Introduction

As osteosarcoma (OSA) is the most common bone tumor in dogs representing up to 85% of all skeletal tumors, this presentation is focused on the current knowledge of the medical approach to this cancer. Several tissue subtypes exist such as osteoblastic, chondroblastic, telangiectatic, fibroblastic and non-differentiated. It is estimated that up to 10,000 new cases are diagnosed yearly. OSA is usually observed in middle-aged to older large breed or giant breed dogs with certain breeds such as Rottweiler, Irish Wolfhounds and Greyhounds being overrepresented. Several risk factors have been identified, but in the past 20 years no real breakthroughs or improvements in long-term outcome have been reported in the medical approach to this devastating disease. Patients still succumb to the metastatic disease which develops in 90% of all dogs within 1 year if not treated with chemotherapy. The past 30 years the standard of care (SOC) management recommendation has been amputation or limb sparing surgery of the affected limb/site followed by single agent chemotherapy with either carboplatin or cisplatin. This approach has resulted in overall reported 1 and 2 year survival times of 38–45%/16–18% with cisplatin (70 mg/m² q 21 days) as single agent chemotherapy and 35–37%/19–22% for carboplatin (300 mg/m² q 21 days) as single agent chemotherapy. Immunotherapy has been continuously investigated since the late 1980s and few adjunctive immunotherapeutic approaches have enabled survival times comparable to chemotherapy. Recent advances in the immunotherapy field in human oncology holds promise to change this and clinical trials using a variety of approaches are ongoing. A phase I clinical trial with administration of a recombinant Listeria monocytogenes vaccine (recombinant HER2/neu-expressing Listeria) following amputation and chemotherapy have demonstrated a reduced incidence of metastatic disease and shown prolonged survival rates in dogs with appendicular OSA with minimal residual disease compared to historical reports.

The main challenge veterinarians face with many dog owners is the hesitation to amputate. The past 10–15 years palliative care for patients managed without amputation has improved significantly due to knowledge of the pathophysiology and efficient management of cancer-induced bone pain combining local radiation therapy, aminobisphosphonates, and oral pain medication such as NSAIDS, synthetic opioids and gabapentin.

Standard of Care?

Recent veterinary consensus statements regarding SOC for initial evaluation, diagnosis and medical management of canine OSA are not available but based on recent OSA reviews (Szewczyk et al. Vet Res Com, 2015; Wycislo et al. JVIM, 2015) and publications the following represents the current medical management of OSA with and without amputation, respectively.

Work up and diagnosis of canine OSA is aimed at diagnosis, staging and grading. This includes a minimum database (hemogram, biochemistry profile, urinalysis), local imaging (X-ray/CT/MRI) as well as work up for distant metastasis including pulmonary imaging (pulmonary CT superior to 3 view thoracic radiographs), lymph node evaluation and potentially bone scans. Delineation of local disease using advanced imaging procedures (contrast enhanced CT or MRI) is important if management without amputation is attempted. Some recommend pre-surgical FNAsp for cytology with or without ALP staining or biopsy for histopathology whereas others use only imaging prior to surgery. As imaging modalities mainly differentiates between aggressive and non-aggressive bone lesions, prognosis and choice of treatment (e.g., limb salvage surgery vs. amputation) can only be accurate determined in combination with cytology and/or histopathology as other bone malignancies can resemble osteosarcoma.

Medical management after amputation: Single agent chemotherapy with either Carboplatin (300 mg/m² q 21 days for 3–6 cycles) or cisplatin (70 mg/m² q 21 days for 1–6 cycles). At our institution carboplatin is preferred over cisplatin because of lesser adverse effects and ease of administration. If bone metastasis develop before pulmonary metastasis pain management combining radiation therapy (2 to 4 individual treatments of 6 to 10 Gy fractions), bisphosphonates and traditional oral analgetics.

Medical management w/o amputation: Single agent chemotherapy with either carboplatin (300 mg/m² q 21 days for 3–6 cycles) or cisplatin (70 mg/m² q 21 days for 1–6 cycles). In addition, pain management is essential combining local radiation therapy, bisphosphonates and NSAIDS, synthetic opioids and gabapentin. Because of the risk of pathologic fractures and quality of life issues secondary to pain frequent control visits are needed to monitor the patient.

On the Horizon

The future medical management of canine OSA will likely involve novel molecular or immunotherapies, as well as monitoring tools such as molecular biomarkers, molecular diagnostic techniques, molecular imaging (PET-CT, PET-MRI).

Consensus guidelines for conveying clinical trials as well as standardized diagnostic work up and management of human osteosarcoma have been published by several groups and could act as inspiration for future veterinary osteosarcoma guidelines.

References

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2.  Wycislo KL, Fan TM. The immunotherapy of canine osteosarcoma: a historical and systematic review. J Vet Intern Med. 2015;29(3):759–769.

3.  Mason NJ, Gnanandarajah JS, Engiles JB, et al. Immunotherapy with a HER2-Targeting listeria induces HER2-specific immunity and demonstrates potential therapeutic effects in a phase I trial in canine osteosarcoma. Clin Cancer Res. 2016;22(17):4380–4390.

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6.  Whelan JS, Bielack SS, Marina N, et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre­randomisation treatment. Ann Oncol. 2015;26:407–414.

7.  Falk S, Dickenson AH. Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol. 32:1647–1654.

8.  Ramirez III O, Dodge RK, Page RL, et al. Palliative radiotherapy of appendicular osteosarcoma in 95 dogs. Vet Radiol Ultrasound. 1999;40(5):517–522.

9.  Barger A, Graca R, Bailey K, et al. Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. Vet Pathol. 2005;42(2):161–165.