Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma.

Soft tissue sarcomas (STSs) are locally invasive and surgery with or without radiation therapy is the current standard of care in dogs. Typical protocols for treating incompletely excised STSs involve curative intent radiation with total dose in excess of 50 Gy. Forty-eight dogs with histologically confirmed incomplete or closely excised STSs were treated with a hypofractionated protocol that is typically reserved for palliative radiation therapy (RT) (6-8 Gy/weekly fractions to a total dose of 24-32 Gy). Ten dogs (21%) developed local recurrence, 11 dogs (23%) developed metastasis, and 3 dogs developed both (included in each group). The median progression free survival was 698 days. The local failure-free probability at 1 and 3 years was 81 and 73%. The 1 and 3 years tumour-specific overall survival was 81 and 61%. Long-term local tumour control was achieved in the majority of dogs. This protocol is reasonable to prescribe in older patients or when financial limitations exist.

Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology.

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Multilobular osteochondrosarcoma of the hard palate in a dog.

A 14-year-old castrated male Rhodesian Ridgeback was presented with a history of sneezing and epistaxis. Diagnostic procedures included physical examination, regional and thoracic radiography, computed tomography and histological examination of an incisional biopsy. A multilobular osteochondrosarcoma of the hard palate with pulmonary metastases was diagnosed. Surgical resection of the primary tumour was achieved with clean margins and the defect was repaired using bilateral mucosal transposition flaps from the lips. Wound dehiscence and oesophageal stricture were postoperative complications, but these resolved with treatment. A long-term survival time of 14 months resulted, with good quality of life and function during this time.

Matrix metalloproteinase-2 and -9 involvement in canine tumors.

Matrix metalloproteinases (MMPs) are a family of enzymes implicated in the degradation and remodeling of extracellular matrix and in vascularization. They are also involved in pathologic processes such as tumor invasion and metastasis in experimental cancer models and in human malignancies. We used gelatin zymography and immunohistochemistry to determine whether MMP-2 and MMP-9 are present in canine tumors and normal tissues and whether MMP production correlates with clinicopathologic parameters of prognostic importance. High levels of pro-MMP-9, pro-MMP-2, and active MMP-2 were detected in most canine tumors. Significantly higher MMP levels were measured in canine tumors than in nontumors, malignancies had higher MMP levels than benign tumors, and sarcomas had higher active MMP-2 than carcinomas. Cartilaginous tumors produced higher MMP levels than did nonsarcomatous malignancies, benign tumors, and normal tissues, and significantly greater MMP-2 than osteosarcomas and fibrosarcomas. Pro-MMP-9 production correlated with the histologic grade of osteosarcomas. The 62-kd form of active MMP-2 was detected only in high-grade, p53-positive, metastatic malignancies. Zymography proved to be a sensitive and quantitative technique for the assessment of MMP presence but has the limitation of requiring fresh tissue; immunohistochemistry is qualitative and comparatively insensitive but could be of value in archival studies. MMP presence was shown in a range of canine tumors, and their link to tumor type and grade was demonstrated for the first time. This study will allow a substantially improved evaluation of veterinary cancer patients and provides baseline information necessary for the design of clinical trials targeting MMPs.

Transposition of first digital pad for reconstruction of a palmar antebrachial soft tissue defect in a cat.

An 8-year-old female neutered Siamese cat was presented with a recent history of incomplete excision of an apocrine gland adenocarcinoma from the palmar aspect of the right antebrachium, just proximal to the carpal joint. There was no evidence of metastasis. Wide surgical excision of the previous surgery site was performed resulting in a soft tissue defect. Partial reconstruction was achieved using digital pad transposition of the first digit (dewclaw), forming a local axial pattern flap that was transposed into the adjacent defect. The remaining defect was closed by primary apposition. The skin flap healed successfully. Some breakdown of the skin closed by primary apposition necessitated open wound management. The cosmetic and functional result of the first digital pad transposition was considered excellent, rendering it a useful means to reconstruct soft tissue defects in the carpal region.

