Abstract 3658: Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system

Abstract Background: Cancer Genome Profiling (CGP) tests are now widely available in daily practice. However, only a very small fraction of patients have the opportunity for genome-guided therapies. Somatic mutations from cancer specimens are unique to individual patients and hold utility as individual tumor markers in blood. We have developed an original circulating tumor DNA (ctDNA) monitoring system, called OTS (Off-The-Shelf)-Assay, at Iwate Medical University Hospital, Yahaba, Japan. Patients and Methods: Between April 2022 and October 2023, 79 patients who received the OTS-Assay were enrolled in the present analysis. The OTS-Assay includes three steps: (a) OTS-Scan (somatic mutation identification by either tissue or blood), (b) OTS-Select (somatic mutation selection), and (c) OTS-Monitor (periodical somatic mutation quantification as ctDNA). For the OTS-Select, we established an originally developed >90 stepwise selection algorithm. One of the determinants is the availability of appropriate digital PCR (dPCR) probes for individual patients. Here, we search the probes for individual patients from the dPCR probe library, OTS-1000ex, which consists of >1000 probes against frequently reported human somatic mutations (Quantdetect, Tokyo, Japan). Results: All 79 patients were subject to the analysis. The cancer stage of all the patients was advanced. More than 10 tumor types were enrolled, including esophagus (n=42), colorectal (n=12), breast (n=7), lung (n=4), pancreas (n=3), hematological (n=3), and others (n=8). Fifty patients received OTS-Scan, and 29 patients had received a CGP test before the OTS-Assay (i.e., OTS-Scan was not needed). Seventy-five patients received OTS-Select, meaning that four patients had somatic mutations that were designated for ctDNA monitoring. All 79 patients received at least one OTS-monitor. The number of OTS-Monitors received ranged from 1 to 11 during the 19-month period, and the average interval was 3.0 months. The average pretreatment variant allele frequency (VAF) was 4.96% and the majority of the follow-up VAF was less than 1%. More than 90% of the patients had at least one clinical validity defined by: (a) early relapse prediction, (b) treatment efficacy evaluation, or (c) no relapse corroboration. Conclusion: The OTS-Assay system provides stable longitudinal ctDNA monitoring at the range of less than 1% of VAF using the originally developed dPCR probe library. The sensitivity and affordability of the OTS-Assay system allows frequent monitoring, which leads to obtaining important clinical information in the context of advanced cancer therapy. Citation Format: Satoshi S. Nishizuka, Hayato Hiraki, Akiko Yashima-Abo, Takeshi Iwaya. Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3658.