Update in Veterinary Radiation Oncology: Focus on Stereotactic Radiation Therapy.

Stereotactic radiotherapy (SRT) involves the precise delivery of highly conformal, dose-intense radiation to well-demarcated tumors. Special equipment and expertise are needed, and a unique biological mechanism distinguishes SRT from other forms of external beam radiotherapy. Families find the convenient schedules and minimal acute toxicity of SRT appealing. Common indications in veterinary oncology include nasal, brain, and bone tumors. Many other solid tumors can also be treated, including spinal, oral, lung, heart-base, liver, adrenal, and prostatic malignancies. Accessibility of SRT is improving, and new data are constantly emerging to define parameters for appropriate case selection, radiation dose prescription, and long-term follow-up.

Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity.

OBJECTIVE: To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST). ANIMALS: 129 dogs. PROCEDURES: In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome. RESULTS: After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462). CLINICAL RELEVANCE: This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.

A retrospective study of 101 dogs with oral melanoma treated with a weekly or biweekly 6 Gy × 6 radiotherapy protocol.

One radiotherapy (RT) protocol used for canine oral melanoma (OM) gives 36 Gy total, in six weekly or biweekly fractions (6 Gy × 6). This retrospective study characterizes oncologic outcomes for a relatively large group of dogs treated with this protocol and determines whether radiation dose intensity (weekly vs. biweekly) affected either progression-free or overall survival (PFS and OS). Dogs were included if 6 Gy × 6 was used to treat grossly evident OM, or if RT was used postoperatively in the subclinical disease setting. Kaplan-Meier statistics and Cox regression modelling were used to determine the predictive or prognostic value of mitotic count, bony lysis, World Health Organization (WHO) stage (I, II, III, or IV), using systemic anti-cancer therapies, tumour burden at the time of RT (macroscopic vs. subclinical), radiation dose intensity (weekly vs. biweekly), and treatment planning type (manual vs. computerized). The median PFS and OS times for all dogs (n = 101) were 171 and 232 days, respectively. On univariate analysis PFS and OS were significantly longer (p = <.05) with subclinical tumour burden, WHO stages I or II, and weekly irradiation. On multivariable analysis, only tumour stage remained significant; therefore, cases were grouped by WHO stage (I/II vs. III/IV). With low WHO stage (I/II), PFS and OS were longer when irradiating subclinical disease (PFS: risk ratio = 0.449, p = .032; OS: risk ratio = 0.422, p = .022); this was not true for high WHO stage (III/IV). When accounting for other factors, radiation dose intensity had no measurable impact on survival in either staging group.

Re-irradiation of canine non-lymphomatous nasal tumours using stereotactic radiation therapy (10 Gy x 3) for both courses: Assessment of outcome and toxicity in 11 dogs.

No uniformly beneficial treatments exist for dogs with non-lymphomatous nasal tumours (NLNT) that relapse after radiotherapy (RT). Reirradiation may prolong survival and improve quality of life. In this retrospective study, we describe outcomes for 11 dogs that had CT-confirmed locoregional progression of NLNT after an initial course of stereotactic RT (SRT#1; 10 Gy × 3) and were then re-treated with the same type of protocol (SRT#2, also 10 Gy × 3). The median time between SRT #1 and SRT #2 was 243 days (95% CI: 78-385 days). Ten dogs (91%) had a clinical benefit after SRT#1; five dogs (45%) had clinical benefit after SRT#2. Adverse events after SRT#2 included nasocutaneous or oronasal fistula formation (N = 3 at 180, 270, and 468 days), seizures (N = 2 at 78 and 330 days), bacterial or fungal rhinitis (N = 2 at 240 and 385 days), and facial swelling (N = 1 at 90 days). All 11 dogs have died, due to disease progression, presumed radiotoxicity, or declining quality of life; in most cases, it was difficult to discern between these conditions. The median overall survival time (OST) from SRT#1 was 745 days (95% CI: 360-1132). The median overall survival time (OST) from SRT #2 was 448 days (95% CI: 112-626). For these dogs, survival was prolonged, but adverse events after SRT#2 were common (8/11; 73%). Therefore, before consenting to re-irradiation with this protocol, pet owners should be counselled about survivorship challenges, including risk for severe toxicities, and persistence of clinical signs.

Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy).

OBJECTIVE: To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS: 14 client-owned cats. PROCEDURES: Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS: Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE: The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

Retrospective evaluation of intranasal carcinomas in cats treated with external-beam radiotherapy: 42 cases.

BACKGROUND: Little is known regarding the comparative efficacy of various irradiation strategies used to treat intranasal carcinomas (INC) in cats. OBJECTIVES: Investigate outcomes and prognostic factors associated with survival for cats with INC. ANIMALS: Forty-two cats with INC that underwent radiotherapy (RT). METHODS: Single-arm retrospective study. Medical record review for cats with INC that underwent RT at 1 of 7 veterinary RT facilities. Irradiation protocols categorized as: definitive-intent fractionated RT (FRT), definitive-intent stereotactic RT (SRT), and palliative-intent RT (PRT). Median overall survival time (OST) and disease progression-free survival (PFS; documented by advanced transverse imaging, or recurrence of symptoms) were calculated. Associations between tumor stage, RT protocol/intent, and adjunctive treatment usage and outcome were calculated. RESULTS: Cats underwent SRT (N = 18), FRT (N = 8), and PRT (N = 16). In multivariate modeling, cats received definitive-intent treatment (DRT; FRT/SRT) had significantly longer median PFS (504 days, [95% confidence interval (CI): 428-580 days] vs PRT 198 days [95% CI: 62-334 days]; p = 0.006) and median OST [721 days (95% CI: 527-915 days) vs 284 days (95% CI: 0-570 days); p = 0.001]). Cats that underwent second DRT course at time of recurrence lived significantly longer than cats that received 1 RT course (either DRT or PRT [median OST 824 days (95% CI: 237-1410 days) vs 434 days (95% CI: 277-591 days); p = .028]). CONCLUSION: In cats with INC, DRT is associated with prolonged OST and PFS as compared to PRT. If tumor progression occurs, a second course of DRT should be considered.

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.

Treatment of feline gastrointestinal intermediate- or large-cell lymphoma with lomustine chemotherapy and 8 Gy abdominal cavity radiation therapy.

OBJECTIVES: The goal of this study was to document the outcomes and toxicity of a novel multimodality treatment protocol for feline gastrointestinal intermediate- or large-cell lymphoma (FGL) in which cats were treated at 21-day intervals. METHODS: This was a prospective, single-arm study. Twelve client-owned cats with cytologically diagnosed FGL were treated with a combination of abdominal cavity radiation therapy (RT; 8 Gy total dose administered in two 4 Gy fractions, 21 days apart), lomustine chemotherapy (approximately 40 mg/m2, administered orally at 21-day intervals for four treatments), prednisolone (5 mg PO q24h) and cobalamin (250 µg/week SC). RESULTS: Three cats were euthanized prior to the second treatment and it was difficult to discern treatment-associated toxicity from progressive disease. Four of the remaining cats developed cytopenias, resulting in 7-14-day lomustine treatment delays and/or dose reductions. Six cats had a partial response to treatment and three had stable disease based on ultrasound at day 21 (50% overall response rate). Three of these six cats completed the study and lived >240 days; one died of refractory diabetes mellitus with no clinical evidence of FGL, and the other two died as a result of FGL. The median overall survival time was 101 days (95% confidence interval [CI] 9-240). The median progression-free survival time was 77 days (95% CI 8-212). Necropsies were performed in eight cats, which revealed multifocal lymphoma throughout the gastrointestinal tract and other organs. CONCLUSIONS AND RELEVANCE: Oncological outcomes reported herein are comparable to those achieved with multiagent injectable chemotherapy (eg, CHOP). Treatment was seemingly well tolerated in most cats and was relatively cost-effective. It is therefore plausible that improved disease control may be achievable through continued optimization and intensification of the combinatorial chemoradiotherapy protocol.

Treatment outcomes and target delineation utilizing CT and MRI in 13 dogs treated with a uniform stereotactic radiation therapy protocol (16 Gy single fraction) for pituitary masses: (2014-2017).

