Table 2.

Consideration for canine melanoma surrogate-clinical trial development strategy¹.

Elements of strategy	Fundamental Action/Procedure	Constructive Consideration
Clinical documentation
• Patient data	Presentation/history, duration, previous work up, management	Breed and other background information useful to generate data on incidence
• Gross lesion documentation	Extent of disease. Description of specific anatomic location (not just indication of oral cavity); dimensions in mm, two axes; ulceration, evidence of dissemination.	Photograph lesion with a ruler if possible
• Biopsy	Inclusion for diagnostic intent/therapeutic intent (excisional, incisional); preservation for correlative molecular analysis.	Consideration of lateral extent as well as vertical depth of invasion; Attention paid to quality of sampling, preservation, QA, and utilization
• Pathology review	Development of features of malignancy for initial assessment for trial enrollments: Differentiation, proliferation, growth pattern, invasion, and dissemination, etc. Continue refining prognostic summation; Inclusion of IHC panel if needed for diagnosis	Incorporate Table 3 (Smedley, et al., 2011b); Capture classical features outlined – Adapt how used initially vs. what becomes useful from adjunct molecular data and outcomes
Clinical staging/prognosis and monitoring
• Imaging for dissemination	Ultrasound of lymph nodes to detect metastasis (includes submandibular)	+/− consideration of removal for staging; alternative consideration ultrasound-guided fine needle aspirate cytology for staging
• CT (MRI) imaging evaluation	Lung particularly; lymph node; abdomen	Consideration of monitoring for brain involvement; inclusion of cranial imaging
• Biopsy	Monitoring response to therapy, as appropriate	Lymph nodes or other palpable disease is recommended
• Endpoint assessment	Necropsy examination, with collection of tissue for research, and documentation of extent of disease / host response.
Quality of life measures	Assessments of fatigue, cardiac function, mucositis, altered mentation, serial assessments of metabolic and hemotologic toxicity, threshold of toxicity vs. response.	Harmonized approach for multicenter trials; similar to (Paoloni and Vail, 2013)
Client education	Informed consent; Necropsy education; Should include education on how the initiative intended to benefit both dogs and humans relies upon evidence obtained from patient specimens;	Necropsy education; emphasis on historical shortcomings impediment to progress. Education design beyond pro forma consent for necropsy
Follow up	Directly with owner/clients and indirectly with primary care clinician
Genomics	Global discovery genomics, proteomics and informatic methods: develop and apply. Database and clinical monitoring integration.

¹Strategic approach for trial design represents an initial outline to be developed further with medical and veterinary oncologists, pathologists, and basic and clinical melanoma research investigators for use in developing multidisciplinary trials for piloting therapeutics for human melanoma. Research outcomes are anticipated to produce parallel benefits for canine melanoma patients.