Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, F-18-FDG PET/CT, circulating cell-free DNA, metastatic colorectal cancer, metabolically active tumor volume, multikinase inhibitors, BIOMARKER, BURDEN, APPRAISAL, SURVIVAL, BLOOD, MICE, 18F-FDG PET/CT, Adult, Aged, Aged, 80 and over, Cell-Free Nucleic Acids, Colorectal Neoplasms, DNA Mutational Analysis, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Fluorodeoxyglucose F18, Humans, Male, Medical Oncology, Middle Aged, Multimodal Imaging, Multivariate Analysis, Neoplasm Metastasis, Positron Emission Tomography Computed Tomography, Prognosis, Prospective Studies, Radiopharmaceuticals, Risk, Treatment Outcome, Tumor Burden, 1103 Clinical Sciences, Nuclear Medicine & Medical Imaging, 3202 Clinical sciences

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. Methods: 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. Results: Baseline WB-MATV and cfDNA were strongly correlated (r = 0.70; P < 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; P = 0.02). Conclusion: 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.