Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy

Abstract

<h3>Introduction/Background</h3><p>Many patients with early stage non–small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool.</p><h3>Materials and Methods</h3><p>We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built.</p><h3>Results</h3><p>A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (<em>P</em> < .001 and hazard ratio [HR], 1.02 per mL; <em>P</em> < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) − (0.00525 × dose [BED₁₀]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (<em>P</em> < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively.</p><h3>Conclusion</h3><p>GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.</p>