Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis

• DOI: 10.3389/fonc.2022.855463
• Publication Date: 2022-03-28T22:55:05Z
• Authors: Ioannis D. Kyroch...; Georgios K. Glant...; Anna Goussia; Alexia Eliades; Achilleas Achilleos; Kyriakos Tsangaras; Irene Hadjidemetriou; Marilena Elpidorou; Marios Ioannides; George Koumbaris; Michail Mitsis; Philippos C. Pats...; Dimitrios Roukos
• Keywords: Tumor Heterogeneity; Liquid biopsy; Precision oncology; Primary tumor; Targeted Therapy; Circulating tumor cell

Introduction The mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) liver metastasis (LM) remain poorly understood. Objective We evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary matched metastatic intratumor (ITH) coupled circulating tumor DNA (ctDNA) variability. Methods A total 122 multi-regional perioperative liquid biopsies from 18 were analyzed via targeted next-generation sequencing (NGS). Results proportion ITH 53% 56% CRC LM respectively, while 35% harbored de novo mutations indicating spatiotemporal evolution necessity multiregional analysis. Among alterations biopsies, cfDNA identified 25% patients, which undetectable both LM. All 17 driver targetable by molecularly drugs, either approved or currently under evaluation. Conclusion Our proof-of-concept prospective study provides initial evidence on clinical superiority IPH warrants conduction precision oncology trials to utility I PH-driven therapy.