Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma

Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy, after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved complete remission for a median 1st remission duration of 20 weeks. Forty-eight dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st remission had been short, and they received maintenance chemotherapy; the other 8 dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that remained on protocol was 44 weeks, which was not markedly shorter than for dogs treated with a previously reported protocol in which maintenance chemotherapy was instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that were febrile and dogs that were dyspneic were less likely to achieve a complete remission to induction chemotherapy. Of dogs that achieved a complete remission, those that were thrombocytopenic at entry had a shorter 1st remission, and dogs that were anorexic at entry had shorter overall disease control. There was a correlation between 1st remission duration and length of any subsequent remission obtained. The incidence of toxicity was high, particularly after the combination of doxorubicin and vincristine. Dose reductions because of toxicity did not markedly reduce remission duration. We conclude that discontinuous chemotherapy may reduce patient visits in a small number of patients because of long-term disease control. Delaying maintenance chemotherapy until after 2nd remission is achieved does not markedly affect overall disease control.     

Evaluation of a Multidrug Chemotherapy Protocol (ACOPA II) in Dogs With Lymphoma

A chemotherapeutic protocol using cyclophosphamide, vincristine, prednisone, doxorubicin, and L-asparaginase (ACOPA II) was evaluated in dogs with lymphoma. The response rate for 68 dogs treated with ACOPA II (complete remission [CR] 65%, partial remission [PR] 10%) was lower than that for 41 dogs treated with a related protocol previously evaluated (ACOPA I; CR 76%, PR 12%). Initial treatment with doxorubicin and prednisone did not decrease the prevalence or severity of toxicity during induction. The mortality during induction was 22%. The median duration of CR for dogs treated with ACOPA II was 9 months, with 40% still in remission at 1 year and 21% at 2 years. The rate of CR was lower for dogs with signs of illness at presentation (substage b ) and for dogs weighing less than 15 kg. Age was negatively correlated with survival time and duration of remission. Dogs with immunoblastic lymphoma had a more favorable prognosis than did those with lymphoblastic lymphoma. Survival times were also longer for dogs in substage a at presentation. Seven dogs in which treatment was discontinued while in remission had comparable remission duration to that achieved by dogs receiving long-term maintenance chemotherapy.     

Comparison of results of clinicians' assessments, cytologic examination of fine-needle lymph node aspirates, and flow cytometry for determination of remission status of lymphoma in dogs

OBJECTIVE: To determine interclinician agreement when assessing remission of lymphoma in dogs and the association among results of clinicians' assessments via lymph node palpation, cytologic examination of fine-needle lymph node aspirates, and flow cytometry as determinants of remission. DESIGN: Prospective study. ANIMALS: 23 dogs with untreated lymphoma. PROCEDURE; Two clinicians independently measured large lymph nodes and cytologic examination and flow cytometry of cells from a mandibular or popliteal lymph node were performed 1 week prior to initiating treatment. Lymph node measurements with clinicians' remission assessments and cytologic examination were repeated at weeks 2, 3, and 5; flow cytometry was repeated at week 5. RESULTS: Significant correlation was identified between clinicians' remission assessments. Significant correlation between lymph node palpation and cytologic examination was identified at week 5, but not at weeks 2 and 3. Lymphoma was diagnosed in 16 of 23 (70%) dogs at initial evaluation by use of flow cytometry, although it was of limited use at subsequent evaluations and results were not diagnostic of lymphoma in any dog at week 5, including 1 dog in which lymphoma was diagnosed cytologically. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that physical examination and measurement of lymph node volume may not be sufficient for accurately determining remission, that flow cytometry alone should not be relied on as a means for diagnosis, and that cytologic examination of fine-needle lymph node aspirates should be considered as the most accurate means of determining remission status at times in which treatment modifications are considered.     

