Osteosarcoma: What chemo? When? (Proceedings)
Osteosarcoma (OSA) is the most common primary bone tumor in the dog (85% of skeletal malignancies). It is estimated to occur in over 8,000 dogs/year in the United States.
Incidence and Risk Factors
Osteosarcoma (OSA) is the most common primary bone tumor in the dog (85% of skeletal malignancies). It is estimated to occur in over 8,000 dogs/year in the United States. OSA has bimodal age incidence peaks at 18-24 months and 7 years and occurs predominately in large to giant breed dogs in the appendicular skeleton at metaphyseal sites, whereas smaller breed dogs generally have their OSA in the axial skeleton. For appendicular OSA, the saying "Away from the elbow and close to the knee" is a good generalization; however, OSA can occur at sites such as distal tibia and others. In addition OSA is seen in the oral cavity (maxilla or mandibular), nasal cavity, ribs, digits and many other bony sites. The etiology of OSA is unknown but thought to be related to traumatic microfractures.
Pathology and Behavior
OSA is a malignant mesenchymal tumor of primitive bone cells. The presence of extracellular matrix production of osteoid helps differentiate OSA from other bone sarcomas such as chondrosarcoma, lymphosarcoma, Hemangiosarcoma, and others. There are multiple histologic sub-classifications (osteoblastic, fibroblastic, chondroblastic, telangiectatic, etc.) for OSA; however, sub-classifications do not presently appear to be prognostic. OSA causes bone lysis, production of bone, or both; pathological fractures can occur. Less than 5% of dogs present with radiographically detectable pulmonary metastasis whereas > 90% have micrometastases at presentation.
History and Clinical Signs
Most dogs with OSA present for lameness and/or swelling at the local site if appendicular in origin. For non-appendicular OSA, the history and clinical signs are dependant on the specific site of origin.
Local radiographs document soft tissue swelling, bone lysis, production of bone, or a combination of both. The differential diagnosis for OSA includes: Primary or secondary bone tumor, myeloma, lymphoma, and osteomyelitis. The definitive diagnosis of OSA requires bone biopsy. While most biopsies of cancer aim for the periphery of a lesion, bone biopsies should be taken from the center of the lesion and multiple biopsies should be performed. In addition, a full physical examination with close palpation of local lymph nodes (aspirate & examine if enlarged) is also recommended. For additional staging, three view thoracic radiographs are strongly recommended. The utility of additional staging diagnostics such as bone survey radiographs and/or nuclear medicine bone scanning are somewhat controversial. A surgical staging system suggests most OSA are stage IIb (high-grade, extracompartmental and no gross metastasis).
Therapy: The median survival times reported for appendicular OSA are summarized in the table below.
History and Clinical Signs
• No overt metastasis
• tumor necrosis (neoadjuvant chemotherapy only)
• ↑↑ Mandibular location
• < 5 yr age
• ↑↑ tumor size
• Proximal humerus
» 40 kg weight
• ↑↑ ALP
• ↑↑ grade
1. Spodnick GJ, Berg J, Rand WM et al. (), Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978-1988), Journal of the American Veterinary Medical Assoc 1992;200: 995-999
2. Brodey RS, Riser WH (), Canine osteosarcoma. A clinicopathologic study of 194 cases, Clin.Orthop. 1969;62: 54-64
3. Mauldin GN, Matus RE, Withrow SJ et al. (), Canine osteosarcoma. Treatment by amputation versus amputation and adjuvant chemotherapy using doxorubicin and cisplatin, J Vet.Intern.Med. 1988;2: 177-180
4. McEntee MC, Page RL, Novotney CA et al. (), Palliative Radiotherapy for Canine Appendicular Osteosarcoma, Vet.Radiol.Ultrasound 1993;34: 367-370
5. Ramirez O, III, Dodge RK, Page RL et al. (), Palliative radiotherapy of appendicular osteosarcoma in 95 dogs, Vet.Radiol.Ultrasound 1999;40: 517-522
