ACVR and ECVDI consensus statement: Reporting elements for toxicity criteria of the veterinary radiation therapy oncology group v2.0.

The toxicity criteria of the veterinary radiation therapy oncology group (VRTOG) version 2 guidelines are a substantial update to reflect significant advances in radiation oncology over the last three decades. Radiation therapy techniques provide precise and spatially accurate radiation delivery, which facilitates treating tumors in more anatomic locations and incorporating hypofractionated protocols. The purpose of this update is to aid radiation oncology teams in capturing and grading clinically relevant data that impacts the decision-making process in everyday practice and the assessment of clinical trials involving radiation therapy. A dedicated committee initially updated the criteria to include more anatomical sites and grades to characterize a broad spectrum of possible radiation-induced acute and late tissue changes. Through the revision process, which solicited and incorporated feedback from all radiation oncologists within the American College of Veterinary Radiology (ACVR) and specialists outside the ACVR, the authors endeavored to create a grading structure reflective of clinical decision-making in daily radiation oncology. The updated VRTOG v2 toxicity criteria guideline complements the updated Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) guidelines. Because radiation oncology continues to progress rapidly, the VRTOG toxicity criteria should be regularly updated as adverse event data that will be collected following this update further informs the practice of radiation oncology.

Safety and feasibility of an in situ vaccination and immunomodulatory targeted radionuclide combination immuno-radiotherapy approach in a comparative (companion dog) setting.

RATIONALE: Murine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor in situ vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer. METHODS: The three component of the combination immuno-radiotherapy approach were employed either separately or in combination in companion dogs with advanced stage cancer. In situ vaccination was achieved through the administration of hypofractionated external beam radiotherapy and intratumoral hu14.18-IL2 fusion immunocytokine injections to the index tumor. In situ vaccination was subsequently combined with targeted radionuclide therapy using a theranostic pairing of IV 86Y-NM600 (for PET imaging and subject-specific dosimetry) and IV 90Y-NM600 (therapeutic radionuclide) prescribed to deliver an immunomodulatory 2 Gy dose to all metastatic sites in companion dogs with metastatic melanoma or osteosarcoma. In a subset of dogs, immunologic parameters preliminarily assessed. RESULTS: The components of the immuno-radiotherapy combination were well tolerated either alone or in combination, resulting in only transient low grade (1 or 2) adverse events with no dose-limiting events observed. In subject-specific dosimetry analyses, we observed 86Y-NM600 tumor:bone marrow absorbed-dose differential uptakes ≥2 in 4 of 5 dogs receiving the combination, which allowed subsequent safe delivery of at least 2 Gy 90Y-NM600 TRT to tumors. NanoString gene expression profiling and immunohistochemistry from pre- and post-treatment biopsy specimens provide evidence of tumor microenvironment immunomodulation by 90Y-NM600 TRT. CONCLUSIONS: The combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing.

A survey of stereotactic radiation therapy in veterinary medicine.

Radiotherapy plays an important role in curative and palliative cancer treatment. As a novel radiation delivery technique, stereotactic radiotherapy utilizes three-dimensional-conformal treatment planning, high-precision beam delivery technology, and patient specific position verification to target tumors, often in one to five high-dose fractions. Currently, there is no consensus about best stereotactic radiotherapy practices in veterinary radiotherapy. The objective of this study was to document the breadth of perspectives, techniques, and applications of stereotactic radiotherapy in veterinary medicine. We conducted an online survey of American College of Veterinary Radiology members specializing in radiation oncology to assess how, when, and why stereotactic radiotherapy is being used. Both stereotactic radiotherapy users and nonusers completed the survey. The overall response and survey completion rates were 54% (67/123) and 87% (58/67), respectively. Overall, 55% of respondents reported providing stereotactic radiotherapy at their facility, with a median of 4.5 canine cases and one feline case per month. Delivery methods included C-arm linear accelerator with multi-leaf collimator, helical tomotherapy, and CyberKnife. Nonpituitary intracranial tumors, pituitary tumors, and sinonasal tumors were the most common cancers treated using stereotactic radiotherapy in both species. The most common fractionation scheme was three fractions of 10 Gy/fraction. The results of this survey suggest common availability of stereotactic radiotherapy in veterinary radiation facilities. These results provide valuable information regarding current stereotactic radiotherapy practices in veterinary medicine, and may provide an initial step toward standardizing methods and establishing consensus guidelines.

SINGLE INSTITUTION VARIABILITY IN INTENSITY MODULATED RADIATION TARGET DELINEATION FOR CANINE NASAL NEOPLASIA.

