Impact of Waiting Response Evaluation to First-Line Systemic Therapy before Considering Local Ablative Therapy in Metastatic Non-Small-Cell Lung Cancer

SIMPLE SUMMARY: Stereotactic radiotherapy (SRT) is becoming increasingly important in managing metastatic non-small-cell lung cancer (mNSCLC). However, the optimal timing of SRT in relation to systemic treatment remains unclear. Herein, we aimed to determine whether waiting response evaluation to first-line systemic therapy (FLST) before considering local SRT treatment could exclude poorer prognosis progressive tumor that may not benefit from SRT. We compared survival data for 50 patients locally treated before or within 90 days of initiating FLST (early SRT), with 49 patients treated at least 90 days after initiating FLST (late SRT). In patients receiving conventional chemotherapy, late SRT resulted in significantly better survival outcomes compared to early SRT. For patients receiving an immune checkpoint inhibitor (ICI), there was no difference between late and early SRT. These results suggest that delaying SRT treatment may be less necessary when ICI is administered in mNSCLC ABSTRACT: Stereotactic radiotherapy (SRT) is gaining increasing importance in metastatic non-small-cell lung cancer (mNSCLC) management. The optimal sequence of tumor irradiation relative to systemic treatment remains unclear. If waiting response evaluation to first-line systemic therapy (FLST) before considering local treatment may allow for the exclusion of poorer prognosis progressive tumors that may not benefit from SRT, performing irradiation near immune check point inhibitor (ICI) first administration seems to improve their synergic effect. Herein, we aimed to determine whether delaying SRT after response evaluation to FLST would result in better prognosis. We compared overall survival (OS), progression-free survival (PFS), and time to first subsequent therapy (TFST) for 50 patients locally treated before or within 90 days of initiating FLST (early SRT), with 49 patients treated at least 90 days after initiating FLST (late SRT). Patients treated with conventional chemotherapy alone exhibited significantly poorer median OS, PFS, and TFST in the early SRT arm: (in months) 16.5 [8.33-NR] vs. 58.3 [35.05-NR] (p = 0.0015); 4.69 [3.57–8.98] vs. 8.20 [6.66–12.00] (p = 0.017); and 6.26 [4.82–11.8] vs. 10.0 [7.44–21.8] (p = 0.0074), respectively. Patient receiving ICI showed no difference in OS (NR [25.2-NR] vs. 36.6 [35.1-NR], p = 0.79), PFS (7.54 [6.23-NR] vs. 4.07 [2.52-NR], p = 0.19), and TFST (13.7 [9.48-NR] vs. 10.3 [3.54-NR], p = 0.49). These results suggest that delaying SRT treatment in order to filter a rapidly growing tumor may be less necessary when ICI is administered in mNSCLC.