Use of mandibular symphysiotomy to allow extensive caudal hemimaxillectomy in a dog.

A 5-year-old dog was presented with a large caudal maxillary osteosarcoma, which was causing extreme pain on opening of the mouth. The mass was not resectable through a standard oral approach. This article describes the successful use of mandibular symphysiotomy to allow extensive caudal hemimaxillectomy to remove the mass and provide excellent postoperative quality of life for the dog.

Outcome following treatment of vertebral tumors in 20 dogs (1986-1995).

Twenty dogs with histopathologically confirmed primary (n=15) or metastatic (n=5) osteosarcoma (n=14) or fibrosarcoma (n=6) of the vertebral column were treated with surgery (n=4), radiation therapy and chemotherapy (n=6), surgery and chemotherapy (n=2), or surgery, radiation, and chemotherapy (n=8). All dogs died due to their disease; 15 died due to local failure, and five died due to nonvertebral metastasis. Overall median survival time was 135 days, with a range of 15 to 600 days. Of the factors evaluated, only postoperative neurological status had a significant influence on outcome by multivariate analysis. This study supports the overall guarded prognosis for dogs with vertebral neoplasia. Better combinations of surgery, chemotherapy, and radiation therapy remain to be defined for this difficult subset of animal cancer.

Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice.

OBJECTIVE: To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis. ANIMALS: 42 female C3H-HeJ mice. PROCEDURE: Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (i.p. cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed. RESULTS: Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the i.p. cisplatin group and 14 of 14 mice in the control group. Median (+/-SD) number of days to tumor regrowth was 13.5+/-0.64 and 7.79+/-0.87 in the i.p. cisplatin and control groups, respectively. Mice in the i.p. cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals.

Apparent interaction of dimethyl sulfoxide with cisplatin released from polymer delivery devices injected subcutaneously in dogs.

Local tissue toxicity, systemic toxicity and platinum pharmacokinetics were evaluated in 6 normal healthy beagle dogs injected subcutaneously with two formulations of a polylactide biodegradable polymer (Atrigel) system containing cisplatin. Dogs were injected 4 times at 30 day intervals at platinum dosages of 70, 105 and 157.5 mg/m2 (dose escalation). Once pharmacokinetics were established, 29 dogs with spontaneous stage IIb appendicular osteosarcoma were treated with 4 injections of the same polymer system containing cisplatin at 70 mg/m2 (20 dogs) and 100 mg/m2 (9 dogs) to establish efficacy against micrometastatic disease. Local tissue toxicity was variable. Systemic toxicity, as judged by clinicopathologic evaluation was not noted at any dose level or injection number. Interim (6 month) survival analysis revealed a median disease-free interval of 180 days. Consistent platinum release characteristics were found, however, the lack of toxicity and decreased disease-free-interval raised concerns over the biologic activity of the cisplatin. Prior to completion of the study, it was discovered that dimethyl sulfoxide, the solvent used in the co-polymer system, may be responsible for biologic inactivation of cisplatin. This was subsequently demonstrated in tissue culture assays. The clinical trial was suspended and dogs were treated with traditional chemotherapy.

Limb salvage surgery for osteosarcoma of the proximal humerus: outcome in 17 dogs.

OBJECTIVE: To describe function and identify factors that affect outcome in dogs undergoing limb salvage surgery for osteosarcoma (OS) of the proximal humerus. STUDY DESIGN: A retrospective study of dogs in which OS of the proximal humerus was treated with limb salvage surgery. ANIMALS: 17 client-owned dogs. METHODS: Records were analyzed for functional outcome, recurrence, metastasis, and survival. RESULTS: Outcome was good to excellent in 12% of dogs. Recurrence, metastasis, and survival were significantly affected by completeness of surgical margins. Double plating of the distal allograft-host junction significantly reduced frequency of biomechanical failure. CONCLUSIONS: Limb salvage surgery for OS of the proximal humerus did not result in acceptable function and was fraught with postoperative complications. Outcome was significantly affected by completeness of surgical margins. CLINICAL RELEVANCE: Limb salvage surgery for OS of the proximal humerus in dogs cannot be recommended until improvement in functional outcome and reduction in postoperative complications can be achieved. The dependence of outcome on completeness of surgical margins supports aggressive en bloc resection and marking and evaluating surgical margins.

