The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer
(2015) PLoS One — Vol. 10, n° 9, p. e0138341 (2015)
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- (en) BACKGROUND: Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). METHODS: Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions. RESULTS: Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8-10.5) and 4.2 months (95% CI: 3.4-4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21-0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36-0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS. CONCLUSION: The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01290926.
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Hendlisz, A., Deleporte, A., Delaunoit, T., Maréchal, R., Peeters, M., Holbrechts, S., Van den Eynde, M., Houbiers, G., Filleul, B., Van Laethem, J.-L., Ceyssens, S., Barbuto, A.-M., Lhommel, R., Demolin, G., Garcia, C., ElMansy, H., Ameye, L., Moreau, M., Guiot, T., et al. (2015). The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer. PLoS One, 10(9), e0138341. https://doi.org/10.1371/journal.pone.0138341 (Original work published 2015)