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.

A retrospective study of sinonasal tumors in 182 dogs treated with stereotactic radiotherapy (3 × 10 Gy) (2010-2015).

BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging treatment for sinonasal tumors in dogs. Reported results regarding tumor control and incidence of acute and late radiation morbidities are inconsistent. OBJECTIVES: To determine treatment efficacy and prognostic indicators of SRT in dogs with sinonasal tumors and to quantify acute and late radiation morbidities. ANIMALS: One hundred and eighty-two client-owned dogs with sinonasal tumors diagnosed cytologically, histologically, or radiographically that underwent SRT. METHODS: Single-arm retrospective study by reviewing medical records of dogs treated with SRT (10 Gy × 3) between 2010 and 2015. Kaplan-Meier analysis was used to determine overall survival (OST; from the first day of SRT to death by any cause) and disease-specific survival times (DSST; OST but censoring tumor/treatment-unrelated death). Tumors were staged using modified Adams criteria. RESULTS: Median OST and DSST of dogs treated with 1 course of SRT was 441 (95% CI: 389-493 days) and 482 (428-536 days) days, respectively with skin/oral cavity acute morbidities observed in 3% of dogs. DSST in dogs with stage 4 disease showed no statistical difference compared to other stages (P = .64). Oro-nasal (n = 2) or naso-cutaneous (n = 11) fistula development occurred in 7.1% of dogs with median time of 425 days (range: 83-1733 days). Possible chronic rhinitis after SRT was recorded in 54 of 88 dogs (61%) where information was available. CONCLUSIONS AND CLINICAL IMPORTANCE: Results are comparable to other reports of treatment of SRT. Acute morbidities were minimal. Modified Adams stage scheme appeared to be inappropriate for prognostication for dogs with sinonasal tumors treated with SRT.

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.

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.

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.

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy.

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.

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.

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.

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.

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study.

BACKGROUND: Locoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: To characterize event-free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions). ANIMALS: Fifty-one client-owned dogs treated between 2008 and 2017. METHODS: Dogs were retrospectively categorized into treatment groups: (a) first-line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first-line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment-induced toxicoses, event-free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment-related factors on survival was assessed using Cox proportional hazards modeling. RESULTS: Median EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self-limiting. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.

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).

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma.

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 cm3 (range, 2.7-452.8 cm3 ). 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.

Potential for BioXmark liquid fiducial marker to improve identification of superficial component of canine oral tumors for computer-based radiation therapy planning.

The objective of this study was to evaluate a novel liquid fiducial marker, BioXmark, to improve identification of the superficial component of oral tumors in dogs with computed tomography imaging. Liquid fiducial marker was injected in 6 patients at the visible and palpable extent of each tumor. Gross tumor volumes with and without BioXmark were compared in terms of volume and conformity using a Paddick conformity index, Dice similarity coefficient, and gross tumor volumes mismatch analysis. All patients showed an increase in gross tumor volumes defined by BioXmark compared with the conventionally identified post-contrast gross tumor volumes contours. Volumetric conformity and gross tumor volumes mismatch analysis of the superficial component of gross tumor volumes resulted in a median conformity index of 0.61 and median Dice similarity coefficient of 0.76. The superficial gross tumor volumes showed a median increase of 47% when BioXmark was used. This study demonstrated a potential utility to combining liquid fiducial markers to post-contrast computed tomography images for improved oral tumor localization and gross tumor volumes contouring for radiation therapy planning.

Potentiel du marqueur de repère liquide BioXmark à améliorer l'identification d'éléments superficiels de tumeurs orales canines pour la planification de radiothérapie assistée par ordinateur. L'objectif de la présente étude était d'évaluer un nouveau marqueur de repère liquide, BioXmark, à améliorer l'identification des éléments superficiels des tumeurs orales canines par tomodensitométrie. Le marqueur de repère liquide fut injecté à six patients à la limite visible et palpable de chaque tumeur. Les volumes bruts des tumeurs avec et sans BioXmark furent comparés en termes de volume et de conformité en utilisant l'index de conformité de Paddick, le coefficient de similarité de Dice, et une analyse de disparité des volumes bruts des tumeurs. Tous les patients montrèrent une augmentation des volumes bruts des tumeurs déterminés par BioXmark comparativement aux volumes bruts des tumeurs déterminés par la méthode conventionnelle d'identification des contours post-contrastes. La conformité volumétrique et l'analyse de disparité des volumes bruts des tumeurs du composant superficiel des volumes bruts des tumeurs a résulté en un index de conformité médian de 0,61 et un coefficient de similarité de Dice médian de 0,76. Les volumes bruts superficiels des tumeurs montraient une augmentation médiane de 47 % lorsque le BioXmark était utilisé. La présente étude a démontré une utilité potentielle à combiner des marqueurs de repère liquides aux images de tomodensitométrie post-contraste pour améliorer la localisation de tumeurs orales et la détermination des volumes bruts des tumeurs pour la planification de la radiothérapie.(Traduit par Dr Serge Messier).

