Lung Cancer as a Subsequent Malignant Neoplasm in Survivors of Childhood Cancer

Background: Lung cancer, the most common cause of cancer-related death in adults, has not been well studied as a subsequent malignant neoplasm (SMN) in childhood cancer survivors. We assessed prevalence, risk factors, and outcomes for lung SMN in the Childhood Cancer Survivor Study (CCSS) cohort. Methods: Among 25,654 5-year survivors diagnosed with childhood cancer (<21 years), lung cancer was self-reported and confirmed by pathology record review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, comparing survivors to the general population, and hazard ratios (HR) were estimated using Cox regression for diagnosis and treatment exposures. Results: Forty-two survivors developed a lung SMN [SIR, 4.0; 95% confidence interval (CI), 2.9–5.4] with a cumulative incidence of 0.16% at 30 years from diagnosis (95% CI, 0.09%–0.23%). In a treatment model, chest radiation doses of 10–30 Gy (HR, 3.4; 95% CI, 1.05–11.0), >30–40 Gy (HR, 4.6; 95% CI, 1.5–14.3), and >40 Gy (HR, 9.1; 95% CI, 3.1–27.0) were associated with lung SMN, with a monotone dose trend (P_trend < 0.001). Survivors of Hodgkin lymphoma (SIR, 9.3; 95% CI, 6.2–13.4) and bone cancer (SIR, 4.4; 95% CI, 1.8–9.1) were at greatest risk for lung SMN. Conclusions: Survivors of childhood cancer are at increased risk for lung cancer compared with the general population. Greatest risk was observed among survivors who received chest radiotherapy or with primary diagnoses of Hodgkin lymphoma or bone cancer. Impact: This study describes the largest number of observed lung cancers in childhood cancer survivors and elucidates need for further study in this aging and growing population.