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

Sep 21, 2026

Uploaded by Oliver

Early-stage nonsmall cell lung cancer (NSCLC) is commonly treated with surgery-based combination therapy, but postoperative radiotherapy (PORT) may be associated with later second primary malignancies (SPMs), particularly in young-onset patients. A retrospective cohort study quantified SPM risk after PORT in young-onset NSCLC using Surveillance, Epidemiology, and End Results data, estimating risks with multivariate logistic regression and Fine-Gray competing-risk regression. Among 30,308 patients, 3,728 received PORT.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background

Study objective

Methods

Data source and cohort

Statistical analyses

Results

Overall SPM risk after PORT

Site-specific second malignancies

Factors associated with higher risk

Conclusion

Clinical implication: long-term surveillance

Highlights

Comparative Study-Retrospective Cohort ’ Association between postoperative radiotherapy for young-onset nonsmall cell lung cancer and risk of second primary malignancies: comparative study Zuwei Li, MD, Minzhang Guo, PhD, Lunxu Liu, MD, Senyi Deng, PhD* 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. Keywords: nonsmall cell lung cancer, postoperative radiotherapy, second primary malignancy, SEER Background Lung cancer is one of the most common and deadly malignancies. In 2024, there are estimated 234 580 new lung cancer cases and 125 070 deaths in the USA, ranking for 11.7% of all cancer cases and 20 .4% of all cancer-related deaths, respectively[1] . About 90% of lung cancer cases are nonsmall cell lung cancer (NSCLC) . The 5-year overall survival (OS) rate for NSCLC cases remains poor, from 68% in stage IB cases to 0–10% in stage IVA–IVB Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Zuwei Li and Minzhang Guo contributed equally to this manuscript. Sponsorships or competing interests that maybe relevant to content are disclosed atthe end of this article. *Corresponding author. Address: Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China. Tel.: + [86 199 831 379 78. E-mail: senyi_deng@scu.edu.cn](86 199 831 379 78. E-mail: senyi_deng@scu.edu.cn)[ ](86 199 831 379 78. E-mail: senyi_deng@scu.edu.cn)(S. Deng). Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. International Journal of Surgery (2024) 110:4617–4623 Received 6 March 2024; Accepted 25 April 2024 Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTM

FAQs

What was the study purpose regarding PORT and young-onset NSCLC?

To quantify how postoperative radiotherapy (PORT) affects the risk of developing second primary malignancies (SPMs) in patients with early-stage young-onset NSCLC.

How were SPM risks estimated in the study?

Risks of SPM developing over more than 5 years were assessed using Surveillance, Epidemiology, and End Results data with multivariate logistic regression and Fine-Gray competing risk regression for cumulative incidence.

Which second malignancies showed increased risk after PORT?

PORT was associated with higher risks of second solid malignancies, including lung cancer, breast cancer, and colon and rectum cancers, while the risk for second hematologic malignancies was negligible.

Sep 21, 2026

Uploaded by Oliver