Abstract 4592: Early detection for strategic prevention of a terminal canine cancer: A model to reduce the impact of cancer in our society
Authors: Modiano Jaime F. , DePauw Taylor A. , Khammanivong Ali , Schulte Ashley J. , Winter Amber L. , Kim Jong , Stuebner Kathleen , Fahrenkrug Andrea , Vallera Daniel A. , Borgatti Antonella , Dickerson Erin B. , Henson Michael S. 
Published: September 2020

Abstract
Cancer mortality has surpassed all other causes of human death in parts of the developed world. Domestic dogs and cats are the only other species where cancer has an equivalent impact in overall mortality. Rapid gains in longevity over the past two centuries are sufficient to explain the increased incidence of cancer in all three species. Not only does longevity increase the probability of exposures to environmental mutagens, but it also allows for introduction of mutations in each somatic cell replication. In this context, an increase in the incidence of cancer becomes almost inevitable because the evolutionary, cancer protective adaptations of humans, dogs, and cats are insufficient to provide protection over the 2 to 6-fold extension in lifespan achieved by these species. We believe this problem is addressable by developing tests to detect malignancies at their earliest stages and pairing these tests with strategic interventions to eliminate tumors before they form. To test this premise, we have developed a blood test to detect the presence of hemangiosarcoma in dogs, a rapidly fatal malignancy. The shorter lifespan of dogs, compared to humans, and the similar shorter latency of disease provide an ideal opportunity to assess the feasibility of our approach. The test uses flow cytometry for detection of rare, non-leukocyte nucleated cells in blood, combining 42 parameters for analysis in a machine learning environment. Samples from 126 dogs with a confirmed diagnosis of hemangiosarcoma (n=28); other cancers (n=29); benign vascular pathology of the spleen (n=27); or apparently healthy and under 4 years of age (n=41) were used for training and 10-fold cross validation. The expected sensitivity and specificity for the diagnosis of hemangiosarcoma in this training set were approximately 90% and 95%, respectively. We then used our trained models to assign a risk category to apparently healthy dogs, 6 years of age or older, from three breeds with a predisposition for hemangiosarcoma (up to 20% lifetime risk): samples from 105 golden retrievers, 52 boxers and 52 Portuguese Water Dogs (N=209) were included in the study. Our results suggest that the probability of developing hemangiosarcoma or one of the other included pathological conditions within 6-18 months of testing was less than 2% in dogs with a negative result (low risk), but &gt;90% in dogs with a positive result (high risk). We will follow the dogs in this study for the duration of their lifetime to assess the predictive value of the blood test over time. Dogs at high risk of hemangiosarcoma are eligible to receive eBAT, a drug capable of eliminating the cells that maintain and propagate the tumor, while making the environment inhospitable for tumor growth. This will provide means to explore the safety and efficacy of eBAT in the setting of prevention. This study serves as proof of concept for a new paradigm of early detection and strategic prevention to reduce the societal impact of canine and human cancers.
Citation Format: Jaime F. Modiano, Taylor A. DePauw, Ali Khammanivong, Ashley J. Schulte, Amber L. Winter, Jong Kim, Kathleen Stuebner, Andrea Fahrenkrug, Daniel A. Vallera, Antonella Borgatti, Erin B. Dickerson, Michael S. Henson. Early detection for strategic prevention of a terminal canine cancer: A model to reduce the impact of cancer in our society [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4592.