Abstract 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 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 years and ≥ 2 years, respectively. The Fine-Gray subdistribution 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 (sHR = 2.13; P 0.001). 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 = 0.036), further decreasing to 2.27% after 2001 compared to those treated in 1975-2001 (sHR = 0.59; P = 0.030). Brachytherapy alone increased the risk of pelvic SPMs (sHR = 3.04; P 0.001), but the combination of brachytherapy with EBRT did not further elevate the risk of pelvic SPMs (sHR = 1.35; P = 0.092). 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.
Wang et al. (Tue,) studied this question.