Prognostic factors for tumor remission and survival in dogs after surgery for primary lung tumor: 76 cases (1975-1985)

The association of various prognostic factors with remission and survival after the excision of lung tumors was evaluated in 76 dogs. Overall, the median survival time of treated dogs was 120 days; 72% had tumor that underwent remission (median duration of remission, 120 days). Dogs with tumors that underwent remission had significantly (P = 0.001) increased survival time (median, 330 days vs 28 days for dogs with tumors that did not undergo remission). The finding of normal-sized lymph nodes at the time of therapeutic thoracotomy was significantly (P = 0.001) correlated with increased remission probability (85.4% remission rate vs 43.6% in dogs with large lymph nodes). Use of various diagnostic methods to find normal regional lymph nodes before surgery indicated that such finding was significantly (P less than or equal to 0.01) correlated with increased remission duration (median remission duration, 365 days, vs 60 days for tumors in dogs with large lymph nodes), and the finding of normal lymph nodes at the time of surgery was significantly (P less than or equal to 0.01) correlated with increased survival time (median, 345 days, vs 60 days for dogs with large lymph nodes).     

Treatment of basophilic leukemia in a dog.

Basophilic leukemia in a 6-year-old dog was characterized by marked splenomegaly, anemia, and leukocytosis in which 89% of the circulating leukocytes were basophilis. After an attempt at busulfan therapy, the dog was treated with hydroxyurea and was maintained on this drug for 2 months. After withdrawl of hydroxyurea, the dog remained in remission and was still in remission at the time of writing (8 months later).     

Alveolar clearance in horses with chronic obstructive pulmonary disease

OBJECTIVE: To assess sensitivity of scintigraphic alveolar clearance rate as an indicator of alveolar epithelium damage in horses. ANIMALS: 5 healthy horses (group A) and 5 with chronic obstructive pulmonary disease (COPD; group B). PROCEDURE: Horses underwent clearance rate (k [%/min]) determination. Clearance rate of group-B horses was determined after remission of the disease following 2 months at pasture (remission 1), stabling in a controlled environment (remission 2), and during crisis induced by exposure to moldy hay and straw. Methacholine challenge test was performed at each investigation period to determine nonspecific pulmonary airway hyperresponsiveness. Pulmonary function tests (PFT) also were performed, and cell populations in bronchoalveolar lavage (BAL) fluid were determined on another occasion. RESULTS: Group-B horses had significantly faster mean clearance rate during crisis (k = 4.30+/-0.95%/min), compared with that for remission 1(k = 1.98+/-0.55%/min), which did not differ from the rate in group-A horses (k = 1.95+/-0.33%/min). Despite lack of clinical signs of COPD during remission when stabled in a controlled environment, an intermediate value was found (k = 3.20+/-0.72%/min). CONCLUSIONS: This technique allowed grading of lung damage induced by COPD, whereas use of PFT and determination of BAL fluid cell populations failed to differentiate between remission 1 and remission 2. CLINICAL RELEVANCE: Determination of alveolar clearance rate by use of scintigraphy is a sensitive indicator of lung damage. A modified clearance rate was found despite the lack of clinical and functional changes.     

Monitoring of Minimal Residual Disease (MRD) after Multidrug Chemotherapy and Its Correlation to Outcome in Dogs with Lymphoma: A Proof‐of‐Concept Pilot Study

Background: Tumor cell burden in dogs with lymphoma cannot be assessed accurately by diagnostic evaluation during clinical complete remission (CR). Recent advances in polymerase chain reaction (PCR)‐based methods enabled us to quantify minimal residual disease (MRD) in canine lymphoma. Hypothesis/Objectives: To quantify MRD in dogs with lymphoma treated with multidrug chemotherapy and to correlate it with remission duration after chemotherapy. Animals: Seventeen dogs with lymphoma that achieved CR by multidrug chemotherapy. Methods: Rearranged immunoglobulin heavy chain or T‐cell receptor γ chain gene fragments from lymphoma cells were PCR amplified and sequenced to prepare clone‐specific primers and probes for real‐time PCR to quantify MRD. MRD in the peripheral blood was monitored during and at the end of a 25‐week multidrug chemotherapy protocol. Correlation between MRD at the end of chemotherapy and remission duration after chemotherapy was analyzed. Results: MRD gradually decreased after initiation of multidrug chemotherapy, reached a nadir as low as <0.019–1.0 cells/μL at weeks 4–17, and remained low or slightly increased until week 25. MRD at the end of chemotherapy was negatively correlated with remission duration from the end of chemotherapy to relapse. Conclusion and Clinical Importance: MRD could be an objective marker to indicate tumor cell burden in dogs with lymphoma even in clinical CR. MRD at the end of chemotherapy could be a prognostic factor to predict remission duration after chemotherapy.     

