Cancer In Greyhounds
Cancer In Greyhounds and Other Sighthounds
The most common cause of death in retired racers (RRGs) is cancer (58%), as is in AKC Greyhounds (23%), and Galgos Españoles (38%). In a recent health survey conducted at OSU, the prevalence of cancer was similar among the 3 breeds, occurring in 13% of RRG, 9% of AKCGs, and 7% of Galgos. Osteosarcoma (OSA) was the most prevalent form of cancer reported in RRGs, with a prevalence of 45% for dogs with cancer and 6% for the overall population; in striking contrast, there were no OSAs among the AKC Greyhounds, and there was only one Galgo with OSA (9% of all cancers, and 0.6% of the overall population). Interestingly, OSAs are also the most common primary bone neoplasm in dogs and the most common tumor in Greyhounds in the United Kingdom, where it accounted for 50% of all tumors, and for 22% of the deaths in the breed. In our study, soft tissue sarcomas (ie; hemanigiopericytoma, neurofibroma, fibrosarcoma) were second in prevalence in RRGs, whereas there was an even distribution of tumor types in AKCGs; hemangiosarcoma and mammary tumors were the most common neoplasia in GEs.
Primary bone neoplasms are common in dogs. Most primary bone tumors in dogs are malignant, in that they usually cause death as a result of local infiltration (e.g., pathologic fractures or extreme pain leading to euthanasia) or metastasis (e.g., pulmonary metastases in osteosarcoma). Neoplasms that metastasize to the bone are extremely rare in dogs; some malignant tumors that occasionally metastasize to bones are transitional cell carcinoma of the urinary tract, OSA of the appendicular skeleton, hemangiosarcoma, mammary adenocarcinoma, and prostatic adenocarcinoma.
OSA can affect either the appendicular or axial skeletons, and occur primarily in large (and giant)–breed, middle age–to-older dogs. Preferential locations for OSA include the distal radius, proximal humerus, and distal femur, although they can occur in any bone or location.
Their biologic behavior is characterized by aggressive local infiltration of the surrounding tissues and rapid hematogenous dissemination (usually to the lungs). Although historically it was believed that OSAs of the axial skeleton had a low metastatic potential, it now appears that their metastatic rate is similar to that of the appendicular OSAs.
Clinical Features of Bone Cancer
Appendicular OSAs occur predominantly in the metaphyses of the proximal humerus, distal radius, and distal femur, (“TOWARDS THE KNEE AND AWAY FROM THE ELBOW”), although other metaphyses can also be affected. The proximal humerus is the most common primary site in RRGs. Owners seek veterinary care because of lameness or swelling of the affected limb. Physical examination usually reveals a painful swelling in the affected area, with or without soft tissue involvement. The pain and swelling can be acute in onset, leading to the presumptive diagnosis of a nonneoplastic orthopedic problem, and thus considerably delaying diagnosis and definitive therapy for the neoplasm. In contrast with other breeds, where dogs with OSA typically present for bone swelling and/or lameness, in Greyhounds, they frequently present as a spontaneous pathological fracture.
Radiographically, OSAs exhibit a mixed lytic-proliferative pattern in the metaphyseal region of the affected bone. Adjacent periosteal bone formation leads to the development of the so-called Codman’s triangle, which is composed of the cortex in the affected area and the periosteal proliferation. In Greyhounds, most OSAs are lytic (not proliferative). OSAs do not cross the articular space, but occasionally they can infiltrate adjacent bone (e.g., ulnar lysis resulting from an adjacent radial OSA). Because other primary bone neoplasms and some osteomyelitis lesions can mimic the radiographic features of OSAs, fine needle aspiration (FNA) specimens of every lytic or lytic-proliferative bone lesion should be obtained before the owners decide on a specific treatment. An exception to this rule is an owner who has already decided that amputation is the initial treatment of choice for that lesion (i.e.; the limb is amputated and the lesion is submitted for histopathologic evaluation).
Once a presumptive radiographic diagnosis has been established and if the owners are contemplating treatment, thoracic and/or bone (i.e., skeletal survey) radiographs should be obtained to determine the extent of the disease. We usually obtain three radiographic views of the thorax and do not do a skeletal radiographic survey (or radionuclide bone scan). Only 5-10% of dogs with OSA initially have radiographically detectable lung lesions; the presence of metastases is a strong negative prognostic factor.
The radiographic diagnosis can be confirmed before surgery (i.e., limb amputation or limb salvage) on the basis of the findings yielded either by FNA (if there is considerable cortical lysis); if not enough lysis is present, ultrasonography cabn be used to find a “window: into the bone for an FNA. OSA cells are usually round or oval, have distinct cytoplasmic borders, have a bright blue, granular cytoplasm, and have excentric nuclei with or without nucleoli. The diagnostic yield of this procedure is quite high (>75%).
