The Impact of Radiotherapy on the Incidence of Secondary Malignancies: A Pan-Cancer Study in the US SEER Cancer Registries

The population of cancer patients with second primary malignancies (SPMs) is rapidly growing. The relationship between radiotherapy and SPMs for some types of tumors is unknown or debated. In this study, we identify 24 types of first primary malignancies (FPMs) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the radiotherapy group were matched to those in the no radiotherapy group with a matching ratio of 1:1. After propensity-score matching (PSM), additional competing risk regression analyses were performed to calculate the efficacy of radiotherapy to SPMs in the PSM-adjusted population. In addition, the Fine and Gray model was utilized in the primary cohorts, and stratified analyses were performed based on surgery. This study includes a total of 2,831,789 eligible patients with tumors diagnosed from 2004 to 2015 in the SEER 18 database, amongst whom 100,194 (3.5%) patients developed SPMs. We observe higher risks of SPMs associated with radiotherapy in several types of tumors in the PSM-adjusted populations (small bowel adenocarcinoma, small cell lung carcinoma, prostate adenocarcinoma, urinary bladder transitional cell carcinoma, invasive ductal breast carcinoma, invasive lobular breast carcinoma, and Hodgkin lymphoma). The results in the PSM-adjusted populations were consistent with outcomes in the multivariable competing risk models. Meanwhile, in subgroup analyses stratified by surgery, some other types of tumor (except for those with positive results in the PSM-adjusted cohorts) with radiotherapy were also associated with a higher prevalence of SPMs in the subgroups of surgical treatment (pancreatic adenocarcinoma, rectal adenocarcinoma, lung adenocarcinoma and follicular thyroid carcinoma in the surgery subgroups). The impact of radiotherapy on the incidence of secondary malignancies is distinct in different types of cancer. These findings merit further investigation and may ultimately impact treatment decision-making for tumor management.