Canine pituitary tumours are increasingly treated with stereotactic radiotherapy (SRT). Here, we report clinical outcomes in dogs treated with single-fraction SRT; we also explore technical aspects of SRT treatment planning. A single-institution retrospective study was performed, including any dog with a pituitary mass (PM) that was treated using a standardized single-fraction (16 Gy) SRT protocol between 2014 and 2017. Via medical records review, 13 cases were identified. Nine dogs neurologically improved after SRT. Four dogs experienced MRI-documented tumour volume reduction. Nine dogs experienced neurologic decline in 1.5 to 18 months after SRT and were euthanized. The median overall survival time was 357 days, with 15% alive 18 months after SRT. To better understand whether SRT target delineation is predictably altered by use of magnetic resonance imaging (MRI) in addition to computed tomography (CT), two radiation oncologists (RO) retrospectively re-evaluated all imaging studies used for SRT planning in these 13 cases. Gross tumour volume (GTV) was contoured on co-registered CT and MRIs for each case. In seven cases, CT alone was deemed inadequate for GTV contouring by at least one RO. T1 post-contrast MRI was considered the ideal image for GTV contouring in 11 cases. Contouring on MRI yielded larger GTV than CT for 11 cases. Inter-observer variability existed in each case and was greater for MRI. In summary, use of co-registered CT and MRI images is generally considered advantageous for PM delineation when using SRT. Notably, survival times reported herein are shorter than what has previously been reported for PM treated with finely fractionated full-course RT protocols.

Evaluation of variables associated with outcomes in 41 dogs with incompletely excised high-grade soft tissue sarcomas treated with definitive-intent radiation therapy with or without chemotherapy.

OBJECTIVE: To evaluate potential prognostic indicators for local recurrence, distant metastasis, and survival time in dogs with incompletely excised high-grade soft tissue sarcomas (HGSTSs), as defined by a mitotic index ≥ 9, that underwent definitive-intent radiation treatment (RT; ≥ 48 Gy total dose) with or without adjuvant chemotherapy. ANIMALS: 41 client-owned dogs with HGSTSs treated with surgical resection followed by definitive-intent RT between January 1, 2000, and December 31, 2016. PROCEDURES: Medical records were reviewed retrospectively, and data were collected. The Kaplan-Meier method was used to evaluate the overall survival time (OST) of dogs and time to progression (TTP) of disease, starting from the first day of RT. The Cox proportional hazards model was used to analyze the impact of results for several variables on OST and TTP. RESULTS: The median OST was 981 days, with 1-, 3-, and 5-year survival rates of 85%, 43%, and 18%, respectively. The median TTP was not reached; however, the mean TTP was 1,581 days. Ten of the 41 (24%) dogs developed metastasis, and 8 (20%) developed local recurrence. Sixteen of the 41 dogs received chemotherapy. The hazard of disease progression over the study period increased as the mitotic index (hazard ratio [HR], 1.115) or duration of RT (HR, 1.427) increased. The hazard of death over the study period increased as the RT duration (HR, 1.372) or surgical scar length (HR, 1.272) increased. CONCLUSIONS AND CLINICAL RELEVANCE: Although adjuvant chemotherapy was not associated with improved survival time in dogs of the present study, results indicated that improved OST and TTP could be achieved through strict adherence to the prescribed irradiation schedule and avoidance of unnecessary prolongation of the course of RT.

Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases.

Radiotherapy is often considered in the management of canine multilobular osteochondrosarcoma (MLO), but its efficacy against bulky MLO tumours is poorly described. This retrospective case series describes the clinical outcomes of pet dogs with MLO treated with a stereotactic radiation therapy (SRT) prescription of 30 Gy in three consecutive daily 10 Gy fractions. Dogs with an imaging (via computed tomography [CT] scan) and/or pathologic diagnosis of MLO were included. Patient demographics, tumour characteristics, radiation plan dosimetry, toxicity and outcome data were obtained retrospectively from the records. The median progression-free survival time (MPFST) and median overall survival time (MST) were calculated using a LOGLOG test. Eight dogs were included. None had evidence of metastasis at the time of SRT. Clinical signs associated with the MLO included a mass noted by owner, stertor, vestibular signs, exophthalmos and abnormal mentation. Of the five dogs that had CT scans performed 3 to 9 months after SRT, tumour volume decreased by 26% to 87% in four dogs and increased by 32% in one dog. Late radiation toxicity was documented in three dogs (VRTOG Grade 1 skin and/or ocular, n = 2; Grade 3 central nervous system, n = 1). Confirmed local disease progression (n = 3; two were treated with a second course of SRT) and suspected pulmonary metastasis (n = 2) occurred 90 to 315 days after SRT. The MPFST was 223 days (interquartile range [IQR]: 144.5-276.5 days). The MST was 329 days (IQR: 241.5-408 days). This protocol was well-tolerated, but the duration of response was short-lived.

