Long-term radiation therapy-related risk of second primary malignancies in patients with lung cancer

Background: With the improvement of cancer therapy, a second primary malignancy (SPM) occurs more commonly among cancer survivors. At present, it remains unclear whether the radiation therapy for the initial lung cancer will increase the risk of developing a SPM. This study aims to investigate the long-term risk of a SPM attributable to the radiation therapy in patients with the initial lung cancer. Methods: Patients initially diagnosed with lung cancer between January 1975 and November 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. SPM was defined as the occurrence of a second cancer at least five years after the diagnosis of the initial lung cancer. Age-and propensity score matching (PSM)-adjusted competing risk analyses were performed to compare the risk of SPM. Results: Of 47,911 patients, 9,162 (19.1%) underwent radiotherapy for the initial lung cancer. The PSMadjusted competing risk analyses showed that radiation therapy was associated with a lower overall risk of SPM (HR: 0.89, 95% CI: 0.84-0.94, P<0.001). Specifically, the risk of second primary melanoma (HR: 0.49, 95% CI: 0.29-0.81, P=0.006), second primary female breast cancer (HR: 0.65, 95% CI: 0.50-0.85, P=0.001), second primary prostate cancer (HR: 0.69, 95% CI: 0.58-0.84, P<0.001) and second primary thyroid cancer (HR: 0.23, 95% CI: 0.07-0.77, P=0.017) was found to decrease, while the risk for second primary esophageal cancer dramatically increased (HR: 1.76, 95% CI: 1.26-2.45, P<0.001). Conclusions: In patients who received radiotherapy for the initial lung cancer, the risk decreased for second primary melanoma as well as for second primary cancers of female breast, prostate and thyroid gland but increased for second primary cancer of esophagus. On the whole, radiation therapy for initial lung cancer may not increase the overall risk of SPM.