Predictors of Clinical Remission in Cats with Diabetes Mellitus

Background: Clinical remission is frequent in cats with well‐controlled diabetes mellitus, but few studies explored predictors of this phenomenon. Hypothesis: Data retrieved from medical records at admission might be valuable to identify likelihood of remission and its duration in diabetic cats. Animals: Ninety cats with newly diagnosed diabetes, followed‐up until death or remission. Methods: Retrospective cohort study. Data were collected from records at admission, including history, signalment, physical examination, haematology, and biochemical profile, and the occurrence and duration of remission, defined as normoglycemia without insulin for ≥4 weeks. Predictors of remission were studied with univariate and multivariate logistic regression. Factors associated with remission duration were analyzed with Kaplan‐Meier and Cox proportional hazard models. Results: Forty‐five (50%) cats achieved remission, after a median time of 48 days (range: 8–216). By study end, median remission duration was 114 days (range: 30–3,370) in cats that died and 151 days (range: 28–1,180) in alive cats. Remission was more likely with higher age (OR: 1.23, 95% CI: 1.04–1.46; P= .01) and less likely with increased serum cholesterol (OR: 0.36, 95% CI: 0.11–0.87; P= .04). Remission was longer with higher body weight (HR: 0.65, 95% CI: 0.42–0.99; P= .04) and shorter with higher blood glucose (HR: 1.01, 95% CI: 1.00–1.02; P= .02). Conclusions and Clinical Importance: Age, body weight, cholesterol, and glucose levels are suggested for prediction of remission or its duration in diabetic cats. Older cats developing diabetes may have a better outcome, possibly suggesting a slower disease progression.     

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.     

Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy

Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p = 0.021). Higher baseline VVTI was associated with higher subsequent scores (p < 0.001). VVTI also correlated with anxiety level (p = 0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma.     

RADIOTHERAPY WITH AND WITHOUT CHEMOTHERAPY FOR LOCALIZED LYMPHOMA IN 10 CATS

A retrospective study was undertaken to determine the efficacy of radiotherapy with and without chemotherapy for treatment of localized lymphoma in 10 cats. Tumor location included nasal cavity (3 cats), retrobulbar area (3 cats), mediastinum (1 cat), subcutaneous tissue (1 cat), maxilla (1 cat) and mandible (1 cat). Six cats were treated with radiation alone and 4 cats also received chemotherapy during and/or after radiotherapy. Complete remission was achieved locally in 8 of 10 cats, whereas 2 cats had partial remission. Five of the 6 cats treated with radiotherapy alone achieved complete remission. Overall mean and median remission times for the 8 cats with complete remission were 123 weeks and 114 weeks, respectively (range 4 to 277 weeks). Three of the 8 cats have been in complete remission for more than 131 weeks and are still alive. Three cats achieving complete local remission developed lymphoma outside the radiation field. One cat had recurrence at the site of irradiation. Results of the retrospective study suggest that radiotherapy with and without chemotherapy may be effective for the treatment of localized lymphoma in the cat.     

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type‐1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type‐2 DM. Hypothesis/Objectives: Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Animals: Twelve cats with DKA and 7 cats with uncomplicated DM. Methods: Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Results: Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Conclusions and Clinical Importance: Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.     

