Three‐dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three‐dimensional conformal radiation therapy (3D‐CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross‐sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272–829 days; range = 30–1942 days) when all deaths were considered and 906 days (interquartile range = 336–912 days; range = 101–1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D‐CRT may be a viable alternative to surgery.     

Use of surgical hemoclips in radiation treatment planning

The goal of this prospective study was to determine the effect of hemoclip use on the size of radiation treatment fields based on a 3-cm margin around a surgical incision alone (field setup 1) vs. a 3-cm margin around the surgical incision plus hemoclips (field setup 2). Forty-seven dogs that underwent surgical resection of a total of 55 soft tissue masses had surgical hemoclips placed at the time of surgery and orthogonal radiographs made immediately postoperatively. Radiation treatment field simulation was done and field areas measured. Additional determinations included number of hemoclips outside of the radiation treatment field based on a margin around the incision alone, hemoclip distance from the incision, and association between incision length and greatest distance of hemoclips from the incision. There was a significant difference in radiation treatment field size using information regarding the location of hemoclips in conjunction with the surgical scar compared with the surgical scar alone for truncal (P = 0.0003) vs. extremity tumors (P = 0.087). In simulating radiation treatment fields hemoclips were located outside of field setup 1 for the majority of tumors (79%) resected from the trunk but only in a minority of tumors (10.7%) resected from extremity sites. The findings from this study suggest that surgical hemoclips have potential utility in simulation of radiation treatment fields in the postoperative setting.     

A comparison of two dose calculation algorithms—anisotropic analytical algorithm and Acuros XB—for radiation therapy planning of canine intranasal tumors

Although anisotropic analytical algorithm (AAA) and Acuros XB (AXB) are both radiation dose calculation algorithms that take into account the heterogeneity within the radiation field, Acuros XB is inherently more accurate. The purpose of this retrospective method comparison study was to compare them and evaluate the dose discrepancy within the planning target volume (PTV). Radiation therapy (RT) plans of 11 dogs with intranasal tumors treated by radiation therapy at the University of Georgia were evaluated. All dogs were planned for intensity‐modulated radiation therapy using nine coplanar X‐ray beams that were equally spaced, then dose calculated with anisotropic analytical algorithm. The same plan with the same monitor units was then recalculated using Acuros XB for comparisons. Each dog's planning target volume was separated into air, bone, and tissue and evaluated. The mean dose to the planning target volume estimated by Acuros XB was 1.3% lower. It was 1.4% higher for air, 3.7% lower for bone, and 0.9% lower for tissue. The volume of planning target volume covered by the prescribed dose decreased by 21% when Acuros XB was used due to increased dose heterogeneity within the planning target volume. Anisotropic analytical algorithm relatively underestimates the dose heterogeneity and relatively overestimates the dose to the bone and tissue within the planning target volume for the radiation therapy planning of canine intranasal tumors. This can be clinically significant especially if the tumor cells are present within the bone, because it may result in relative underdosing of the tumor.     

Palliative radiation therapy in a dog with malignant trichoepithelioma

An 11-year-old male Bearded Collie was brought to the Gifu University Animal Medical Centre with a skin mass on the lateral right thigh. Physical examination revealed a 30 × 65-mm oval mass with an alopecic and ulcerated surface. Histopathology of the surgically excised sample confirmed malignant trichoepithelioma. Five months after the surgery, the dog experienced lumbar pain resulting from metastasis to the lumbar vertebrae. Radiation therapy (RT) was performed and it alleviated the lumbar pain. Nine months after the surgery, multiple skin metastases were identified. RT was performed at each occurrence, which reduced the size of each tumour and resulted in a partial response; however, systemic metastasis occurred and the dog died 17 months after the initial surgery. Canine malignant trichoepithelioma is a rare tumour, so an effective treatment has not been determined. Data from our case study indicate that RT has potential for pain control of primary and metastatic malignant trichoepithelioma.     

Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma

Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi‐institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post‐radiation temozolomide in dogs with chemotherapy‐naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m^?2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post‐radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT.     

Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour‐bearing animals

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour‐bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed‐loop temperature feedback control system, and a tool for patient‐specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients.     

Three‐dimensional conformal versus non‐graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002–2007)

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non‐graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under‐dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.     

Interobserver reliability of canine urine specific gravity assessed by analog or digital refractometers

Refractometry is utilized routinely to evaluate canine urine specific gravity (USG) in veterinary clinical settings. We aimed to determine if the magnitude of interobserver reliability when assessing canine USG via refractometry could impact clinical judgment. USG was determined in 38 dogs by 3 registered veterinary technicians (RVTs) using both an optical analog refractometer and a digital refractometer. Summary statistics were reported, interobserver reliability was assessed via intraclass correlation coefficient (ICC) analysis through a 2-way mixed-effects model, and agreement between RVT pairs was compared through Bland–Altman plots. The median analog refractometer USG measurement was 1.018 (range: 1.004–1.040) and for the digital refractometer was 1.0176 (1.0035–1.0357). The analog refractometer average measure ICC was 0.995 (95% CI: 0.992, 0.997; p < 0.001). The digital refractometer average measure ICC was 0.999 (95% CI: 0.999, 1.000; p < 0.001). Strong agreement between all pairs of RVTs was seen via Bland–Altman plots for both analog and digital refractometers, with 95% CIs spanning no more than 0.002 in either the positive or negative direction for all pairings. The interobserver variability in canine USG measurements by RVTs was trivial and did not impact clinical judgment and decision-making.     

Evaluation of weight loss in canine cancer bearing patients undergoing radiation therapy

Critical weight loss, as defined by ≥5% decrease in body weight, has been associated with increased morbidity and mortality in human patients with cancers of the head and neck. Weight loss has anecdotally been reported to occur frequently in veterinary patients undergoing radiation therapy and is hypothesized to be more severe in patients with cancers of the head and neck, along with those hospitalized during radiation therapy. The primary objective of this retrospective study was to evaluate the occurrence of critical weight loss in canine cancer bearing patients undergoing either definitive or palliative radiation protocols and to determine if weight changes were associated with radiation toxicity, tumour location or patient hospitalization status. Data from 47 dogs who underwent definitive and 43 dogs who underwent palliative radiation protocols at the University of Tennessee were included for analysis. Dogs were categorized based on tumour location (head/neck or other), hospitalization status (boarded or non‐boarded) and radiation toxicity score. Weight recorded at the start of treatment, midway through treatment and at the final treatment was used for analysis. No significant differences were found in regard to weight change over time, location or hospitalization status when evaluated for both protocols. Overall, 5/90 dogs (5.5%) lost 5% or more of their body weight during therapy, and 7/90 dogs (7.7%) gained 5% or more of their body weight. The results of the current study suggest that critical weight loss occurs in a small percentage of canine patients undergoing radiation therapy, contrary to what is often anecdotally reported.     

Outcome of intensity‐modulated radiation therapy‐based stereotactic radiation therapy for treatment of canine nasal carcinomas

Stereotactic radiation therapy (SRT) has emerged as a convenient definitive treatment modality in veterinary medicine, but few studies exist evaluating outcome with treatment for canine nasal tumors, and no studies report the treatment of one single tumor histotype. This retrospective, observational study evaluates toxicity, response, and survival in 17 dogs with nasal carcinomas treated with SRT. Dogs received a median of 3000 centigray in three fractions via 6‐MV linear accelerator. Eighty‐eight percent of patients (n = 15) demonstrated clinical benefit. Of dogs with repeated CT imaging (n = 10), 60% (n = 6) achieved a partial response and 10% (n = 1) achieved a complete response. Median progression‐free survival (PFS) was 359 days. Median survival time (MST) was 563 days. Among dogs evaluable for acute toxicity, 50% (n = 10) developed low grade toxicity (grade 1, n = 4; grade 2, n = 1). No patients developed grade 3 toxicity. 16 dogs (87%) evaluable over the long term developed signs consistent with possible late toxicity. The majority of late toxicities were mild (alopecia, hyperpigmentation, and leukotrichia n = 10; ocular discharge and keratoconjunctivitis sicca n = 5). Thirty‐seven percent of patients (n = 6) developed seven possible grade 3 late toxicities (blindness, n = 3; fistula, n = 1; seizures, n = 3), which were difficult to distinguish from progressive disease in most patients. Of the prognostic factors evaluated (demographics, tumor stage, dosimetric data, epistaxis, facial deformity, clinical response, image‐based response, nonsteroidal anti‐inflammatory drugs, and chemotherapy), only clinical response was a positive prognostic factor on MST (P < .00). No factors were found to be significantly associated with PFS.     

Canine acute radiation dermatitis, a survey of current management practices in North America

Acute radiation‐induced dermatitis (ARID) is a common sequela of radiation therapy in dogs. There is no consensus regarding ARID management in human medicine and the standard of care in veterinary medicine has not been reported. The objective was to report the practice standards for ARID management in dogs in North America. The design used was a questionnaire survey. Fifty‐eight private and university teaching veterinary hospitals were contacted, 54 participated. The topical and oral medications used to treat ARID, prevent or treat bacterial infection, control pain and the indications for and timing of treatment initiation were the outcome measures. A minority of facilities (4/54, 7.5%) use exactly the same protocol regarding all parameters. There was agreement (>75% of facilities) with respect to the general use of oral antibiotics (77.8%), the need for pain control (92.6%) and the use of tramadol for pain control (76%), although the details of their use varied widely. There is a divergence of opinions regarding all details of ARID management in dogs except the general use of oral antibiotics and pain control medications.     

Safety and feasibility of short course pre-operative radiation therapy followed by surgical excision for canine solid tumours

Surgical resection of solid tumours, especially in early stages of disease, remains a cornerstone of cancer treatment in dogs and cats. There are numerous publications that show a strong association between local tumour control and outcome. To achieve local control in some cases radiation therapy and surgery are combined, with radiation therapy being delivered in the neoadjuvant or adjuvant setting. The objective of the study was to report acute toxicity and surgical site complication data in dogs that received a short-course pre-operative (SCPO) radiation therapy protocol, followed by surgical excision for various solid tumours. Medical records were reviewed, and data was analysed retrospectively. Dogs were included if a dermal or subcutaneous solid tumour was treated with SCPO radiation therapy and then was resected on the last day of radiation or 2–3 weeks later. A total of 34 dogs with 35 primary tumours were included. Acute radiation toxicity was diagnosed in 14 sites (40%). VRTOG scores were grade 1 in 50%, grade 2 in 43%, and grade 3 in 7%. Surgical site complications were identified in 17% of dogs with an overall surgical site infection rate of 11%. According to the Clavien-Dindo classification, two dogs required medical intervention (grade 2), 1 dog required surgical intervention under general anaesthesia (grade 3b), and 1 dog died as a result of complications (grade 5). Logistic regression analysis found that anatomic site was significantly associated with complications, where tumours located on the extremity was protective (P = .02; OR 0.06).     

The Elekta Fraxion™ system is not suitable for maxillary fixation in canine conformal radiation therapy techniques

In this prospective, exploratory study, we evaluated the positioning accuracy in a group of 15 dogs undergoing fractionated stereotactic radiotherapy for tumors affecting the head, using a modified human maxillary fixation device (Elekta Fraxion? system). Positioning was assessed using on‐board volumetric imaging, with a six‐degrees‐of‐freedom image registration technique. Prior to treatment delivery, CBCT images were obtained and patient alignment was corrected, in both translational and rotational planes, using a six‐degrees‐of‐freedom robotic patient positioning system (HexaPOD Evo RT System). The maximum angular inter‐fraction motions observed were 6.1° (yaw), 10.9° (pitch), and 4.5° (roll). The mean systematic translational errors were 4.7, 2.6, and 2.3 mm, mean random translational errors were 3.0, 2.2, and 2.5 mm, and mean overall translational errors were 2.4, 0.7, and 2.3 mm in the cranial‐caudal, lateral, and dorsal‐ventral directions, respectively. The mean systematic rotational errors were 1.17°, 0.77°, and 1.43°, the mean rotational random errors were 1.65°, 1.46°, and 1.34° and the mean overall rotational errors were 0.56°, 0.22°, and 0.29° in the yaw, pitch, and roll directions, respectively. The mean error of the three‐dimensional vector was 6.9 mm with a standard deviation of 3.8 mm. Ninety‐five percent of the three‐dimensional vectors were <14.8 mm. This study demonstrates that this maxillary fixation device relies on six‐degrees‐of‐freedom registration and an ability to apply corrections using a six‐degrees‐of‐freedom couch for accurate patient positioning and tumor targeting. Its use in conformal radiation therapy in dogs is not recommended.     

