Objectives: Stereotactic body radiotherapy (SBRT) is an excellent treatment option for medically inoperable early stage lung cancer. Failure rates following SBRT are low, but ideal salvage treatments remain unclear. This study aims to analyze the pattern of salvage treatment following SBRT for stage I non-small cell lung cancer (NSCLC) and impact on survival.

Methods: We identified patients at a single institution undergoing SBRT for stage I NSCLC between 2005 and 2016. Patients with a prior lung cancer diagnosis, receiving a biologic effective dose <100 Gy, or receiving prior chemotherapy were excluded. Treatment received after SBRT failure was analyzed. Systemic therapy was defined as chemotherapy, immunotherapy, or targeted agents. Local therapy was defined as thoracic radiation or surgery, either alone or in combination with systemic therapy. The primary endpoint was overall survival (OS) at 2 years. Fisher’s exact test was used to analyze differences in treatment between recurrence type groups. Overall survival was estimated using the Kaplan-Meier method, and differences between groups were analyzed using the log-rank test.

Results: A total of 197 patients were included, with median age of 75 (range, 49-96) and median follow-up of 24 months (range, 2-129). A majority of the patients were female (63%), and 22% of patients were current smokers at diagnosis. Forty-eight patients were found to have failure after SBRT, either with extrapulmonary metastasis (n=20) or thoracic progression (n=28). Patients with extrapulmonary metastasis had a median time to recurrence of 270d and OS at 2 years following recurrence was 28.3% (95% CI:  5.6%- 51.0%). For patients with thoracic progression, median time to recurrence was 388d and OS at 2 years following recurrence was 59.7% (95% CI: 37.4- 82.0%). Salvage treatment following SBRT failure differed by recurrence type (p = 0.027). Compared to those with extrapulmonary metastases, those with thoracic progression were more often treated with local therapy (57.1% vs. 20.0%) and less often untreated or treated with systemic treatment alone (28.6% vs. 45.0% and 14.3% vs. 35.0%, respectively). In unadjusted analysis, overall survival following failure differed by salvage treatment type (p = 0.002). Two year OS among patients receiving local therapy was 65.4% (95% CI: 40.3- 90.5%), 45.5% (95% CI: 13.0- 78.0%) in the systemic therapy alone group, and 12.2% (95% CI: 0-34.0%) for those who received no salvage treatment following SBRT failure.

Conclusions: Patients with recurrent NSCLC following SBRT have shortened survival times despite a variety of salvage therapies. Understanding the pattern of failure and salvage treatment may inform clinical trial design to help identify patients who may benefit from adjuvant and salvage therapies to complement SBRT.