1224 - Role of Consolidation Radiotherapy in Mutation-Positive vs. Mutation-Negative Patients with Stage 4 Oligopersistent NSCLC

Purpose/Objective(s): To evaluate the differential impact of comprehensive local consolidative radiotherapy (CRT-LM) versus lung-only consolidation (CRT-L) in Stage IV oligopersistent non-small cell lung cancer (NSCLC), stratified by oncogenic driver mutation status.

Materials/Methods: We analyzed subgroups from a prospective randomized trial of patients with 1–5 metastatic sites who achieved disease control after first-line systemic therapy. Patients were stratified into mutation-negative and mutation-positive (EGFR) cohorts, then randomized to CRT-L or CRT-LM. CRT-L utilized fractionated or stereotactic body radiotherapy (SBRT) regimens (e.g., 55Gy/20Fx or 40Gy/5Fx) to the primary tumor only. CRT-LM added concurrent highly conformal stereotactic ablative radiotherapy (SABR, typically 30Gy/5Fx) to all metabolically active metastatic sites. Progression patterns and progression-free survival (PFS) were compared.

Results: Eighty-seven patients were evaluable (57 mutation-negative, 30 mutation-positive). Treatment was well-tolerated, with a 100% completion rate in both arms and no severe interruptions. Distinct progression patterns emerged based on molecular status. In the mutation-negative cohort, treating only the primary tumor (CRT-L, n=29) resulted in an 89.7% progression rate (26 events). Comprehensive treatment of all sites (CRT-LM, n=28) dramatically reduced the progression rate to 14.3% (4 events), yielding a significant PFS benefit (HR 0.13; 95% CI: 0.06–0.31, p=0.003). In the mutation-positive cohort, CRT-L (n=13) still allowed a 53.8% progression rate (7 events). Conversely, comprehensive ablation (CRT-LM, n=17) completely prevented progression during the study period (0 events). While both groups benefited significantly from treating all metastatic sites, the data underscore its disproportionate importance for mutation-negative patients. Lacking the background disease control of targeted therapies, nearly 90% of mutation-negative patients experienced rapid progression when metastases were left untreated.

Conclusion: Comprehensive consolidation (CRT-LM) utilizing precise SABR is a feasible, highly effective strategy across NSCLC molecular subtypes. However, it is exceptionally critical for mutation-negative patients. In the absence of targeted systemic therapies, ablating all macroscopic metastatic sites is essential to prevent rapid dissemination and alter the disease trajectory.