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

[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.