Prospective pilot study utilizing changes in quantitative values obtained on serial fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in dogs with appendicular osteosarcoma before and after stereotactic body radiation therapy (SBRT) and carboplatin chemotherapy to assess for prediction of survival and therapeutic effectiveness.

Serial fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography-CT (PET/CT) is commonly used in human oncology to prognosticate and evaluate for therapeutic effectiveness. In this pilot study, dogs with naturally occurring appendicular osteosarcoma were evaluated with serial 18F-FDG PET/CT in an attempt to assess for response to therapy, prognostic factors, and appropriateness of imaging intervals. Fourteen dogs were enrolled in the trial. All dogs had the initial 18F-FDG PET/CT (PET1), with nine dogs having their end-of-therapy 18F-FDG PET/CT (EoT PET) 3 months after stereotactic body radiation therapy (SBRT) to the primary tumor. The median percent change from the PET1 to the EoT PET for the standard uptake value maximum (SUVmax%) was -58% (range: -17 to -88%), metabolic tumor volume (MTV%) was -99.8% (range: -65 to -100%), and total lesion glycolysis (TLG%) was -99.8% (range: -75 to -100%), all of which were significant (P < .05, <.05, and <.05, respectively). On evaluation, it was found that volumes of GTV and CTV were significant for survival (P < .05 and <.05), MTV1, TLG1, and SUVmax on the EoT PET (SUVmaxEoT) were predictive of metastasis (P < .05), and the SUVmax% was significantly correlated to the time to first event (P < .05). Based on this data, serial 18F-FDG PET/CT performed 3 months after SBRT can show a significant reduction in avidity, and the quantitative data collected may help predict metastatic disease in canine appendicular osteosarcoma.

Outcomes of 35 dogs with craniomaxillofacial osteosarcoma treated with stereotactic body radiation therapy.

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.

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs.

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.

Partial ulnar ostectomy, stereotactic body radiation therapy, and palliative radiation therapy as local limb sparing treatment modalities for ulnar tumors in dogs.

Background: Information on dogs that undergo limb preserving local treatment for ulnar tumors is currently limited. Objective: To describe the clinical characteristics and outcomes in dogs that underwent partial ulnectomy or radiation therapy (RT) for ulnar bone tumors, and to evaluate potential risk factors for outcomes as well as pre-treatment factors for association with treatment modality selected. Animals: Forty client-owned dogs that underwent partial ulnectomy or RT for an ulnar tumor from July 2006 to July 2021. Methods: The medical records database from a single institution were retrospectively reviewed, and data were recorded and analyzed. Results: Radiation therapy was performed in 24 dogs, with 12 stereotactic body RT (SBRT) and 12 palliative RT (PRT) plans, and partial ulnectomy was performed in 16 dogs. Biomechanical complications occurred in 6/12 (50%) dogs that underwent SBRT, 6/12 (50%) dogs that underwent PRT, and 3/16 (18.8%) dogs that underwent ulnectomy. The majority of dogs had a good functional outcome following partial ulnectomy, and no dogs required surgical stabilization of the carpus even with lateral styloid process excision. Pathologic fracture occurred in 4/12 (33.3%) dogs following SBRT and 5/12 (41.7%) dogs following PRT. Local progression or recurrence was documented in 5/12 (41.7%) dogs that underwent SBRT, 2/12 (16.7%) dogs that underwent PRT, and 2/16 (12.5%) dogs that underwent ulnectomy. The overall median survival time was 198 days, and factors that were significantly associated with improved survival time included adjuvant chemotherapy administration and partial ulnectomy as local treatment method for dogs that received chemotherapy. Clinical relevance: Both RT and ulnectomy were effective and well tolerated local treatment modalities for dogs with ulnar tumors.

Efficacy of stereotactic radiation therapy for the treatment of confirmed or presumed canine glioma.

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.

Canine salivary gland carcinoma treated with stereotactic body radiation therapy: a retrospective case series.

