Soft tissue sarcomas comprise a heterogenous population of malignant tumors that arise from a variety of mesenchymal cell types.1 Although STSs can occur anywhere in the body, the skin and subcutaneous tissues are the most common locations.1 Grossly, STSs are pseudoencapsulated, and histologically, they are ill defined with infiltration into fascial planes. Grade 1 and 2 STSs are generally characterized as being locally invasive with low metastatic potential, making local tumor control crucial in successful treatment.1
Tumor excision with wide surgical margins is currently the standard of care for STSs in dogs. Unfortunately, adequate margins are often difficult to achieve without radical surgery owing to the tumors’ infiltrative characteristics. Furthermore, aggressive procedures are often considered unacceptable to pet owners. Local recurrence rates following marginal surgical excision alone have been reported to range from 4 of 35 (11%) to 5 of 16.2,3 In addition, primary re-excision of incompletely excised STSs has been shown to decrease the rate of local tumor recurrence.4
When wide surgical margins cannot be achieved during excision of STSs, postoperative RT has historically been recommended as an adjunctive treatment.1 Full-course postoperative RT has been shown to provide long-term local control of incompletely excised STSs in dogs.5,6 Adverse effects following definitive RT have been reported to occur infrequently and have typically been described as mild. In 1 study5 that included 48 dogs with incompletely excised STSs treated by means of definitive RT, acute adverse effects consisted of radiodermatitis, mild persistent alopecia, and hyperpigmentation of affected skin.
Postoperative hypofractionated RT for treatment of marginally excised STSs has been investigated as well, resulting in local tumor control and long-term survival rates similar to those achieved with definitive RT protocols.7 Clinically important complications related to surgery and hypofractionated RT for treatment of STSs were reported for 6 of 56 (11%) dogs in 1 study,7 and these consisted of wound dehiscence, self-induced traumatic injury, and osteonecrosis of underlying bone.
Currently, the role of systemic chemotherapy in the treatment of STS remains to be clearly defined.1,8 Traditional cytotoxic chemotherapy with doxorubicin was reported to be of little benefit when used alone or in combination with surgical excision in a retrospective study8 of 39 canine patients with high-grade STSs. However, other investigators found that metronomic therapy with piroxicam and low-dose cyclophosphamide significantly delayed local tumor recurrence for dogs with incompletely excised STS, compared with that of dogs that had similar surgical results and did not undergo chemotherapy.9
Although surgery followed by RT and metronomic chemotherapy has proven to be effective at delaying recurrence of STSs in dogs,5–7,9 these treatment modalities are often declined by owners because of financial limitations, inability to comply with time schedules, or both. For this reason, other localized treatment options continue to be investigated.
Intralesional chemotherapy has been used in veterinary and human medicine; intralesional cisplatin treatment, in particular, has been used to combat cutaneous neoplasia in canine and equine patients.10–12 Cisplatin delivered IV has been used to treat many types of neoplasia in dogs, but despite its antitumor efficacy, this treatment has been associated with severe adverse effects including nephrotoxicosis, bone marrow suppression, and gastrointestinal effects such as anorexia, vomiting, and diarrhea.10 To avoid systemic toxicosis while taking advantage of the antitumor effects of cisplatin, intralesional administration of the drug has been explored in dogs with STSs and other tumor types.13–16 An investigation was performed to assess the complication rate and local tumor recurrence rate in canine patients with STS treated with marginal excision and intraoperative implantation of cisplatin in a biodegradable implant delivery system.13 Wound complications were reported in 16 of 19 dogs, with 1 dog requiring limb amputation.13 Of the 18 dogs still alive at the end of the study, 3 had developed tumor recurrence, with recurrence detected 874, 264, and 214 days after surgery.13 Results of another study15 revealed high complication rates (with 19/32 [59%] implant sites developing swelling) when biodegradable implants of OPLA-Pt were placed in the surgical wound at the time of STS tumor removal with marginal resection. Complication rates related to the OPLA-Pt were determined to be unacceptably high, with 9 of 32 (28%) tumor sites in 30 dogs requiring implant removal and 10 of 32 (31%) tumors recurring locally.15
Implants of OPLA-Pt have also been used in combination with limb-sparing surgical procedures and IV cisplatin administration for treatment of osteosarcoma of the radius in dogs.16 Local complication and infection rates of dogs treated with OPLA-Pt did not differ from those of dogs that received OPLA implants without cisplatin in 1 study.16
Although local adverse effects were common in previous studies13–16 investigating intralesional administration of cisplatin in dogs, systemic adverse effects were not detected. Despite this, the treatment method is not widely used in small animal medicine.
