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Thyroid carcinoma develops spontaneously in dogs, with only 25% to 50% of cases amenable to surgery at diagnosis. Local control for unresectable tumours can be provided with external beam radiotherapy. The aim of this retrospective study is to describe the safety and efficacy of stereotactic body radiation therapy (SBRT) for treatment of canine thyroid carcinoma. Twenty-three dogs met inclusion criteria; median tumour volume before SBRT was 129.9 cm 3 (range, 2.7-452.8 cm 3 ). Sixteen patients (70%) had unresectable tumours. Pulmonary metastasis was present or suspected in 10 patients (44%) before SBRT. Patients were prescribed 15 to 40 Gy to targeted tumour volume in one to five fractions. Twenty patients evaluated had overall response rate of 70% (complete response, n = 4; partial response, n = 10). Thirteen out of sixteen (81%) symptomatic patients had clinical improvement within a median time of 16 days (range, 2-79 days). Median progression free survival (MPFS) was 315 days. Median survival time (MST) was 362 days. Nine patients (39%) had grade 1 acute radiation toxicity. Three patients had grade 1 late radiation toxicity (two leukotrichia and one [4%] with intermittent cough). Responders had significantly longer MPFS (362 vs 90 days; HR 4.3; 95% CI 1.4-13.5; P = .013) and MST (455 vs 90 days; HR 2.9; 95% CI 1-8.4; P = .053). Presenting with metastasis was not a significant negative prognostic factor (MST 347 vs 348 days without metastasis; P = .352). SBRT is a safe and effective treatment modality for non-resectable canine thyroid carcinoma., (© 2020 John Wiley & Sons Ltd.)

Infiltrative lipomas represent a subcategorisation of rarer, potentially more aggressive, lipoma‐related neoplasms. Twenty‐one dogs treated with conventionally fractionated radiotherapy (CFRT) for infiltrative lipomas were included in this retrospective study. One patient had no prior surgical excision, 11 patients had one prior surgery and 9 patients had two or more surgeries prior to CFRT. Five patients (24%) had microscopic disease and 16 patients (76%) had macroscopic disease prior to treatment. A complete response or no regrowth was seen in 10 patients (48%), stable disease in 6 patients (29%) and progressive disease or regrowth in 5 patients (24%). Response to treatment of macroscopic tumours was significantly different between dogs that had one prior surgery versus two or more (p = 0.01). Dogs with a single surgery were most likely to result in stable disease compared with dogs with two or more surgeries resulting in a complete response. The dog without surgery developed progressive disease at 211 days, dogs with one surgery had a median progression or recurrence at 1369 days and dogs with two or more surgeries developed progression or recurrence at 826 days (p = 0.04). Twelve dogs were alive at the time of analysis. Overall median survival time (MST) was 1694 days. The prior number of surgeries did not significantly affect MST. While survival time is comparable to previous reports, the number of patients with progressive disease or recurrence of previous microscopic disease requires more investigation into the most appropriate protocol, dose and treated field size. [ABSTRACT FROM AUTHOR]

Canine craniomaxillofacial osteosarcoma (OSA) is most commonly treated surgically; however, in cases where surgery is not feasible or non‐invasive treatment is desired, stereotactic body radiation therapy (SBRT) may be elected for local tumour control. In this study, we evaluated 35 dogs treated with SBRT. Nine dogs (26%) had calvarial, seven (20%) had mandibular and 19 (54%) had maxillary OSA. Median time to first event (TFE) was 171 days, and overall median survival time (MST) was 232 days. Site‐specific MSTs were 144 days for mandible, 236 days for calvarium and 232 days for maxilla (p =.49). Pulmonary metastatic disease was observed in 12/35 (34%) patients and was detected pre‐SBRT in six dogs (17%) and post‐SBRT in the remaining six dogs (17%). Eighteen adverse events post‐SBRT were documented. Per veterinary radiation therapy oncology group criteria, five were acute (14%) and three were late (9%) grade 3 events. Neurological signs in two dogs were suspected to be early‐delayed effects. Cause of death was local progression for 22/35 (63%) patients, metastasis for 9/35 (26%) patients and unknown for four. On univariate analysis, administration of chemotherapy was associated with a longer TFE (p =.0163), whereas volume of gross tumour volume was associated with a shorter TFE (p =.023). Administration of chemotherapy and five fractions versus single fraction of SBRT was associated with increased survival time (p =.0021 and.049). Based on these findings, a treatment protocol incorporating chemotherapy and five fractions of SBRT could be considered for dogs with craniomaxillofacial OSA electing SBRT with careful consideration of normal tissues in the field. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment. [ABSTRACT FROM AUTHOR]

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non‐modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy‐confirmed glioma or a presumptive diagnosis of intra‐cranial glioma based on MRI characteristics that were treated with SRT. Twenty‐three client‐owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty‐one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162–584). Median disease specific survival time was 413 days (95% CI, 217–717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable. [ABSTRACT FROM AUTHOR]

