Conventionally fractionated radiation therapy is associated with long-term survival in dogs with infiltrative lipomas.

OBJECTIVE: To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data. ANIMALS: 24 dogs from 2000 to 2020. METHODS: In this retrospective study, dogs received 1 to 3 surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions. RESULTS: Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days [range, 741 to 1,870 days]), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female. CLINICAL RELEVANCE: This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.

Long-term outcomes with conventional fractionated and stereotactic radiotherapy for suspected heart-base tumours in dogs.

Published radiotherapy results for suspected heart-based tumours in dogs are limited. In this retrospective longitudinal study (3/2014-2019), eight dogs with either clinical signs attributable to a heart-base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post-radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post-treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114-868 days, [range 114-1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days-not reached [range 155-1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days-not reached [range 114-414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow-up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart-base masses.

Long-term survival with stereotactic radiotherapy for imaging-diagnosed pituitary tumors in dogs.

Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging-diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009-2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226-410 days [range 1-2134 days]). Thirty-two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221-427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2-626 days]). Twenty-nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P = 0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.

A NOVEL, REMOVABLE, CERROBEND, BEAM-BLOCKING DEVICE FOR RADIATION THERAPY OF THE CANINE HEAD AND NECK: PILOT STUDY.

Radiation therapy of the head and neck can result in mucositis and other acute affects in the oral cavity. This prospective pilot study evaluated a novel, intraoral, beam-blocking device for use during imaging and therapeutic procedures. The beam-blocking device was made from a metal alloy inserted into a coated frozen dessert mold (Popsicle® Mold, Cost Plus World Market, Oakland, CA). The device was designed so that it could be inserted into an outer shell, which in turn allowed it to be placed or removed depending on the need due to beam configuration. A Farmer type ionization chamber and virtual water phantom were used to assess effects of field size on transmission. Six large breed cadaver dogs, donated by the owner after death, were recruited for the study. Delivered dose at the dorsal and ventral surfaces of the device, with and without the alloy block in place, were measured using radiochromic film. It was determined that transmission was field size dependent with larger field sizes leading to decreased attenuation of the beam, likely secondary to scatter. The mean and median transmission on the ventral surface without the beam-blocking device was 0.94 [range 0.94-0.96]. The mean and median transmission with the beam-blocking device was 0.52 [range 0.50-0.57]. The mean and median increase in dose due to backscatter on the dorsal surface of the beam-blocking device was 0.04 [range 0.02-0.04]. Findings indicated that this novel device can help attenuate radiation dose ventral to the block in dogs, with minimal backscatter.

VALIDATION OF AN INDEXED RADIOTHERAPY HEAD POSITIONING DEVICE FOR USE IN DOGS AND CATS.

Setup variability affects the appropriate delivery of radiation and informs the setup margin required to treat radiation patients. Twenty-four veterinary patients with head and neck cancers were enrolled in this prospective, cross-sectional study to determine the accuracy of an indexed board immobilization device for positioning. Couch position values were defined at the first treatment based on setup films. At subsequent treatments, patients were moved to the previously defined couch location, orthogonal films were acquired, table position was modified, and displacement was recorded. The mean systematic displacement, random displacement, overall displacement, and mean displacement values of the three-dimensional (3D) vector were calculated. Three hundred thirty-two pairs of orthogonal setup films were analyzed for displacement in cranial-caudal, lateral, and dorsal-ventral directions. The mean systematic displacements were 0.5, 0.8, and 0.5 mm, respectively. The mean random displacements were 1.0, 1.1, and 0.7 mm, respectively. The overall displacements were 1.1, 1.4, and 0.9 mm, respectively. The mean 3D vector value was 1.6 mm with a standard deviation of 1.2 mm. Ninety-five percent of the vectors were <3.6 mm. These values were compared to data obtained with a previously used immobilization device. A t-test was used to compare the two devices. The 3D vector, random displacement in all directions, and overall displacement in the cranial-caudal and dorsal-ventral directions were significantly smaller than displacements with the previous device. The precision and accuracy of the indexed board device was superior to the historical head and neck device.

Computed tomographic appearance of equine sinonasal neoplasia.

