High FDG Uptake in the Non-cancerous Lung Predicts Immune-Related Adverse Events and Poor Prognosis in Patients with Lung Cancer Treated with Immune Checkpoint Inhibitors.
Authors
Affiliations (3)
Affiliations (3)
- Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan (M.Y., M.T., T.Y., Y.G., H.I.).
- Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan (S.W., K.K., R.S., N.Y., M.S., T.T., K.N., Y.S., T.K.). Electronic address: [email protected].
- Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan (S.W., K.K., R.S., N.Y., M.S., T.T., K.N., Y.S., T.K.).
Abstract
Immune checkpoint inhibitors (ICIs) have improved survival in non-small cell lung cancer (NSCLC); however, predicting immune-related adverse events (irAEs) remains a clinical challenge. We previously showed that high <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG) uptake in the non-cancerous lung (NCL) on PET/CT is associated with the risk of interstitial lung disease. This study further investigated whether NCL FDG uptake predicts the risk of irAEs, including both ILD and non-ILD events, as well as survival outcomes in patients with lung cancer receiving ICIs. We retrospectively analyzed 165 patients with lung cancer who underwent PET/CT before ICI therapy. FDG uptake in the NCL, defined as the lung contralateral to the primary tumor and free of metastatic lesions, was quantified using AI-based segmentation. Total glycolytic activity in the NCL (NCL-TGA<sub>1.0</sub>) was calculated as the product of the mean SUV and the lung volume, both measured within regions with SUV ≥1.0. Associations of NCL-TGA<sub>1.0</sub> with irAE incidence and survival outcomes were assessed using multivariable and Kaplan-Meier analyses. High NCL-TGA<sub>1.0</sub> (≥149.45) was independently associated with increased risk of irAEs in multivariate analysis (odds ratio [OR]: 6.910; p=0.005), including non-ILD irAEs (OR: 4.244; p=0.020). In survival analysis of 84 unresectable NSCLC patients, high NCL-TGA<sub>1.0</sub> was associated with significantly shorter progression-free survival (median: 4.30 vs. 9.90 months, p=0.007) and overall survival (median: 6.93 vs. 22.03 months, p=0.029). High FDG uptake in the NCL is a predictor of irAEs and poor survival in patients with lung cancer receiving ICIs. These results may help to identify high-risk patients prior to treatment.