Validation of Metabolically Active Tumor Volume and Total Lesion Glycolysis as 18F-FDG PET/CT–derived Prognostic Biomarkers in Chemorefractory Metastatic Colorectal Cancer.

This study aimed to validate the prognostic value of baseline whole-body metabolic active tumor volume (WB-MATV) and total lesion glycolysis (WB-TLG) measured with [F]fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET/CT) in a large cohort of chemorefractory metastatic colorectal cancer (mCRC) patients treated with multikinase inhibitors (MKI). The secondary objective of this study was to compare WB-MATV and WB-TLG respective prognostic values to commonly used clinical prognostic factors. Out of 238 patients pooled from two successive prospective multicenter trials investigating MKI in chemorefractory mCRC, 224 were considered suitable for analysis. The patients were retrospectively randomly assigned to a development set ( = 155 patients) and a validation set ( = 69 patients). WB-MATV and WB-TLG optimal cutoffs for prediction of overall survival (OS) were determined by Contal and O'Quigley's method. Univariate analyses were performed to assess the prognostic values of WB-MATV and WB-TLG. Multivariate analyses were performed for WB-MATV and WB-TLG along with clinical factors to identify the independent prognostic factors of OS. The prognostic weight for each parameter was obtained from the Cox's model. WB-MATV and WB-TLG optimal cutoffs for OS prediction were 100 cm and 500 g, respectively. Univariate analyses showed that WB-MATV and WB-TLG parameters were strongly related to outcome in both the development and validation sets. In the validation set, the median OS was 5.2 months vs 12.8 months for high vs low WB-MATV (HR: 3.12, < 0.001), and 4.7 months vs 13.9 months for high vs low WB-TLG (HR: 3.67, < 0.001). The multivariate analyses identified that both high WB-MATV and WB-TLG were independent negative prognostic parameters for OS, with the highest prognostic weight among the well-known clinical prognostic factors (HR: 2.46 and 2.23, respectively, < 0.001). Baseline WB-MATV and WB-TLG parameters were validated as strong prognosticators of outcome in a large cohort of chemorefractory mCRC patients treated with MKI. These parameters were identified as independent prognostic imaging biomarkers with the highest prognostic values among the commonly used clinical factors. These biomarkers should therefore be used to support the optimal therapeutic strategy.