Abstract 4558: Comparative analysis of blood- and tissue-informed MRD studies in SCLC
Authors: Haoran Tang, Wei Tan, Pu Sun, Yang Shi, Cancan Jia, Feng Xie, Yue Zhang, Qin Luo
Journal: Cancer Research (2025)

Abstract Introduction: Minimal residual disease (MRD) reflected by specific genetic alterations in ctDNA was considered to be closely related to disease status in solid tumors. MRD detection was reported to be promising to monitor therapeutic effects and identify recurrence risks. Next-generation sequencing (NGS) based MRD assays usually require tissue samples to identify tumor-specific mutations for subsequent monitoring (tissue-informed MRD). However, baseline tissue samples were not always available in clinical settings, limiting their applications. In this study, we explored using baseline blood samples to identify mutations for post-treatment ctDNA MRD detection (blood-informed MRD) as well as tissue-informed MRD in 62 limited-stage small cell lung cancer (LS-SCLC) patients receiving CRT combined with IO treatments (NCT04952597). Methods: 62 patients with LS-SCLC underwent MRD testing using both tissue-informed and blood-informed PredicineBEACON assays during CRT treatment, either alone or in combination with IO. The assays utilized enhanced whole-exome sequencing (PredicineWES+) on initial tissue and blood samples to identify somatic mutations. Personalized MRD panels were developed for each patient, incorporating up to 50 mutations identified through bioinformatics analysis from either baseline tissue or blood, along with a standard panel of 500 key tumor mutations. The study conducted ultra-deep sequencing at 100, 000X coverage using these tailored panels to detect MRD at two critical time points: cycle 1 day 1 (C1D1) and cycle 3 day 1 (C3D1). Results: In this study, 62 patients were subjected to both tissue-informed and blood-informed MRD testing. PredicineWES+ at baseline identified 13, 542 somatic mutations in tissue samples and 12, 133 in plasma samples, with medians of 181 and 155 mutations per patient, respectively. There was a notable overlap where 10, 503 mutations were recognized by both methods, resulting in a median concordance rate of 86.4% per patient, highlighting the WES assay's reliability in mutation detection across biopsy types. Upon MRD assessment at C3D1, a high concordance in MRD status was observed between the two methods: 35 patients tested MRD-positive and 26 MRD-negative in both assays. One patient displayed discordant results, being MRD-positive in the tissue-informed but negative in the blood-informed assay. Additionally, the study found a significant correlation in tumor fractions between the MRD tests at both C1D1 and C3D1 (R2=0.96, p&amp;lt;2.2e-16), as established by linear regression, underscoring their robustness in evaluating tumor dynamics. Conclusions: This study demonstrated high concordance of tumor-informed and blood-informed MRD assay in LS-SCLC patients treated with IO and CRT. These outcomes highlight the potential clinical applicability of using baseline ctDNA NGS assays for personalized MRD detection. Citation Format: Haoran Tang, Wei Tan, Pu Sun, Yang Shi, Cancan Jia, Feng Xie, Yue Zhang, Qin Luo. Comparative analysis of blood- and tissue-informed MRD studies in SCLC [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 4558.