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.     

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.     

Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service

Cancer cachexia is a well-recognized syndrome in human patients that is characterized by progressive involuntary weight loss. The prevalence of this syndrome in veterinary cancer patients is unknown. This study's objective was to investigate the occurrence of weight loss and cachexia, as characterized by body condition scoring, in dogs presented to a veterinary oncology service. Information collected on 100 dogs included signalment, diagnosis, weight at time of diagnosis, and, when available, weight from a time approximately 12 months before diagnosis. Body condition was assessed by using a 9-point system based on body silhouette and palpation of adipose tissue (4-5 = optimal, 1 = extreme cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of the dogs exhibited cachexia as defined by a body condition score < or = 3, whereas 29% were classified as markedly overweight (> or = 7). Fifteen percent had evidence of clinically relevant muscle wasting (< or = 1). Body weight from a time before the diagnosis of cancer was available for 64 dogs. At the time of diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the percentage of dogs with signs indicating a decline in nutritional status was less than what has been reported for human cancer patients. Future studies should investigate the extent to which weight loss occurs in canine patients on an appropriate plane of nutrition as well as to establish whether an association exists between poor nutritional status and outcome in canine cancer patients.     

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.     

Irradiation of brain tumors in dogs with neurologic disease

Radiation therapy is the treatment of choice for many primary canine brain tumors. The radiation dose tolerated by surrounding healthy brain tissue can be a limiting factor for radiation treatment and total dose as well as fractionation schedules, and volume effects may play a role in the outcome of patients undergoing radiation therapy. The purpose of this retrospective study was to evaluate the efficacy of radiation therapy in dogs with brain tumors that showed signs of neurologic disease. Forty-six dogs with brain tumors were included in the analysis. In 34 dogs, computer-generated treatment plans were available, and dose-volume data could be obtained. The totally prescribed radiation therapy doses ranged from 35 to 52.5 Gy (mean = 40.9 [SD +/- 2.91) applied in 2.5- to 4-Gy fractions (mean = 3.2). The median overall survival time calculated for deaths attributable to worsening of neurologic signs was 1,174 days (95% confidence interval [CI], 693-1,655 days). Assuming that all deaths were due to disease or treatment consequences, the median survival time was 699 days (95% CI, 589-809 days). No prognostic clinical factors such as the location or size of the tumor or neurologic signs at presentation were identified. With computerized treatment planning and accurate positioning, high doses of radiation (> 80% of the total dose) could be limited to mean relative brain volumes of 35.3% (+/- 12.6). These small volumes may decrease the probability of severe late effects such as infarction or necrosis. In this study, very few immediate or early delayed adverse effects and no late effects were noted, and quality of life was good to excellent.     

Interobserver reliability of computed tomographic contouring of canine tonsils in radiation therapy treatment planning

In radiation therapy (RT) treatment planning for canine head and neck cancer, the tonsils may be included as part of the treated volume. Delineation of tonsils on computed tomography (CT) scans is difficult. Error or uncertainty in the volume and location of contoured structures may result in treatment failure. The purpose of this prospective, observer agreement study was to assess the interobserver agreement of tonsillar contouring by two groups of trained observers. Thirty dogs undergoing pre‐ and post‐contrast CT studies of the head were included. After the pre‐ and postcontrast CT scans, the tonsils were identified via direct visualization, barium paste was applied bilaterally to the visible tonsils, and a third CT scan was acquired. Data from each of the three CT scans were registered in an RT treatment planning system. Two groups of observers (one veterinary radiologist and one veterinary radiation oncologist in each group) contoured bilateral tonsils by consensus, obtaining three sets of contours. Tonsil volume and location data were obtained from both groups. The contour volumes and locations were compared between groups using mixed (fixed and random effect) linear models. There was no significant difference between each group's contours in terms of three‐dimensional coordinates. However there was a significant difference between each group's contours in terms of the tonsillar volume (P < 0.0001). Pre‐ and postcontrast CT can be used to identify the location of canine tonsils with reasonable agreement between trained observers. Discrepancy in tonsillar volume between groups of trained observers may affect RT treatment outcome.     

