Research update from Dr. Modiano for Shine-On Hemangiosarcoma project looking into treatment of this disease.
The hypothesis of our project was that identifying dogs at risk for the earliest signs of hemangiosarcoma, and using the drug eBAT (called BEAT in the original proposal) to target the cancer‐stem cell compartment in these dogs, would create an effective means for prophylaxis. We proposed two aims and three milestones. The aims were that (1) our test could detect hemangiosarcoma cells in the circulation prior to the onset of grossly detectable disease, and (2) that eBAT would be safe to eliminate the incipient cancer cells. The milestones were to (1) confirm the sensitivity and specificity of the test in dogs with active disease and expand its predictive value; (2) confirm the utility of the test to monitor relapse; and (3) establish the performance parameters of the test in the “early detection” setting (dogs at risk without gross disease) and the potential to prevent hemangiosarcoma by eradicating the cancer stem cells using eBAT.
We have refined and improved the detection test, so we are confident that it can achieve clinically useful metrics for diagnosis. Our current estimates for sensitivity (can we find the disease if it is present?) and specificity (is it really the disease if the test calls it as such?) are close to 90% and 95%, respectively. We have evidence that the hemangiosarcoma-associated cells change over time in dogs receiving treatment. The dogs participating in this part of the study (prediction of relapse) are still being followed up and the results through the end of 2019 will be reported in the next and final progress report. In terms of early detection, it appears that about 50% of dogs at or over the age of 10 years have some pathology that can be detected by our test. This is consistent with the “textbook” expectation of 50% of dogs over 10 probably dying from cancer.
In the case of dogs that enrolled in phase-3 (early detection) and had a known outcome of death or tumor diagnosis, our test so far indicated the presence of an abnormality in 19 of 21 (91%). While we cannot yet say that the test matched the outcome in all these dogs, it does tell us that the use of the screening test to trigger more thorough diagnostic testing would benefit a large proportion of dogs. On the other hand, 98 of 99 (99%) dogs that were called “unaffected” by the test, and where at least six months had elapsed since the testing, had not developed disease in the interim time since the test was done.
As far as establishing the efficacy of eBAT as a tool for prevention, there is a very high bar for proof. Experiments done in parallel to this project (with funding outside AKC CHF) suggest that eBAT can delay or prevent development of hemangiosarcoma or the associated terminal hemorrhage caused by hemangiosarcoma in mice harboring canine hemangiosarcoma tumors. These are not perfect models and the results are still preliminary. Nonetheless, combined with the remarkable safety of eBAT, they provide support to continue testing dogs at risk, and to eventually be able to formally test the hypothesis that fewer dogs in the population receiving eBAT prevention would develop hemangiosarcoma than in the population that did not receive it.
Regardless of the final result, we have introduced significant innovation in this trial that will be of interest to the biomedical and translational communities, and we remain excited to provide support for additional large-scale trials for early cancer detection in companion dogs.
Mid-Year 4 Research Update Dr. Modiano for treatment of hemangiosarcoma.