Contouring variability is a significant barrier to the accurate delivery and reporting of radiation therapy. The aim of this descriptive study was to determine the variation in contouring radiation targets and organs at risk by participants within our institution. Further, we also aimed to determine if all individuals contoured the same normal tissues. Two canine nasal tumor datasets were selected and contoured by two ACVR-certified radiation oncologists and two radiation oncology residents from the same institution. Eight structures were consistently contoured including the right and left eye, the right and left lens, brain, the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Spinal cord, hard and soft palate, and bulla were contoured on 50% of datasets. Variation in contouring occurred in both targets and normal tissues at risk and was particularly significant for the GTV, CTV, and PTV. The mean metric score and dice similarity coefficient were below the threshold criteria in 37.5-50% and 12.5-50% of structures, respectively, quantitatively indicating contouring variation. This study refutes our hypothesis that minimal variation in target and normal tissue delineation occurs. The variation in contouring may contribute to different tumor response and toxicity for any given patient. Our results also highlight the difficulty associated with replication of published radiation protocols or treatments, as even with replete contouring description the outcome of treatment is still fundamentally influenced by the individual contouring the patient.

A survey of Southeastern United States veterinarians' preferences for managing cats with diabetes mellitus.

This study evaluated primary practitioners' perceptions of managing feline diabetics. Surveys distributed during local continuing education events achieved a response rate of 46% (90/195). A mean of 74% feline diabetics required chronic insulin; 26% were transient diabetics. Choice of insulin was most influenced by duration of action: human recombinant protamine zinc insulin was ranked first (42%) and glargine second (27%). Dietary management was always/usually recommended by 97% respondents, with prescription or proprietary low-carbohydrate, high-protein diets recommended in 93% responses. More recent graduates (P=0.0419), those who worked in larger practices (P=0.0315), and those who saw more transient diabetics (P=0.0288) were more likely to recommend dietary change. In-house blood glucose curves (BGCs) were the most popular method of assessing glycemic control, while at-home BGCs were least popular, although their use correlated positively with annual diabetic caseload (r=0.43, P=0.0239). Owners mishandling insulin was cited as the most common cause of poor glycemic control, while clinical signs of acromegaly were rarely recognized.

Proof of principle of ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT-treated and 2D-treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D-RT.

Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003).

OBJECTIVE: To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. DESIGN: Retrospective case series. ANIMALS: 139 dogs with histologically confirmed nasal carcinomas. PROCEDURES: Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. RESULTS: Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.

Does L-asparaginase influence efficacy or toxicity when added to a standard CHOP protocol for dogs with lymphoma?

The purpose of this study was to evaluate response rates, 1st remission duration (FRD), and toxicity in dogs with previously untreated lymphoma receiving an identical CHOP-based combination chemotherapy protocol with or without L-asparaginase (LASP). One hundred fifteen dogs with lymphoma were scheduled to receive an identical CHOP-based chemotherapy protocol that included L-ASP. However, because of manufacturer-imposed random rationing, 31 dogs did not receive L-ASP as scheduled. The 2 treatment groups were statistically similar with respect to signalment and presence of historical negative prognostic factors. No difference was observed in the median FRD whether dogs did or did not receive L-ASP (206 versus 217 days, respectively; P = .67). No difference was observed in the median overall survival times between dogs receiving or not receiving L-ASP (310 versus 308 days, respectively; P = .84). No statistical difference was observed with respect to overall response rate between dogs that did or did not receive L-ASP (89.3% versus 87.1%, respectively; P = .75). Complete response rates between the groups also were no different (83.3% and 77.4% for L-ASP and non-L-ASP groups, respectively; P = .59). Prevalence of toxicity (neutropenia, diarrhea, or vomiting) and treatment delays (P = .80) also were similar between groups. The results of this study suggest that exclusion of L-ASP in this multidrug protocol does not significantly impact outcome. Therefore, it may be more appropriate to reserve the use of L-ASP for treating relapse in dogs with lymphoma that have failed induction therapy.

Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature.

Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses associated with internal malignancy. Their recognition can facilitate detection and timely treatment of underlying cancer. More than 30 such disorders have been identified in the human scientific literature, whereas only a few are described in veterinary medicine. This may reflect a lower incidence in animals than in people or may be the result of failure to recognize an association between certain skin lesions and neoplasia. Establishing a relationship between a cutaneous disorder and neoplasia can be difficult unless the skin lesions are rare and almost always associated with a particular tumour type, as is the case for most recognized veterinary paraneoplastic dermatoses. Among these are feline paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis, nodular dermatofibrosis, feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both people and animals.