Description and efficacy of a response-based "QUAD" cyclical hypofractionated palliative-intent radiation protocol in dogs with macroscopic solid tumours: 108 cases.

Palliative-intent radiation therapy can alleviate pain and clinical signs in dogs with cancer, but optimal fractionation scheme is unknown. The objective of this retrospective case series is to evaluate clinical benefit, objective response, adverse effects, and outcomes in 108 dogs with macroscopic solid tumours treated with a cyclical "QUAD" hypofractionated palliative-intent radiation therapy protocol. Median QUAD dose was 14 Gy (14-16 Gy). Median total dose was 28 Gy (14-48 Gy). Clinical benefit rate was 93%, with median onset of subjective palliation 21 days after the first QUAD, lasting a median of 134 days. Tumour volumetric objective response was assessed with CT prior to the third QUAD in 36 dogs, with stable disease in 24 dogs (67%) and partial response in 9 dogs (25%). Sinonasal and oral were the most common tumour locations in 32 and 30 dogs, respectively. Median progression-free survival was 153 days (95% CI 114-200). Median overall survival was 212 days (95% CI 152-259). Number of QUAD cycles completed, clinical benefit achieved, anti-inflammatory received, total radiation dose, time to maximum clinical benefit, and response duration were positively associated with progression-free and overall survival. Acute toxicities were observed in 15 dogs (14%) with 3 high-grade (grade 3) toxicities (3%). Low-grade (grade 1 and 2) late skin and ocular toxicities were observed in 31 dogs (29%), predominantly leukotrichia, alopecia, keratoconjunctivitis sicca, and cataracts. This report demonstrates that QUAD radiation is an alternative protocol to be considered for palliation of dogs with inoperable or advanced stage solid tumours.

Relationship between histological tumor margins and magnetic resonance imaging signal intensities in brain neoplasia of dogs.

BACKGROUND: Intracranial neoplasia is relatively common in dogs and stereotactic radiotherapy, surgical debulking, or both, are the most successful treatment approaches. A key component of treatment planning involves delineating tumor margin on magnetic resonance imaging (MRI) examinations. How MRI signal intensity alterations relate to histological tumor margins is unknown. OBJECTIVES: Directly compare histological brain sections to MRI sequence images and determine which sequence alteration best correlates with tumor margins. ANIMALS: Five dogs with glioma, 4 dogs with histiocytic sarcoma, and 3 dogs with meningioma. METHODS: Retrospective cohort study. Histological brain sections were registered to in vivo MRI scan images obtained within 7 days of necropsy. Margins of signal intensity alterations (T2-weighted, fluid-attenuating inversion recovery [FLAIR], T1-weighted and contrast enhancement) were compared directly to solid tumor and surgical margins identified on histology. Jacquard similarity metrics (JSM) and cross-sectional areas were calculated. RESULTS: In glioma cases, margins drawn around T2-weighted hyperintensity were most similar to surgical margins (JSM, 0.66 ± 0.17) when compared to other sequences. In both meningioma (JSM, 0.57 ± 0.21) and histiocytic sarcoma (JSM, 0.75 ± 0.11) margins of contrast enhancement were most similar to surgical margins. CONCLUSIONS AND CLINICAL IMPORTANCE: Signal intensities correspond to tumor margins for different tumor types and facilitate surgical and radiation therapy planning using MRI images.

The effect of cannabidiol on canine neoplastic cell proliferation and mitogen-activated protein kinase activation during autophagy and apoptosis.

Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (eg, p38, JNK, AKT and mTOR) potentially involved in the response to treatment with CBD. CBD significantly reduced canine cancer cell proliferation far better than CBDA across five canine neoplastic cell lines when treated with concentrations ranging from 2.5 to 10 µg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti-proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signalling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy. In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.

Comparison of lateral surgical margins of up to two centimeters with margins of three centimeters for achieving tumor-free histologic margins following excision of grade I or II cutaneous mast cell tumors in dogs.

OBJECTIVE: To determine whether conservative lateral surgical margins (equal to tumor diameter for tumors < 2 cm in diameter or 2 cm for larger tumors) were noninferior to wide (3-cm) lateral surgical margins for achieving tumor-free histologic margins following excision of grade I and II cutaneous mast cell tumors (MCTs) in dogs. ANIMALS: 83 grade I and II MCTs excised with a deep surgical fascial margin and requisite lateral surgical margins from 68 dogs from 2007 to 2017. Tumors representing scar revision or local recurrence were excluded. PROCEDURES: A pathology department database was searched to identify qualifying MCTs, and medical records were cross-referenced to obtain data regarding patients and tumors. Outcome (complete vs incomplete excision as histologically determined) was compared between conservative- and wide-margin groups. A noninferiority margin of ≥ 0.9 was used for the risk ratio (probability of complete excision for the conservative- vs wide-margin group), implying that noninferiority would be established if the data indicated that the true risk of complete excision with the conservative-margin approach was at worst 90% of that for the wide-margin approach. RESULTS: The proportion of excised MCTs with tumor-free histologic margins was similar between the conservative- (43/46 [93%]) and wide- (34/37 [92%]) margin groups. There were no differences in tumor diameter or location between treatment groups. The risk ratio (1.02; 95% confidence interval, 0.89 to 1.19) met the criterion for noninferiority. CONCLUSIONS AND CLINICAL RELEVANCE: The conservative-margin approach appeared to be noninferior to the wide-margin approach for achieving tumor-free histologic margins in the dogs of this study, and its use could potentially reduce the risk of postoperative complications. (J Am Vet Med Assoc 2020;256:567-572.