Combining ¹⁸F-FDG PET/CT–Based Metabolically Active Tumor Volume and Circulating Cell-Free DNA Significantly Improves Outcome Prediction in Chemorefractory Metastatic Colorectal Cancer

Abstract

Baseline whole-body metabolically active tumor volume (WB-MATV) measured by ¹⁸F-FDG PET/CT and circulating cell-free DNA (cfDNA) have been separately validated as predictors of overall and progression-free survival (OS/PFS) in chemorefractory metastatic colorectal cancer (mCRC) patients. This study assessed the correlation between WB-MATV and cfDNA, evaluating the added prognostic value of these in combination, along with clinical parameters. <b>Methods:</b> Of 141 mCRC patients included in a prospective multicenter trial, 132 were evaluable for OS/PFS. cfDNA was extracted from 3 mL of plasma and quantified using a fluorometer. All target lesions were delineated on ¹⁸F-FDG PET/CT, and their metabolic volumes were summed to obtain the WB-MATV. <b>Results:</b> Baseline WB-MATV and cfDNA were strongly correlated (<i>r</i> = 0.70; <i>P</i> < 0.001) but showed discordance in 23 of 132 (17%) patients. A multivariate analysis identified 3 independent negative predictors of PFS (high cfDNA, short time since diagnosis, and body mass index < 30) and 5 of OS (high cfDNA, high WB-MATV, body mass index < 30, poor performance status, and short time since diagnosis). Combining WB-MATV and cfDNA increased the overall prognostic value and allowed identification of a subgroup of patients with low cfDNA and high WB-MATV who were associated with intermediate survival (median OS of 8.1 for low-cfDNA/high-MATV patients vs. 12.7 mo for low-cfDNA/low-MATV patients; hazard ratio, 2.04; <i>P</i> = 0.02). <b>Conclusion:</b> This study confirms the added prognostic value of combined circulating cfDNA and PET-based WB-MATV in chemorefractory mCRC patients. The combination of these two biomarkers should provide a firm basis for risk stratification, both in clinical practice and in research trials.