Factors affecting prognosis in canine subcutaneous mast cell tumors: 45 cases.

OBJECTIVE: To evaluate the clinical outcome of subcutaneous mast cell tumors (SQMCT) and to identify clinical and histological characteristics of more aggressive disease. STUDY DESIGN: Retrospective study. ANIMALS: Forty-five dogs with 48 SQMCTs. METHODS: Medical records were reviewed (2011-2021) for patient information, clinical, and histopathological data including multinucleation, necrosis, invasion into local muscle, an infiltrative growth pattern, tumor grade (if listed), mitotic index, and surgical margins. The presence of local recurrence, lymph node metastasis, survival time, and other parameters evaluating patient outcome were also recorded. RESULTS: Local recurrence occurred in 17.8% (8/45) of dogs, 11.1% (5/45) developed metastatic recurrence, and 26.7% (12/45) developed lymph node metastasis. Dogs with lymph node metastases had a median disease-free interval (DFI) of 194 days (18-1864), while median DFI was not reached for dogs without lymph node metastasis (p = .0012). Median survival time for dogs with lymph node metastasis was 551 days (110-2050) compared to 1722 days (10-1722) without metastasis (p = .0432). Local recurrence resulted in a significantly shorter median survival time of 551 days (80-2050) compared to 1722 days (10-1722) for dogs without local recurrence (p = .0038). Dogs with infiltrative tumors had a median DFI of 268 days (3-1722) and DFI for dogs without an infiltrative pattern had not reached median at 1864 days (10-1864) (p = .011). CONCLUSION: Lymph node metastasis decreased disease-free interval and survival. CLINICAL SIGNIFICANCE: Subcutaneous mast cell tumors may be a more aggressive disease than previously reported.

A prospective, multi-centre, Veterinary Radiation Therapy Oncology Group study reveals potential efficacy of toceranib phosphate (Palladia) as a primary or adjuvant agent in the treatment of canine nasal carcinoma.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.

Retrospective analysis of nonradiation complications in dogs undergoing radiation therapy.

Dogs receiving radiation can develop complications unrelated to the radiation treatment. No study to date has described these complications in clinical patients undergoing multiple radiation therapy treatments. The purpose of this retrospective case-control study was to characterize the incidence and type of complications that occur in these dogs. A secondary goal was to evaluate whether patient and treatment characteristics could be identified to predict the risk of these complications. Medical records of 268 dogs receiving at least one radiation treatment at a single institution, between September, 2004 and June, 2007 were reviewed. Age, breed, gender, body weight, tumor type, tumor location, number of treatments, pre-treatment blood work abnormalities, and whether chemotherapy, glucocorticoids, or nonsteroidal anti-inflammatory drugs were given were collected. Number, type, and severity of nonradiation complications were recorded. Complications attributed to the tumor or to the radiation were excluded. Statistical analyses were performed to determine whether demographic and clinical characteristics were associated with development of a complication. General anesthesia was used for all treatments. Complications occurred in 101 (37%) cases including diarrhea, vomiting, cough, and loss of appetite, which were typically mild. Seventeen dogs (6%) developed severe complications. Eight dogs (3%) died from their complication. Dogs that developed complications were younger, received more treatments, had leukocytosis, received glucocorticoids, and were less likely to have thrombocytopenia. On multivariate analysis, number of treatments and leukocytosis were significantly associated with complications. Findings indicate that nonradiation complications are common in dogs receiving radiotherapy under general anesthesia. In this population, complications were usually mild or self-limiting.

Tolerability of toceranib phosphate (Palladia) when used in conjunction with other therapies in 35 cats with feline oral squamous cell carcinoma: 2009-2013.

Objectives Squamous cell carcinoma (SCC) is the most common oral tumor in cats and typically carries a poor prognosis with current treatment options. The objective of this study was to evaluate the toxicity of toceranib phosphate (Palladia; Pfizer) in cats with oral SCC in combination with other treatment modalities. Methods In this study, 35 cats were retrospectively evaluated to determine toxicity when treated with toceranib in combination with other treatment modalities. Cats received toceranib at a median dose of 2.75 mg/kg (range 1.9-4.17 mg/kg) 3 days a week. Cats also underwent additional therapies, including surgical excision, radiation therapy, chemotherapy and/or use of non-steroidal anti-inflammatory drugs. Results Toxicity was seen in six cats, with five cases of grade 1 or 2 gastrointestinal (GI) toxicity and one grade 4 metabolic toxicity. Toceranib was discontinued in one cat and two cats received dose reductions. None of the cats required treatment delays or hospitalization due to toxicity. Median toceranib treatment duration was 77 days (range 7-741 days). Conclusions and relevance This study revealed that toceranib was well tolerated by the majority of cats, with five cases of low-grade GI toxicity and one case of metabolic toxicity. Given the favorable toxicity profile, future studies further evaluating the safety and efficacy of toceranib for cats with oral SCC should be considered.

