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

Abstract

[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. <b>Methods:</b> 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. <b>Results:</b> Patients were chronologically divided into a discovery set (<i>n</i> = 234; mean age, 64 ± 11 y) and test set (<i>n</i> = 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; <i>P</i> < 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; <i>P</i> < 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; <i>P</i> = 0.02), which was confirmed in the test set (<i>P</i> < 0.001). Brain SUV_mean was independent of the radiomic features quantifying tumor involvement (<i>r</i> < 0.24, <i>n</i> = 380) and significantly correlated but complementary to several blood biomarkers including C-reactive protein (<i>r</i> = -0.37, <i>n</i> = 110 patients). The prognostic significance of brain SUV_mean persisted in patients without brain metastases (<i>P</i> < 0.001). <b>Conclusion:</b> 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.