Risk for Subsequent Lung Cancer after Childhood Cancer Diagnosis and Treatment

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Risk for Subsequent Lung Cancer after Childhood Cancer Diagnosis and Treatment

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Abstract Introduction: With 5-year survival following childhood cancer diagnosis exceeding 85% there is a growing need to develop surveillance rationale for significant late effects, particularly subsequent neoplasms, in adult survivors to optimize their long-term care. Lung cancer is the most common cancer seen in the general adult population but has not been well studied in the childhood cancer survivor population. We aimed to assess the prevalence of and risk factors for lung cancer in the Childhood Cancer Survivor Study (CCSS) cohort. Methods: Among 25,654 five-year survivors participating in the CCSS, lung cancer was self-reported and then confirmed by pathologic record review. Cancer treatment exposures were evaluated including chemotherapy and chest radiation by field size (none, small, large) and dose group (0-10 Gy, 10-30 Gy, 30-40 Gy, and > 40 Gy). Standardized incidence ratios (SIR) were calculated using rates from the Surveillance, Epidemiology, and End Results program. Hazard ratios (HR) were estimated for demographic and treatment variables within CCSS using Cox proportional-hazards models. Results: Forty-two survivors developed subsequent malignant lung cancer (SIR 4.0, 95% CI 2.9-5.4), including 25 carcinomas, 7 mesotheliomas and 10 others. Two benign neoplasms were also identified. The cumulative incidence of lung SNs was 0.18% at 30 years (95% CI 0.10-0.25). Median time from primary diagnosis was 28 years (range 11-46); median age at diagnosis was 45 years of age (range 15-65). A multivariable model, including all covariates with a p-value < 0.2 in univariate analysis, showed significant associations between lung cancer and older age at childhood cancer diagnosis (HR 10.5, 95% CI 1.4-76.4, for 15-21 years vs. 0-4 years), as well as with primary diagnoses (Hodgkin lymphoma, HR 8.7, 95% CI 1.1-66.0; neuroblastoma, HR 20.7, 95% CI 1.3-331.0; and bone cancer, HR 21.4, 95% CI 2.3-202.7, with leukemia as the reference). In a treatment model, maximum chest radiation dose (HR 4.1, 95% CI 1.4-11.7, for 30-40 Gy; and HR 8.1, 95% CI 3.0-22.2, for > 40 Gy, relative to 0-10Gy) were associated with lung cancer. History of smoking and chemotherapy exposures were not associated with lung cancer in this study. At the end of follow-up, 65.9% of survivors with lung cancer were deceased vs. 14.1% of survivors without lung cancer (p< 0.001). Conclusions: Survivors of childhood cancer are at increased risk of subsequent lung cancer compared to the general population, with highest risks observed among survivors who received high doses of chest radiotherapy, and with primary diagnoses of Hodgkin lymphoma, bone cancer, or neuroblastoma. Risks related to chemotherapy exposures were not observed. Associations between subsequent lung cancers and specific primary diagnoses may be secondary to underlying germline mutations. As such, survivors with underlying germline mutations may benefit from lung cancer screening, with screening being initiated at an earlier age than the general at-risk population. Future studies are needed to determine additional diagnosis and treatment-related risks to help guide the development of screening rationale for lung cancer in the survivor population.



University of Minnesota M.S. thesis. 2020. Major: Clinical Research. Advisor: Lucie Turcotte. 1 computer file (PDF); 34 pages.

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Ghosh, Taumoha. (2020). Risk for Subsequent Lung Cancer after Childhood Cancer Diagnosis and Treatment. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/241283.

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