Radiotherapy for Canine Apocrine Gland Anal Sac Adenocarcinoma: Survival Outcomes and Side Effects of a Palliative Treatment Protocol of 20 Gy in Five Consecutive Fractions.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198-569) and 628 days (95% CI 579-676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282-391 days), and 402 days (95% CI 286-517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.

Surgery and postoperative definitive radiotherapy for management of canine soft tissue sarcoma: a multi-institutional retrospective study of 272 dogs (2010-2020).

OBJECTIVE: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival. METHODS: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted. Selected variables were assessed for association with local progression and overall survival. RESULTS: 272 dogs were included. Histologic grade was reported in 249 dogs: 102 were grade 1 (40.9%), 120 were grade 2 (48.2%), and 27 were grade 3 (10.8%). Local progression was suspected or confirmed in 56 dogs. Local progression rates were similar for grade 1 (24 of 89 [26.7%]), grade 2 (23 of 111 [20.7%]), and grade 3 tumors (6 of 22 [27.3%]). Previous recurrence (P = .010) and subsequent distant metastasis (P = .014) were associated with more frequent local progression; intensity-modulated radiotherapy was associated with decreased local progression (P = .025) compared to other forms of delivery. Age (P = .049), grade (P = .009), previous recurrence (P = .009), and institution type for surgery (P = .043) were associated with overall survival. CONCLUSIONS: Outcomes for most dogs were good; however, the frequency of local progression indicates an ongoing need to critically appraise local management strategies, particularly for low-grade STS. Intensity-modulated radiotherapy was associated with lower rates of local progression and may be preferred to less precise forms of delivery. CLINICAL RELEVANCE: These data may guide clinicians when making decisions regarding dRT for management of STS.

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic.

Many successful preclinical findings fail to be replicated during translation to human studies. This leads to significant resources being spent on large clinical trials, and in some cases, promising therapeutics not being pursued due to the high costs of clinical translation. These translational failures emphasize the need for improved preclinical models of human cancer so that there is a higher probability of successful clinical translation. Companion-animal cancers offer a potential solution. These cancers are more similar to human cancer than other preclinical models, with a natural evolution over time, genetic alterations, intact immune system, and a permanent adaptation to the microenvironment. These advantages have led pioneers in veterinary radiation oncology to aid human medicine by elucidating basic principles of radiation biology. More recently, the veterinary and human radiation oncology fields have increasingly collaborated to achieve advancements in education, radiotherapy techniques, and trial networks. This review describes these advancements, including significant prior research findings and the evolution of the veterinary radiation oncology discipline. It concludes by describing how companion-animal models can help shape the future of human radiotherapy. Taken as a whole, this review suggests companion-animal cancers may become widely used for preclinical radiotherapy research.

Retrospective comparison of side effects and outcomes of three-dimensional conformal vs. intensity-modulated radiation therapy in the palliative-intent treatment (4 Gy × 5 daily fractions) of canine intranasal tumors (2010-2017).

Objective: To compare the occurrence of radiation side effects and treatment outcomes in dogs with intranasal tumors treated with a total dose of 20 Gy delivered in 5 daily 4 Gy fractions using computer-based 3D conformal (3DCRT) or intensity-modulated (IMRT) radiation therapy plans. Design: Retrospective case series. Materials and methods: Medical records for dogs with intranasal tumors treated with 4 Gy × 5 fractions between 2010 and 2017 were reviewed. Radiation side effects, time to local progression (TTLP), progression-free survival (PFS) and survival time (OS) were evaluated. Results: Thirty-six dogs (24 carcinomas, 10 sarcomas and 2 others) met the inclusion criteria. Sixteen were treated with 3DCRT and 20 with IMRT. Clinical signs improvement or resolution were reported in 84% of dogs. The median time to clinical signs improvement was 12 days (1-88 days) after the end of treatment. Eight dogs treated with 3DCRT (8/16, 50%) and 5 with IMRT (5/20, 25%) were documented acute radiation side effects. Almost all were classified as grade 1 skin, oral or ocular acute side effects. Only one dog in 3DCRT group was demonstrated grade 2 skin acute effects. The median TTLP for dogs treated with 3DCRT or IMRT was 238 days and 179 days, respectively (p = 0.967). The median PFS for 3DCRT or IMRT was 228 days and 175 days, respectively (p = 0.940). The median OS for 3DCRT or IMRT was 295 days and 312 days, respectively (p = 0.787). No significantly differences were observed in side effects, TTLP, PFS and OS between 3DCRT and IMRT groups. Conclusions: Palliative-intent conformal radiation therapy given in five daily 4 Gy fractions relieved clinical signs with minimal radiation side effects, with no statistical difference in occurrence between 3DCRT and IMRT dogs.

Single institution study of the immune landscape for canine oral melanoma based on transcriptome analysis of the primary tumor.

Introduction: Understanding a tumor's immune context is paramount in the fight against cancer. Oral melanoma in dogs serves as an excellent translational model for human immunotherapy. However, additional study is necessary to comprehend the immune landscape of dog oral melanomas, including their similarity to human melanomas in this context. Methods: This retrospective study utilizes formalin-fixed paraffin-embedded (FFPE) tissue samples to analyze RNA sequences associated with oral melanoma in dogs. Nanostring Technologies was used for conducting RNA sequencing. The focus is on understanding the differences between melanoma tumors restricted to the oral cavity (OL) and the same primary oral tumors with a history of metastasis to the lymph nodes or other organs (OM). Normal buccal mucosa samples are also included as a normal tissue reference. Results: In the OM patient group, gene signatures exhibit significant changes relative to the OL patient group, including significantly decreased expression of S100, BRAF, CEACAM1, BCL2, ANXA1, and tumor suppressor genes (TP63). Relative to the OL tumors, the OM tumors had significantly increased expression of hypoxia-related genes (VEGFA expression), cell mobility genes (MCAM), and PTGS2 (COX2). The analysis of the immune landscape in the OM group indicates a shift from a possible "hot" tumor suppressed by immune checkpoints (PDL1) to significantly heightened expression not only of those checkpoints but also the inclusion of other immune blockades such as PD1 and IDO2. In addition, the OM group had significantly reduced expression of Toll-like receptors (TLR4) and IL-18 relative to the OL group, contributing to the tumor's immune escape. Additionally, signs of immune cell exhaustion are evident in both the OM and OL groups through significantly increased expression of TIGIT relative to normal tissue. Both the OM and OL groups had significantly increased expression of the immune cell marker CD4 expression relative to normal tissue. Further, CD4 expression significantly decreased in OM relative to OL; however, this study cannot determine the specific cell types expressing CD4 in OM and OL tumors. Discussion: This preliminary study reports significant changes in gene expression for oral melanoma between canine patients with localized disease relative to those with metastatic disease. In the future, a more in-depth investigation involving immunohistochemistry analysis and single-cell RNA expression is necessary to confirm our findings.

Accuracy and Precision of a Veterinary Neuronavigation System for Radiation Oncology Positioning.

Conformal radiation treatment plans such as IMRT and other radiosurgery techniques require very precise patient positioning, typically within a millimeter of error for best results. CT cone beam, real-time navigation, and infrared position sensors are potential options for success but rarely present in veterinary radiation centers. A neuronavigation system (Brainsight Vet, Rogue Research) was tested 22 times on a skull for positioning accuracy and precision analysis. The first 6 manipulations allowed the authors to become familiar with the system but were still included in the analyses. Overall, the targeting mean error in 3D was 1.437 mm with SD 1.242 mm. This system could be used for positioning for radiation therapy or radiosurgery.