Most primary bone tumors in dogs are malignant, and approximately 85 % are osteosarcomas. Osteosarcomas are highly aggressive tumors, characterized by local invasion/destruction and distant metastasis (spread to other organs). Osteosarcoma commonly affects the appendicular skeleton (limbs) of large to giant breed dogs, but can also occur in the axial skeleton (skull, ribs, vertebrae, pelvis), which is a more common primary site in smaller dogs. Other bone tumors include chondrosarcoma, fibrosarcoma, hemangiosarcoma, liposarcoma, multiple myeloma, and metastatic bone tumors. The biological behavior, prognosis, and treatment of these tumors depends on tumor type, primary site (location), and extent of disease (stage). Therefore, various diagnostic tests such as radiographs (X-rays), bloodwork, and a biopsy are required to determine the most appropriate treatment.
The signs associated with a bone tumor may be nonspecific and depend on the primary site. Tumors in the limbs often cause various degrees of lameness and pain, and a firm swelling may become evident as the tumor size increases. The pain can cause other problems such as irritability, aggression, loss of appetite, weight loss, whimpering, crying, sleeplessness, and reluctance to exercise. Tumors in non-weight-bearing bones may initially appear as a solid, firm mass. Other clinical signs may vary, depending on the primary site and involvement of underlying structures.
DIAGNOSIS AND WORKUP (STAGING)
Initial evaluation of a dog with a suspected bone tumor often includes: complete physical exam, blood tests, radiographs (both the primary site and the lungs), and a biopsy. The biopsy can be incisional or excisional. An incisional biopsy is performed for diagnosis only. A small sample of the tumor is removed to determine the specific tumor type. An excisional biopsy involves removing the entire tumor, both for diagnostic as well as therapeutic purposes. The work-up and staging are important for two reasons: it is necessary to determine the tumor type and extent of the cancer, but also provides the clinician with information regarding the dog’s general health and may identify concurrent medical or musculoskeletal problems, all of which may influence the treatment recommendations.
As stated above, the treatment recommendations for bone tumors depend on multiple factors, and a complete physical exam and work-up may be necessary to accurately determine the most appropriate treatment for an individual dog.
Since osteosarcoma is by far the most common tumor type, this treatment discussion will focus on osteosarcoma. We often classify osteosarcomas as appendicular or axial, because the location of the tumor may have implications both for the surgical approach as well as the tumor’s biological behavior, and therefore require different follow-up treatments.
Appendicular (limb) osteosarcoma commonly causes lameness and pain because of invasion and destruction of normal bone and periosteum (sensitive structures surrounding bone). These tumors are also highly metastatic (likely so spread to other organs), and the average dog with appendicular osteosarcoma will live 4-6 months if treated with surgery alone. Surgery at VHUP usually involves amputation of the affected limb, but limbsparing procedures may be an option in selected cases. The surgery serves two purposes; it removes the primary tumor which is necessary for cancer control, but it also removes the source of pain, and may therefore dramatically improve the quality of life of the patient.
The most common cause of death is lung metastasis. Because of this, systemic chemotherapy is recommended as follow-up therapy for dogs with appendicular osteosarcoma. Chemotherapy is not likely to cure most dogs with osteosarcoma, but can prolong a good quality survival. We currently recommend to use a combination of 2 different drugs: Adriamycin (doxorubicin) and cisplatin or carboplatin. Most dogs tolerate this chemotherapy well, with only mild, self-limiting side effects such as depressed appetite, nausea, occasional vomiting and diarrhea for a few days. Less than 5 % of dogs will experience severe, life-threatening side effects requiring hospitalization and supportive care. If your dog’s side effects are severe and compromise his/her quality of life, the dosages of these drugs are reduced in the subsequent treatments. The average survival in dogs with osteosarcoma treated with surgery and chemotherapy is approximately 1 year.
Axial osteosarcomas are often diagnosed as a firm, solid mass. Other clinical signs vary, depending on the tumor location and the involvement of normal adjacent tissues. Because of the location of most axial osteosarcomas, a complete surgical removal is often not possible. Microscopic tumor cells are left behind, and the tumor is therefore likely to recur at the same site. The average survival in dogs with axial osteosarcomas is 4-5 months, and the most common cause of treatment failure is local tumor recurrence. Therefore follow-up treatment is focused on improving local tumor control, and radiation therapy is a reasonable choice. There is currently limited information regarding the effect of adjuvant radiation therapy in dogs with axial osteosarcomas. The metastatic potential of these osteosarcomas vary depending on the location, and chemotherapy may be indicated in some cases as well.
The above are general treatment guidelines for dogs with osteosarcoma. In addition, palliative measures might be suggested for dogs that are not candidates for any of these options for various reasons. A palliative treatment is given to alleviate pain and symptoms from the tumor, and may involve the use of different types of pain medication and/or a few high doses of radiation therapy. Such treatments may help control the pain in dogs with osteosarcoma and therefore provide the client and pet with additional good quality time together.
