Stereotactic Versus Standard Tumor Irradiation in Unresectable Locally Advanced Non-small Cell Lung Cancer With Durvalumab Maintenance: A Multicenter Study With Propensity Score Matching.

Abstract

Tumor control in locally advanced non-small cell lung cancer (LA-NSCLC) is associated with patient prognosis, sustaining ongoing research in dose-escalation strategies. This study evaluates the efficacy and safety of tumor stereotactic body radiation therapy (T-SBRT) compared with tumoral normofractionated chemoradiation therapy followed by immunotherapy. This retrospective multicenter study included patients with unresectable LA-NSCLC treated between July 2017 and January 2023. Eligible patients received ≥60 Gy normofractionated radiation therapy, ≥1 cycle of chemotherapy, and ≥1 cycle of durvalumab. The T-SBRT group received mediastinal normofractionated radiation therapy and ultrahypofractionated primary tumor irradiation. Propensity score matching (PSM) was performed to limit confounding effects. Among the 208 included patients, 21 (10%) received T-SBRT. Median age was 64.0 years, and most had adenocarcinoma (59.1%). There were no differences in patients' characteristics except stages and T stages (not observed in T stage after PSM). The most frequent SBRT regimen was 50 Gy in 5 fractions (28.6%). After a median follow-up of 38 months (95% CI, 26.0-57.0), T-SBRT was associated with longer progression-free survival in overall cohort (median not reached vs 22.8 months; hazard ratio [HR] = 0.46; 95% CI 0.21-0.99; P = .046), and after PSM (HR = 0.41; 95% CI, 0.18-0.92; P = .031). T-SBRT also tended to be associated with longer overall survival in both overall and PSM cohorts (HR = 0.54, 95% CI 0.22-1.33, P = .18; HR = 0.46, 95% CI, 0.18-1.18, P = .11, respectively). Acute grade 3 toxicities were comparable, without grade 4-5 events. However, given the limited number of patients, these results should be interpreted with caution and considered exploratory. T-SBRT in LA-NSCLC is significantly associated with longer progression-free survival with a trend toward prolonged overall survival, without increasing toxicity. Further studies are needed to refine optimal timing and immunologic synergy.