As long as the owners understand the biologic behavior of the neoplasm (i.e., the high likelihood of their dog dying of metastatic lung disease within 4-6 months of amputation if no chemotherapy is used) and as long as the clinical and radiographic features of the lesion are highly suggestive of OSA, the limb can be amputated in the absence of a cytologic or histopathologic diagnosis. However, the amputated leg (or representative samples) should always be submitted for histopathologic studies.
Treatment and Prognosis
The treatment of choice for dogs with OSA is amputation with adjuvant single-agent or combination chemotherapy. The median survival time in dogs with appendicular OSA treated with amputation alone is approximately 4 months, whereas in dogs treated with amputation and cisplatin, amputation and carboplatin, or amputation and doxorubicin it is approximately 1 year. Survival and remission times in Greyhounds do not appear to be any different than those in other breeds. Amputation in Greyhounds with OSA frequently results in severe postoperative bleeding around the surgical site, leading to subcutaneous blood accumulation in the other limbs, ventral thorax, and ventral abdomen; these dogs typically have normal hemostasis profiles, and the severity of bleeding decreases after administration of aminocaproic acid (500 mg PO q8h for 5 days).
A novel surgical approach for dogs with distal radial osteosarcomas consists of sparing the affected limb. Instead of amputation, the affected bone is resected and an allograft from a cadaver or a prostehetic device is used to replace the neoplastic bone; novel biomaterials are also currently being investigated for this purpose. The dogs are also treated with intravenous carboplatin or doxorubicin and, in general, have almost normal limb function. The main complication is the development of osteomyelitis in the allograft; if that occurs, the limb frequently needs to be amputated. Survival times in dogs treated with limb-sparing procedures are comparable to those in those that undergo amputation plus chemotherapy, with the added benefit to the owners of having a four-legged pet.
The dosages and the recommended ways of administering chemotherapy for dogs with OSA are given in Table 1. At our hospital, we use either of the drugs mentioned above immediately after amputation, and for a total of 4 to 5 treatments.
We are currently investigating a novel approach to modulation of chemotherapy in Greyhounds with OSA, by administering suramin, a polysulfonated naphthylurea that, at low doses, has been shown to increase sensitivity to doxorubicin in in vitro and laboratory animal models of cancer, by inhibiting binding of fibroblast growth factor (FGF) to its receptors. Preliminary results are encouraging, and the administration of suramin prior to doxorubicin does not appear to potentiate the toxicity of the chemotherapeutic agent. Long-term survivors appear to be more common with this combination.
If owners are reluctant to allow the veterinarian to amputate the limb, local radiotherapy plus carboplatin or doxorubicin may be of some benefit. However, in our limited experience, most dogs are eventually euthanized within 3 to 4 months of the initial diagnosis because of the development of pathological fractures (i.e., after radiotherapy the tumor is not as painful; therefore the dog regains normal use of the limb and fractures the area), osteomyelitis, or metastatic lesions. Interestingly, we have seen survival times >2years in some Greyhounds treated with this combination.
Pain control is essential in dogs where surgery is not an option; we have used either NSAIDs (carprofen, deracoxib, meloxicam) at recommended doses, or bisphosphonates such as pamidronate (Aredia), at a dose of 1 mg/kg IV every 3-6 weeks. Drugs such as tramadol at dosages of 1-4 mg/kg, PO, q8-12 hs may also be beneficial.
Chemotherapy may modify the biologic behavior of the tumor, resulting in a higher prevalence of bone metastases and a lower prevalence of pulmonary metastases. Moreover, the doubling time (i.e., growth rate) of metastatic lesions appears to be longer than that in dogs that have not received chemotherapy, and there appear to be fewer metastatic nodules in treated than in untreated dogs. Therefore, surgical removal of the metastatic nodules (i.e., metastasectomy) followed by additional cisplatin or carboplatin therapy may be recommended for a dog that has been treated with chemotherapy after amputation of the limb and in which one to three pulmonary metastatic lesions are detected.
Table 1: Chemotherapy Protocols for Dogs with Osteosarcoma
- Carboplatin (Paraplatin®): 300 mg/m2, IV, q3-4 weeks
- Doxorubicin (Adriamycin®): 30 mg/m2, IV, every 2 weeks, for 5 doses
- Carboplatin (Paraplatin®): 300 mg/m2, IV, on weeks 1 and 6 plus Doxorubicin (Adriamycin®): 30 mg/m2, IV, on weeks 3 and 9. THIS PROTOCOL HAS RESULTED IN SHORT REMISSION TIMES IN GREYHOUNDS!!