Multilobular osteochondrosarcoma in 39 dogs: 1979-1993.

Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO) each presented primarily with a fixed mass involving the flat bones of the skull. Twenty-five dogs were treated with surgical resection alone, nine were treated with adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had local tumor recurrence, and 56% had metastasis. Median time to recurrence, median time to metastasis, and median survival time were 797, 542, and 797 days, respectively. Histological grade, surgical margins, and tumor location affected outcome. Long-term remission can be obtained with aggressive treatment of MLO, although it is locally invasive and moderately metastatic.

Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996).

OBJECTIVE: To determine results of surgery for treatment of soft-tissue sarcomas in dogs and to identify prognostic variables that can be used to predict outcome. DESIGN: Retrospective case series. ANIMALS: Dogs with soft-tissue sarcomas that had surgical treatment only. PROCEDURE: Records were examined for clinically relevant data. Histologic samples were reviewed. Follow-up information was obtained by physical examination or telephone conversations with referring veterinarians or owners. RESULTS: 75 dogs with soft-tissue sarcomas of the trunk and extremities were identified. Median age was 10.6 years. Malignant peripheral nerve sheath tumors were of a significantly lower grade than other tumors. Tumors recurred locally in 11 of 75 (15%) dogs. Evaluation for lack of tumor cells at surgical margins was prognostic for local recurrence. Metastatic disease developed in 13 of 75 (17%) dogs. Tumor mitotic rate was prognostic for development of metastasis. Twenty-five of 75 (33%) dogs died of tumor-related causes. Percentage of tumor necrosis and tumor mitotic rate were prognostic for survival time. Median survival time was 1,416 days. CLINICAL IMPLICATIONS: On the basis of a low local recurrence rate and high median survival time, wide excision of tumor margins or radical surgery appeared to be an effective means for managing soft-tissue sarcomas of the trunk and extremities. Analysis of histologic characteristics for prognosis supported use of preoperative biopsy. Surgical margins should be evaluated, and early use of aggressive surgery is indicated in the management of soft-tissue sarcomas in dogs.

Adjuvant chemotherapy using cisplatin by subcutaneous administration.

BACKGROUND-MATERIALS: Based on previous polymer release experience, this study was conducted to evaluate the toxicity, efficacy and systemic absorption of cisplatin administered subcutaneously in dogs. METHODS-RESULTS-CONCLUSIONS: Fifty to 70 mg/m2 cisplatin was suspended in saline and injected subcutaneously in 6 dogs as an adjunct to their primary treatment for sarcoma. Gastrointestinal, bone marrow, renal or local tissue toxicity occurred following the first (dogs 1-3,5,6) and second (dogs 1 and 2) treatments. Low, yet measurable levels of platinum were present in serum through day 14 following injection in all dogs. Due to the toxicity seen, all further planned treatments were discontinued and adjuvant regimes were completed with intravenous carboplatin. Although slow systemic absorption of platinum can occur following subcutaneous administration, the degree of toxicity seen following this treatment would indicate that a drug delivery vehicle may be necessary if cisplatin is to be administered for sustained release and adsorption.

Digital pad transposition for replacement of the metacarpal or metatarsal pad in dogs.

A technique for digital pad transposition is described and illustrated. This technique has application for use in cases of metacarpal or metatarsal pad neoplasia or severe trauma. The transposed digital pad will provide a weight-bearing surface of heavy, keratinized epidermis in cases where the normal metacarpal or metatarsal footpad has been removed. The use of the technique in four clinical cases of footpad neoplasia also is reported.

Feline cutaneous squamous cell carcinoma of the nasal planum and the pinnae: 61 cases.

