%0 Journal Article
%T Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis.
%A Kyrochristos ID
%A Glantzounis GK
%A Goussia A
%A Eliades A
%A Achilleos A
%A Tsangaras K
%A Hadjidemetriou I
%A Elpidorou M
%A Ioannides M
%A Koumbaris G
%A Mitsis M
%A Patsalis PC
%A Roukos D
%J Front Oncol
%V 12
%N 0
%D 2022
%M 35402285
%F 5.738
%R 10.3389/fonc.2022.855463
%X <B>UNASSIGNED: </B>The mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood.<BR><B>UNASSIGNED: </B>We evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability.<BR><B>UNASSIGNED: </B>A total of 122 multi-regional tumor and perioperative liquid biopsies from 18 patients were analyzed via targeted next-generation sequencing (NGS).<BR><B>UNASSIGNED: </B>The proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored de novo mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies, de novo mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored mutations targetable by molecularly targeted drugs, either approved or currently under evaluation.<BR><B>UNASSIGNED: </B>Our proof-of-concept prospective study provides initial evidence on potential clinical superiority of IPH and warrants the conduction of precision oncology trials to evaluate the clinical utility of I PH-driven matched therapy.