3659 - Prognostic Analysis of Radiotherapy Timing in Driver Gene-Negative Advanced NSCLC with Different Metastatic Patterns
Presenter(s)
Y. Wang1,2, J. Wang3, J. Liu3, J. Yuan1, F. Wang1, B. Tian4, Y. Xu1, J. Zhang5, and D. Chen1; 1Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 3Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 4Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 5Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s):
To evaluate the impact of thoracic primary tumor radiotherapy (RT) timing on outcomes in driver mutation–negative advanced non–small cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy, stratified by metastatic burden.Materials/Methods:
We retrospectively reviewed 126 patients with driver mutation–negative advanced NSCLC who received first-line chemotherapy plus immunotherapy. Based on metastatic burden at diagnosis, patients were classified as oligometastatic (n=59) or polymetastatic (n=67). Within each cohort, thoracic RT timing was categorized as early RT (eRT), initiated within 4 cycles from systemic therapy start, or consolidative RT (ConRT), initiated after 4 cycles. Primary endpoints were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Secondary endpoints included overall adverse events (AEs) and radiation pneumonitis (RP). Survival was estimated using the Kaplan–Meier method and compared with log-rank tests; multivariable Cox regression was performed. AEs were graded per CTCAE v5.0.Results:
In the oligometastatic cohort, ConRT resulted in significantly longer median PFS than eRT (34.2 vs 15.3 months; P<0.05), whereas OS was similar (P=0.29). ORR was higher with ConRT (29.6% vs 21.9%) but not statistically significant (P=0.49). Grade =2 RP occurred in 14.80% (ConRT) vs 12.50% (eRT) (P=1.00). Multivariable analysis showed that PD-L1 expression =50% independently predicted improved PFS (P=0.02; HR=0.28; 95% CI, 0.10–0.80). In the polymetastatic cohort, ConRT also showed a longer median PFS compared with eRT (18.6 vs 9.3 months; P<0.05), with comparable OS (P=0.24). ORR favored ConRT (26.2% vs 12.0%), but the difference was not significant (P=0.167). Grade =2 RP was significantly higher with ConRT (30.95% vs 9.10%; P<0.01). BMI =24 kg/m² was an independent favorable factor for PFS (P=0.02; HR=0.51; 95% CI, 0.29–0.88), while non-targetable co-mutations predicted worse PFS (P<0.01; HR=2.92; 95% CI, 1.59–5.35). Age =65 years independently predicted worse OS (P=0.04; HR=1.93; 95% CI, 1.03–3.62). Overall AEs were manageable, with grade 1–2 hematologic and gastrointestinal toxicities, and no significant differences between groups.Conclusion:
In driver mutation–negative advanced NSCLC treated with first-line chemo-immunotherapy, ConRT was associated with longer PFS in both oligometastatic and polymetastatic disease, but no clear OS benefit. ORR was improved with ConRT but not significantly. In polymetastatic patients, ConRT was associated with a higher risk of grade =2 RP, emphasizing the need for careful patient selection and toxicity management. These findings warrant prospective validation in larger, multi-institutional cohorts.