Canine Cutaneous and Subcutaneous Soft Tissue Sarcoma: An Evidence-Based Review of Case Management.

Canine cutaneous and subcutaneous soft tissue sarcomas (STS) account for 20.3% of malignant neoplasms of the skin. This article makes recommendations for the diagnosis, treatment, and follow-up in dogs with STS, using evidence-based medicine concepts. Although our review of the literature on the management of canine STS found many of the studies to be less than rigorous, board-certified specialists in internal medicine, surgery, pathology, oncology, and radiation oncology were able to make several recommendations based on the literature review: cytology and biopsy are important for presurgical planning; wide (>3 cm margins) surgical excision decreases the likelihood of tumor recurrence; the use of a histologic grading scale is useful in predicting biologic behavior; and, in select cases, chemotherapy and radiation therapy may be beneficial adjunct treatments to surgical excision. More research is necessary to determine minimum size of surgical margins, the impact of radiation therapy on incompletely resected tumors, the ideal chemotherapy protocol for high grade STS, and the optimal methods of monitoring dogs for tumor recurrence and metastasis.

A survey of veterinary radiation facilities in 2010.

A survey of veterinary radiation therapy facilities in the United States, Canada, and Europe was done in 2010, using an online survey tool, to determine the type of equipment available, radiation protocols used, caseload, tumor types irradiated, as well as other details of the practice of veterinary radiation oncology. The results of this survey were compared to a similar survey performed in 2001. A total of 76 facilities were identified including 24 (32%) academic institutions and 52 (68%) private practice external beam radiation therapy facilities. The overall response rate was 51% (39/76 responded). Based on this survey, there is substantial variation among facilities in all aspects ranging from equipment and personnel to radiation protocols and caseloads. American College of Veterinary Radiology boarded radiation oncologists direct 90% of the radiation facilities, which was increased slightly compared to 2001. All facilities surveyed in 2010 had a linear accelerator. More facilities reported having electron capability (79%) compared to the 2001 survey. Eight facilities had a radiation oncology resident, and academic facilities were more likely to have residents. Patient caseload information was available from 28 sites (37% of radiation facilities), and based on the responses 1376 dogs and 352 cats were irradiated in 2010. The most frequently irradiated tumors were soft tissue sarcomas in dogs, and oral squamous cell carcinoma in cats.

Completeness of reporting of radiation therapy planning, dose, and delivery in veterinary radiation oncology manuscripts from 2005 to 2010.

Surrounding a shift toward evidence-based medicine and widespread adoption of reporting guidelines such as the Consolidated Standards of Reporting Trials (CONSORT) statement, there has been a growing body of literature evaluating the quality of reporting in human and veterinary medicine. These reviews have consistently demonstrated the presence of substantive deficiencies in completeness of reporting. The purpose of this study was to assess the current status of reporting in veterinary radiation oncology manuscripts in regards to treatment planning methods, dose, and delivery and to introduce a set of reporting guidelines to serve as a standard for future reporting. Forty-six veterinary radiation oncology manuscripts published between 2005 and 2010 were evaluated for reporting of 50 items pertaining to patient data, treatment planning, radiation dose, delivery of therapy, quality assurance, and adjunctive therapy. A mean of 40% of checklist items were reported in a given manuscript (range = 8-75%). Only 9/50 (18%) checklist items were reported in > or = 80% manuscripts. The completeness of reporting was best in regards to a statement of prescription radiation protocol (91-98% reported) and worst in regards to specification of absorbed dose within target volumes and surrounding normal tissues (0-6% reported). No manuscripts met the current International Commission of Radiation Units and Measurements (ICRU) dose specification recommendations. Incomplete reporting may stem from the predominance of retrospective manuscripts and the variability of protocols and equipment in veterinary radiation oncology. Adoption of reporting guidelines as outlined in this study is recommended to improve the quality of reporting in veterinary radiation oncology.

