Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011‐2018

Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of toceranib phosphate for dogs with HBT. Twenty‐eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty‐seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis. Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68‐1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77‐679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that toceranib phosphate is a well‐tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease.     

Survival in Dogs with Nasal Adenocarcinoma: 64 Cases (1981–1995)

Case records of 64 dogs with nasal adenocarcinoma were reviewed. The effects of age, gender, tumor stage, presence of metastatic lesions, and treatment method on survival time were examined. Surgery groups included rhinotomy (n = 9), transnasal curettage (n = 29), and no surgery (n = 26). Chemotherapy groups included fluorouracil-cyclophosphamide combination therapy (n = 15), mitoxantrone (n = 7), and no chemotherapy (n = 42). Fifty-three dogs received fractionated cobalt 60 radiation therapy. Surgical procedure, chemotherapy group, and stage of primary tumor were not significantly associated with survival time ( P > .05). Dogs that received radiation therapy had a significantly longer median survival time (424 days) than dogs that did not (126 days) ( P = .0001). The presence of either regional lymph node or pulmonary metastasis was associated with significantly shorter median survival time (109 days) when compared to dogs without metastases (393 days) ( P = .0125). When only dogs that had received radiation therapy were considered, neither surgical treatment nor chemotherapy group was associated with significant changes in median survival time. An alternate staging system emphasizing the presence or absence of metastases is proposed. Key words: Chemotherapy; Metastasis; Radiotherapy.     

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.     

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999–2013)

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252–448 days). Median progression free survival was 289 days (range: 224–469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC.     

SURVIVAL TIMES FOR CANINE INTRANASAL SARCOMAS TREATED WITH RADIATION THERAPY: 86 CASES (1996–2011)

Sarcomas comprise approximately one‐third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily‐fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily‐fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily‐fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits.     

Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation

A prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary-dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at     

Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985-1995)

OBJECTIVE: To characterize the signalment, clinical signs, biological behavior, and response to treatment of carcinoma of the apocrine glands of the anal sac in dogs. DESIGN: Retrospective study. ANIMALS: 113 dogs with histologically confirmed carcinoma of the apocrine glands of the anal sac. PROCEDURE: Data on signalment, clinical signs, and staging were reviewed and analyzed along with treatment modality for potential association with survival time. RESULTS: Sex distribution was approximately equal (54% female, 46% male). One hundred four dogs underwent treatment consisting of surgery, radiation therapy, chemotherapy, or multimodal treatment. Median survival for treated dogs was 544 days (range, 0 to 1,873 days). Dogs treated with chemotherapy alone had significantly shorter survival (median, 212 days) than those receiving other treatments (median, 584 days). Dogs not treated with surgery had significantly shorter survival (median, 402 days) than those that underwent surgery as part of their treatment (median, 548 days). Dogs with tumors > or = 10 cm2 had significantly shorter survival (median, 292 days) than dogs with tumors < 10 cm2 (median, 584 days). Hypercalcemia was identified in 27% (n = 29) of dogs, and those dogs had significantly shorter survival (median, 256 days), compared with those that were normocalcemic (median, 584 days). Dogs with pulmonary metastasis had significantly shorter survival (median, 219 days) than dogs without evidence of pulmonary metastasis (median, 548 days). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike most previous reports, this study revealed an approximately equal sex distribution, and results suggest a more favorable prognosis.     

Adjuvant medical therapy provides no therapeutic benefit in the treatment of dogs with low‐grade mast cell tumours and early nodal metastasis undergoing surgery

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low‐grade cMCT (Patnaik grade 1‐2 and Kiupel low‐grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy‐three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow‐up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow‐up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low‐grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.     

Endoscopic photodynamic therapy using talaporfin sodium for recurrent intranasal carcinomas after radiotherapy in three dogs

Radiation is the treatment of choice for canine nasal tumours but, in almost all cases, there is local recurrence associated with poor prognosis. This report describes the effect of endoscopic photodynamic therapy using talaporfin sodium for canine intranasal carcinoma recurring after radiation therapy. Rhinoscopic photodynamic therapy was administered after radiation therapy in three dogs with recurrent intranasal carcinoma. Two to 24 illuminations of a 665‐nm diode laser were performed two hours after intravenous bolus injection of 5·0 mg/kg of talaporfin sodium. Photodynamic therapy induced almost complete remission and prolonged survival time in all cases suggesting that it might be a useful treatment for intranasal carcinomas that recur after radiation.     

Histiocytic sarcomas in flat-coated retrievers: a summary of 37 cases (November 1998–March 2005)

Thirty‐seven cases of histiocytic‐like sarcomas (HLSs) in flat‐coated retriever dogs were evaluated retrospectively. This tumour accounted for 36% of the malignant tumours seen in this breed during the study period. The median age at presentation was 8.2 years. Thirty‐four dogs presented with a swelling or mass in a muscle group or surrounding a joint. The remaining three presented for rib (1), cutaneous (1) or primary splenic origin (1). A high rate of metastasis to local lymph nodes (45%), thorax (20%) and abdominal organs (20% confirmed) was seen. Overall metastastic rate by the time of death was 70%. The median survival for all dogs was 123 days. The most significant prognostic indicator was presence of distant metastasis at the time of diagnosis with median survival of 68 or 200 days, with or without metastasis, respectively. Chemotherapy and radiation therapy significantly improved survival. Dogs given chemotherapy survived a median of 185 versus 34 days for dogs that were not (P = 0.0008). Dogs treated with radiation survived a median of 182 versus 60 days for those that were not (P = 0.0282). Dogs receiving only palliative therapy survived a median of 17 versus 167 days in dogs receiving any kind of radiation, chemotherapy, surgery or combinations. A set protocol of radiation and CCNU (RTCCNU) induced minimal toxicity and provided a median survival of 208 versus 68 days for all other dogs. While this tumour carries a poor long‐term prognosis in flat‐coated retrievers, it is reasonable to treat these dogs for palliation of signs and extension of life.     

Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs

Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.     

Electrochemotherapy in treatment of canine oral non‐tonsillar squamous cell carcinoma. A case series report

Non‐tonsillar squamous cell carcinoma (ntSCC) is a common and locally aggressive oral tumour in dogs. The treatments of choice are currently surgery and radiotherapy. Electrochemotherapy (ECT) is a local ablative anti‐tumour technique using electric pulses to enhance the intracellular diffusion of cytotoxic drugs. The aim was to retrospectively evaluate the outcome of patients with oral ntSCC treated with ECT. Twelve dogs with ntSCC were retrospectively enrolled. ECT was combined with IV bleomycin (15 000 UI/m²) alone in 11 cases and post‐surgery in 1. Parameters considered were: tumour site and size, electroporation parameters, response rate (complete remission [CR], partial remission [PR]), median survival time (MST), recurrence rate (RR), median disease‐free interval (DFI) and treatment toxicity (6‐point scale). Median tumour size was 1.65 cm (range 0.3‐8.0 cm) and the response rate was 90.9% (10/11; 8 CR and 2 PR). Two dogs underwent a second ECT. MST for dogs dead with tumour (n = 2) was 110 days and for dogs dead without tumour (n = 3) was 831 days. Among five surviving dogs, one experienced tumour recurrence and four were in CR. Results from two dogs were analysed separately. Overall RR was 27.3%. DFI and MST for dogs with recurrence were 50 and 115 days, respectively. Treatment toxicity was very low. We noticed that all dogs with tumours smaller than 1‐2 cm achieved CR without recurrence suggesting a favourable prognosis when using ECT. ECT for canine ntSCC could be considered a valid treatment option especially for smaller tumours, but a larger caseload would be needed to confirm this statement.     

Efficacy of mitoxantrone against various neoplasms in dogs

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.     

TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW‐DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA

Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross‐sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once‐daily fractions (Monday–Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first‐line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction.     

