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 (Ptrend < 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.
Bibliographical noteFunding Information:
A.C. Dietz reports other support from bluebird bio, Inc and Shape Therapeutics outside the submitted work. G.T. Armstrong reports grants from NIH during the conduct of the study. R.M. Howell reports grants from St. Jude Children’s Research Hospital during the conduct of the study. S.A. Smith reports other support from St. Jude Research Hospital during the conduct of the study. D.A. Mulrooney reports grants from NCI CA55727 (G.T. Armstrong, PI) and NCI Cancer Center Support (CORE grant CA21765; C. Roberts, principal investigator) during the conduct of the study. Y. Yuan reports grants from St Jude Children’s Research Hospital during the conduct of the study. No disclosures were reported by the other authors.
We would like to acknowledge the NCI and the American Lebanese-Syrian Associated Charities (ALSAC) for providing funding support for this study. We would like to acknowledge the Childhood Cancer Survivor Study (CCSS) for providing access to previously collected data used in this study. This work was supported by the NCI (CA55727, to G.T. Armstrong, principal investigator). Support to St. Jude Children’s Research Hospital also provided by the Cancer Center Support (CORE grant CA21765, C. Roberts, principal investigator) and the American Lebanese-Syrian Associated Charities (ALSAC).
© 2021 American Association for Cancer Research
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't