Objective: The aim of this study was to describe the therapeutic outcomes of dogs with locally advanced salivary gland carcinomas (SGC) following stereotactic body radiation therapy (SBRT). Methods: A single institution retrospective study was conducted of client-owned dogs with macroscopic SGC treated with SBRT. Patient signalment, clinical characteristics, and treatment parameters were recorded. Clinical benefit was determined based on follow-up physical examination and medical history. Progression-free interval (PFI), median survival time (MST), and disease-specific survival (DSS) were calculated using Kaplan-Meier analysis. Acute and late toxicity were recorded according to Veterinary Radiation Therapy Oncology Group (VRTOG) criteria. Results: Six patients were included in the study. Tumor origins were mandibular (n = 3), parotid (n = 2), and zygomatic (n = 1) salivary glands. The SBRT prescription was 10 Gy × 3 daily or every other day. All patients (100%) experienced clinical benefit from treatment at a median time of 34 days (range 28-214). No local or regional nodal failure was reported following SBRT. Progressive pulmonary metastatic disease was documented in three dogs (50%). The median PFI was 260 days (range 43-1,014) and the MST was 397 days (range 185-1,014). Median DSS was 636 days (range 185-1,014). Four dogs (66.6%) died of confirmed or suspected metastatic SGC. The reported acute side effects included grade 2 mucositis (n = 1) and vision loss (n = 1). No late side effects were recorded. Conclusion: This study suggests that SBRT may provide durable local control for invasive SGC in dogs. Further investigation in a larger cohort of patients is warranted. The incidence of reported acute and late toxicity was low.

Superficial kilovoltage x-ray radiotherapy for the treatment of cutaneous mast cell tumors on the head in three dogs and one cat: a limited retrospective case series.

OBJECTIVE: To report preliminary findings of hypofractionated superficial radiotherapy for treatment of cutaneous mast cell tumors (MCTs) and report the acute and late toxicity associated with its use. ANIMALS: 3 dogs and 1 cat. PROCEDURES: In this retrospective study, medical records from January 2021 through July 2022 were searched for animals that received superficial radiation therapy for MCTs of the head. RESULTS: 4 patients with 5 MCTs were included. Three of the masses were periocular and required protection of the globe with a tungsten eye shield. One patient did not complete the intended protocol due to diffuse metastatic spread noted after the second fraction. Of the 3 patients that completed their protocol, 100% had a complete response. Two canine patients were treated adjunctively with toceranib. Two of the 4 patients experienced grade 1 acute veterinary radiation therapy oncology group (VRTOG) toxicity, and the 3 patients that completed their protocol experienced grade 1 late VRTOG toxicity. No radiation effects were documented to the cornea or lens in any patient. CLINICAL RELEVANCE: Superficial radiation therapy was effective in our limited study population, and patients experienced minimal side effects for treatment of cutaneous MCTs.

Configuration of pathologic fractures in dogs with osteosarcoma following stereotactic body radiation therapy: A retrospective analysis.

For some cases of canine appendicular osteosarcoma (OSA), limb-sparing treatment options are often desired, one of which is stereotactic body radiation therapy (SBRT). A major complication of SBRT is fracture of the irradiated bone at the site of treatment. The present study evaluated 127 appendicular OSA sites in 122 dogs treated with SBRT to identify the most common pathologic fracture locations and configurations. A total of 50 tumours experienced a pathologic fracture, and 38 had imaging sufficient to identify fracture configuration. The distal tibia was more likely to develop a fracture than other sites. Multiple types of fracture configuration (transverse, oblique, spiral and comminuted) were observed. The distal radius was significantly more likely to develop a transverse fracture than other sites. Documentation of fracture location and configuration leads to the identification of the forces contributing to fracture occurrence, since each configuration is a result of different forces acting on each affected bone. Such knowledge is imperative for the development of new approaches to diminish the occurrence of pathologic fractures.

Outcomes in dogs undergoing surgical stabilization and non-stereotactic radiation therapy for axial and appendicular bone tumors.

