Abstract P049: A simplified, potentially point-of-care (POC), electrode method detects changes in the amount of cfDNA/ctDNA and evaluates the response of advanced cancer patients to therapy

Abstract

Abstract Rapid assessment of therapy for advanced cancer, especially immunotherapy (IO), is critical. For advanced cancers most therapies, even targeted/personalized ones fail. Even worse, IO has been reported to cause more than doubling in the cancer growth rate (defined as hyper-progressive disease or HPD) in 5-40% (typically ~20%) of patients. Early identification of HPD, or any inactive therapy, and switching to an effective therapy can be lifesaving. Though a consensus has not emerged, there are several reports that describe sensitization to chemotherapy following failed immunotherapy, this suggests that, at least in some cases, switching results in dramatic benefit. Due to inflammatory infiltrates causing “pseudoprogression” (false readings of cancer progression) early during treatment with IO, ineffective IO is often continued for 4-6 months before imaging can definitively say the IO is failing. During this time progressive, potentially fatal cancer growth, as well as medical and financial side effects can occur. The cost of this ineffective or counterproductive IO is typically $10,000 to over $20,000 a month. There are numerous reports of highly sensitive mutation based, or methylation sequence based, cfDNA signatures and methods. Unfortunately, they are inherently difficult tests which typically cost thousands of dollars and do not report the results to clinicians for 1 to 2 weeks. They have not been adopted for routine use to monitor on every visit basis and allow near real-time adjustment of therapy. Rapid detection of failure can lead to lifesaving therapy changes; detection of benefit can enhance compliance and improve clinical outcomes. Previously a research lab style solid gold electrode, requiring artful polishing and reuse, has been reported to be selectively sensitive to cancer DNA due to ctDNA’s altered pattern of methylation. Electrochemical detection of the binding of cfDNA, following a 10-minute incubation, has been published. Details of the dramatically revised and optimized binding methodology are in the methods section of this poster. Compared to previous methods an over 2-fold increase in cfDNA binding is shown. Cancer samples not distinguishable from normal with the previous method show statistically significant detection with the new method. Dramatically increased ability to separate cancer from normal DNA is shown. The new method uses inexpensive, clinically and POC suitable, disposable electrodes; it is highly sensitive to clinical samples. 5 µL of a 10 pg/ul sample provides reproducible readings. cfDNA from normal persons generates readings significantly different than from those with cancer (p < .01). Patient time courses illustrate the correlation of the electrode response with cancer burden and suggests this is a monitoring tool that should be compared to, and may have benefits over, previously approved monitoring tests for advanced cancer such as carcinoembryonic antigen (CEA). Citation Format: Floyd Taub, Matt Russo, Shannon Tunney, Suzin Wright, Chuck Henry. A simplified, potentially point-of-care (POC), electrode method detects changes in the amount of cfDNA/ctDNA and evaluates the response of advanced cancer patients to therapy. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P049.