Abstract 1957: MORIOKA study: Tumor-informed frequent ctDNA monitoring for quantitative tumor burden assessment using digital PCR across 23 cancer types during treatment

Abstract Background: The ultimate goal of post-treatment surveillance in advanced cancer is the quantification of tumor burden, represented by somatic mutations identified in the treatment-targeted tumor. However, as most circulating tumor DNA (ctDNA) variant allele frequencies (VAFs) during treatment are below 1%, it has been challenging to measure ctDNA without mutation-specific probes for target sequences. To address this, we developed a digital PCR (dPCR) primer/probe library, OTS-Probes, comprising over 1, 000 probes targeting human cancer-related mutations. This study investigates the clinical validity of frequent ctDNA monitoring across 23 types of advanced cancers. Patients and Methods: From May 2019 to May 2023, 314 patients were enrolled in the MORIOKA study, representing 23 tumor types, including lung (n=57), colorectal (53), esophagus (26), uterus (25), liver (22), stomach (17), ovary (13), brain (12), bone and soft tissue (10), prostate (10), bile duct (10), urothelium (9), renal (8), breast (7), head and neck (7), pancreas (6), bladder (5), malignant melanoma (5), cervix (3), pediatric (3), gallbladder (2), multiple myeloma (2), and unknown primary (2). Tumor-specific somatic mutations were identified and then selected for ctDNA monitoring. Blood samples were collected approximately every three months until patients were censored or observed for up to 730 days. ctDNA VAFs were quantified using dPCR with the OTS-Probes, and ctDNA dynamics were analyzed in conjunction with clinical and imaging data. Results: As of November 20, 2024, analyzable patients had received at least one treatment regimen across 585 treatment opportunities. A total of 1, 568 imaging studies were conducted, averaging 5.6 per patient. Panel sequencing identified somatic mutations for ctDNA monitoring in 89.7% of tumors. During treatment, approximately 90% of ctDNA VAFs from 2, 474 time points were below 1%. Among ctDNA-analyzable cases, the median pre-treatment ctDNA VAF was 0.12%, with ctDNA undetectable in 27% of cases. Using OTS-Probes, nearly 80% of somatic mutations were promptly monitored via dPCR without the need for additional validation. Changes in ctDNA VAFs before and after treatment correlated with imaging results: VAFs increased in progressive disease (PD), decreased in partial response (PR), and decreased in many cases of stable disease (SD). Further analyses of ctDNA monitoring by tumor type, treatment regimen, and metastasis pattern are ongoing. Conclusion: Tumor-informed frequent ctDNA monitoring enabled timely quantitative tumor burden estimation across a broad range of cancer types. ctDNA dynamics were particularly useful in clarifying ambiguous imaging findings, such as decreased ctDNA levels in SD. The timely assessment of ctDNA demonstrated robust clinical validity, supporting imaging diagnoses and treatment decisions. Citation Format: Satoshi S. Nishizuka, Hayato Hiraki, Akiko Yashima-Abo, Takeshi Iwaya. MORIOKA study: Tumor-informed frequent ctDNA monitoring for quantitative tumor burden assessment using digital PCR across 23 cancer types during treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1957.