3635 - Consolidative Stereotactic Ablative Radiotherapy to the Residual Primary Tumor After First-line Systemic Therapy: Impact on New Distant Metastases in Advanced Non-Small Cell Lung Cancer

Purpose/Objective(s):

Distant progression after initial response to first-line systemic therapy remains one of the dominant failure patterns in advanced non–small cell lung cancer (NSCLC). Residual primary lung tumors may serve as a source of metastatic seeding. We evaluated whether consolidative stereotactic ablative radiotherapy (SABR) to the residual primary lung lesion after first-line systemic therapy reduces the incidence of new distant metastases.

Materials/Methods:

We conducted a single-institution retrospective cohort study of patients with stage IIIb-IV NSCLC who achieved stable disease or partial response after standard first-line systemic therapy between Jan 2019 and Jul 2025. Patients with =1 residual primary lung lesion amenable to SABR and no uncontrolled extrathoracic progression were included. Consolidative SABR was delivered to the residual primary tumor. The primary endpoint was the 12-month new distant metastasis rate (NDM), defined as progression in an anatomic site not initially involved. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v5.0). Time-to-event outcomes were estimated using the Kaplan–Meier method.

Results:

A total of 251 patients were screened, and 65 patients were eligible for enrollment in this study. First-line systemic therapy included targeted therapy (n = 35), chemotherapy plus immunotherapy (n = 20), targeted therapy plus chemotherapy (n = 3), chemotherapy ± bevacizumab (n = 6), and immunotherapy alone (n = 1). Median follow-up was 23.3 months. New distant metastases after SABR occurred in 24 patients. The 12-month NDM rate was 20.2% (95% CI 10.4%–30.0%). The NDM rate at 2 years was 35.3% (95% CI 21.8%–48.8%). Median PFS from SABR was 28 months (95% CI, 20.7%–35.3%). The 1-year and 2-year OS rates were 88.4% (95% CI 79.6%–97.2%) and 80.6% (95% CI 68.8%–92.4%), respectively. Patterns of failure demonstrated a predominance of distant-only progression (80%, 24/30), with intracranial metastases accounting for 37.5% (9/24) of new distant failures. No grade =3 SABR-related toxicities were observed. Grade 2 pneumonitis occurred in 13.8% (9/65) of patients. No treatment-related deaths occurred.

Conclusion:

Consolidative SABR to the residual primary lung tumor following first-line systemic therapy was associated with a low 12-month NDM rate compared with historical controls, with minimal toxicity. These findings support the hypothesis that ablating residual primary disease may reduce metastatic seeding and improve distant disease control. Prospective randomized trials are warranted to validate the benefit of consolidative SABR in the era of modern systemic therapies.