Caroline Vandeputte, Pashalina Kehagias, Hakim El Housni, Lieveke Ameye, Jean-François Laes, Christine Desmedt, Christos Sotiriou, Amélie Deleporte, Francesco Puleo, Karen Geboes, Thierry Delaunoit, Gauthier Demolin, Marc Peeters, Lionel D’Hondt, Jos Janssens, Javier Carrasco, Raphaël Marechal, Maria Gomez Galdon, Pierre Heimann, Marianne Paesmans, Patrick Flamen and Alain Hendlisz
Oncotarget. 2018; 9:17756-17769
Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.