LINKS FOR ADDITIONAL INFORMATION ON OSTEOSARCOMA
ONGOING CLINICAL TRIALS FOR OSTEOSARCOMA
Clinic Seeks Dogs with Appendicular Osteosarcoma for Trial
The University of Illinois Cancer Care Clinic recently secured resources to initiate a funded clinical trial involving osteosarcoma (OSA), by far the most common primary bone tumor in dogs. The main goal of this trial is to objectively assess the effectiveness of aminobisphosphonates for the management of bone pain associated with canine appendicular OSA. Aminobisphosphonates have been used effectively in humans for more than 10 years, and our Cancer Care Clinic has been safely using them in dogs since 1996.
Dogs with appendicular OSA meeting study inclusion criteria will be provided FREE aminobisphosphonate every 28 days for palliative therapy of bone pain. (The normal cost of this aminobisphosphonate is fairly expensive: for a dog weighing greater than 75 pounds, it would be approximately $600/dog/treatment.) The provision of up to three doses of aminobisphosphonate at no cost may serve as a significant financial incentive. Additionally, owners will be compensated in the amount of $300 when returning for the first monthly scheduled recheck appointment.
Background on Treatment of OSA:
It is estimated that over 8,000 dogs per year will be diagnosed with OSA in the United States. Canine patients diagnosed with OSA are often middle-aged to older dogs of large or giant body size, with definite over-representation of certain breeds such as the Rottweiler, Saint Bernard, Golden retriever, Irish wolfhound, and Greyhound. Conventional standard therapy for canine appendicular OSA includes amputation of the affected limb, and administration of adjuvant chemotherapy.
A fair number of patients may be poor candidates for amputation, due to complicating factors such as severe degenerative joint disease, significant obesity, and multiple tumor sites, or because of owner reluctance for this radical procedure. Therefore, other means to effectively control local bone pain, and possibly halt or slow the progression of the primary bone tumor growth, should be investigated. While pain management is recommended through the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, these analgesic agents usually do not provide adequate pain control in dogs with advanced osteolytic diseases, including OSA.
Although palliative radiation therapy has proven to be effective in significantly decreasing bone pain in 75 to 80 percent of dogs with OSA, this form of therapy is not readily available everywhere, and can be relatively expensive. In the past decade, human beings suffering from painful bone cancers have demonstrated a survival advantage, and benefited from significant pain reduction, when treated with a class of potent antiresorptive agents known as aminobisphosphonates.
For a more detailed description of the Funded Clinical Trial for Appendicular Osteosarcoma, please contact the following individuals at the University of Illinois Veterinary Teaching Hospital:
Timothy M. Fan, DVM
Louis-Philippe de Lorimier, DVM
Sarah Charney, DVM
CLINICAL TRIAL RESULTS
TRIAL Results: J Vet Intern Med. 2000 Sep-Oct;14(5):495-8.
Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: a pilot study.
Chun R, Kurzman ID, Couto CG, Klausner J, Henry C, MacEwen EG.
Kansas State University, Manhattan, USA. firstname.lastname@example.org
Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).
PMID: 11012111 [PubMed – indexed for MEDLINE]
TRIAL RESULTS: Mol Ther. 2003 Feb;7(2):163-73
A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model
Hemminki A, Kanerva A, Kremer EJ, Bauerschmitz GJ, Smith BF, Liu B, Wang M, Desmond RA, Keriel A, Barnett B, Baker HJ, Siegal GP, Curiel DT.
Division of Human Gene Therapy, Department of Medicine, Department of Pathology, Department of Surgery, and the Gene Therapy Center, Birmingham, Alabama, UK
Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent premature abrogation of replication, may have been a partial reason. Improving the oncolytic potency of agents has been hampered by the inability to study host-vector interactions in immune-competent systems, since human serotype adenoviruses do not productively replicate in animal tissues. Therefore, approaches such as immunomodulation, which could result in sustained replication and subsequently increased oncolysis, have not been studied. Utilizing the osteocalcin promoter for restricting the replication of a canine adenovirus to dog osteosarcoma cells, we generated and tested the first nonhuman oncolytic adenovirus. This virus effectively killed canine osteosarcoma cells in vitro and yielded a therapeutic benefit in vivo. Canine osteosarcoma is the most frequent malignant disease in large dogs, with over 8000 cases in the United States annually, and there is no curative treatment. Therefore, immunomodulation for increased oncolytic potency could be studied with clinical trials in this population. This could eventually translate into human trials.
PMID: 12597904 [PubMed – in process]
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PubMed, Published for MEDLINE, National Library of Medicine