Stereotactic radiation therapy (SRT) has emerged as a convenient definitive treatment modality in veterinary medicine, but few studies exist evaluating outcome with treatment for canine nasal tumors, and no studies report the treatment of one single tumor histotype. This retrospective, observational study evaluates toxicity, response, and survival in 17 dogs with nasal carcinomas treated with SRT. Dogs received a median of 3000 centigray in three fractions via 6-MV linear accelerator. Eighty-eight percent of patients (n = 15) demonstrated clinical benefit. Of dogs with repeated CT imaging (n = 10), 60% (n = 6) achieved a partial response and 10% (n = 1) achieved a complete response. Median progression-free survival (PFS) was 359 days. Median survival time (MST) was 563 days. Among dogs evaluable for acute toxicity, 50% (n = 10) developed low grade toxicity (grade 1, n = 4; grade 2, n = 1). No patients developed grade 3 toxicity. 16 dogs (87%) evaluable over the long term developed signs consistent with possible late toxicity. The majority of late toxicities were mild (alopecia, hyperpigmentation, and leukotrichia n = 10; ocular discharge and keratoconjunctivitis sicca n = 5). Thirty-seven percent of patients (n = 6) developed seven possible grade 3 late toxicities (blindness, n = 3; fistula, n = 1; seizures, n = 3), which were difficult to distinguish from progressive disease in most patients. Of the prognostic factors evaluated (demographics, tumor stage, dosimetric data, epistaxis, facial deformity, clinical response, image-based response, nonsteroidal anti-inflammatory drugs, and chemotherapy), only clinical response was a positive prognostic factor on MST (P < .00). No factors were found to be significantly associated with PFS.

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Feline transitional cell carcinoma (TCC) is a rare neoplasia of cats with an estimated prevalence of 0.18%. Cats with TCC share clinical signs with common pathologies like feline idiopathic cystitis or urinary tract infections. Nonspecific clinical signs include hematuria, pollakiuria, or stranguria. The literature lacks a feline-specific ultrasound description of TCC. The aim of this multicenter retrospective descriptive study was to report ultrasound findings of a collection of feline TCC and then assess if feline TCC and canine TCC have similar ultrasound appearances. It was hypothesized that the ultrasound characteristics would be similar between feline and canine TCC. Ultrasound studies were assessed for tumor shape, number of isolated mural masses, location within the bladder, presence of Doppler signal, echogenicity of urine, mineralization within the mass, extension of the mass into the proximal urethra or ureters, urethral/ureteral obstruction, pyelectasia, and sublumbar lymphadenopathy. Feline studies were compared to 20 cases of confirmed canine TCC.A total of 20 cats with histologically or cytologically confirmed diagnosis of TCC were included.Feline and canine TCC had similarities when viewed using ultrasound. Statistically significant differences were identified for location of the bladder mass (cats were more likely to be mid-body vs trigonal in dogs, P = .011) and urethral extension of the tumor was less likely in cats than dogs (P = .0436). Based on this sample of 20 cats, feline TCC was most commonly a singular, broadbased mass within the mid-body or apex of the urinary bladder. K E Y W O R D Sbladder tumor, cat, comparative oncology, hematuria, mural wall tumor 1

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Introduction: The disialyl gangliosides GD2/GD3 have been implicated in the enhancement of malignancy in a number of human and animal cancers and as a tumor antigen target for immunotherapy. In a recent abstract presented at an AACR Conference we reported on the coexpression of GD2/GD3 in four canine osteosarcoma (OSA) cell lines (1). In a prospective IACUC approved clinical trial we vaccinated dogs with a GD3-based vaccine with naturally occurring OSA receiving surgery and carboplatin chemotherapy to investigate the expression profiles of immune modulating cells overtime. Methods: Dogs will be entered into the study only if they meet the following inclusion criteria: have a confirmed diagnosis of OSA and no other life-threatening diseases. The study will accrue 40 cases; 20 will receive the vaccine plus standard of care and 20 dogs will receive only the standard of care (amputation and intent to treat with 6 doses of carboplatin). On admission blood will be collected according to the protocol for monitoring of the immune response. The dogs will then be vaccinated according to a predetermined protocol during chemotherapy and staged. The immune response profile of the vaccine group will be compared to dogs receiving standard of care alone and normal dogs. Flow cytometric platforms were developed to monitor changes in immune cells (CD5, CD21, CD4, CD8, CD14, CD11b, MHCII, and Foxp3). In addition, IHC arrays and RNA Scope will be developed for checkpoints of immunity PD1, PDL-1 and expression of intratumoral immune cells. Results: Currently twenty dogs with osteosarcoma have enrolled into the study and have received standard of care and vaccination. Complete flow cytometric immune profiles are available for nine dogs with osteosarcoma. On admission, all dogs with OSA showed elevated cell counts of Treg (FoxP3+/CD4+) cells, Monocytic (m-) and Granulocytic (g-) myeloid derived suppressor cells (MDSCs) when compared to normal dogs (all dogs had normal CBCs). All m-MDCSs and g-MDSCs and Treg cells decreased significantly after the first dose of chemotherapy. Serial sampling over weeks showed sustained inhibition even after chemotherapy was completed (18 weeks). Two OSA cases which relapsed with metastasis to the lungs showed significant increases in Treg cells at the time of restaging. Complete necropsy post-therapy in three dogs showed changes in metastatic profiles; 2/3 showed no metastatic disease to the lungs, but metastases occurred to bone and kidneys. Discussion: MDSCs series of cells and Treg cells are increased in OSA compared to normal dogs and may be a factor in maintaining a welcoming tumor microenvironment and resistance to immunotherapy. MDSCs are reported to be elevated in other cancers, but not in naturally occurring OSA. Furthermore, canine OSA cell lines show increased expression of CCL2 and COX2 (data not shown). Recruitment of MDSCs to the cancer micro-tumor environment are thought to be mediated by the chemokine CCL2 and COX2. Abrogation of these pathways with chemotherapy and possibly immunotherapy may enhance overall survival. Early necropsy data seem to support the attenuation of the metastatic profile in dogs receiving standard of care and GD3-based vaccine. Conclusions: Anticipated results from the study will be used to adjust the vaccine protocol according to the changes in immune profiles. Data is not mature enough to evaluate survival at this time. Acknowledgment: The study is funded by a grant from the American Kennel Club Health Foundation and The UF CVM. Reference: 1. Milner RJ, Chimura N, Bowles KD, Salute M. Abstract A29: Differential expression of the gangliosides GD3 and GD2 in canine and human osteosarcoma cell lines: An immunotherapy target. Cancer Immunol Res 2015 Oct 1;3(10 Supplement):A29. Citation Format: Bikash Sahay, Shana Hutchison, Matt Cascio, Amandine Lejeune, Carlos Souza, Anna Szivek, Keijiro Shiomitsu, Kayla Harding, Stacey Fox-Alvarez, Mia Livaccarri, Lindsay Powers, Rowan James Milner. Changes in immune profiles of osteosarcoma dogs receiving a GD3-based vaccine concurrently with carboplatin chemotherapy and surgery [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A07.