Association between Long-Term Second Malignancy Risk and Radiation – A Comprehensive Analysis of the Entire: Surveillance, Epidemiology, and End Results Database (1973 – 2014)

Abstract Background and purpose: Second malignancies (SM) after radiotherapy are rare but serious sequelae of treatment. This study is to investigate if radiotherapy use is associated with changes in baseline SM risk. Materials and methods We extracted all cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2014, with or without SM. Cumulative incidence of SM for patients stratified by radiotherapy status was calculated using a competing risk model, both for the entire cohort and for subgroups based on primary tumor’s anatomical location. Results We identified 2,872,063 cancer patients, including 761,289 patients who received radiotherapy and 2,110,774 who did not. The SM rate at 20 years for patients receiving radiotherapy versus no radiotherapy were 21.4% versus 18.8%. The relative risk for SM associated with radiotherapy for the overall group was 1.138 at 20 years. The relative risks for SM associated with radiotherapy to malignancies arising from central nervous system and orbits, head and neck, thorax, abdomen and pelvis at 20 years were 0.704, 1.011, 0.559, 0.646 and 1.106 for men, and 0.792, 1.298, 1.265, 0.780 and 0.988 for women. Conclusion The association between SM and radiotherapy varies with both gender and disease anatomical location, with the largest increase in SM seen in females irradiated to the head and neck region. Overall, the absolute change in SM rates associated with radiotherapy remains small, with differences in various clinical contexts.