Evaluation of strontium 90 irradiation in treatment of cutaneous mast cell tumors in cats: 35 cases (1992-2002).

OBJECTIVE: To determine the efficacy of strontium 90 beta irradiation in the management of cutaneous mast cell tumors (CMCTs) in cats. STUDY DESIGN: Retrospective case series. ANIMALS: 35 client-owned cats with CMCTs. PROCEDURE: Medical records of cats with CMCTs in which tumors were radiated by use of a strontium 90 ophthalmic applicator from 1992 to 2002 were reviewed. Cats were included if CMCT was diagnosed, there were no other sites of MCT involvement at the time of treatment, and records contained adequate follow-up information to permit retrospective assessment of local tumor control. RESULTS: 54 tumors in 35 cats were treated with a median dose of 135 Gy of strontium 90 beta irradiation, resulting in local tumor control in 53 of 54 (98%) tumors with a median follow-up time of 783 days after treatment. Median survival time was 1,075 days. Adverse effects of treatment appeared to be infrequent and of mild severity. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that strontium 90 beta irradiation resulted in long-term tumor control and should be considered an effective alternative to surgical resection in management of CMCTs in cats.

Hypofractionated radiation therapy of oral melanoma in five cats.

Five cats with melanoma involving the oral cavity were treated with hypofractionated radiation therapy (RT). Cobalt photons were used to administer three fractions of 8.0 Gray (Gy) for a total dose of 24 Gy. Four cats received radiation on days 0, 7, and 21 and one cat received radiation on days 0, 7, and 13. One of the cats received additional irradiation following the initial treatment course. Two cats received chemotherapy. Their age ranged from 11 to 15 years with a median age of 12 years. Three cats had a response to radiation, including one complete response and two partial responses. All five cats were euthanized due to progression of disease, with one cat having evidence of metastatic disease at the time of euthanasia. The median survival time for the five cats was 146 days (range 66-224 days) from the start of RT. The results of this study suggest that oral melanoma in cats may be responsive to hypofractionated RT, but response does not seem to be durable.

Principles and applications of radiation therapy.

Radiation therapy is emerging as a beneficial and increasingly accessible treatment option for companion animals with cancer. Various types of radiation are available with different properties that may make one more suitable than another for treating a specific tumor type. Radiation therapy can be used as the sole treatment or as part of a multimodality treatment course to result in local or locoregional tumor control, or as palliative therapy for pain control. When radiation is a potential treatment option, it should be considered early in the decision-making process to ensure that the appropriate diagnostics and other treatment modalities are considered to provide the best potential outcome. This article is intended to provide an overview of the types of radiation therapy that are available, the indications, and the potential acute and late radiation side effects.

Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial.

PURPOSE: Canine malignant melanoma (CMM) is a spontaneous, aggressive, and metastatic neoplasm. Preclinical mouse studies have shown that xenogeneic DNA vaccination with genes encoding tyrosinase family members can induce antibody and cytotoxic T-cell responses, resulting in tumor rejection. These studies provided the rationale for a trial of xenogeneic DNA vaccination in CMM using the human tyrosinase gene. EXPERIMENTAL DESIGN: Three cohorts of three dogs each with advanced (WHO stage II, III, or IV) CMM received four biweekly i.m. injections (dose levels 100, 500, or 1500 micro g, respectively/vaccination) of human tyrosinase plasmid DNA i.m. via the Biojector2000 delivery device. RESULTS: Mild local reactions at injection sites were the only toxicities observed, with no signs of autoimmunity. One dog with stage IV disease had a complete clinical response in multiple lung metastases for 329 days. Two dogs with stage IV disease had long-term survivals (421 and 588+ days) in the face of significant bulky metastatic disease, and two other dogs with locally controlled stage II/III disease had long-term survivals (501 and 496 days) with no evidence of melanoma on necropsy. Four other dogs were euthanized because of progression of the primary tumor. The Kaplan-Meier median survival time for all nine dogs was 389 days. CONCLUSIONS: The results of this trial demonstrate that xenogeneic DNA vaccination of dogs with advanced malignant melanoma is a safe and potentially therapeutic modality. On the basis of these results, additional evaluation of this novel therapeutic is warranted in locally controlled CMM and advanced human melanoma.