ISSN 2398-2969      

Osteosarcoma

icanis

Synonym(s): OSA


Introduction

  • Definition: malignant mesenchymal tumor of primitive bone cells. 
  • 85% of all bone tumors (50% of all bone tumors in small breeds).
  • 75% of all OSA affect the appendicular skeleton.
  • Most commonly affects distal radius; other common sites are distal femur, proximal tibia and proximal humerus ('away from the elbow, close to the stifle').
  • Also affects axial skeleton and (rarely) soft tissues (extraskeletal OSA).
  • Appendicular OSA most common in large and giant breeds (95% for dogs weighing more than 40 kg).
  • Signs: sudden onset lameness/metaphyseal swelling.
  • Treatment: surgery and chemotherapy.
  • Prognosis: poor long-term as metastatic spread common, if treated, good short-term prognosis.
    Print off the owner factsheet on Canine osteosarcoma Canine osteosarcoma to give to your client.

Pathogenesis

Etiology

  • Unknown.
  • A hereditary basis has been suspected based on increased prevalence in related families and genetic loci have been identified to contribute to heritable OSA in Greyhounds, Rottweilers, and Irish Wolfhounds.   
  • Mutation within tumor suppressor genes (p53, retinoblastoma, PTEN) are genetic factors suspected to cause OSA.

Predisposing factors

General

  • Size of animal: breeds weighing >35 kg are 60 times more at risk compared with breeds <10 kg. There is speculation that because OSA is more common in heavy dogs, it could be induced by multiple minor trauma in the physeal region.
  • Breeds 20-35 kg are 8 times more at risk compared with breeds <10 kg.
  • OSA has been associated with metallic implants (for fracture repair or TPLO/TTA), chronic osteomyelitis, radiotherapy (incidence of less than 5% for the latter).

Pathophysiology

  • Malignant tumor of bone cells.
  • Fast growing, rapidly metastasize to lungs (hematogenous route) Osteosarcoma: pulmonary metastases at post-mortem , spread to local lymph nodes is uncommon.
  • Radiographic evidence of metastasis to other bones in 6.4% of cases at time of diagnosis.
  • Skip metastases (ie synchronous regional bone metastases) have been reported in dogs.
  • If treated with surgery and chemotherapy, 50% of cases develop bone metastases and 50%, pulmonary metastases Osteosarcoma: pulmonary metastases at post-mortem.
  • OSA has been shown to secrete nociceptive ligands potentially generating pain.