Background: Information on dogs that undergo radiation therapy (RT) with non-stereotactic protocols in addition to surgical stabilization with implant placement for treatment of bone tumors is limited. Objective: Our primary objectives were to describe the clinical characteristics as well as short- and long-term outcomes, including complications, function, and disease progression, in dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor. Methods: A bi-institutional retrospective case series was performed. Animals: Eight client-owned dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor were included. Results: Tumor types included osteosarcoma or suspected osteosarcoma (5), plasma cell tumor (2), and grade 3 fibrosarcoma (1). Radiation protocols were hypofractionated (palliative intent) in 5 dogs and fractionated (definitive intent) in 3 dogs. Five dogs experienced complications following both RT and surgery, including grade 1 complications in two dogs, a grade 2 complication in one dog, both grade 1 and 2 complications in one dog, and both grade 2 and 3 complications in one dog. Clinical signs subjectively improved in all dogs that had outcomes relative to function documented post-surgery/RT (7). Of these 7 dogs, 4 maintained long-term improvement in function and clinical signs, whereas 3 experienced subsequent recurrence/progression of clinical signs at a median of 133 days (range 91-186) postoperatively in association with biomechanical complications (screw loosening), surgical site infection, and local disease progression in 1 dog each; subsequent treatment resulted in improved clinical signs for each of these 3 dogs, such that overall good long-term functional outcomes were experienced. No dogs required amputation or additional vertebral surgery as salvage for local disease control or palliation. The median progression free interval was 206 days (range 25-1078), and the median survival time was 253 days (range 122-1078) with 1 additional dog lost to follow-up at 575 days. Two dogs experienced local disease progression, and 6 dogs experienced systemic disease progression; both dogs that developed local disease progression received palliative intent RT protocols. Clinical relevance: In this cohort, dogs with primary bone tumors that underwent surgical stabilization with implant placement and hypofractionated or fractionated non-stereotactic RT for local treatment had a low incidence of major complications, good limb function and ambulation post-treatment, and relatively prolonged survival times despite disease progression.

Retrospective Evaluation of Outcome in Dogs With Appendicular Osteosarcoma Following Hypofractionated Palliative Radiation Therapy With or Without Bisphosphonates: 165 Cases (2010-2019).

Objective: To report the survival times in dogs that received a standardized palliative-intent radiation therapy (RT) protocol for the treatment of canine appendicular osteosarcoma (OSA), alone or in combination with bisphosphonates (BPs), and to determine whether the addition of BPs affects survival. A secondary objective was to identify prognostic features that may influence outcome in dogs undergoing treatment. Design: Retrospective case series. Materials and Methods: Dogs with presumed or confirmed OSA of the appendicular limb treated with daily hypofractionated RT (8 Gy x 2) at the Flint Animal Cancer Center between 2010 and 2019 were evaluated retrospectively. Clinical data were abstracted from the medical records, and adjuvant therapies were noted. Outcome was assessed using medical records and electronic follow up. Results: One hundred and sixty-five dogs were included. Sixty-eight dogs received BPs as a part of their palliative-intent treatment. The median survival time from first RT treatment to death was not significantly different between groups (119 vs. 109 days for BP and non-BP groups, respectively, p = 0.758). Only age (>9 years) was found to be prognostic in this population (p = 0.031). Factors that were not found to be associated with survival time included BP drug type, timing of BP administration, tumor location, weight, breed, sex, time to treatment, concurrent administration of chemotherapy, and salvage amputation. Conclusions: This study suggests no difference in outcome for dogs treated with and without BPs in addition to hypofractionated RT. Prospective studies are needed to determine if the addition of BPs to hypofractionated RT leads to an improved quality of life in dogs undergoing palliative-intent treatment for OSA.

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats.

BACKGROUND: The safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described. HYPOTHESIS: Stereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well-tolerated treatment for localized nasal lymphoma in cats. ANIMALS: Thirty-two client owned cats referred to Colorado State University for the treatment of nasal lymphoma. METHODS: Retrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded. RESULTS: Progression free survival was 225 days (95% CI 98-514) and median survival time (MST) was 365 days (95% CI 123-531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty-four cats (75%) had signs consistent with chronic rhinitis. CONCLUSIONS: SBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam's stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy.

CD4 T cell-intrinsic STING signaling controls the differentiation and effector functions of TH1 and TH9 cells.

BACKGROUND: While stimulator of interferon genes (STING) activation in innate immune cells of the tumor microenvironment can result in CD8 T cell-dependent antitumor immunity, whether STING signaling affects CD4 T-cell responses remains elusive. METHODS: Here, we tested whether STING activation modulated the effector functions of CD4 T cells in vivo by analyzing tumor-infiltrating CD4 T cells and evaluating the contribution of the CD4 T cell-derived cytokines in the antitumor activity of the STING ligand 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) in two mouse tumor models. We performed ex vivo experiments to assess the impact of STING activation on CD4 T-cell differentiation and investigate the underlying molecular mechanisms. Finally, we tested whether STING activation enhances TH9 cell antitumor activity against mouse melanoma upon adoptive transfer. RESULTS: We found that activation of STING signaling cell-intrinsically enhances the differentiation and antitumor functions of TH1 and TH9 cells by increasing their respective production of interferon gamma (IFN-γ) and interleukin-9. IRF3 and type I interferon receptors (IFNARs) are required for the STING-driven enhancement of TH1 cell differentiation. However, STING activation favors TH9 cell differentiation independently of the IFNARs/IRF3 pathway but through mammalian target of rapamycin (mTOR) signaling, underscoring that STING activation differentially affects the fate of distinct CD4 T-cell subsets. The therapeutic effect of STING activation relies on TH1 and TH9-derived cytokines, and STING activation enhances the antitumor activity of TH9 cells upon adoptive transfer. CONCLUSION: Our results reveal the STING signaling pathway as a therapeutic target to boost CD4 T-cell effector functions and antitumor immunity.

CT characteristics and proposed scoring scheme are predictive of pathologic fracture in dogs with appendicular osteosarcoma treated with stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) is an established limb-sparing treatment for dogs with appendicular osteosarcoma (OSA) and pathologic fractures are a common sequela. The objectives of this retrospective, observational, and descriptive study were to develop and evaluate objective CT criteria for predicting pathologic fractures and assess impacts on survival time. Included dogs had confirmed or suspected appendicular OSA, available CT scans, available outcome data, and were treated with SBRT. For each study, the number of quartiles affected by lysis on the most severely affected transverse slice, longest measurable length of contiguous full cortical lysis, presence of subchondral bone lysis, and ratio of the length of the affected bone to normal bone were recorded. A scoring system was developed for assigning grades (summed score 1-4 = grade 1, 5-7 = grade 2, and 8 or greater = grade 3.) A total of 127 CT datasets were sampled (123 patients). The median summed score was 7. The grade was correlated with pathologic fracture development (23% of grade 1, 35% of grade 2, and 57% of grade 3 resulting in fracture, P = 0.028). Subchondral bone lysis was correlated with fracture (odds ratio, 2.2, P = 0.02). Percent affected bone ≥40% was associated with decreased survival (P = 0.002). Dogs with <40% of affected bone had a median survival of 256 days versus 178 days for dogs with ≥40% affected bone. Findings from the current study can be used to assist in determining prognosis and planning radiation therapy for future dogs affected by appendicular OSA.

Therapeutic Intervention Using a Smad7-Based Tat Protein to Treat Radiation-Induced Oral Mucositis.