The computed tomography (CT) features of tumors involving the nasal cavity and/or paranasal sinuses of 15 horses were reviewed. The 15 tumors included five neuroendocrine tumors/neuroblastomas, two undifferentiated carcinomas, two myxosarcomas, and one each of nasal adenocarcinoma, hemangiosarcoma, chondroblastic osteosarcoma, anaplastic sarcoma, myxoma, and ossifying fibroma. All tumors except the ossifying fibroma were iso- or hypoattenuating relative to masseter muscle. Thirteen of the fifteen tumors exhibited moderate or marked osteolysis of adjacent cortical bone and 14/15 were characterized by destructive changes of the nasal turbinates, nasal septum, and/or infraorbital canal. Ten horses had moderate or marked involvement of the cribriform plate and six had clear intracranial extension of the mass. CT features were compared to radiographic findings for 10 horses. A mass was observed in 10/10 radiographic studies and mass within the caudal maxillary sinus (7/8) and rostral maxillary sinus (6/7) was identified correctly in most horses. The radiographs were least sensitive for identifying masses within the sphenopalatine sinus (0/5), cranium (0/4), and retrobulbar space (1/7) compared to CT. The radiographs also underestimated potential features of malignancy, such as severity of osteolysis or osseous production. While radiographs are a useful screening tool for identification of sinonasal masses, CT provides greater information regarding mass extent, features of malignancy, and important prognostic indicators.

Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs.

BACKGROUND: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy. HYPOTHESIS: Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs. ANIMALS: Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses. METHODS: Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome. RESULTS: Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.

Evaluation of strontium Sr 90 for the treatment of superficial squamous cell carcinoma of the nasal planum in cats: 49 cases (1990-2006).

OBJECTIVE: To determine progression-free and overall survival times of cats with squamous cell carcinoma (SCC) of the nasal planum following treatment with a single fraction of strontium Sr 90 ((90)Sr). DESIGN: Retrospective case series. ANIMALS: 49 cats with SCC of the nasal planum. PROCEDURES: Information including FIV infection status, diagnosis of SCC vs SCC in situ (ie, evidence that the tumor did or did not penetrate the epidermal basement membrane, respectively), (90)Sr dose and number of probe applications, treatment-related response and complications, and recurrence of SCC and new lesion development was obtained from medical records. The relationships of these variables with calculated progression-free and overall survival times were assessed. RESULTS: Of 49 cats that underwent (90)Sr plesiotherapy (median dose, 128 Gy), 48 (98%) had a response to treatment and 43 (88%) had a complete response. Median progression-free and overall survival times were 1,710 and 3,076 days, respectively. Treatment complications were infrequent (4 [8%] cats) and mild. Following treatment, the SCC recurrence rate was 20% (10/49 cats); 16 (33%) cats developed new lesions in other locations. Overall survival time was significantly longer for cats with a complete response to treatment than for those with a partial response. None of the other variables evaluated had a significant effect on progression-free or overall survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of cats with SCC of the nasal planum with a single fraction of (90)Sr appeared to be effective and well tolerated. Initial response to treatment was predictive of overall survival time.

Response of nineteen cats with nasal lymphoma to radiation therapy and chemotherapy.

The records of 19 cats treated for stage I nasal lymphoma with radiation therapy and chemotherapy were reviewed to determine response to therapy, treatment outcome and possible prognostic indicators. All cats were treated with megavoltage radiation therapy to a total dose ranging from 22 to 48 Gy (median dose = 42 Gy). All cats were prescribed at least 6 months of multiagent chemotherapy. The median progression-free interval for all cats was 945 days (31 months). Two cats did not achieve clinical remission. Of 17 cats evaluable for relapse, 10 (58.8%) were progression free during the entire follow-up period. Four cats (23.5%) suffered local recurrence, while three (17.6%) experienced distant relapse. The median survival time was 955 days (31.4 months). The only variable found to have a significant negative impact on survival was destruction of the cribriform plate before therapy (P= 0.002). The long progression free and survival times reported here indicate that cats with stage I nasal lymphoma treated with aggressive local and systemic therapy can have a favorable outcome when compared with other anatomic forms of lymphoma. Despite strong clinical responses to the multimodality therapy used, the fact that three (17.6%) cats relapsed distantly supports the recommendation that treatment with radiation therapy alone is insufficient until further prospective studies can be performed.

Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995-2004).

OBJECTIVE: To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae. DESIGN: Retrospective case series. ANIMALS: 573 equidae with 630 cutaneous tumors. PROCEDURES: Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed. RESULTS: 549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell carcinomas (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16). Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids, 96% for lymphomas, 88% for squamous cell carcinomas, 85% for soft tissue sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior treatment were significant prognostic factors for tumor control. Treatment efficacy was lower for large tumors, those with gross postoperative residual disease, and those that had been treated previously with other modalities. Treatment was well tolerated. Local reactions were more likely to occur and to be more severe after the third and fourth treatment sessions. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirmed the value of intratumoral chemotherapy with cisplatin for treatment of cutaneous tumors in equidae. The results cannot be extrapolated to other formulations of cisplatin or other protocols that might be used.