An 11‐year‐old, female, spayed border collie displayed vomiting and diarrhoea for a period of 3 months and presented with severe emaciation. A laparotomy confirmed the presence of a gastric lesion, and histopathologic evaluation revealed a diagnosis of gastric carcinoma. The dog was treated with hypofractionated intensity‐modulated radiation therapy and achieved clinical improvement for approximately 3 months after treatment. Given the improvement of clinical signs following treatment in this case, the use of radiation therapy as a treatment option may be explored for palliation for dogs with advanced gastric carcinoma. [ABSTRACT FROM AUTHOR]

Canine thymomas are routinely treated with radiotherapy (RT). In this study, we investigate the response and toxicity of canine thymoma treated with intensity‐modulated stereotactic body radiation therapy (SBRT) relative to dogs treated with hypofractionated non‐modulated radiation therapy (NMRT). A retrospective study was performed of dogs with thymoma treated with RT (total: n = 15; SBRT: n = 8, NMRT: n = 7). Tumour response was evaluated in six dogs (40%); following SBRT, three dogs (100%) experienced stable disease (SD); following NMRT, one dog (33%) had a PR, and two dogs (67%) had SD. Median PFS was 116 days (range 66–727 days) for the SBRT group and 134 days (range 10–405 days) for the NMRT group. The MST for the SBRT group was 250 days (range 1–727 days) and 155 days (range 10–405 days) for NMRT. Median disease‐specific survival was 250 days (range 1–727 days) for the SBRT group and 169 days (range 20–405 days) for the NMRT group. No significant differences in survival data were found between the treatment groups, however the results from the small number of dogs analysed are likely underpowered for statistical comparisons. Reported acute and late side effects were limited to the lungs and heart and were statistically significantly more common in the NMRT (71%) compared to the SBRT group (25%) (p =.04). We suggest similar treatment efficacy may be provided for canine thymoma treated with either approach, but SBRT could provide the clinical benefit of reduced incidence of radiation‐induced toxicity and completion of RT in a shorter time frame. [ABSTRACT FROM AUTHOR]

Laboratory and clinical research are essential for advancing radiation research; however, there is a growing awareness that conventional laboratory animal models and early-phase clinical studies in patients have not improved the low success rates and late-stage failures in new cancer therapy efforts. There are considerable costs and inefficiencies in moving preclinical research into effective cancer therapies for patients. Canine translational models of radiation research can fill an important niche between rodent and human studies, ultimately providing valuable, predictive, translational biological and clinical results for human cancer patients. Companion dogs naturally and spontaneously develop cancers over the course of their lifetime. Many canine tumor types share important similarities to human disease, molecularly and biologically, with a comparable clinical course. Dogs receive state-of-the-art medical care, which can include radiotherapy, experimental therapeutics, and novel technologies, offering an important opportunity for radiobiology and radiation oncology research. Notably, the National Cancer Institute has developed the Comparative Oncology Program to promote this area of increased research interest. In this review, the benefits and limitations of performing translational radiation research in companion dogs will be presented, and current research utilizing the canine model will be highlighted, including studies across research areas focusing on common canine tumor types treated with radiotherapy, comparative normal tissue effects, radiation and immunology research, and alternative radiation therapy approaches involving canine cancer patients. [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinase inhibitors (TKIs) are used to treat human and canine cancers and may be combined with radiation therapy (RT) to enhance tumor control due their anticancer and antiangiogenic effects; however, recent case reports have emerged describing incidences of gastrointestinal toxicity when antiangiogenic therapies are combined with hypofractionated radiotherapy in human cancer patients. We evaluated the incidence of gastrointestinal (GI) toxicity in dogs receiving concurrent hypofractionated abdominal RT and the TKI toceranib (TOC) compared to those receiving abdominal RT alone, TOC alone, or concurrent non‐abdominal RT and TOC. Medical records of canine cancer patients were retrospectively reviewed and identified dogs were included in the following treatment categories: dogs which received RT to a portion of the abdomen and concurrent TOC (n = 19), abdominal RT alone (n‐29), TOC alone (n = 20), or non‐abdominal RT plus TOC (n = 9). Toxicities were graded using the Veterinary Cooperative Oncology Group ‐ Common Terminology Criteria for Adverse Events criteria and compared to published data on TOC‐associated GI toxicity. Patients receiving TOC while undergoing abdominal RT had significantly increased rates of any grade of diarrhea (p = 0.002), hyporexia (p = 0.0045), and vomiting (p = 0.003), as well as severe hyporexia (p = 0.003) when compared across the treatment groups. This retrospective study reveals significantly increased incidences of GI toxicity when abdominal RT is combined with TOC in canine patients. These findings are in‐line with the clinical concerns reported for increased normal tissue toxicity in human patients when antiangiogenics are combined with RT. [ABSTRACT FROM AUTHOR]