Palliative radiation therapy in the treatment of canine appendicular synovial sarcoma

Synovial sarcoma is a rare tumor in dogs, occurring in approximately 27% of neoplasms involving joints, with the elbow representing a common site of occurrence. The recommended treatment of canine synovial sarcoma is amputation. The authors describe the use of palliative radiation therapy for the treatment of synovial sarcoma involving the elbow of a dog and conclude that this treatment modality may have use in some patients affected with synovial sarcoma.     

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.     

Effects of palliative radiation therapy on nonsplenic hemangiosarcoma in dogs

Medical records for 20 dogs with histologically confirmed nonsplenic hemangiosarcomas treated with palliative radiation therapy were reviewed to evaluate factors influencing tumor response and survival time. The Kaplan-Meier median survival time of dogs that received palliative radiation therapy was 95 days (range 6 to 500 days). Subjective reduction in tumor size was seen in 14 dogs, with four complete responses. Tumor location was a significant univariate prognostic factor for survival, and dogs with retroperitoneal masses had longer survival times.     

A SURVEY OF VETERINARY RADIATION FACILITIES IN THE UNITED STATES DURING 2001

A survey of veterinary radiation therapy facilities in the United States was done in 2001 to determine the type of equipment available, radiation protocols used, case load, tumor types irradiated, as well as other details of the practice of radiation oncology. A total of 42 sites were identified and included 17 (40%) academic institutions, and 25 (60%) private practice external beam radiation facilities. The overall response rate was 79% (33/42 responded). Based on this survey there is substantial variation between facilities in all aspects ranging from equipment and personnel to radiation protocols and caseloads. American College of Veterinary Radiology boarded radiation oncologists direct 76% of the radiation facilities at academic institutions and 60% of the private practice facilities. Three facilities had orthovoltage radiation units only, and 30 facilities had mega-voltage equipment: cobalt 60 or linear accelerator. A total of 18 facilities had linear accelerators with three of these off site at a human radiation facility. Patient load information was available from 31 sites (74% of the radiation facilities in the United States), and based on the responses 2790 dogs and 1081 cats were irradiated in 2001. Canine mast cell tumors were the most frequently irradiated tumor. This represents the first survey of veterinary radiation facilities in the United States and provides information on the specialty of veterinary radiation oncology.     

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.     

Use of oseltamivir in the treatment of canine parvoviral enteritis

Objective – To determine if oseltamivir with standard therapy for canine parvoviral enteritis ameliorates disease morbidity, mortality, or both; to document significant adverse effects associated with its use.
Design – Prospective, randomized, blinded, placebo-controlled clinical trial.
Setting – University veterinary teaching hospital.
Animals – Thirty-five dogs.
Interventions – Standard therapy was administered to all dogs. Treatment dogs also received oseltamivir, while control dogs received an equivalent volume of placebo.
Measurements and Main Results – Dogs were monitored daily according to a clinical scoring system, physical parameters, and diagnostic evaluations. Dogs in the treatment group gained a significant percentage of weight during hospitalization (mean, +2.6%; SD, 7.1%) versus the control dogs (mean, −4.5%; SD, 6.9%) ( P =0.006). Treatment dogs did not have any significant changes in their white blood cell (WBC) count, while control dogs experienced a significant drop in their WBC counts during their initial stay. In addition, it did not appear that oseltamivir use was associated with any major adverse clinical effects.
Conclusions – While a clear advantage to the use of oseltamivir was not established, a significant weight loss during hospitalization, as well as a significant decrease in WBC count were documented in the control group. No major adverse effects were identified that could be associated with oseltamivir administration. Based on these results, the true role of oseltamivir in the treatment of parvoviral enteritis remains speculative, although it is believed that further investigation is warranted.     

Prostate cancer in dogs: comparative and clinical aspects

The canine prostate gland shares many morphological and functional similarities with the human prostate and dogs are the only other large mammals that commonly develop spontaneous prostate cancer. However, the incidence of prostate cancer is much lower in dogs and the precise cell of origin is not known. Dogs with prostate cancer usually present with advanced disease that does not respond to androgen deprivation therapy. Similar to humans, affected dogs often develop osteoblastic bone metastases in the pelvis and/or lumbar spine with associated pain and neurological deficits. Other clinical signs include weight loss, lethargy, and abnormal urination and/or defecation. Surgery, chemotherapy, and radiation have been used to treat dogs with prostate cancer, but success has been limited by the location and aggressive nature of the disease. It is evident that better methods of early detection and more effective therapies are needed for prostate cancer in dogs and advanced prostate carcinoma in men. Dogs with naturally-occurring prostate cancer are relevant models for the disease in humans and pre-clinical studies of new diagnostics and therapies in dogs may benefit both humans and dogs with prostate cancer.     

Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours

The goal of this study was to determine the significance of tumour depth, tumour location and multiple synchronous tumour masses for the prognostic evaluation of canine cutaneous mast cell tumours (MCTs). The study population consisted of 100 formalin-fixed, paraffin-embedded cutaneous MCTs that had been surgically removed from 100 dogs and submitted to the Diagnostic Center of Population and Animal Health at Michigan State University between 1998 and 2001. None of the dogs had received chemotherapy or radiation therapy. For each case the following data were obtained from the referring veterinarians: sex, breed, weight, age at diagnosis, diagnostics performed, adjunct medications given at the time of surgery, tumour location, number of tumour masses, tumour recurrence (development of MCTs at the surgical site), development of additional MCTs at distant sites (outside the surgical margins), tumour duration before removal, survival time and cause of death, if applicable. Tumour depth was determined through microscopic evaluation of 5 microm sections stained with haematoxylin and eosin. Based on univariable and multivariable survival analysis, dogs with multiple synchronous cutaneous MCTs at the time of diagnosis have a worse prognosis compared with dogs with single tumours. Additional treatment beyond surgical excision alone should be considered for these animals. Older dogs and Boxers with cutaneous MCTs were at higher risk to develop additional MCTs at distant sites (outside the surgical margins), and older and male dogs with cutaneous MCTs had significantly shorter survival times. Univariable analysis also determined that dogs with cutaneous MCTs located on the head and neck had an increased risk of additional MCT development at distant sites and that sterilized dogs with cutaneous MCTs had shorter survival times. However, these findings were not confirmed by multivariable analysis. Tumour depth was of no prognostic significance for dogs with cutaneous MCTs.     

Retrospective study and review of ocular radiation side effects following external-beam Cobalt-60 radiation therapy in 37 dogs and 12 cats

This retrospective study evaluated the ocular side effects of cancer-bearing dogs and cats treated with external–beam Cobalt-60 (Co-60) radiation in which one or both orbit(s) were included in the radiation field. A total of 37 dogs and 12 cats presented to the Ontario Veterinary College during the 10-year study period (1999–2009) were evaluated. The radiation protocols ranged from a maximum of 60 Gray (Gy) in 24 fractions for curative intent to a minimum of 8 Gy in 1 fraction for palliative treatment. The main ocular side effect reported in both dogs and cats was conjunctivitis (79% and 55%, respectively). Other common ocular side effects included eyelid lesions in dogs (44%), ulcerative keratitis in cats (36%), and keratoconjunctivitis sicca in both dogs and cats (44% and 27%, respectively). The high incidence of ocular side effects in both patient populations indicates a need for regular ophthalmic examinations as a component of routine follow-up for radiation therapy involving the orbit. Radiation damage to ocular tissues is also reviewed.     

Definitive‐intent intensity‐modulated radiation therapy for treatment of canine prostatic carcinoma: A multi‐institutional retrospective study

No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive‐intent, intensity‐modulated radiation therapy (RT) in dogs with PC. Medical records review was performed, including 18 patients from four institutions undergoing definitive‐intent intensity‐modulated radiotherapy to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco‐regional lymph nodes at diagnosis. Seventeen patients received concurrent non‐steroidal anti‐inflammatory drugs; 15/18 (83%) patients received maximally‐tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48 to 54 Gy (median 50 Gy) delivered as daily doses of 2.5‐2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1‐2 diarrhoea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture and hindlimb oedema) was observed in three patients. Median event‐free survival (EFS) following RT was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 vs 220 days in symptomatic dogs, P = .042). EFS was significantly longer in patients treated with MTD chemotherapy (241 vs 25 days, P < .001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = .008). These findings suggest that definitive‐intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity.