Association between radiotherapy and risk of secondary primary malignancies in patients with esophageal cancer: A population-based study utilizing 17 Surveillance, Epidemiology, and End Results cancer registries

Purpose

Despite the frequent use of radiotherapy as a standard treatment for esophageal cancer, the potential risk of developing second primary malignancies as a result of radiation-related side effects remains underinvestigated.

Methods

We conducted a comprehensive analysis using data from the large cohort of 17 cancer registries within the Surveillance, Epidemiology, and End Results (SEER) database. To estimate the incidence of second primary malignancies associated with radiotherapy, we employed Poisson regression and competing risk regression models.

Results

A total of 54,844 patients diagnosed with esophageal cancer were identified from the SEER database. Among them, 8351 patients did not receive radiotherapy, while 15,555 patients were treated with radiation. The incidence of second primary malignancies among patients who had radiotherapy was 6.28 % (977 patients) compared to an incidence of 7.09 % (592 patients) for those who had not (P < 0.0001). After adjusting for potential confounders, such as age, gender, year of diagnosis, tumor grade, and chemotherapy, the incidence rates of patients who received radiotherapy were significantly higher compared to those who had not (odds ratio [OR] _{Poisson regression} = 1.18, 95 % confidence interval [CI]: 1.05–1.32, P = 0.018; OR _{multivariable competing risk regression} = 1.15, 95 %CI: 1.04–1.26, P = 0.018). Notably, patients who received radiotherapy were found to be at an increased risk of developing lung cancer, breast cancer, and gastric cancer. Additionally, younger patients with esophageal cancer appeared to be more susceptible, with the highest risk of developing subsequent primary malignancies observed more than 10 years after the esophageal cancer diagnosis.

Conclusion

Our findings indicated that radiotherapy for esophageal cancer was associated with an increased risk of developing overall cancer. It is crucial to address and mitigate the risk of second primary malignancies associated with radiotherapy, while also improving the prognosis for patients affected by these secondary malignancies.