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

Abstract

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.

The metabolic clinical risk score as a new prognostic model for surgical decision‐making in patients with colorectal liver metastases

“…16,30 In contrast, all metabolic parameters, including SUV max and SUV peak , with the exception of MTV, were significantly increased in the patients who rapidly relapsed as compared with the patients with prolonged RFS, suggesting that metabolic characteristics could potentially predict the benefit of surgery in individual cases. In contrast with other reports, MTV did not appear as a strong predictive factor, 25,31 even if a tendency toward a higher MTV was observed in ER patients. This could be related to the limited size of the groups but also to the fact that the prognostic impact of tumor burden Accordingly, this study evaluates intrinsic tumor behavior, independent of the response to chemotherapy, as the prognostic value of the response to chemotherapy may vary in patients with CRLM, depending on the number of cycles and on the method used for assessment.…”

Total tumour volume as a prognostic factor in patients with resectable colorectal cancer liver metastases

“…A recent study of patients with chemorefractory metastatic colorectal cancer found that those with a high metabolically active tumour volume, as measured via fluorodeoxyglucose (FDG)‐PET–CT, had a significantly shorter OS. Although that study was similar to the present one, the analysis included extrahepatic metastases and detected only FDG‐PET‐positive lesions.…”

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

“…Contal and O'Quigley's method (26) was used to determine the optimal cfDNA cutoff for survival prediction. The optimal cutoff for WB-MATV was determined to be 100 cm 3 , as previously reported (16). The SUV max , SUV mean , and SUV peak PET parameters were considered as continuous variables for survival prediction.…”

“…Whole-body 18 F-FDG PET/CT allows the assessment of both tumor burden and its glycolytic activity (14,15). Baseline wholebody metabolically active tumor volume (WB-MATV), representing the patient's active tumor load before treatment, was recently validated by our group as a strong prognostic imaging biomarker in a large cohort of chemorefractory mCRC patients (16). Interestingly, another PET parameter evaluating the glycolytic activity of the disease, SUV max , was recently reported to be correlated with cfDNA in advanced non-small cell lung cancer patients (17).…”