Circulating tumor DNA monitoring in the LIMA project - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Ekaterina Pisareva ^1,2 Brice Pastor ^1,2 Pieter J. van der Zaag ³ Rémi Dangla ⁴ Barbara André ⁴ Jordan Madic ⁴ Alexander Sartori ⁵ David Coorey ⁵ Barbara Ottolini ⁶ Alain R. Thierry ^1,2

¹IRCM, Montpellier Cancer Research Institute, Montpellier, France
²U1194, French National Institute of Health and Medical Research (INSERM), Montpellier, France
³High Tech Campus 11, Philips Research, Eindhoven, Netherlands
⁴Stilla Technologies, Stilla Technologies, Villejuif, France
⁵AGENA Bioscience GmbH, AGENA Bioscience GmbH, Hamburg, Germany
⁶DiaDx, DiaDx, Montpellier, France

Liquid biopsies and IMAging for improved cancer care (LIMA) is a four year project funded by the EU Horizon 2020 program. LIMA’s overall objective is the development and validation of new technologies and tools in oncology to include liquid biopsies in the clinical workflow, aiming at introducing a more precise and dynamic genetic characterization of the tumor at diagnosis and during the treatment phases. This will be done by combining molecular information from liquid biopsies (circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) and direct in-vivo tumor characterization from advanced magnetic resonance imaging (MRI).

In this ongoing program we are focusing on locally advanced rectal and breast cancers eligible for neoadjuvant therapy (NAT) followed by surgery. The aim of the LIMA project is to improve the monitoring of patient’s response at diagnosis and during NAT, to stratify between good and poor NAT responders, based on the molecular profile of the tumor. This strategy requires a personalized approach with careful matching of patient to drug therapy, based on current mutational profile of the tumor. The goal of the first LIMA work package (WP1) is to provide the more appropriate and efficient technologies in detecting various mutations in various genes in respect to the breast and rectal cancer to be further implemented in clinical study. Three ctDNA-based technologies were evaluated with regard to sensitivity, specificity and other parameters: IntPlex (DiaDx/INSERM), Crystal Digital PCR (Stilla Technologies), UltraSEEK (Agena Bioscience). These technologies are based on advanced Q-PCR, digital PCR and MALDI-TOF methods, respectively. Each of these technologies will be used for fast and accurate molecular profiling tumor heterogeneity, not only at the first diagnosis but during the NAT to monitor the treatment effectiveness. The combination of ctDNA, CTCs and advanced MRI will be assessed towards an optimal rectal and breast cancer management care.