The onset characteristics and prognosis of patients with radiation-associated second primary malignancy: a pancancer study in the US SEER cancer registries

Background: Cancer survivors have an elevated risk of developing a second primary malignancy (SPM) after radiation therapy (RT). Data on the association between RT and SPM are limited. Our aim was thus to investigate the impact of RT on the risk of developing SPMs and to evaluate the specific characteristics and prognostic outcomes. Methods: We enrolled a pancancer cohort using data from the Surveillance, Epidemiology, and End Results registries spanning from January 1973 to December 2015. Multivariable Cox and the Fine-Gray competing risk regression were employed to assess the hazard ratio (HR) and 95% confidence interval (CI) of SPMs in patients who received RT in comparison to those with no RT (NRT). Poisson regression was used to evaluate the RT-associated risks (RR) and the standardized incidence ratio (SIR) for SPMs. Results: The analysis identified 24 types of risk-increased SPMs (RI-SPMs), including malignancies of the oropharynx, hypopharynx, larynx, esophagus, lung, breast, liver, pancreas, stomach, colon, rectum, ovary, corpus uteri, ureter, vagina, urinary bladder, penis, testis, and kidney, among others. The cumulative incidence of those with RI-SPMs was higher than that of the NRT patients (19.8% vs. 15.3%; P<0.001). The RR for RI-SPMs decreased with increasing age at FPM diagnosis (aged 20-49 years: RR 1.52; age 50-69 years: RR 1.31; age 70 years: RR 1.21), and the RR increased with longer latency period following FPM diagnosis (60-119 months: RR 1.28; 120-239 months: RR 1.24; 240-360 months: RR 1.46). The 10-year overall survival of those with RI-SPMs was significantly lower than that of the matched NRT patients (28.5% vs. 31.7%; P<0.001). Conclusions: Patients with RI-SPMs warrant greater attention given their time-cumulative onset risk and poor prognosis. Long-term surveillance is necessary for cancer survivors treated with RT.