Main Session
Sep 28
SS 12 - Small Cell Lung Cancer and Thymic Malignancies

156 - Prognostic Value of Baseline Genomic Profiling and Longitudinal ctDNA-Based MRD Monitoring in Limited-Stage Small-Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

08:20am - 08:30am ET
Room 157

Presenter(s)

Chen Li, MD - Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin

S. Huo1, C. Wu1, Y. Chen1, S. Yu1, J. Zhang2, S. Wang2, Z. Yuan1, Y. Song1, and C. Li3; 1Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China, 2Nanjing Geneseeq Technology Inc., Nanjing, China, 3Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

Purpose/Objective(s): This prospective study evaluated the prognostic utility of pretreatment tissue genomic profiling and longitudinal circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) monitoring in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing concurrent chemoradiotherapy (cCRT). We specifically aimed to identify biomarkers for risk stratification to guide personalized management, particularly regarding Prophylactic Cranial Irradiation (PCI) and consolidation strategies.

Materials/Methods: Between December 2023 and August 2025, 41 patients with unresectable LS-SCLC receiving cCRT were enrolled prospectively. Baseline tumor tissue and plasma were collected prior to cCRT (TP1); plasma was subsequently collected at 1, 3, and 6 months post-cCRT (TP2–TP4) and at radiographic progression (PD). Next-generation sequencing (NGS) covering 2,365 cancer-relevant genes was performed on tissue and plasma ctDNA. ctDNA-MRD positivity was defined as the detection of baseline-matched mutations or post-treatment unique Tier I/II variants (per AMP/ASCO/CAP guidelines). The primary endpoint was progression-free survival (PFS).

Results: At a median follow-up of 8.4 months (range, 2.33-20.9 months), 17 patients (41.5%) experienced disease progression (median PFS: 572 days).

  1. Baseline Predictors & PCI Benefit: TP53 (97.1%), RB1 (79.4%), and LRP1B (32.4%) were the most frequently altered genes. In multivariate analysis, wild-type LRP1B was identified as an independent predictor of inferior PFS (HR=5.85, 95% CI 1.13-30.30, P=0.036). Notably, patients receiving PCI exhibited significantly longer PFS (HR=0.31, 95% CI 0.11-0.92, P=0.026), confirming its protective role in this cohort.
  2. Dynamic ctDNA Monitoring: Baseline ctDNA levels were not prognostic (P=0.110). However, longitudinal monitoring revealed that MRD status at 3 months post-cCRT (TP3) was a critical stratification factor. Recurrence occurred in 10.0% of MRD-negative patients versus 66.7% of MRD-positive patients (P=0.036). Consequently, TP3 MRD positivity was associated with significantly worse PFS (median: 437 days vs. Not Reached; HR=10.33, 95% CI 1.14-94.00, P=0.01).
  3. Lead Time Analysis: Among relapsed patients with longitudinal samples, 83.3% (10/12) were MRD-positive at or before radiographic progression, demonstrating the potential of ctDNA for earlier relapse identification compared to standard imaging.

Conclusion: Pretreatment LRP1B status and post-treatment MRD status at 3 months are powerful independent prognostic biomarkers in LS-SCLC treated with cCRT. Longitudinal ctDNA monitoring enables early relapse detection and precise risk stratification. Incorporating these biomarkers into clinical practice may guide personalized decision-making regarding PCI selection and intensification of systemic therapy, advancing the paradigm of precision radiation oncology. This study is registered at ChiCTR (ChiCTR2300078296).