Pet Dogs with Subclinical Acute Radiodermatitis Experience Widespread Somatosensory Sensitization.

Radiation-induced dermatitis (RID) is a common and painful complication of radiotherapy. When severe, radiation-associated pain (RAP) can reduce the efficacy of radiotherapy by limiting the radiation dose given, and/or necessitating breaks in treatment. Current RAP mitigation strategies are of limited efficacy. Our long-term goal is to develop a comparative oncology model, in which novel analgesic interventions for RAP can be evaluated. The aim of this study was to validate quantitative end points indicative of RAP in pet dogs with subclinical and low-grade RID. Extremity soft tissue sarcomas were treated with post-operative irradiation (54 Gy in 18 fractions). Visual toxicity scores, questionnaire-based pain instruments and objective algometry [mechanical quantitative sensory testing (mQST)], were evaluated regularly. Breed-matched control populations were also evaluated to address the effect of potential confounders. Skin biopsies from within the irradiated field were collected at baseline and after 24 Gy irradiation, for analysis of pain-related genes using the nanoString nCounter platform. Relative to control populations, mechanical thresholds decreased in irradiated test subjects as the total radiation dose increased, with the most pronounced effect at the irradiated site. This was accompanied by increased mRNA expression of GFRα3, TNFα, TRPV2 and TRPV4. In a separate set of dogs with moderate-to-severe RID, serum concentrations of artemin (the ligand for GFRα3) were elevated relative to controls (P = 0.015). Progressive reduction in mechanical thresholds, both locally and remotely, indicates widespread somatosensory sensitization during radiation treatment. mQST in pet dogs undergoing radiation treatment represents an innovative tool for preclinical evaluation of novel analgesics.

Radiotherapy isocenters verified by matching to bony landmarks of the canine and feline head differ when localized using volumetric versus planar imaging.

The "gold standard" for verification of patient positioning before linear accelerator-based stereotactic radiation therapy is kilovoltage cone-beam computed tomography (kV-CBCT), which is not uniformly available or utilized; planar imaging is sometimes used instead. The primary aim of this study was to determine if the position of the bony skull, when used as a surrogate for isocenter verification, is different when orthogonal megavoltage (MV) portal or kilovoltage (kV/kV) radiographs are used for image guidance, rather than kV-CBCT. A secondary aim was to determine the influence of intra-observer variability, body size and skull conformation on positioning, as determined using these three imaging modalities. Dogs and cats receiving radiotherapy of the head were recruited for this prospective analytical study. Planar (MV portal and kV/kV images) and volumetric (kV-CBCT) images were acquired before treatment, and manually coregistered with reference images. Differences in skull position when matched based on MV portal, kV/kV images and kV-CBCT were compared. A total of 65 subjects and 148 unique datasets were evaluated. The Wilcoxon rank-sum test was used to evaluate effects of transitioning between imaging modalities. When comparing magnitude of shifts in MV to kV-CBCT, MV to kV/kV and kV/kV to kV-CBCT, there were statistically significant differences. Results were not measurably impacted by body size, skull conformation or interobserver differences. Based on shift magnitude and direction, an isotropic setup margin of at least 1 mm should be incorporated within the planning target volume when MV or kV planar imaging is used for position verification.

Update in Veterinary Radiation Oncology: Focus on Stereotactic Radiation Therapy.

Stereotactic radiotherapy (SRT) involves the precise delivery of highly conformal, dose-intense radiation to well-demarcated tumors. Special equipment and expertise are needed, and a unique biological mechanism distinguishes SRT from other forms of external beam radiotherapy. Families find the convenient schedules and minimal acute toxicity of SRT appealing. Common indications in veterinary oncology include nasal, brain, and bone tumors. Many other solid tumors can also be treated, including spinal, oral, lung, heart-base, liver, adrenal, and prostatic malignancies. Accessibility of SRT is improving, and new data are constantly emerging to define parameters for appropriate case selection, radiation dose prescription, and long-term follow-up."

Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias.

A total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall-mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source-to-axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.

Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs.

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow-up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20-24 Gy to the central portion of the tumor. Thirty-two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment-associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross-sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330-708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.

Cytologic comparison of the percentage of mast cells in lymph node aspirate samples from clinically normal dogs versus dogs with allergic dermatologic disease and dogs with cutaneous mast cell tumors.

OBJECTIVE To compare percentages of mast cells in lymph node (LN) aspirate samples from clinically normal dogs, dogs with allergic dermatologic disease (ADD), and dogs with cutaneous mast cell tumors (MCTs). DESIGN Prospective cross-sectional study. ANIMALS 20 healthy dogs (group 1), 20 dogs with ADD (group 2), and 20 dogs with an MCT on the head or limbs (group 3). PROCEDURES LN aspirate samples were obtained from easily accessible LNs in group 1, affected skin regions in group 2, and the likely draining LN or LNs of the MCT in group 3; the percentage of mast cells was manually determined for each LN. For group 3, LNs were cytologically categorized with a modified version of a published metastasis categorization scheme. RESULTS Median (range) percentage of mast cells in aspirate samples was 0% (0% to 0.1%) for group 1, 0.05% (0% to 0.55%) for group 2, and 0.4% (0% to 77.4%) for group 3. In group 3, 16 LNs (13 dogs) were palpably normal in size; 6 of these had evidence of possible or certain metastasis. Seven LNs (7 dogs) in group 3 were palpably enlarged, and 5 of these had evidence of certain metastasis. CONCLUSIONS AND CLINICAL RELEVANCE This study provided evidence to support the use of a uniform cytologic grading system to further define nodal metastasis in dogs with MCTs as well as estimates of the percentage of mast cells in LN aspirate samples for healthy dogs and dogs with ADD. Palpably normal LNs in dogs with cutaneous MCT may contain metastasis.

The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

Dans cette étude pilote, 10 chiens avec un ostéosarcome (OSA) ont été traités par amputation et chimiothérapie subséquente avec du carboplatin (300 mg/m2 IV q3sem × 4 doses) suivi de phosphate de toceranib (2,75 mg/kg PO q48h débutant au jour 14 suivant le carboplatin). Un suivi clinique mensuel et une mesure des taux sériques du facteur de croissance de l'endothélium vasculaire (FCEV) et de la matrice de la métalloprotéinase-9 (MMP-9) ont été obtenus. Aucun chien ne fut retiré de l'étude pour cause de toxicité. Les niveaux de FCEV et MMP-9 n'ont pas changé dans le temps. Sept chiens sont décédés dues à une rechute locale et/ou des métastases osseuses et les autres sont morts d'autres causes. La durée médiane de survie libre d'OSA était de 238 j avec 34 % de survie sans progression de la condition après 1 an. La durée de survie médiane était de 253 j avec 30 % en vie après 1,5 an et 10 % en vie après 2 ans. Bien que ce traitement ait été bien toléré, les temps de survie n'ont pas excédé les résultats publiés antérieurement pour des chiens traités par amputation et chimiothérapie uniquement.(Traduit par Docteur Serge Messier).

Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model.

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID ( P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy.

External Beam Radiation Therapy of Squamous Cell Carcinoma in the Beak of an African Grey Parrot (Psittacus timneh).

Squamous cell carcinoma has been reported in a variety of bird species, most commonly psittacine and gallinaceous birds. The long-term prognosis in nongallinaceous birds is generally poor if complete surgical excision is not possible. Squamous cell carcinoma of the rhinotheca was diagnosed in a 34-year-old timneh African grey parrot (Psittacus timneh) with a 2-year history of beak abnormalities. No evidence of metastasis or local invasion were found on results of radiographs or computed tomography scan. The bird was treated with surgical debulking and palliative megavoltage radiation therapy. After 4 radiation treatments, the affected tissue was necrotic and was debrided to reveal healthy granulation tissue. The bird died approximately 7 months after diagnosis and 4 months after cessation of radiation treatment. At the time of death, a small scab lesion remained at the left oral commissure, but no visible tumor regrowth was evident. A postmortem examination was not performed, however, and tumor recurrence could not be ruled out in this bird.