Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3527 - Obesity and the Risk of Radiation-Induced Interstitial Lung Disease in Lung Cancer Patients: Evidence for a Renin-Mediated Mechanism
Presenter(s)
Pengwei Li, MD, MS - Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong
P. Li1, Z. Zhang2, Y. Qin3, X. Liang4, B. Tian1, F. Wang2, Y. Xu2, J. Yuan2, Y. Mo1, and D. Chen2; 1Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 2Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 3Shandong University Cancer Center, Jinan, Shandong, China, 4Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s):
Obesity is a serious public health challenge known to adversely affect cancer outcomes, but its relationship with radiation-induced interstitial lung disease (RILD) in lung cancer patients is poorly investigated. This study aims to investigate the impact of obesity on RILD and identify key mediating factors, hypothesizing that obesity is associated with a higher incidence of RILD in lung cancer patients.Materials/Methods:
A total of 256 patients with lung cancer who received radiotherapy were enrolled and divided into two independent cohorts, comprising a retrospective training cohort (N = 169) from November 2018 to February 2024 and a prospective validation cohort (N = 87) from March 2024 to June 2025. Exclusion criteria included surgery, targeted therapy, combination IO, palliative treatment, or driver gene mutations. Patients with previous thoracic radiotherapy or total radiotherapy dose < 40 Gy were also excluded. Patients were categorized into three groups according to Chinese adult BMI standards: normal weight (18.5-23.9 kg/m²), overweight (24.0-27.9 kg/m²), and obese (= 28.0 kg/m²). Baseline characteristics were compared using t-tests and ?² tests. The cumulative incidence of RILD was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A two-step Mendelian randomization (MR) analysis explored the mechanism by which obesity influences ILD through renin, further validated by enzyme-linked immunosorbent assay (ELISA). Missing data were handled by complete case analysis, where patients with any missing covariate data were excluded from multivariable regression models. RILD was assessed using Common Terminology Criteria for Adverse Events, Version 5.0.Results:
In the retrospective training cohort overweight and obesity were associated with higher risk of = grade 2 RILD versus normal weight (P = 0.002), with a similar trend in the prospective validation cohort (P = 0.017). Furthermore, Renin levels were higher in obesity than normal weight (P < 0.001) and correlated with RILD grade (R = 0.670, P < 0.001). Finally, Two-step MR supported a causal effect of higher BMI on ILD (OR = 1.483, P < 0.001), partially mediated by renin (mediated proportion = 9.9%, P = 0.040).Conclusion:
Obesity is associated with = grade 2 RILD in lung cancer patients through renin-mediated mechanisms in this study. These findings underscore the importance of risk stratification for patients with obesity and highlight renin as a potential therapeutic target for preventing and treating RILD. However, the relatively small overall sample size and modest size of the prospective cohort may limit the generalizability of these results. Nonetheless, these findings will provide valuable insights for the design of future RCTs.