Association Between Radiotherapy and Non-Gastric Second Primary Malignancies in Patients with Resectable Gastric Cancer : A propensity-adjusted, population-based SEER analysis

Abstract Background The study aims to investigate the relationship between radiotherapy (RT) and the risk of second primary malignancies (SPMs) in GC patients, and assess the prognostic impact of RT. Patients and methods: We retrieved data on patients with primary GC from the SEER database. The study focused on the association between RT and the occurrence of hematologic malignancies at least 2 years post-diagnosis, as well as the emergence of solid cancers at least 5 years post-diagnosis. For the analysis, we employed competing risk regression analysis and Poisson regression following propensity score matching, along with implemented stratified analysis. Furthermore, we evaluated the impact of RT on the prognosis of GC patients using Kaplan-Meier and Cox regression analysis. Results A total of 24,390 surgically treated patients with pathologically confirmed GC were enrolled in the study. The median OS was 37.0 months (95%CI 16.0-100.0) in the RT group and 24.0 months (IQR, 8.0–24.0) in the NRT group (HR = 0.77, 95%CI 0.74–0.80, P < 0.001). Among the survivors who lived beyond 2 years, 56 (0.70%) were diagnosed with second hematologic malignancies. Additionally, both competing risks and Poisson regressions indicate that RT is not linked to second hematologic malignancies (HR = 0.96, 95%CI: 0.57–1.62, P = 0.87; RR = 0.99, 95%CI: 0.59–1.69, P = 0.97). In 5-year survivors, 362 (7.10%) were diagnosed with second primary solid malignancies, and RT was also not associated with overall second solid malignancies (HR = 1.05, 95%CI, 0.86–1.32, P = 0.61; RR = 1.10, 95%CI, 0.89–1.35, P = 0.39). In subgroup analyses, no association was found between RT and SPM occurrence at any site, and no specific population was identified regarding the effect of RT on the development of SPMs. Conclusion RT improves the prognosis for patients with resectable GC, with no evidence of increasing the risk of developing second primary hematologic or solid malignancies.