6. Green EM, Adams WM, Forrest LJ (), Four fraction palliative radiotherapy for osteosarcoma in 24 dogs, J Am Anim Hosp Assoc 2002;38: 445-451
7. Straw RC, Withrow SJ, Richter SL et al. (), Amputation and cisplatin for treatment of canine osteosarcoma, J.Vet.Intern.Med. 1991;5: 205-210
8. Kraegel SA, Madewell BR, Simonson E et al. (), Osteogenic sarcoma and cisplatin chemotherapy in dogs: 16 cases (1986-1989)., Journal of the American Veterinary Medical Assoc 1991;199(8): 1057-1066
9. Thompson JP, Fugent MJ (), Evaluation of survival times after limb amputation, with and without subsequent administration of cisplatin, for treatment of appendicular osteosarcoma in dogs: 30 cases (1979-1990), Journal of the American Veterinary Medical Assoc 1992;200: 531-533
10. Berg J, Weinstein MJ, Springfield DS et al. (), Results of surgery and doxorubicin chemotherapy in dogs with osteosarcoma, Journal of the American Veterinary Medical Association 1995;206: 1555-1560
11. Bergman PJ, MacEwen EG, Kurzman ID et al. (), Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993),J Vet.Intern.Med. 1996;10: 76-81
12. Straw RC, Withrow SJ, Douple EB et al. (), Effects of cis-diamminedichloroplatinum II released from D,L-polylactic acid implanted adjacent to cortical allografts in dogs, J.Orthop.Res. 1994;12: 871-877
13. Bailey D, Erb H, Williams L et al. (), Carboplatin and doxorubicin combination chemotherapy for the treatment of appendicular osteosarcoma in the dog, J Vet.Intern.Med. 2003;17: 199-205
14. Chun R, Kurzman ID, Couto CG et al. (), Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: a pilot study, J Vet.Intern.Med. 2000;14: 495-498
15. Kurzman ID, MacEwen EG, Rosenthal RC et al. (), Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin, Clin.Cancer Res. 1995;1: 1595-1601
16. Vail DM, Kurzman ID, Glawe PC et al. (), STEALTH liposome-encapsulated cisplatin (SPI-77) versus carboplatin as adjuvant therapy for spontaneously arising osteosarcoma (OSA) in the dog: a randomized multicenter clinical trial, Cancer Chemother.Pharmacol. 2002;50: 131-136
17. Kirpensteijn J, Teske E, Kik M et al. (), Lobaplatin as an adjuvant chemotherapy to surgery in canine appendicular osteosarcoma: a phase II evaluation, Anticancer Res. 2002;22: 2765-2770
18. Kent MS, Strom A, London CA et al. (), Alternating carboplatin and doxorubicin as adjunctive chemotherapy to amputation or limb-sparing surgery in the treatment of appendicular osteosarcoma in dogs, J Vet Intern Med 2004;18: 540-544
19. Kirpensteijn J, Kik M, Teske E et al. (), TP53 gene mutations in canine osteosarcoma, Vet.Surg. 2008;37: 454-460
20. Dimopoulou M, Kirpensteijn J, Moens H et al. (), Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma, Vet.Surg. 2008;37: 466-471
21. Liptak JM, Kamstock DA, Dernell WS et al. (), Oncologic outcome after curative-intent treatment in 39 dogs with primary chest wall tumors (1992-2005), Vet.Surg. 2008;37: 488-496
22. Knapp-Hoch HM, Fidel JL, Sellon RK et al. (), An expedited palliative radiation protocol for lytic or proliferative lesions of appendicular bone in dogs, J.Am.Anim Hosp.Assoc. 2009;45: 24-32
23. Phillips B, Powers BE, Dernell WS et al. (), Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs, J.Am.Anim Hosp.Assoc. 2009;45: 33-38
24. Fan TM, Charney SC, de Lorimier LP et al. (), Double-blind placebo-controlled trial of adjuvant pamidronate with palliative radiotherapy and intravenous doxorubicin for canine appendicular osteosarcoma bone pain, Journal of Veterinary Internal Medicine 2009;23: 152-160
25. Selvarajah GT, Kirpensteijn J, van Wolferen ME et al. (), Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times, Mol.Cancer 2009;8: 72
26. Paoloni M, Davis S, Lana S et al. (), Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression, BMC.Genomics 2009;10: 625
27. Selvarajah GT, Kirpensteijn J (), Prognostic and predictive biomarkers of canine osteosarcoma, Vet.J. 2010.