Brain Metabolic Activity Measured by [ 18 F]FDG PET/CT Predicts Survival in Patients with Advanced Non–Small Cell Lung Cancer

[¹⁸F]FDG PET/CT images play a key role in the management of patients with non–small cell lung cancer (NSCLC). In these scans, the focus is on detected tumors and their characteristics, neglecting information from other organs or tissues. We investigated whether the mean brain [¹⁸F]FDG uptake (brain SUV_mean) is associated with overall survival (OS) in patients with advanced NSCLC. Methods: This retrospective study included patients with advanced NSCLC who underwent pretreatment [¹⁸F]FDG PET/CT scans between 2010 and 2023. Clinical and biologic data, tumor radiomic features, and brain SUV_mean were collected. The ability of these features to predict OS was evaluated using univariable and multivariable Cox regression models. The correlation between brain SUV_mean and clinical, imaging, and blood biomarkers was investigated using Spearman correlation coefficients. Results: Patients were chronologically divided into a discovery set (n = 234; mean age, 64 ± 11 y) and test set (n = 146; mean age, 66 ± 11 y). In the discovery set, univariable analysis showed that high brain SUV_mean (greater than or equal to the median) was associated with longer OS (hazard ratio [HR], 0.83; 95% CI, 0.76–0.92; P < 0.001). Brain SUV_mean was significantly lower in patients who died within 1 y compared with those who were still alive at the same time point (median brain SUV_mean, 4.9 ± 1.4 vs. 5.7 ± 1.5, respectively; P < 0.001). Multivariable analysis revealed that brain SUV_mean was an independent prognostic factor for OS (HR, 0.89; 95% CI, 0.80–0.98; P = 0.02), which was confirmed in the test set (P < 0.001). Brain SUV_mean was independent of the radiomic features quantifying tumor involvement (r < 0.24, n = 380) and significantly correlated but complementary to several blood biomarkers including C-reactive protein (r = −0.37, n = 110 patients). The prognostic significance of brain SUV_mean persisted in patients without brain metastases (P < 0.001). Conclusion: Low brain metabolic activity was associated with increased mortality in patients with advanced NSCLC. Brain SUV_mean was an independent prognostic factor that may aid in patient stratification, although its interpretation requires further investigation.