A Comparison of Doxorubicin and COP for Maintenance of Remission in Cats With Lymphoma

Thirty-eight cats with lymphoma were treated with vincristine, cyclophosphamide, and prednisone (COP). They were randomized at entry to receive maintenance chemotherapy consisting of either single-agent doxorubicin or continued COP therapy, starting on week 4 of treatment and continuing for 6 months or until relapse. Eighteen cats achieved complete clinical remission after COP induction chemotherapy. The median remission duration for 11 cats continuing to receive COP was 83 days, which was significantly shorter than for 7 cats that received doxorubicin (281 days). Thus, doxorubicin should be considered a well-tolerated and efficacious agent for the maintenance of remission in cats with lymphoma.     

Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer

The purpose of this study was to assess the toxicoses and antitumor activity of metronomic chlorambucil at a dosage of 4 mg m(-2) daily in dogs with naturally occurring cancer. Thirty-six dogs were enrolled in the study. The protocol was well tolerated with no grade 3 or 4 toxicoses noted. Complete remission was achieved, and lasted over 35 weeks in three dogs (mast cell tumour, soft tissue sarcoma and thyroid carcinoma). Partial remission was noted in 1 dog with histiocytic sarcoma (39 weeks duration) for an overall remission rate of 11% (4 of 36). Stable disease was noted in 17 dogs (47%) with various other cancers. The median progression-free interval was 61 days, and the median survival time was 153 days. Chlorambucil given in a metronomic protocol showed antitumor activity in dogs with a variety of naturally occurring cancers.     

Autologous marrow transplantation as consolidation therapy for canine lymphoma: efficacy and toxicity of various regimens of total body irradiation

Dogs with malignant lymphoma were given chemotherapy consisting of nitrogen mustard, vincristine sulfate, prednisone, L-asparaginase, and 6-mercaptopurine (MOPA-6) for 14 days. Among 62 dogs that completed treatment with MOPA-6, 47 (76%) had complete remission, and 13 (21%) had partial remission and 2 had no response to chemotherapy. Twenty-two of the 62 dogs were not returned by their owners for additional therapy and died 15 to 391 (median 21) days after MOPA-6 from infections or recurrent disease. A median of 1 month after starting MOPA-6 therapy, 40 dogs (35 in complete remission, 5 in partial remission) were given total body irradiation (TBI), followed by infusion of fresh autologous marrow. Twenty dogs were given 13.5 Gray (Gy) of TBI at 4 centi-Gray (cGy)/min. Among 16 evaluable dogs, 7 had recurrence of lymphoma at a median of 169 days. Two dogs died with veno-occlusive disease of the liver, 3 with pneumonia, 3 with hemorrhage, and 1 was killed. Twenty dogs were given 11.8 to 14.7 Gy of TBI at 2 cGy/min. Among 14 evaluable dogs, 9 had recurrence of lymphoma at a median of 117 days. The remaining 5 dogs were killed at 110 to 680 days; lymphoma was not present at necropsy. The results indicated that doses of TBI of 11.8 to 14.7 Gy did not reduce the recurrence of lymphoma, compared with results obtained in a previous study with 8.4 Gy of TBI. Furthermore, increased doses of TBI increased acute and delayed toxicities. Alternatively, recurrent disease may have been due to lymphoma cells contained in the infused remission marrow.     

