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. 2025 Sep 1;157(5):941-953.
doi: 10.1002/ijc.35452. Epub 2025 Apr 18.

Risk of second primary lung cancer among cancer survivors stratified by the site of first primary cancer and the lung cancer screening eligibility status

Sara Nofal  1 , Edwin J Ostrin  2 , Jianjun Zhang  3 , Jia Wu  4 , Paul Scheet  5 , Mara B Antonoff  6 , John V Heymach  3 , Iakovos Toumazis  1
Affiliations

Risk of second primary lung cancer among cancer survivors stratified by the site of first primary cancer and the lung cancer screening eligibility status

Sara Nofal et al. Int J Cancer. .

Abstract

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer survivors. We found that among lung, head and neck (H&N), bladder, cervical, breast, and prostate cancer survivors, the risks of second primary lung cancer were statistically significantly higher compared to the overall risk among all cancer survivors (i.e., all cancer sites combined). Risk ratios (RR) ranged between 1.14 (95%CI:1.00-1.28, p = 0.0431) among prostate cancer survivors to 2.9 (95%CI:2.58-3.26, p < 0.001) among H&N cancer survivors. Other than first primary lung cancer (RR: 1.33; 95%CI:1.14-1.57; p < 0.001), H&N (RR: 1.73; 95%CI:1.45-2.05; p < 0.001) and bladder (RR: 1.32; 95%CI:1-1.74; p = 0.0483) cancer survivors, who were non-eligible for LCS, had significantly higher lung cancer risk than all cancer survivors. In conclusion, H&N, bladder, cervical, breast, and prostate cancer survivors have a high risk of developing second primary lung cancer. Specifically, personal history of H&N and bladder cancer, even among non-eligible for LCS individuals, remain at a sufficiently high risk, which warrants further consideration as an independent eligibility factor for LCS guidelines.

Keywords: cancer survivors; lung cancer; lung cancer screening guidelines; personal history of cancer; risk factors.

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Conflict of interest statement

All authors have no conflicts of interest except the following: Sara Nofal reports support for the submitted work from the National Cancer Institute grant R37CA271187 (PI: Toumazis). Edwin Ostrin reports grant/contract by the Early Detection Research Network Clinical Validation Center (NCI) and payment/honoraria for Astra Zeneca (April 2021) outside the submitted work. He also reports having served on scientific advisory boards for Grail, Inc., and 20/20 GeneSystems, which have concluded as of December 2023. Jianjun Zhang reports grants from Merck, grants and personal fees from Johnson and Johnson and Novartis, personal fees from Bristol Myers Squibb, AstraZeneca, GenePlus, Innovent, and Hengrui outside the submitted work as well as support for the submitted work from the National Cancer Institute of the National Institute of Health Research Project Grant (R01CA234629), the AACR‐Johnson & Johnson Lung Cancer Innovation Science Grant (18‐90‐52‐ZHAN), and the MD Anderson Physician Scientist Program, MD Anderson Lung Cancer Moon Shot Program. Iakovos Toumazis reports support for the submitted work from the National Cancer Institute grant R37CA271187 (PI: Toumazis), and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Lung Moon Shot (in part).

Figures

FIGURE 1
FIGURE 1
CONSORT flowchart of study sample. (A) Ascertainment of the sample stratification based on the development of second primary lung cancer. (B) Ascertainment of lung cancer screening eligibility status.
FIGURE 2
FIGURE 2
Risk of second lung cancer diagnosis by first primary cancer site relative to the overall risk (i.e., all cancers combined).
FIGURE 3
FIGURE 3
Risk of second lung cancer diagnosis in the lung cancer screening non‐eligible groups by First Primary Cancer Site relative to the overall risk (i.e., all cancers combined). LCS: Lung Cancer Screening.
FIGURE 4
FIGURE 4
Risk of second lung cancer diagnosis in the lung cancer screening eligible groups by First Primary Cancer Site relative to the overall risk (i.e., all cancers combined). LCS: Lung Cancer Screening.
See this image and copyright information in PMC

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