Cutaneous squamous cell carcinoma is a common tumor in cats and frequently occurs on the nasal planum and the pinnae. The medical records of 61 cats were reviewed for this retrospective study. Typical presentation was an older (median age, 12 years) cat with an erythematous, crusty, and erosive lesion. Methods of treatment included surgery, radiation, and cryotherapy. Disease-free interval and survival time were calculated for each case and grouped according to lesion location and treatment type. All treatments were found to be effective, with surgery resulting in the longest disease-free interval (median, 594 days).

Intracavitary treatment of soft tissue sarcomas in dogs using cisplatin in a biodegradable polymer.

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy against local disease recurrence of soft tissue sarcomas (STS) in dogs using intracavitary cisplatin released from a polymer device (OPLA-Pt). MATERIALS AND METHODS: OPLA-Pt was placed into the wound following marginal (histologically incomplete) resection of STS in 30 dogs (32 tumors) with a median tumor diameter of 3 cm (range = 1-14 cm). Median cisplatin dose was 35.5 mg/m2 (body surface area) with a range of 5.3-133.3 mg/m2. RESULTS: The OPLA-Pt was removed from 9/32 (28%) sites due to local wound complication. Local recurrence occurred in 10/32 (31%) tumors. Higher tumor grade had a significant negative influence on local tumor recurrence (p = 0.031). CONCLUSIONS: The rate of recurrence appeared to be similar using intracavitary cisplatin compared to previous reports of STS treated by marginal surgery followed by radiotherapy. The complication rate indicates the need for further refinement of the polymer/cisplatin system.

Total and partial orbitectomy for the treatment of periorbital tumors in 24 dogs and 6 cats: a retrospective study.

Total or partial orbitectomy were used to treat 24 dogs and six cats with invasive periorbital tumors. The surgical procedure and clinical results were evaluated in this retrospective study. The most common types of tumors treated in this series of patients were multilobular osteochondrosarcoma and squamous cell carcinoma. Two patients died of cardiopulmonary arrest within 24 hours after surgery. One patient developed neurological signs after total orbitectomy that resolved with conservative therapy. Minor complications, which included infection, strabismus, and conjunctivitis, occurred in seven patients. Regrowth of tumor in the periorbital region occurred in 11 patients (36.7%). Tumor resection by orbitectomy provided local disease-free interval of more than 1 year in more than 50% of patients. Survival rate for the first year was 70.4% in this series of patients as determined by life table analysis. Orbitectomy requires detailed knowledge of regional anatomy and experience with performing a combination of surgical procedures. Preoperative diagnostic tests should include imaging techniques to define the extent of the disease. When performed properly, orbitectomy is a valuable procedure that can be used to effectively treat invasive tumors of the orbit.

Canine mandibular osteosarcoma: 51 cases (1980-1992).

Fifty-one dogs treated for mandibular osteosarcomas (OSs) were studied retrospectively. Treatments were partial mandibulectomy (n = 32); partial mandibulectomy and chemotherapy (n = 10); partial mandibulectomy and radiation therapy (n = 3); partial mandibulectomy, radiation therapy, and chemotherapy (n = 4); and radiation therapy alone (n = 2). The overall one-year survival rate was 59.3%. Dogs treated with surgery alone had a one-year survival rate of 71%, which is higher than the one-year survival rate for dogs with appendicular OSs treated with surgery alone (p of 0.001 or less; hazard ratio of 0.29). There was no apparent effect of various treatment modalities, nor institution where treatment was given, nor histological type. Histological score and, to a lesser extent, histological grade were predictive of survival outcome.

Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993).

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights ( < 40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m2. Neutropenia was the dose-limiting toxicity in this study.

Limb-sparing surgery versus amputation for dogs with bone tumors.

Recently, limb-sparing surgeries have been used in the treatment of dogs with malignant bone tumors. These new techniques are fraught with potential complications. As amputation is a time-honored technique in veterinary medicine for the control of primary bone tumors, the use of newer, more complicated surgeries such as limb sparing may be considered controversial. In this article, amputation and limb sparing are discussed with reference to case selection, outcome, and possible complications.