A Novel Nomogram for Predicting Distant Metastases After Lung Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer

Abstract

While stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) results in excellent local control, distant metastases (DM) remain the most prevalent form of failure. In this analysis, we developed and internally validated a nomogram to predict DM following SBRT for NSCLC. Materials/Methods: We queried our institutional registry of patients treated with lung SBRT over the past decade (2003e2014) and identified 729 patients with early-stage NSCLC eligible for analysis. All patients were treated with definitive intent. Initial patient and tumor variables predicting the likelihood of developing distant metastases were identified from a multivariable Cox proportional hazard model. A nomogram was developed from the initial model using 16 candidate variables and was reduced to the find the best fitting parsimonious model. The nomogram was then internally validated using a 1 000 bootstrap resampling process. Accuracy of the nomogram was measured using c-statistics. Results: The median follow-up was 15.2 months. One hundred fifty-seven patients (22%) developed DM at a median time of 10.3 (range, 0.2e68.4) months. The median time to death after development of DM was 4.5 months. Sites of DM included lung (113/157 patients), bone (36/157 patients), liver (27/157 patients), brain (25/157 patients), adrenal (8/157 patients), and other (7/157 patients). Age at start of radiation therapy (P Z 0.051), tumor size (P Z .009), PET SUV (P Z .026), and the presence of synchronous primaries (P Z .048) were all predictive of DM on multivariable analysis. Using seven patient and tumor variables (Age, BMI, Charlson Comorbidity Index, tumor size, PET SUV, medical operability, and presence of a synchronous primary NSCLC), our nomogram successfully predicted distant metastasis and has an internally validated cstatistic of 0.606 (95% CI: 0.563, 0.648). Internal validation with bootstrapping demonstrated persistent validity of the nomogram in predicting distant metastases. Conclusion: This novel internally validated nomogram can predict the risk of distant metastases in early-stage NSCLC treated with SBRT. External validation of this nomogram is warranted. This nomogram may help define subgroups for stratification in future clinical trials and identify patients who may benefit from adjuvant systemic therapies following lung SBRT.

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

“…With a median follow up of 15.2 months, they found that larger GTV volume was a predictor for worse distant relapse-free survival [18]. Other studies similarly have shown that larger tumor size is associated with the development of distant metastasis [13,14]. However, tumor size was reported to not be associated with nodal failure after SBRT in a single institutional study [19].…”

“…A small study of 81 patients identified tumor size (<2.5 vs. >2.5cm), location (central vs. peripheral), stage (IA vs. IB), and use of certain drugs (metformin, statin, ACE inhibitor) as risk factors for distant metastasis; the final model achieved a 0.80 receiver operating characteristic (ROC) area under the curve (AUC) [13]. A similar effort using a larger cohort of 729 patients identified age, tumor size, FDG avidity, and presence of synchronous primaries as potential predictors of distant metastatic disease [14]. A nomogram built from these variables and several additional factors (body mass index (BMI), Charlson Comorbidity Index, medical operability) had a c-statistic of 0.606 [14].…”

“…A similar effort using a larger cohort of 729 patients identified age, tumor size, FDG avidity, and presence of synchronous primaries as potential predictors of distant metastatic disease [14]. A nomogram built from these variables and several additional factors (body mass index (BMI), Charlson Comorbidity Index, medical operability) had a c-statistic of 0.606 [14]. Due to the limited M A N U S C R I P T A C C E P T E D available data and the clinical implications of metastatic failure for these patients, we sought to identify risk factors for metastatic recurrence after lung SBRT for early stage NSCLC.…”