Brain Metabolic Activity on FDG PET/CT Predicts Survival in Non-Small Cell Lung Cancer

Background: [18F]FDG-PET/CT images play a key role in the management of patients with Non-Small Cell Lung Cancer (NSCLC). However, in these scans, the focus is always on the detected tumors and on their characteristics, neglecting information from other organs or tissues. Purpose: To investigate whether the mean brain FDG uptake (SUVmeanbrain) is associated with overall survival (OS) in metastatic NSCLC patients. Materials and Methods: This retrospective study included metastatic NSCLC patients who underwent pre-treatment [18F]FDG-PET/CT scans between 2010 and 2023. Clinical and biological data, tumor radiomic features, and SUVmeanbrain were collected. The ability of these features to predict OS was evaluated using univariable and multivariable Cox regression models. The correlation between SUVmeanbrain and clinical/imaging/blood biomarkers was investigated using Spearman correlation coefficients (rS). Results: Patients were chronologically divided into a discovery (n = 234, mean age 64 years ± 11 [SD], 135 male) and test set (n = 146, mean age 66 years ± 11, 83 male). In the discovery set, univariable analysis showed that high SUVmeanbrain (≥ median) was associated with longer OS (HR = 0.83, 95% CI 0.76-0.92, P < .001). SUVmeanbrain was significantly lower in patients who died within one year compared to those who were still alive (P < .001). In multivariable analysis, SUVmeanbrain remained an independent prognostic factor for OS (HR, 0.88; 95% CI: 0.80, 0.98; P = .02), which was confirmed in the test set (P < .001). SUVmeanbrain was independent of the radiomic features quantifying tumor involvement (|rS| < 0.24, n = 380 patients) and significantly correlated but complementary to several blood biomarkers including CRP (rS = -0.37, n = 110 patients). Conclusion: Low brain metabolic activity was associated with increased mortality in metastatic NSCLC patients. SUVmeanbrain was an independent prognostic factor that could contribute to patient stratification, although its interpretation requires further investigation.