Abstract 5189: The potential of minimal residual disease (MRD) in guiding adjuvant therapy (AT) decisions in non-small cell lung cancer (NSCLC)
Authors: Lei Siyu , Xu Haiyan , Yang Yaning , Tian Linyan , Ma Ting , Wang Yan 
Published: March 2024

Abstract
Background: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection has become a strong prognostic stratification factor in post-operation non-small cell lung cancer (NSCLC). Here we sought to investigate the guiding potential of MRD in informing adjuvant therapy (AT) decisions.
Methods: Patients with stage IA-IIIB NSCLC who had undergone confirmed R0 resection were enrolled. Blood samples were collected prospectively one month after surgery before initiation of AT (landmark) and longitudinally every 3-6 months since surgery. Postoperative AT was conducted according to the guideline recommendations and regular radiographical examinations were recommended for relapse surveillance. MRD detection was conducted via the MinerVa platform (Genecast Biotechnology Co., Ltd) using a tumor-informed strategy based on a fixed next-generation sequencing (NGS) panel spanning 769 cancer-related genes.
Results: 168 patients were included in this study, with 11 (6.5%) experiencing confirmed relapse. Positive MRD was detected in 10.2% (16/157) of patients at landmark and was associated with a significantly higher risk of shorter disease-free survival (DFS)(HR: 26.2[6.7-102.7], P&lt;0.001), irrespective of disease stage or gene alteration. Dynamic changes in ctDNA status further stratified patients into three subgroups with different prognosis. Consistent negative MRD detected at the landmark and all longitudinal timepoints represented the group with the best prognosis, while positive MRD detected at either the landmark or one subsequent timepoint showed a worse prognosis (Neg-Pos vs. Neg-Neg, HR: 37[3.2-438], P=0.004; Pos-Neg vs. Neg-Neg, HR: 14[1.2-172], P=0.035). The group with the worst prognosis occurred with consistent positive MRD (Pos-Pos vs. Neg-Neg, HR: 50[5.3-473], P&lt;0.001). For patients with negative landmark MRD, there was no significant difference between the DFS of patients who received AT and those who didn’t(P=0.241), and the result was replicated in a highly controversial subgroup: stage I patients with high-risk factors (P=0.130). Besides, whether chemotherapy was applied before targeted therapy in the EGFR-mutant subgroup showed no influence on DFS provided that landmark MRD was negative (P=0.197). In multivariate analysis considering pathological high-risk factors, poor differentiation was identified as an independent risk factor for landmark MRD positivity (HR: 10.6[1.96-168.01], P=0.030).
Conclusions: MRD is a strong and steady prognostic factor in post-operative NSCLC. AT may be waved for stage I patients with high-risk factors given that they had negative landmark MRD, same as the adjuvant chemotherapy before targeted therapy for patients with sensitive EGFR mutation. More attention should be paid to poorly differentiated tumors, indicative of a high-risk subgroup with potential residual diseases.
Citation Format: Siyu Lei, Haiyan Xu, Yaning Yang, Linyan Tian, Ting Ma, Yan Wang. The potential of minimal residual disease (MRD) in guiding adjuvant therapy (AT) decisions in non-small cell lung cancer (NSCLC) [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 5189.