Canine appendicular osteosarcoma is commonly treated with limb amputation; however, limb‐sparing options are frequently desired or necessary for a subset of patients. We evaluated 123 patients and 130 sites treated with stereotactic body radiation therapy (SBRT). Eighty‐two out of 98 dogs (84%) had maximum lameness improvement at a median of 3 weeks for a median of 6 months duration. Histopathologic evaluation of available samples from amputation or necropsy revealed >80% tumor necrosis in 50% of limbs consistent with local disease control. Of evaluable patients, 41% fractured and 21% pursued an amputation after treatment. Fine needle aspirate (n = 52) and needle core biopsy (n = 28) did not result in increased fracture risk compared to those without tumor sampling (n = 50). Median survival time (MST) was 233 days and time to first event was 143 days. Gross tumor volume and planned target volume were significantly inversely associated with survival and tumor location was significantly associated with survival. Dogs with salvage amputation had a significantly longer MST compared to those without (346 vs 202 days; P =.04). The presence of metastatic disease at the time of treatment in 15 dogs did not significantly impact survival time (200 vs 237 days without metastasis; P =.58). Skin side effects correlated significantly with dose with 33% of patients with acute grade 3 effects developing consequential late grade 3 effects. While SBRT improves lameness in most patients, further investigation is needed to identify candidates with minimal early fracture risk prior to initiating therapy. [ABSTRACT FROM AUTHOR]

Novel synthetic compounds, known as manganese porphyrins (MnPs), have been designed to shift the redox status of both normal cells and cancer cells. When MnPs are coupled with cancer therapies, such as radiation, they have been shown to sensitize tumor cells to treatment and protect normal tissues from damage through the modulation of the redox status of various tissue types. Until now, our preclinical studies have focused on local effects of MnPs and radiation; however, we recognize that successful outcomes for cancer patients involve control of tumor cells throughout the body. In this study, using murine orthotopic mammary tumor models, we investigated how MnPs and radiation influence the development of distant metastasis. We hypothesized that the combination of MnP (MnP/RT), such as MnTnBuOE-2-PyP5+ and radiation treatment (RT) would increase local tumor control via a shift in the intratumoral redox environment, leading to subsequent downregulation of HIF-1 in the primary tumor. Secondarily, we hypothesized that these primary tumor treatment effects would result in a reduction in pulmonary metastatic burden. Balb/c mice with orthotopic 4T1 mammary carcinomas were treated with saline, MnP, RT or MnP/RT. We found MnP/RT did extend local tumor growth delay and overall survival compared to controls and was associated with increased intratumoral oxidative stress. However, the primary tumor growth delay observed with MnP/RT was not associated with a reduced pulmonary metastatic burden. Future directions to investigate the effects of MnP/RT on the development of distant metastasis may include modifications to the radiation dose, the experimental timeline or using a murine mammary carcinoma cell line with a less aggressive metastatic behavior. Clinical trials are underway to investigate the clinical utility of MnTnBuOE-2-PyP5+ for patients undergoing radiotherapy for various tumor types. The promising preclinical data from this study, as well as others, provides support that MnP/RT has the potential to improve local tumor control for these patients. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Conventional fractionated radiotherapy has been shown to be partially effective for management of pituitary tumors in cats that cause acromegaly and diabetes mellitus (DM), but, the efficacy and safety of stereotactic radiation therapy (SRT) as a treatment for acromegalic cats has not been described. Hypothesis: Stereotactic radiation therapy is an effective and safe treatment for controlling acromegaly associated with pituitary adenomas in cats. Additionally, SRT‐treated acromegalic cats with DM will experience a decrease in insulin requirements after radiation therapy. Animals: Fifty‐three client‐owned cats referred to Colorado State University for SRT to treat pituitary tumors causing poorly controlled DM secondary to acromegaly. Methods: Retrospective study of cats treated for acromegaly with SRT between 2008 and 2016 at Colorado State University. Diagnosis of acromegaly was based on history, physical examination, laboratory results, and cross‐sectional imaging of the pituitary. Signalment, radiation protocol, insulin requirements over time, adverse effects, and survival were recorded. Results: Median survival time was 1072 days. Of the 41 cats for which insulin dosage information was available, 95% (39/41) experienced a decrease in required insulin dose, with 32% (13/41) achieving diabetic remission. Remission was permanent in 62% (8/13) and temporary in 38% (5/13) cats. Median duration to lowest insulin dose was 9.5 months. Of the treated cats, 14% developed hypothyroidism and required supplementation after SRT. Conclusions: Stereotactic radiation therapy is safe and effective for treating cats with acromegaly. Cats treated with SRT have improved survival time and control of their DM when compared to previously reported patients treated with non‐SRT. [ABSTRACT FROM AUTHOR]