Adding local gyro-knife radiotherapy to EGFR-TKI improves outcomes in EGFR-mutant NSCLC

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC), yet acquired resistance, particularly local progression, remains a major clinical challenge. The additive role of local stereotactic radiotherapy (e.g., Gyro-Knife-based SBRT) is not well defined.

In this retrospective cohort study, 82 patients with EGFR-mutant (exon 19 deletion or L858R) stage IIIB-IV NSCLC were stratified into either TKI monotherapy (control, n = 41) or TKI plus Gyro-Knife SBRT (observation, n = 41) according to actual clinical treatment received. Baseline characteristics, radiotherapy target selection, multivariable Cox modeling, and exploratory subgroup analyses were further clarified in the revised manuscript.

The observation group showed significantly higher ORR (65.85% vs. 41.46%, P = 0.028) and DCR (92.68% vs. 73.17%, P = 0.020), along with longer median PFS (12.5 vs. 8.2 months, P = 0.005) and OS (22.3 vs. 16.5 months, P = 0.002) compared with controls. Adverse event rates were similar (80.49% vs. 65.85%, P = 0.467), mostly grade 1-2. Subgroup analyses were exploratory and were not adjusted for multiplicity.

In real-world clinical practice, adding local Gyro-Knife SBRT to EGFR-TKI significantly improves tumor response and survival in EGFR-mutant advanced NSCLC with a favorable safety profile. Subgroup analysis suggested potential benefit in both mutation subtypes, with ORR improvement reaching statistical significance only in the Ex19del subgroup; this exploratory finding requires further confirmation.