[¹⁸F]FDG PET/CT Predicts Patient Survival in Patients with Systemic Sclerosis–Associated Interstitial Lung Disease

There are few effective prognostic biomarkers in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). We investigated the potential of [¹⁸F]FDG PET/CT to predict mortality in this population. <b>Methods:</b> In total, 45 patients with SSc-ILD (12 men and 33 women; age, 58.9 ± 9.9 y) were prospectively recruited for [¹⁸F]FDG PET/CT, forming the largest cohort of this type to our knowledge. All patients underwent clinical assessment, including multidisciplinary team review, high-resolution CT evaluation, and pulmonary function tests. The maximum pulmonary uptake on [¹⁸F]FDG PET/CT (SUV_max), minimum pulmonary uptake in unaffected or background lung (SUV_min), and target-to-background ratio (TBR) (SUV_max/SUV_min) were quantified using region-of-interest analysis. Kaplan-Meier analysis identified associations with mortality. Associations between [¹⁸F]FDG PET/CT measurements, pulmonary function tests, and the established model based on sex, age, and lung physiology (known as ILD-GAP) to predict mortality were performed. Stepwise forward Wald-Cox analysis assessed the independence of significant [¹⁸F]FDG PET/CT measurements from the ILD-GAP index. Synergies between pulmonary [¹⁸F]FDG PET/CT measurements and ILD-GAP index for risk stratification in patients with SSc-ILD were investigated. <b>Results:</b> Forty-five patients with SSc-ILD were followed for a mean of 44.8 ± 26.1 mo, with 15 deaths (33%) recorded. The mean ± SD SUV_max was 3.2 ± 1.1, SUV_min was 0.5 ± 0.3, and TBR was 6.8 ± 2.6. Increased mortality was associated with high pulmonary SUV_max (<i>P</i> = 0.027), high SUV_min (<i>P</i> = 0.002), low TBR (<i>P</i> = 0.016), low forced vital capacity (<i>P</i> = 0.021), low carbon monoxide diffusion coefficient (<i>P</i> = 0.021), low transfer factor (<i>P</i> = 0.012), high ILD-GAP score (<i>P</i> = 0.010), and high ILD-GAP index (<i>P</i> = 0.005). Multivariate Cox regression analysis revealed that pulmonary SUV_min (hazard ratio, 4.2; 95% CI, 1.3-13.4; <i>P</i> = 0.017) and ILD-GAP index (hazard ratio, 3.9; 95% CI, 1.2-12.8; <i>P</i> = 0.024) were the only independent predictors of overall survival. Combining [¹⁸F]FDG uptake with ILD-GAP score data in a modified ILD-GAP index refined the ability to predict mortality (<i>P</i> < 0.002). <b>Conclusion:</b> High-background [¹⁸F]FDG uptake in normal-appearing lung independently predicts overall survival in SSc-ILD and may stratify patients' risk when combined with ILD-GAP score data in a modified ILD-GAP index. High pulmonary [¹⁸F]FDG uptake is associated with increased mortality in patients with SSc-ILD.