Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I-IIA Non–small Cell Lung Cancer: A Retrospective Analysis

Abstract

It is well known that some of the most important predictive factors of outcomes in the treatment of lung cancer include tumor related factors, such as size and anatomic structures involved, and tumor staging (extent of tumor). As we continue to utilize stereotactic body radiotherapy as the sole-treatment modality for early stage lung cancer we have shown great local control rates of about 90% at 3 years, with distant failure rates of 22%. The predominant pattern of failure is out-of-field, isolated distant recurrences. With such high rates of local tumor control the next obstacle we face is distant control. In this study we aimed to see if we could identify factors that predict which patients are at risk of distant failure. We hypothesized that certain pathology, increasing T stage and tumor size, and a central location of tumor may pre-dispose patients to distant failure. We retrospectively analyzed a multi-institutional database of 293 patients treated with SBRT for their primary, Stage I-II NSCLC. Doses ranged from 50-60 Gy, delivered in 3 to 8 fractions depending upon tumor location. Patients were followed clinically and radiographically, with a chest CT at 3, 6 and 12 month intervals, and every 6 months thereafter. Dates and sites of local, regional and distant failure were recorded and analyzed by a dedicated multidisciplinary tumor board in the majority of cases. Kaplan-Meier method was utilized to estimate overall survival and distant progression rates. The median follow up was 19.6 months, and estimated survival of 79.5% at 1yr and 63% at 2yrs, respectively. Median time to distant failure was 13.8 months, with distant failure rates of 10.1% at 1 yr and 22.7% at 2 yrs, respectively. Patients with squamous cell histology were at highest risk of distant failure at 2 years, compared to adenocarcinoma or those treated empirically without pathology (32.8% vs 22.1% vs 16.3% respectively; p<0.086). Central tumors showed a trend towards increased rate of distant failure at 2 years compared to peripheral tumors, 26.9% vs 23.4% (p=0.2). T2 tumors also showed a numerically increased distant failure over T1 tumors, 27.1% vs 17.4% (p=0.460), however, further analysis comparing individual T stages, T1a-T2b, did not reveal any statistically significant differences in distant failure. Overall, our cohort had survival and distant failure rates comparable to what has been described in the literature. We were able to identity risk factors including tumor histology, location, and T stage that correlated with those who failed distantly. We will utilize this data to create a prediction model for development of distant metastases and those who may be most likely to benefit from addition of systemic therapies.