Association between postoperative radiotherapy for young-onset nonsmall cell lung cancer and risk of second primary malignancies: comparative study

Background: The most common form of therapy for nonsmall cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. The authors aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. Methods: The authors screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology, and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray’s competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Results: Among the 30 308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies [relative risks (RR)=1.31; 95% CI: 1.17–1.46], lung cancer (RR=1.23; 95% CI: 1.07–1.42), breast cancer (RR=1.74; 95% CI: 1.16–2.74), and colon and rectum cancers (RR=1.37; 95% CI: 1.07–2.06) as well as a negligible risk of second hematologic malignancies (RR=1.15; 95% CI: 0.82–1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60–69 years (RR=1.33), in white race (RR=1.36), diagnosed in 1975–2000 (RR=1.23) and 2001–2015 (RR=1.40), or diagnosed with lung adenocarcinoma (RR=1.55). Conclusion: PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer, as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.