Timecourse

  • Untreated - most cases are euthanased withing weeks due to unremitting pain.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Edmunds G L, Smalley M J, Beck S, Errington R J, Gould S et al (2021) Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study. Canine Med Genet 8, 2 PubMed.
  • Al-Khan A A, Nimmo J S, Tayebi M, Ryan S D, Simcock O (2020) Parathyroid hormone receptor 1 (PTHR1) is a prognostic indicator in canine osteosarcoma. Sci Rep 10, 1564 PubMed.
  • Hoddinott K, Oblak M L, Wood G A, Boston S, Mutsaers A J (2020) Effect of timing of bisphosphonate administration on canine osteosarcoma cells undergoing radiation therapy. Can J Vet Res 84(3), 225-229 PubMed
  • Sharma S, Boston S E, Riddle D, Isakow K (2020) Osteosarcoma of the proximal tibia in a dog 6 years after tibial tuberosity advancement. Can Vet J 61(9), 946-950 PubMed
  • Tremolada G, Thamm DH, Milovancev M, Seguin B (2020) Biological behaviour of primary osteosarcoma of the digits, metacarpal and metatarsal bones in dogs. Vet Comp Oncol Sept 2020 PubMed.
  • Laver T , London C A, Vail D M, Biller B J, Coy J, Thamm D H (2018) Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma. Vet Comp Oncol 16(1), E23-E29 PubMed.
  • Kim C, Matsuyama A, Mutsaers A J, Woods J P (2017) Retrospective evaluation of toceranib (Palladia) treatment for canine metastatic appendicular osteosarcoma. Can Vet J 58(10),1059-1064 PubMed
  • Sabattini S, Renzi A, Buracco  P, Defourny S, Garnier‐Moiroux M (2017) Comparative Assessment of the Accuracy of Cytological and Histologic Biopsies in the Diagnosis of Canine Bone Lesions. J Vet Intern Med 31(3), 864-871 PubMed
  • Skorupski K A ,Uhl J M , Szivek A, Allstadt Frazier S D, Rebhun R B, Rodriguez Jr C O (2016) Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial. Vet Comp Oncol 14(1), 81-87 PubMed
  • London C A, Gardner H L,Mathie T, Stingle N, Portela R et al (2015) Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study. PLoS One 10(4), e0124889 PubMed.
  • Shor S, Fadl-Alla B A, Pondenis H C, Zhang X, Wycislo K L (2015) Expression of nociceptive ligands in canine osteosarcoma. J Vet Intern Med 29(1), 268-275 PubMed
  • Amsellem P M, Selmic L E, Wypij J M, Bacon N J, Culp W T N et al (2014) Appendicular osteosarcoma in small-breed dogs: 51 cases (1986-2011). J Am Vet Med Assoc 245(2), 203-210 PubMed.
  • Bracha S, Walshaw R, Danton T, Holland S, Ruaux C, Obradovich J (2014) Evaluation of toxicities from combined metronomic and maximal-tolerated dose chemotherapy in dogs with osteosarcoma. J Small Anim Pract 55(7), 369-374 PubMed
  • Culp W T N, Olea-Popelka F, Sefton J, Aldridge C F, Withrow S J (2014) Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997-2008). J Am Vet Med Assoc 245(10), 1141-1146 PubMed.
  • Sartor A J, Ryan S D, Sellmeyer T, Withrow S J, Selmic L E (2014) Bi-institutional retrospective cohort study evaluating the incidence of osteosarcoma following tibial plateau levelling osteotomy (2000-2009). Vet Comp Orthop Traumatol 27(5), 339-345 PubMed
  • Selmic L E, Lafferty M H, Kamstock D A, Garner A, Ehrhart N P et al (2014) Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986-2012). J Am Vet Med Assoc 245(8), 930-938 PubMed.
  • Selmic L E, Ryan S D, Boston S E, Liptak J M, Culp W T N et al (2014) Osteosarcoma following tibial plateau leveling osteotomy in dogs: 29 cases (1997-2011). J Am Vet Med Assoc 244(9), 1053-1059 PubMed.  
  • Selmic L E, Burton J H, Thamm D H, Withrow S J, Lana S E (2014) Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 d5ogs after amputation for treatment of appendicular osteosarcoma. J Vet Intern Med 28(2), 554-63 PubMed.
  • Neihaus S A, Locke J E, Barger A M, Borst LB, Goring R L (2011) A Novel Method of Core Aspirate Cytology Compared to Fine-Needle Aspiration for Diagnosing Canine Osteosarcoma.  
    J Am Anim Hosp Assoc 47(5), 317-323 PubMed
  • Hillers K R, Dernell W S, Lafferty M H, Withrow S J & Lana S E (2005) Incidence and prognostic importance of lymph node metastases in dogs with appendicular osteosarcoma: 228 cases (1986-2003). JAVMA 226 (8), 1364-1367 PubMed.
  • Fuchs B & Pritchard D J (2002) Etiology of osteosarcoma. Clin Orth Rel Res 397, 40-52 PubMed.
  • Dickerson M E, Page R L, LaDue T A et al (2001) Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs. JVIM 15 (2), 120-124 PubMed.
  • Langenbach A, McManus P M, Hendrick M J, Shofer F S & Sorenmo K U (2001) Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumours. JAVMA 218 (9), 1424-1428 PubMed.
  • Mehl M L, Withrow S J, Seguin B, Powers B E et al (2001) Spontaneous regression of osteosarcoma in four dogs. JAVMA 219 (5), 614-617 PubMed.
  • Blackwood L (1999) Bone tumours in small animals. In Practice 21 (1), 31-7 VetMedResource.
  • Ehrhart N et al (1998) Prognostic importance of alkaline phosphatase activity in serum from dogs with appendicular osteosarcoma - 75 cases (1990-1996). JAVMA 213 (7), 1002-1006 PubMed.
  • Bergman P J et al (1996) Amputation and carboplatin treatment of dogs with oesteosarcoma - 48 cases (1991 to 1993). J Vet Intern Med 10 (2), 76-81 PubMed.
  • McEntee M C et al (1993) Palliative radiotherapy for canine appendicular osteosarcoma. Vet Radiol 34 (5), 367-370 VetMedResource.
  • Ogilvie G K et al (1993) Evaluation of single-agent chemotherapy for treatment of clinically evident oesteosarcoma in dogs - 45 cases (1987-1991). JAVMA 202 (2), 304-306 PubMed.
  • Berg J et al (1992) Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery - 22 cases (1987-1990). JAVMA 200 (12), 2005-2008 PubMed.
  • Spodnick G J et al (1992) Prognosis for dogs with appendicular oesteosarcoma treated by amputation alone - 162 cases (1978-1988). JAVMA 200 (7), 995-999 PubMed.
  • Straw R C, Cook N L, LaRue S M, Withrow S J & Wrigley R H (1989) Radiographic bone surveys. JAVMA 195 (11), 1458 PubMed.
  • Powers B E, LaRue S M, Withrow S J, Straw R C & Richter S L (1988) Jamshidi needle biopsy for diagnosis of bone lesions in small animals. JAVMA 193 (2), 205-210 PubMed.
  • Carberry C A & Harvey H J (1987) Owner satisfaction with limb amputation in dogs and cats. JAAHA 23 (2), 227-232 VetMedResource.

Other Sources of Information

  • Ehrart N, Christensen N I, Fan T H (2020) Cancer chemotherapy. In: Small Animal Clinical Oncology. 6th edn. Eds Withrow & MacEwen’s. Elsevier Saunders, St. Louis. pp 524-550. 

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Canine osteosarcoma

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