PT - JOURNAL ARTICLE AU - Erwin Woff AU - Lisa Salvatore AU - Federica Marmorino AU - Dario Genovesi AU - Gabriela Critchi AU - Thomas Guiot AU - Lieveke Ameye AU - Francesco Sclafani AU - Alain Hendlisz AU - Patrick Flamen TI - Combined Metabolically Active Tumor Volume and Early Metabolic Response Improve Outcome Prediction in Metastatic Colorectal Cancer AID - 10.2967/jnumed.120.245357 DP - 2021 Jul 01 TA - Journal of Nuclear Medicine PG - jnumed.120.245357 4099 - http://jnm.snmjournals.org/content/early/2021/07/29/jnumed.120.245357.short 4100 - http://jnm.snmjournals.org/content/early/2021/07/29/jnumed.120.245357.full AB - Stratification of metastatic colorectal cancer (mCRC) patients is mostly based on clinical and biological characteristics. This study aimed to validate the prognostic value of 18F-FDG PET/CT-based biomarkers such as baseline whole-body metabolically active tumor volume (WB-MATV) and early metabolic response (mR) in mCRC. Methods: The development cohort included chemorefractory mCRC patients enrolled in two prospective Belgian multicenter trials evaluating last-line treatments (multikinase inhibitors). The validation cohort included mCRC patients from an Italian center treated with chemotherapy and bevacizumab as first-line. Baseline WB-MATV was defined as the sum of metabolically active volumes of all target lesions identified on the baseline 18F-FDG PET/CT. Early metabolic response (mR) assessment was performed following usual response criteria (PERCIST–30%, PERCIST–15%, EORTC) and the so-called CONSIST method, which defines response as a decrease of SULmax ≥ 15% for all target lesions. Baseline WB-MATV and early mR assessment were investigated along with usual clinical factors and correlated with overall and progression-free survival (OS/PFS). Results: Clinical factors, baseline WB-MATV and early mR were evaluable in 192/239 and 94/125 patients of the development and validation cohorts, respectively. Except for PERCIST–30%, all response methods were equivalent in terms of outcome prediction and CONSIST was found to be the most accurate. Baseline WB-MATV and early mR using CONSIST method were independent prognostic parameters after adjustment for clinical factors in the development and validation sets for both OS (HR WB-MATV: 1.87 (1.17-2.97), P = 0.005, and HR early mR: 1.79 (1.08-2.95), P = 0.02 for the validation set), and PFS (HR WB-MATV: 1.94 (1.27-2.97), P = 0.002, and HR early mR: 1.69 (1.04-2.73), P = 0.03 for the validation set). Conclusion: Baseline WB-MATV and early mR are strong independent prognostic biomarkers for OS/PFS in mCRC, regardless of treatment received. Therefore, combining these biomarkers improves risk stratification for OS/PFS in mCRC.