SARS-CoV-2 mRNA Vaccination Improved Survival in NSCLC Treated With Radiotherapy

Stereotactic ablative radiotherapy (SABR) is standard for early stage NSCLC, but strategies to enhance its systemic antitumor immune effects remain limited. Preclinical data suggest that severe acute respiratory syndrome coronavirus 2 mRNA vaccines enhance innate immunity and antigen presentation, raising the possibility that vaccination could augment radiotherapy-induced immune priming. We evaluated the clinical impact of peri-SABR vaccination (defined as within 3 mo before or after SABR) in 413 real-world patients with T1 to 3N0M0 NSCLC who were treated during the pandemic era, including 144 patients who received vaccination within this window. In time-varying analyses, vaccination was associated with improved recurrence-free survival (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.49-0.98, p = 0.039) and a trend toward improved overall survival (HR = 0.66, 95% CI: 0.42-1.03, p = 0.069). In propensity score-matched time-dependent analyses, vaccination remained associated with improved recurrence-free survival (HR = 0.61, 95% CI: 0.40-0.91, p = 0.016) and overall survival (HR = 0.57, 95% CI: 0.34-0.94, p = 0.029), with directionally consistent findings observed after multivariable adjustment. These findings support further investigation into potential interactions between severe acute respiratory syndrome coronavirus 2 mRNA vaccination and SABR-induced antitumor immunity.