Cisplatin-containing biodegradable beads have been used with success in equine patients for local control of various cutaneous neoplasms including sarcoids, fibromas, fibrosarcomas, PNSTs, squamous cell carcinomas, and melanomas (in gray horses).11,12 These beads have been used by direct implantation into tumors at 30-day intervals; however, the treatment is thought to be more effective when combined with reduction of the tumor burden to minimal residual disease.12 The cisplatin-containing beads are made from a commercially available matrix material (calcium sulfate and dextran sulfate), to which cisplatin is added to a final concentration of 7%.12 Each 3-mm-diameter bead contains approximately 1.6 mg of cisplatin.12,17 The product was granted minor use–minor species status for use in horses by the FDA in 2009; there is currently no equivalent product available that is approved for veterinary use. An in vivo investigation of subcutaneously placed cisplatin-containing beads showed that cisplatin traveled to a radial distance of approximately 1.5 cm, with the concentration of drug gradually decreasing as distance from the bead increased.a On the basis of this finding, current recommendations include placement of the beads at approximately 1.5-cm intervals to cover the tumor bed.12 Cisplatin-containing beads were found to be well tolerated in a retrospective study11 of 59 horses with neoplasia, with moderate swelling, erythema, and residual subtle scars being the most commonly reported adverse effects. Overall, complications noted by owners were considered fairly minimal, and most owners reported being pleased with the treatment results.11 To the authors’ knowledge, there are no peer-reviewed studies evaluating the use of cisplatin-impregnated beads in dogs available to date.
The purpose of the study reported here was to evaluate outcomes for dogs following marginal tumor excision and intralesional placement of cisplatin-impregnated beads for the treatment of cutaneous or subcutaneous STSs and to assess local toxic effects of the intralesional cisplatin treatment in these patients. We hypothesized that the local STS recurrence rate and time to local recurrence in dogs undergoing this treatment would be similar to those previously described for dogs treated for STSs by means of marginal or incomplete tumor resection and postoperative RT5–7 and that adverse effects associated with the treatment would be infrequent, local to the bead implantation site, and non–life-threatening.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the 2013 Annual Veterinary Cancer Society Conference, Minneapolis, October 2013.
The authors did not receive any funding or financial support in connection with performing this study or in the writing and publication of the manuscript.
Open-cell polyacetic acid impregnated with cisplatin
Peripheral nerve sheath tumor
Soft tissue sarcoma
Marble GM, Sullins KE. A biodegradable matrix for cisplatin to treat equine skin neoplasia (abstr), in Proceedings. 10th Annu Am Coll Vet Surg Symp 2000;469.
Wedgewood Pharmacy, Swedesboro, NJ.
GraphPad Prism, version 6.07, Graphpad Software Inc, San Diego, Calif.
1. Liptak JM, Forrest LJ. Soft-tissue sarcomas. In: Withrow SJ, Vail DM, eds. Withrow and MacEwen's small animal clinical oncology. 4th ed. St Louis: Saunders Elsevier, 2007;425–453.
3. Stefanello D, Morello E, Roccabianca P, et al. Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996–2006). Vet Surg 2008; 37: 461–465.
4. Bacon NJ, Dernell WS, Ehrhart N, et al. Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999–2004). J Am Vet Med Assoc 2007; 230: 548–554.
5. McKnight JA, Mauldin GN, McEntee MC, et al. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet Med Assoc 2000; 217: 205–210.
6. Forrest LJ, Chun R, Adams WM, et al. Postoperative radiotherapy for canine soft tissue sarcoma. J Vet Intern Med 2000; 14: 578–582.
7. Demetriou JL, Brearley MJ, Constantino-Casas F, et al. Intentional marginal excision of canine limb soft tissue sarcomas followed by radiotherapy. J Small Anim Pract 2012; 53: 174–181.
8. Selting KA, Powers BE, Thompson LJ, et al. Outcome of dogs with high-grade soft tissue sarcomas treated with and without adjuvant doxorubicin chemotherapy: 39 cases (1996–2004). J Am Vet Med Assoc 2005; 227: 1442–1448.
9. Elmslie RE, Glawe P, Dow SW. Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. J Vet Intern Med 2008; 22: 1373–1379.
10. Barabas K, Milner R, Lurie D, et al. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol 2008; 6: 1–18.
11. Hewes CA, Sullins KE. Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000–2004). J Am Vet Med Assoc 2006; 229: 1617–1622.
12. Hewes CA. How to use bioabsorbable cisplatin beads to treat cutaneous neoplasia, in Proceedings. 53rd Annu Conv Am Assoc Equine Pract 2007; 53: 399–400.
13. Havlicek M, Straw RS, Langova V, et al. Intraoperative cisplatin for the treatment of canine extremity soft tissue sarcomas. Vet Comp Oncol 2009; 7: 122–129.
14. Dunn RL, Yewey GL, Fujita SM, et al. Sustained release of cisplatin in dogs from an injectable implant delivery system. J Bioact Compat Polym 1996; 11: 286–300.
15. Dernell WS, Withrow SJ, Straw RC, et al. Intracavitary treatment of soft tissue sarcomas in dogs using cisplatin in a biodegradable polymer. Anticancer Res 1997; 17: 4499–4505.
16. Withrow SJ, Liptak JM, Straw RC, et al. Biodegradable cisplatin polymer in limb-sparing surgery for canine osteosarcoma. Ann Surg Oncol 2004; 11: 705–713.
17. Cisplatin: implantable bead. Available at: www.wedgewoodpetrx.com/items/cisplatin-implantable-bead.html. Accessed Jan 16, 2016.
18. Kuntz CA, Dernell WS, Power BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997; 211: 1147–1151.