Risk of Second Primary Malignancies in Lung Cancer Survivors – The Influence of Different Treatments

Background: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available. Methods: Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population. Results: We identified 52,639 patients with lung cancer and excluded 34,267 patients who had expired within one year after diagnosis. The study included 18,372 subjects with a median follow-up period of 2.24 years. 590 patients developed an SPM. The overall cancer risk was significantly increased (SIR 1.33, 95% confidence interval [CI]: 1.22–1.44, p < 0.001), and there was a significant increase in the incidences of head and neck (SIR 1.60, 95% CI 1.21–2.07, p = 0.001), bone and soft tissue (SIR 2.65, 95% CI 1.27–4.87, p = 0.011), genitourinary (SIR 1.50, 95% CI 1.27–1.76, p < 0.001), and thyroid (SIR 3.85, 95% CI 2.28–6.08, p < 0.001) cancers. Importantly, after multivariate adjustment, the use of tyrosine kinase inhibitors (TKIs) statistically significantly reduced SPM incidence (HR, 0.41; 95% CI, 0.21–0.79; p = 0.008). Conclusions: Our study indicates that lung cancer may be a risk factor for SPM. TKI use was associated with a significantly lower risk of SPM development. However, because patients with epidermal growth factor receptor mutant lung adenocarcinoma (associated with non-smokers) tend to receive TKI treatment, they might have fewer smoking-related SPMs. [Figure not available: see fulltext.]