The use of megavoltage radiation therapy in the treatment of thymomas in rabbits: 19 cases

An overall median survival time (MST) and prognostic factors in rabbits with thymomas treated with megavoltage radiation therapy (RT) were determined in this multi-institutional retrospective case analysis. Medical records for 19 rabbits with suspected or confirmed thymomas treated with RT were evaluated for data including signalment, haematological and serum biochemistry abnormalities, presence of pleural effusion, radiation plan, body weight, total radiation dose and institution administering RT. Statistical significance of these factors related to overall survival was assessed. An overall MST for all 19 rabbits was 313 days; exclusion of 3 rabbits that died acutely during the first 14 days of RT yielded a MST of 727 days. The only factor associated with a significantly decreased survival time was having a body weight lower than mean body weight of 1.57 kg. Radiation treatment-associated complications were infrequent and included radiation-induced myocardial failure, radiation pneumonitis and alopecia.     

Using biologically based objectives to optimize boost intensity‐modulated radiation therapy planning for brainstem tumors in dogs

Irradiated brain tumors commonly progress at the primary site, generating interest in focal dose escalation. The aim of this retrospective observational study was to use biological optimization objectives for a modeling exercise with simultaneously‐integrated boost IMRT (SIB‐IMRT) to generate a dose‐escalated protocol with acceptable late radiation toxicity risk estimate and improve tumor control for brainstem tumors in dogs safely. We re‐planned 20 dog brainstem tumor datasets with SIB‐IMRT, prescribing 20 × 2.81 Gy to the gross tumor volume (GTV) and 20 × 2.5 Gy to the planning target volume. During the optimization process, we used biologically equivalent generalized equivalent uniform doses (gEUD) as planning aids. These were derived from human data, calculated to adhere to normal tissue complication probability (NTCP) ≤5%, and converted to the herein used fractionation schedule. We extracted the absolute organ at risk dose‐volume histograms to calculate NTCP of each individual plan. For planning optimization, gEUD_{(a = 4)} = 39.8 Gy for brain and gEUD_{(a = 6.3)} = 43.8 Gy for brainstem were applied. Mean brain NTCP was low with 0.43% (SD ±0.49%, range 0.01‐2.04%); mean brainstem NTCP was higher with 7.18% (SD ±4.29%, range 2.87‐20.72%). Nevertheless, NTCP of < 10% in brainstem was achievable in 80% (16/20) of dogs. Spearman's correlation between relative GTV and NTCP was high (ρ = 0.798, P < .001), emphasizing increased risk with relative size even with subvolume‐boost. Including biologically based gEUD values into optimization allowed estimating NTCP during the planning process. In conclusion, gEUD‐based SIB‐IMRT planning resulted in dose‐escalated treatment plans with acceptable risk estimate of NTCP < 10% in the majority of dogs with brainstem tumors. Risk was correlated with relative tumor size.     

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.     

Optimization of contrast-enhanced multidetector abdominal computed tomography in sedated canine patients

A major disadvantage of computed tomography for abdominal screening in dogs has been the need for general anesthesia to prevent motion artifacts. With multidetector helical CT, it is possible to decrease examination time, allowing patients to be scanned under sedation. It is also desirable to decrease tube loading to prolong x-ray tube life. To develop a protocol that will allow for examination of sedated patients with minimal image artifacts, milliamperage (mA) and helical pitch were varied, providing 16 experimental scan protocols. A standard clinical protocol was also tested, providing 17 protocols for evaluation. These protocols were tested, using a standard CT phantom, canine tissues in a water bath, and a canine cadaver. The cadaver images were scored semiquantitatively by three reviewers to determine the protocol with the best combination of speed and minimal image artifact. The optimized protocol was then applied to 27 sedated canine patients of three body weight categories. The images obtained were compared to the standard protocol by two reviewers for presence of motion, streak, and quantum mottle artifacts. There was significantly more streak artifact noted by one observer using the optimized study protocol, but no significant difference in any other category. Scanning under sedation was well tolerated in all patients, and sedated CT examination is a promising tool for screening abdominal disease in dogs.