High intensity focused ultrasound for the treatment of solid tumors: a pilot study in canine cancer patients.

PURPOSE: To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model. METHODS: Dogs diagnosed with subcutaneous solid tumors were recruited, staged and pretreatment biopsies were obtained. A single HIFU treatment was delivered to result in partial tumor ablation using a commercially available HIFU unit. Tumors were resected 3-6 days post HIFU and samples obtained for histopathology and immunohistochemistry. Total RNA was isolated from paired pre and post treated FFPE tumor samples, and quantitative gene expression analysis was performed using the nCounter Canine IO Panel. RESULTS: A total of 20 dogs diagnosed with solid tumors were recruited and treated in the study. Tumors treated included Soft Tissue Sarcoma (n = 15), Mast Cell Tumor (n = 3), Osteosarcoma (n = 1), and Thyroid Carcinoma (n = 1). HIFU was well tolerated with only 1 dog experiencing a clinically significant adverse event. Pathology confirmed the presence of complete tissue ablation at the HIFU targeted site and immunohistochemistry indicated immune cell infiltration at the treated/untreated tumor border. Quantitative gene expression analysis indicated that 28 genes associated with T-cell activation were differentially expressed post-HIFU. CONCLUSIONS: HIFU appears to be safe and feasible for the treatment of subcutaneous canine solid tumors, resulting in ablation of the targeted tissue. HIFU induced immunostimulatory changes, highlighting the canine cancer patient as an attractive model for studying the effects of focal ablation therapies on the tumor microenvironment.

International Guidelines for Veterinary Tumor Pathology: A Call to Action.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as "living documents" on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Diffusion weighted magnetic resonance imaging is a feasible method for characterizing regional lymph nodes in canine patients with head and neck disease.

In dogs diagnosed with solid tumors, regional lymph node involvement or evidence of distant metastasis can predict worse prognoses and significantly decreased survival. Lymph node size alone has been shown to be insufficient as a predictor for the accurate clinical staging of some canine neoplasia. However, certain regional lymph nodes (including those of the oral cavity) are difficult to access for routine tissue sampling. Diffusion weighted magnetic resonance imaging (MRI) has demonstrated the ability to differentiate metastatic from inflammatory/benign lymph nodes in clinical studies with human cancer patients through the calculation of quantitative values of diffusion termed apparent diffusion coefficients (ADC). The objective of this prospective, exploratory study was to evaluate diffusion-weighted MRI and ADC as potential methods for detecting metastatic lymph nodes in dogs with naturally occurring disease. We hypothesized that diffusion-weighted MRI would identify significantly different ADC values between benign and metastatic lymph nodes in a group of canine patients with head or neck disease. Our study population consisted of eight client-owned canine patients, with a total of 20 lymph nodes evaluated (six metastatic, 14 benign). Our results demonstrated that two of four observers identified a significant difference between the mean ADC values of the benign and metastatic lymph nodes. When data from all four observers were pooled, the difference between the mean apparent diffusion coefficients values of the benign and metastatic lymph nodes did not reach significance (P-value = 0.0566). Findings indicated that diffusion-weighted MRI is a feasible method for further characterizing enlarged lymph nodes in dogs with head and neck disease, however measured ADC values did not differ for benign vs. metastatic lymph nodes in this small sample of dogs.