Predicting the risk of secondary malignancies associated with stereotactic body radiation therapy.

Abstract

e17562 Background: Treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) is associated with high rates of local control and long-term overall survival. With increasing frequency, SBRT is a treatment option for operable tumors which raises the question of the risk of long-term toxicities such as radiation-induced secondary malignancies. There has been no previous risk assessment or epidemiological studies of secondary malignancies with high-dose hypofractionated SBRT. In this study, we seek to quantify the predicted rates of secondary lung malignancies in patients treated with SBRT for stage I-II NSCLC. Methods: Treatment plans for 14 stage I-II NSCLC patients treated with definitive-intent SBRT at Columbia University Medical Center were retrospectively assessed. Median patient age was 73 years (range 54 - 86) with median tumor size of 2.8 cm (range 1.2 - 5.0). SBRT doses ranged from 40-60 Gy in 3-5 fractions. Dose-volume histograms for target PTV and normal lung were generated from planning CT scans. A biologically-based mathematical model of spontaneous and radiation-induced carcinogenesis was used to determine the excess absolute risk and the median lifetime estimated relative risk of secondary lung malignancies for each plan. These risks were then compared using 2-sided t-tests. Results: For all patients, the median lifetime estimated absolute risk of secondary lung malignancy was 1.06% (95% CI 0.62%-1.98%), and the median lifetime estimated relative risk of secondary lung malignancy was 1.61 (95% CI 1.47-1.75) after SBRT. For patients aged less than 65 years, median estimated absolute risk of secondary malignancies was higher (2.8%) than for patients age 65 and older (0.37%), p < 0.001. PTV volume less than 50 cc vs greater than 50 cc, T1 vs T2 tumors, and gender were not significantly associated with differences in estimated absolute risk or estimated relative risk of secondary malignancies. Conclusions: As SBRT is potentially indicated in younger medically operable patients, the long-term late toxicities need to be determined. This study suggests that the risk of second lung malignancies from high-dose SBRT even in younger patients would be minimal.