperative radiation and preoperative administration of chemotherapy by intra-arterial route, local intravenous perfusion, or slow release polymers. Any of these therapies should be considered in tumours that have extended through the bony cortex and have invaded in the surrounding soft tissues. The use of intravenous, systemic chemotherapy has been unrewarding in preventing recurrence after incomplete resection.
OSA is a highly metastatic tumour and most metastases are observed in the lungs. Macroscopic metastatic disease in canine OSA is not responsive to chemotherapy and the prognosis is often poor. Surgical resection of pulmonary metastasis is useful in limited numbers of patients if less than three nodules are present, if the tumour size has not doubled in a month, and if the disease-free interval is longer than 300 days from the initial date of diagnosis.
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Jolle Kirpensteijn, DVM, PhD, Diplomate ECVS & ACVS