155 - Prognostic Value of Post-Chemoradiotherapy Molecular Residual Disease (MRD) Clearance in Limited-Stage Small Cell Lung Cancer: A Prospective Longitudinal Study
Presenter(s)
Y. Tian1, Z. Sun2, J. Yu3, G. Yang4, X. Jing5, H. Zhu5, W. Jia6, and F. Teng7; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China, 3Biobank, Cancer Research Center, Shandong Cancer Hospital, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China, 4Department of Respiratory Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 5Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 6Department of Radiation Oncology, Shandong Cancer Hospital & Institute Affiliated to Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China., Jinan, Shandong, China, 7Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
Purpose/Objective(s): Limited-stage small cell lung cancer (LS-SCLC) is characterized by high initial sensitivity to chemoradiotherapy but rapid recurrence. With the advent of consolidation immunotherapy (e.g., the ADRIATIC trial), validating biomarkers for molecular residual disease (MRD) is critical to guide personalized management. This prospective study evaluated the prognostic value of longitudinal circulating tumor DNA (ctDNA) monitoring in patients with LS-SCLC undergoing induction chemotherapy followed by concurrent chemoradiotherapy (cCRT).
Materials/Methods: Thirty-six treatment-naive LS-SCLC patients were prospectively enrolled. Plasma samples were collected at baseline (T0), post-induction chemotherapy (T1), post-cCRT (T2), and at disease progression (T3) for targeted next-generation sequencing (425-gene panel). We analyzed the correlations between ctDNA dynamics, landmark MRD status, and survival outcomes, including progression-free survival (PFS) and overall survival (OS).
Results: Although the objective response rate (ORR) was 100%, survival outcomes were heterogeneous. Neither baseline mutations (TP53/RB1) nor traditional tumor markers (NSE/ProGRP) predicted survival. Longitudinal monitoring revealed that ctDNA levels closely mirrored tumor burden dynamics. Notably, while post-induction (T1) ctDNA status correlated with PFS (P = 0.022) but not OS, post-cCRT (T2) MRD clearance emerged as the strongest independent predictor for both PFS (P = 0.032) and OS (P = 0.010). Patients achieving MRD clearance at T2 demonstrated significantly prolonged long-term survival compared with MRD-positive patients.
Conclusion: Post-cCRT MRD clearance (T2) is a critical determinant of long-term survival in LS-SCLC, outperforming traditional markers and early induction responses. Risk stratification based on T2 MRD status holds promise for guiding precise consolidation immunotherapy and radiation strategies.