Tolerance of cutaneous or mucosal flaps placed into a radiation therapy field in dogs.

OBJECTIVE: To determine the clinical outcome and factors affecting cutaneous or mucosal flaps in dogs treated with radiation therapy (RT). STUDY DESIGN: Longitudinal clinical study. ANIMALS: Twenty-six client-owned dogs. METHODS: Dogs entered in the study had a flapping procedure and RT as part of their treatment. The sequence of flapping and RT included: (1) planned preoperative RT, (2) postoperative RT, and (3) flapping as a salvage procedure for management of complications or local tumor recurrence after RT. Flap complications were defined as necrosis, local infection, dehiscence, and ulceration. The risk and severity of flap complication were analyzed independently. RESULTS: Twenty (77%) dogs had a complication; 6 dogs required an additional flapping procedure; and 4 dogs had an unresolved complication. Flapping procedures performed to correct a complication, or failure of RT, had a significantly greater risk for complication; however, postoperative RT decreased the severity of complication. A dose per fraction of 4 Gy compared with 3 Gy was prognostic for increased severity of complications, whereas the head and neck location was prognostic for decreased severity of complication. CONCLUSIONS: Although morbidity was substantial, cutaneous or mucosal flaps were used successfully in an RT field in 85% of the dogs. Flaps that were part of the planned therapy as opposed to those used to correct a complication or failure of RT had a better clinical outcome. CLINICAL RELEVANCE: Cutaneous or mucosal flaps can be part of the treatment of dogs with tumor when adjuvant or neoadjuvant RT is to be used.

Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas.

An activating mutation in codon 599 of BRAF has been identified in approximately 60% of human cutaneous nevi and melanomas, but not melanomas of mucosal origin. The purpose of this study was to determine if BRAF mutations occur in canine oral malignant melanomas. The canine BRAF gene was first cloned from normal canine testicular cDNA, and a novel previously unreported splice variant involving exon 5 was identified during this process. To screen canine melanoma samples for BRAF mutation in codon 599, cDNA and genomic DNA were isolated from canine malignant melanoma cell lines and primary tumor samples respectively, all from cases seen at the Veterinary Medical Teaching Hospital at the University of California, Davis. Polymerase chain reaction (PCR) was performed for exon 15 using primers based at the 5' end of exon 15 and the 5' end of intron 15 and the resultant products were directly sequenced. No mutations in codon 599 or exon 15 were identified in any of the 17 samples evaluated. However, all of the melanoma cell lines expressed BRAF and demonstrated high levels of basal ERK phosphorylation suggesting that dysregulation of this pathway is present. Therefore, similar to the case with human mucosal melanomas, canine oral malignant melanomas do not possess codon 599 BRAF mutations commonly identified in human cutaneous melanomas. This finding supports the notion that melanomas arising from non-sun-exposed sites exhibit distinct mechanisms of molecular transformation.

Biologic behavior and prognostic factors for mast cell tumors of the canine muzzle: 24 cases (1990-2001).

The medical records of 24 dogs with histologically confirmed mast cell tumors (MCT) of the muzzle were retrospectively evaluated to determine their biologic behavior and prognostic factors. Information on signalment, tumor grade and stage, treatment methods, and pattern of and time to failure and death was obtained from the medical record. Twenty-three dogs were treated with combinations of radiotherapy, surgery, and chemotherapy; 1 dog received no treatment. There were 2 Grade 1, 15 Grade 11, and 7 Grade III tumors. Tumors were stage 0 (n = 8), stage 1 (5), stage 2 (6), stage 3 (4), and stage 4 (1). Mean and median survival times of treated dogs were 36 and 30 months, respectively. Prognostic factors affecting survival time included tumor grade and presence of metastasis at diagnosis. Dogs with Grade I and II tumors survived longer than dogs with Grade III tumors. Variables, including sex, age, gross versus microscopic disease, and treatment type were not found to affect survival. Local control rate was 75% at 1 year and 50% at 3 years. Tumor grade was the only variable found to affect local control. Dogs with Grade I tumors had longer disease-free intervals than those with Grade II tumors, and dogs with Grade II tumors had longer disease-free intervals than dogs with Grade III tumors. Eight of 9 dogs dying of MCT had local or regional disease progression. Muzzle MCT a rebiologically aggressive tumors with higher regional metastatic rates than previously reported for MCT in other sites.