Treatment of leiomyosarcoma in a tiger (Panthera tigris) with stereotactic radiotherapy.

A 10-year-old male captive tiger (Panthera tigris) developed right-sided facial asymmetry and enlargement. Computed tomography revealed a destructive mass of the right maxillary bone with right nasal cavity involvement. Histopathology indicated a spindle cell sarcoma. A single fraction of 22 Gy using stereotactic radiotherapy was prescribed. After treatment, the facial conformation returned to normal and the tiger resumed normal behavior. Diagnostics 4 months later indicated severe metastatic disease. Humane euthanasia and necropsy were performed. This is the first case utilizing stereotactic radiotherapy for the treatment of cancer in a tiger.

Stereotactic radiation therapy for the treatment of functional pituitary adenomas associated with feline acromegaly.

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.

Translational research in radiation-induced DNA damage signaling and repair.

Radiotherapy is an effective tool in the fight against cancer. It is non-invasive and painless, and with advanced tumor imaging and beam control systems, radiation can be delivered to patients safely, generally with minor or no adverse side effects, accounting for its increasing use against a broad range of tumors. Tumors and normal cells respond to radiation-induced DNA damage by activating a complex network of DNA damage signaling and repair pathways that determine cell fate including survival, death, and genome stability. DNA damage response (DDR) proteins represent excellent targets to augment radiotherapy, and many agents that inhibit key response proteins are being combined with radiation and genotoxic chemotherapy in clinical trials. This review focuses on how insights into molecular mechanisms of DDR pathways are translated to small animal preclinical studies, to clinical studies of naturally occurring tumors in companion animals, and finally to human clinical trials. Companion animal studies, under the umbrella of comparative oncology, have played key roles in the development of clinical radiotherapy throughout its >100-year history. There is growing appreciation that rapid translation of basic knowledge of DNA damage and repair systems to improved radiotherapy practice requires a comprehensive approach that embraces the full spectrum of cancer research, with companion animal clinical trials representing a critical bridge between small animal preclinical studies, and human clinical trials.

RETROSPECTIVE EVALUATION OF INTERFRACTION URETERAL MOVEMENT IN DOGS UNDERGOING RADIATION THERAPY TO ELUCIDATE APPROPRIATE SETUP MARGINS.

Radiation-induced ureteral damage can result in serious complications (i.e., hydronephrosis). Also, ureters can be included in planning target volume (PTV) such as ureteral invasion of urinary bladder carcinoma. Therefore, knowing the interfractional movement of the ureters is critical for creation of appropriate planning organs at risk (pOAR) and PTV. This retrospective and descriptive study of 17 dogs with genitourinary carcinomas that underwent intensity-modulated, image-guided radiation therapy (IM-IGRT) was conducted to describe the movement and calculate suggested pOAR/PTV expansions at three locations (at the levels of third lumbar vertebra, immediately cranial to vesicoureteral junction [VUJ], and midway between those two) and from two perspectives: during a course of (1) IM-IGRT, where position verification is performed using soft tissue registration when the dogs underwent clinical IM-IGRT; (2) radiation therapy whereby position verification is performed using planar radiography with a corresponding bony registration. This registration was performed by fusing the radiation planning computed tomography (CT) and cone-beam CTs using bony landmarks. With soft tissue registration, findings supported the use of larger pOAR expansion (0.7-1.8 cm) for the mid region of the ureters compared to the areas near VUJ (0.7-1.1 cm). With bony registration, findings supported the use of larger pOAR/PTV expansions (1.6-1.7 cm) for dorsal direction bilaterally at areas near VUJ compared to those with soft tissue registration (0.9-1.0 cm). The results of this study should help radiation oncologists use appropriate ureter expansions for specific patient orientations and positioning verification methods.

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning.