Soft and Hard Tissue Sarcomas
World Small Animal Veterinary Association World Congress Proceedings, 2013
Anthony J. Mutsaers, DVM, PhD, DACVIM (Oncology)
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada

Canine Soft-Tissue Sarcomas

Despite a multitude of names, based on their presumed cells of origin, these tumours are generally considered collectively with regard to prognosis and treatment options (with the notable exception of hemangiosarcoma). These are tumours of mesenchymal tissues, including muscle, adipose, fascial, fibrous, and neurovascular origin. It is sometimes difficult for pathologists to determine the exact histogenesis of the tumour, and immunohistochemical procedures using antibodies to various tissue markers are utilized in this situation.

Treatment of canine soft-tissue sarcomas is primarily by surgical removal that requires extensive margins for cure. These tumours often have poorly defined margins, and are very locally invasive. Presurgical planning with advanced imaging, such as MRI or CT, is recommended to assess the degree of tissue infiltration prior to surgery. These tumours generally have a low metastatic rate (collectively seen as less than 20% risk, but increased likelihood with higher grade); however, as our ability to manage local control continues to improve, the long-term metastatic rate may begin to increase.

In addition to surgery, there is a key role for radiation therapy in the adjuvant setting for cases with incomplete surgical margins. In cases with very large tumours, radiation therapy has also been applied in the neo-adjuvant setting (prior to surgery) to shrink the margins and increase the likelihood of surgical success. Soft-tissue sarcoma tumours are generally considered much more resistant to radiation applied to gross disease, and as a single form of treatment, radiation is considered only palliative. The success of radiation decreases dramatically to approximately 50% response rates when applied in the gross disease setting. The role of chemotherapy for local control is not established, and likely to be of minimal benefit when delivered in conventional protocols. However, there is recent interest in treatment with metronomic cyclophosphamide and piroxicam for prevention of tumour regrowth in dogs with dirty surgical margins and no other ancillary therapy.

The accurate prediction of late metastasis is facilitated by tumour grade, and as in other tumours, mitotic index appears to play a role in prognosis. It is worthy to note that there may occasionally be discrepancy between the grade assigned at presurgical biopsy and review of the surgical specimen, so it is worth cautioning clients about this possibility if treatment decisions were based on a presurgical biopsy report. Overall, if assessed and treated appropriately, the prognosis for canine soft-tissue sarcomas is good. Management of tumours that recur after the first surgery is more difficult than the original primary tumour.

Feline Soft-Tissue and Injection-Site Sarcomas

These two types of sarcoma, while of the same histologic origins, are very different clinical entities. Feline soft-tissue sarcomas are similar to their canine counterparts in terms of growth pattern, metastatic rate, and response to treatment (surgery and radiation). However, sarcomas that are linked to injection-site reactions have a more aggressive behaviour and are typically of a higher histologic grade. Many critical growth factors have been documented to be associated with the characteristic inflammatory infiltrate, fibroblasts, and myofibroblasts associated with these tumours. The vaccine-associated feline sarcoma task force recommends removal of postvaccinal masses still growing after 4 weeks, still evident after 3 months, or > 2 cm in diameter. In order to have the best chance of local control of these tumours, a combination of both wide surgical resection and curative intent radiation therapy are required. Removal of bone, such as dorsal spinous processes and/or scapulae, is commonly recommended for interscapular locations. Recently, the recommended minimum 2-3 cm surgical margin has been challenged by a study of 100 cats treated with 5 cm margins and 2 fascial planes deep, with good outcome.

Canine Hard-Tissue Sarcomas

Osteosarcoma is by far the most common primary bone tumour in dogs, but chondrosarcoma, hemangiosarcoma, and fibrosarcoma, and perhaps also lymphoma can exist as rarer, primary tumours of bone. Although there is a small, early peak age incidence at 1.5-2 years, most dogs are middle age to older and the disease manifests in the appendicular skeleton of large and giant breeds. Small dogs (< 15 kg) are more likely to have osteosarcoma arise in the axial skeleton. The metaphyseal region is the most common location in the bone, and front limbs are affected approximately twice as often as hind limbs. Although not clinically detectable in approximately 85% of cases at diagnosis, over 90% of canine osteosarcoma cases will ultimately die of metastatic disease, with lung being the most common metastatic site. Metastasis to other bone sites is not uncommon as well. Mandibular osteosarcoma has been reported to have a less aggressive biologic behaviour than other anatomic locations. In addition to certain anatomic site-related prognostic factors, elevated serum alkaline phosphatase values have been associated with a shorter disease-free interval and survival in canine osteosarcoma.

Diagnosis of osteosarcoma is frequently suggested based on consistent signalment, history, physical examination, and imaging results. Therefore, it is not unusual for primary surgical tumour removal, most often by amputation, to provide the definitive histologic confirmation of the diagnosis. Limb-sparing techniques for tumours of the distal radius have become more widely available from specialized surgical oncology centres. Provided the tumour fits criteria for complete removal, limb-spare cases have a similar prognosis to amputation cases. Limb-spare surgery has been attempted for other anatomic sites; however, results showed a high complication rate. Interestingly, limb-spare cases that develop postoperative surgical site infection have a better outcome. Radiation with external beam therapy has been used for limb sparing. While the role of radiation therapy is typically palliative for analgesia, the possibility exists that stereotactic delivery of very precise doses may lead to a role for radiation as a definitive treatment choice for select lesions. Another form of radiation therapy using the bone seeking isotope 153samarium has been shown to provide palliation and delay progression of disease. Palliation of bone pain has also been accomplished with systemic bisphosphonate therapy, which decreases osteoclast activity and bone resorption.

Adjuvant cytotoxic chemotherapy is the mainstay of treatment to suppress microscopic metastases following surgical treatment of the primary tumour. Many protocols have been reported with similar efficacies. Carboplatin and doxorubicin are the most commonly utilized chemotherapy agents, alone or in combination. Recently, a study of slow-release carboplatin from a subcutaneously placed infusion pump demonstrated similar survival times after 1 treatment as conventional multidose-treatment protocols. This form of treatment may represent "metronomic" administration of chemotherapy. Immunotherapy has also shown promise in the past treatment of canine osteosarcoma, using liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE). Finally, the molecular targeted agent toceranib (Palladia®), which targets a number of receptor tyrosine kinases that may be active or altered in osteosarcoma, has shown activity in some cases with metastatic disease that is generally an extremely treatment-resistant clinical scenario.

Feline Hard-Tissue Sarcomas

These tumours are rare, but usually malignant osteosarcomas. Feline osteosarcomas are reported to have a lower metastatic rate and may be cured by surgery alone. Metastatic disease, while unusual, has been reported. There are no proven efficacious adjuvant chemotherapy protocols for this disease.

References

1.  Perry JA, Culp WT, Dailey DD, et al. Diagnostic accuracy of pretreatment biopsy for grading soft-tissue sarcomas in dogs. Vet Comp Oncol. 2012 epub May 22.

2.  Phelps HA, Kuntz CA, Milner RJ, et al. Radical excision with five-centimeter margins for treatment of feline injection-site sarcomas: 91 cases (1998-2002). J Am Vet Med Assoc. 2011;239(1):97-106.

3.  Simcock JO, Withers SS, Prpich CY, Kuntz CA, Rutland BE. Evaluation of a single subcutaneous infusion of carboplatin as adjuvant chemotherapy for dogs with osteosarcoma: 17 cases (2006-2010). J Am Vet Med Assoc. 2012;241(5):608-614.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Anthony J. Mutsaers, DVM, PhD, DACVIM (Oncology)
Ontario Veterinary College
University of Guelph
Guelph, ON, Canada


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