Aggressive local therapy combined with systemic chemotherapy provides long‐term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)

This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease‐free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco‐regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local‐regional therapy can provide a median survival in excess of 40 months.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

Biological behaviour of canine mandibular osteosarcoma. A retrospective study of 50 cases (1999–2007)

The purpose of this retrospective study was to describe the biological behaviour of canine mandibular osteosarcoma (OSA) and to examine factors for their impact on metastasis‐free interval (MFI) and survival time (ST). Records from dogs treated with mandibulectomy for OSA (1999–2007) were reviewed. Archived tumour samples were evaluated for mitotic index (MI) and tumour grade. Fifty dogs were included, 21 received chemotherapy. Twenty‐nine dogs (58%) developed metastatic disease. The median MFI was 627 days, and median ST was 525 days. In univariate analysis MI > 40 was prognostic for decreased MFI and ST. Grade also influenced MFI and ST, with 5/21 (24%) dogs with grade II/III tumours metastasis‐free at one year versus 16/22 (72%) dogs with grade I tumours (P = 0.002); and 5/21 (24%) dogs with grade II/III tumours alive versus 17/22 (77%) dogs with grade I tumours (P = 0.001). In multivariate analysis, histological grade and adjuvant chemotherapy were prognostic for MFI and ST.     

Prognostic factors for survival of dogs with inguinal and perineal mast cell tumors treated surgically with or without adjunctive treatment: 68 cases (1994-2002)

OBJECTIVE: To determine the prognostic factors for survival and tumor recurrence in dogs with cutaneous mast cell tumors (MCTs) in the perineal and inguinal regions treated surgically with or without adjunctive radiation therapy, chemotherapy, or both. DESIGN: Retrospective study. ANIMALS: 68 dogs. PROCEDURE: Medical records of dogs with histologically confirmed MCTs in the perineal region, inguinal region, or both treated surgically with or without adjunctive radiation therapy, chemotherapy, or both were reviewed. RESULTS: Mean tumor-free interval was 1,635 days (median not reached), and 1- and 2-year tumor-free rates were 79% and 71%, respectively. Median survival time was 1,111 days (mean, 1,223 days), and 1- and 2-year survival rates were 79% and 61%, respectively. Factors that negatively influenced survival time were age at diagnosis, tumor recurrence, and treatment with lomustine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with MCTs in the inguinal and perineal regions, if appropriately treated, may have survival times and tumor-free intervals similar to dogs with MCTs in other locations.     

Treating the locoregional lymph nodes with radiation and/or surgery significantly improves outcome in dogs with high‐grade mast cell tumours

High‐grade canine mast cell tumours (HG‐MCT) have a high rate of locoregional relapse. In this study, dogs with HG‐MCT treated with radiation therapy (RT) were retrospectively evaluated to determine the benefit associated with treating the locoregional lymph nodes (LNs). Forty‐two dogs were included. Variables assessed for association with overall survival (OS) and progression‐free survival (PFS) included WHO stage, tumour location and size, LN irradiation (prophylactic, therapeutic or none), LN treatment (yes or no), LN status at RT (metastatic or nonmetastatic) and RT intent (definitive vs palliative). Lower‐stage disease at irradiation was significantly associated with prolonged median PFS (425 vs 125 days for stage 0 vs 1‐4), and OS (615 vs 314 days for stage 0 vs 1‐4). Having any LN treatment and definitive RT were both significantly associated with prolonged OS. In order to evaluate the role of LN irradiation, dogs were divided into subgroups: (a) stage 0 at irradiation with no LN treatment (n = 14), (b) stage 0 at irradiation with prophylactic LN irradiation (n = 6), (c) stage 0 at irradiation but previously stage 2 (n = 5) and (d) stage >0 at irradiation (n = 17). Prophylactic LN irradiation significantly prolonged PFS (>2381 vs 197 days; group B vs A). Interestingly, dogs that were stage 2 and had LN treatment (C) had prolonged OS vs dogs with negative LNs and no LN treatment (A) (1908 vs 284 days; P = .012). This study confirms that prophylactic and therapeutic LN irradiation in dogs with HG‐MCT is beneficial and improves outcome.