PURPOSE: Recent studies reported therapeutic effects of Smad7 on oral mucositis in mice without compromising radiation therapy-induced cancer cell killing in neighboring oral cancer. This study aims to assess whether a Smad7-based biologic can treat oral mucositis in a clinically relevant setting by establishing an oral mucositis model in dogs and analyzing molecular targets. METHODS AND MATERIALS: We created a truncated human Smad7 protein fused with the cell-penetrating Tat tag (Tat-PYC-Smad7). We used intensity modulated radiation therapy to induce oral mucositis in dogs and applied Tat-PYC-Smad7 to the oral mucosa in dose-finding studies after intensity modulated radiation therapy. Clinical outcomes were evaluated. Molecular targets were analyzed in biopsies and serum samples. RESULTS: Tat-PYC-Smad7 treatment significantly shortened the duration of grade 3 oral mucositis based on double-blinded Veterinary Radiation Therapy Oncology Group scores and histopathology evaluations. Topically applied Tat-PYC-Smad7 primarily penetrated epithelial cells and was undetectable in serum. NanoString nCounter Canine IO Panel identified that, compared to the vehicle samples, top molecular changes in Tat-PYC-Smad7 treated samples include reductions in inflammation and cell death and increases in cell growth and DNA repair. Consistently, immunostaining shows that Tat-PYC-Smad7 reduced DNA damage and neutrophil infiltration with attenuated TGF-ß and NFκB signaling. Furthermore, IL-1ß and TNF-α were lower in Tat-PYC-Smad7 treated mucosa and serum samples compared to those in vehicle controls. CONCLUSIONS: Topical Tat-PYC-Smad7 application demonstrated therapeutic effects on oral mucositis induced by intensity modulated radiation therapy in dogs. The local effects of Tat-PYC-Smad7 targeted molecules involved in oral mucositis pathogenesis as well as reduced systemic inflammatory cytokines.

Increased incidence of gastrointestinal toxicity in canine cancer patients treated with concurrent abdominal radiation therapy and toceranib phosphate.

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.

Comparative study of the collapsed cone convolution and Monte Carlo algorithms for radiation therapy planning of canine sinonasal tumors reveals significant dosimetric differences.

Computer-based radiation therapy requires high targeting and dosimetric precision. Analytical dosimetric algorithms typically are fast and clinically viable but can have increasing errors near air-bone interfaces. These are commonly found within dogs undergoing radiation planning for sinonasal cancer. This retrospective methods comparison study is designed to compare the dosimetry of both tumor volumes and organs at risk and quantify the differences between collapsed cone convolution (CCC) and Monte Carlo (MC) algorithms. Canine sinonasal tumor plans were optimized with CCC and then recalculated by MC with identical control points and monitor units. Planning target volume (PTV)air , PTVsoft tissue , and PTVbone were created to analyze the dose discrepancy within the PTV. Thirty imaging sets of dogs were included. Monte Carlo served as the gold standard calculation for the dosimetric comparison. Collapsed cone convolution overestimated the mean dose (Dmean ) to PTV and PTVsoft tissue by 0.9% and 0.5%, respectively (both P < 0.001). Collapsed cone convolution overestimated Dmean to PTVbone by 3% (P < 0.001). Collapsed cone convolution underestimated the near-maximum dose (D2 ) to PTVair by 1.1% (P < 0.001), and underestimated conformity index and homogeneity index in PTV (both P < 0.001). Mean doses of contralateral and ipsilateral eyes were overestimated by CCC by 1.6% and 1.7%, respectively (both P < 0.001). Near-maximum doses of skin and brain were overestimated by CCC by 2.2% and 0.7%, respectively (both P < 0.001). As clinical accessibility of Monte Carlo becomes more widespread, dose constraints may need to be re-evaluated with appropriate plan evaluation and follow-up.

Outcomes of dogs with thymoma treated with intensity modulated stereotactic body radiation therapy or non-modulated hypofractionated radiation therapy.

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.

Response of Canine Soft Tissue Sarcoma to Stereotactic Body Radiotherapy.

Canine soft tissue sarcoma (STS) has served as a preclinical model for radiation, hyperthermia, experimental therapeutics, and tumor microenvironmental research for decades. Stereotactic body radiotherapy (SBRT) demonstrates promising results for the control of various tumors in human and veterinary medicine; however, there is limited clinical data for the management of STS with SBRT. In this retrospective study, we aimed to define overall efficacy and toxicity of SBRT for the treatment of macroscopic canine STS to establish this preclinical model for comparative oncology research. Fifty-two canine patients met inclusion criteria. Total radiation dose prescribed ranged from 20-50 Gy delivered in 1-5 fractions. Median progression-free survival time (PFST) was 173 days and overall survival time (OST) 228 days. Best overall response was evaluable in 46 patients, with 30.4% responding to treatment (complete response n = 3; partial response n = 11). For responders, OST significantly increased to 475 days vs. 201 days (P = 0.009). Prognostic factors identified by multivariable Cox regressions included size of tumor and metastasis at presentation. Dogs were 3× more likely to progress (P = 0.009) or 3.5× more likely to experience death (P = 0.003) at all times of follow up if they presented with metastatic disease. Similarly, every 100-cc increase in tumor volume resulted in a 5% increase in the risk of progression (P = 0.002) and death (P = 0.001) at all times of follow up. Overall, 30.8% of patients developed acute toxicities, 7.7% grade 3; 28.8% of patients developed late toxicities, 11.5% grade 3. Increased dose administered to the skin significantly affected toxicity development. SBRT serves as a viable treatment option to provide local tumor control for canine macroscopic STS, particularly those with early-stage disease and smaller tumors. The results of this study will help to define patient inclusion criteria and to set dose limits for preclinical canine STS trials involving SBRT.

Outcome and prognosis for canine appendicular osteosarcoma treated with stereotactic body radiation therapy in 123 dogs.

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.

3D-printed bolus improves dose distribution for veterinary patients treated with photon beam radiation therapy.

Commercial bolus is frequently used to increase dose at the patient's surface for superficial radiotherapy; however, uneven surfaces can create air gaps and discrepancies between prescribed and delivered dose. The purpose of this study was to determine if a customizable, 3D-printed bolus would improve dosimetry compared with a commercial bolus. For each patient, a planned bolus was generated within planning software, then created with 3D-printing. The treatment plan was recalculated with each bolus in situ. When evaluating tumor volumes at prescription, the 3D-printed bolus was closer to prescription compared to the commercial bolus. There was a significant difference in air gaps in patients receiving radiotherapy to the head (P < 0.001) but the difference was not significant for air gaps in caudal body sites (P = 0.05). Overall, the 3D-printed bolus resulted in reduced air gaps, dosimetry closer to prescription, and should be considered for superficial treatment areas of high irregularity.

Un bolus obtenu par impression 3D améliore la distribution de la dose de patients vétérinaires traités par radiation de faisceau de photons. Un bolus commercial est fréquemment utilisé pour augmenter la dose à la surface d'un patient lors de radiothérapie de surface; toutefois, des surfaces inégales peuvent créer des espaces d'air et ainsi des différences entre la dose prescrite et la dose livrée. Le but de la présente étude était de déterminer si un bolus sur mesure, obtenu par impression 3D, améliorerait la dosimétrie comparativement à un bolus commercial. Pour chaque patient, un bolus planifié fut généré à l'aide d'un logiciel de planification, puis créé avec une imprimante 3D. Le plan de traitement fut recalculé avec chaque bolus in situ. Lors de l'évaluation du volume des tumeurs à la prescription, le bolus obtenu par impression 3D était plus près de la prescription comparativement au bolus commercial. Il y avait une différence significative dans les espaces d'air chez les patients recevant la radiothérapie à la tête (P < 0,001) mais la différence n'était pas significative pour les espaces d'air sur les sites corporels en partie caudale (P = 0,05). De manière globale, le bolus obtenu par impression 3D a résulté en une diminution des espaces d'air, une dosimétrie plus près de la prescription et devrait être considéré lors du traitement de surfaces superficielles hautement irrégulières.(Traduit par Dr Serge Messier).