The risk of radiation-associated second cancer in patients with cervical cancer following radiotherapy from 1975 to 2019.

BACKGROUND: Radiation-associated second primary malignancies (SPMs) are a significant risk factor affecting the quality of life in long-term cervical cancer survivors. However, the impact of brachytherapy-boost and advanced radiotherapy techniques on the risk of radiation-related SPMs remains unclear. METHODS: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2019) to assess the risk of radiation-associated SPMs among cervical cancer patients. Radiation-associated second solid and hematologic malignancies were defined as those diagnosed in survivors living for ≥5 and ≥2 years, respectively. The fine-gray sub-distribution hazard model was employed to compare the risk of SPMs across different groups. RESULTS: External beam radiation therapy (EBRT) was associated with an increased risk of pelvic SPMs (sub-distribution hazard ratio [sHR] = 2.13; P < .001). However, no increased risk was observed for extra-pelvic or hematologic SPMs. For radiotherapy-treated patients, the 15-year cumulative incidence of overall pelvic SPMs significantly declined from 3.92% in 1975-1994 to 2.85% in 1995-2006 (sHR = 0.87; P = .036), further decreasing to 2.27% after 2001 compared to those treated in 1975-2001 (sHR = 0.59; P = .030). Brachytherapy alone increased the risk of pelvic SPMs (sHR = 3.04; P < .001), but the combination of brachytherapy with EBRT did not further elevate the risk of pelvic SPMs (sHR = 1.35; P = .092). CONCLUSIONS: The risk of radiation-associated pelvic SPMs has diminished over the past 40 years, and the combination of brachytherapy with EBRT did not further increase the risk of SPMs among cervical cancer patients.