Anemia Is Associated with Decreased Survival Time in Dogs with Lymphoma

Background: Anemia is a common complication in human patients with neoplasia and has been associated with decreased survival time and a poorer quality of life.
Hypothesis: The presence of anemia at diagnosis is negatively associated with survival and remission times in dogs with lymphoma, but not in dogs with osteosarcoma.
Animals: Eighty-four dogs with lymphoma and 91 dogs with osteosarcoma that presented for treatment at the Animal Cancer Center, Colorado State University.
Methods: Retrospective, case-control study. Medical records were reviewed to determine the presence or absence of anemia (PCV < 40) at initial presentation. Median survival and remission times were identified by the Kaplan-Meier product limit method and the association between anemia and survival was determined by a multivariable Cox proportional hazard regression analysis.
Results: Cancer-related anemia is more frequent in dogs with lymphoma than in control dogs or dogs with osteosarcoma. Dogs with lymphoma and anemia had a significantly decreased survival time compared with dogs without anemia. There was no effect of anemia on remission time in dogs with lymphoma. Anemic dogs with osteosarcoma did not have decreased survival or remission time compared with nonanemic dogs with osteosarcoma.
Conclusions and Clinical Importance: Shortened survival time in dogs with lymphoma and anemia at initial presentation has important prognostic significance. Understanding cancer-related anemia in dogs might offer new opportunities to improve quality of life and survival times in these patients.     

Successful use of topical mitomycin C for the treatment of a putative neoplastic vascular mass on the nictitating membrane of a dog

A nine-year-old female desexed Great Dane presented with a painful, proliferative, soft red putative neoplastic vascular mass on the nictitating membrane. Three 7-day cycles of the topical cytotoxic drug mitomycin C 0.04%, applied four times daily to the lesion using a low-dose alternate-week pulse therapy, brought about rapid remission of the lesion. The lesion was still in remission at time of euthanasia some 13 months later.     

CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6‐week combination chemotherapy protocol followed 2 weeks later by whole‐abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, >266 to >1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.     

Monoclonal Antibody C219 Immunohistochemistry Against P-Glycoprotein: Sequential Analysis and Predictive Ability in Dogs With Lymphoma

In the present study, the prevalence of positive staining for P-glycoprotein using C219 monoclonal antibody was assessed in 58 tissue samples of high-grade lymphoma from dogs before initiation of chemotherapy. Samples were also evaluated at relapse in 22 dogs, at necropsy in 34 dogs, and at all 3 times in 15 dogs. The frequency of positive staining was significantly higher than that found prior to the initiation of chemotherapy at the following times: relapse ( P = .0001), necropsy ( P < .0001), and both relapse and necropsy ( P < .001, sequential data). The frequency of positive staining prior to the initiation of chemotherapy was significantly inversely related to remission ( P < .001) and survival times ( P = .0012). Similarly, when populations below and above the median initial C219 score were compared with respect to remission and survival times, the population with scores greater than the median had significantly lower remission ( P < .001) and survival ( P = .008) times, respectively. The frequency of positive staining determined at relapse was significantly inversely related to the time from relapse to death ( P = .0102). Similarly, when populations below and above the median relapse C219 score were compared with respect to the time from relapse to death, the population with C219 scores greater than the median had a significantly lower time from relapse to death ( P = .006). It appears that this immunohistochemical methodology may be used as a predictor of remission time, survival time, and the time from relapse to death. Additional studies are required to confirm the usefulness of C219 as a true marker of P-glycoprotein and to evaluate P-glycoprotein as a useful prognostic factor in dogs with lymphoma.     

Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987-1998)

OBJECTIVE: To determine the efficacy (durations of remission and survival) of an alternating-day radiation protocol for incompletely excised histologic grade-III solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS: 31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol) was delivered to an area bordered by margins > or = 3 cm around the surgical scar and to the associated local-regional lymph nodes. Dogs were not given chemotherapeutic agents concurrently or after radiation. Information on signalment, duration of remission, and survival time was obtained from medical records. RESULTS: Median and mean durations of remission were 27.7 and 17.0 months, respectively (range, 1 to 47 months). Median and mean durations of survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with tumors located on the skin of the pinna, perineum, and prepuce had a median duration of remission greater than dogs with tumors located at other sites (27.7 and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months, respectively). The remission rate was 65% and survival rate was 71% at 1 year after treatment. Sixteen dogs that were euthanatized had complications associated with local-regional tumor progression. Systemic metastases to liver, spleen, intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Without further treatment, incompletely excised grade-III mast cell tumors have high local-regional recurrence; local-regional treatment with radiation may effectively be used to manage many such tumors.