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

Many patients with early stage non small-cell lung cancer develop metastases after stereotactic body radiation therapy. We retrospectively analyzed multiple variables in 406 lesions to develop a predictor for meta-static failure. Gross tumor volume and prescription dose were significantly associated with metastases. A metastasis risk score tool was developed to identify patients at higher risk for metastases after lung stereo-tactic body radiation therapy who might benefit from enrollment in future trials evaluating the benefit of adjuvant or intensified treatment. Introduction/Background: 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. Materials and Methods: 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. Results: 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 (P < .001 and hazard ratio [HR], 1.02 per mL; P < .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 x GTV) - (0.00525 x 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 (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion: 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. (C) 2018 Elsevier Inc. All rights reserved.