Abstract 3096: Liquid biopsy cell-free circulating tumor DNA as prognostic biomarker for stage III colon cancer patients
Authors: Alarcón Carmen Rubio , van der Kruijssen Dave E. , Meiqari Lana , Bosch Linda J. , Simmons John K. , Velculescu Victor E. , van den Broek Daan , Punt Cornelis J. , Coupé Veerle M. , Koopman Miriam , Meijer Gerrit A. , Vink Geraldine R. , Fijneman Remond J. 
Published: September 2020

Abstract
Introduction: Stage III colon cancer patients undergo surgery followed by adjuvant chemotherapy (ACT) according to clinical guidelines. However, 50% would be cured by surgery alone and are being overtreated, while 30-35% will relapse despite adjuvant treatment. This means that only 15-20% of the patients benefit from ACT. Therefore, there is a need for better prognostic biomarkers to stratify patients for ACT. Detection of cell-free circulating tumor DNA (ctDNA) in blood after surgery is indicative of minimal residual disease and highly prognostic for disease recurrence. Hence, detecting liquid biopsy ctDNA is a promising approach to guide treatment decisions in stage III colon cancer.
Aim: Determine prognostic value of ctDNA in stage III colon cancer patients treated with ACT in order to reduce futile treatment.
Methods: 315 stage III colon cancer patients treated with ACT will be included in the prospective observational study “PROVENC3” (PROgnostic Value of Early Notification by Ctdna in Colon Cancer stage 3). The Prospective Dutch Colorectal Cancer Cohort (PLCRC) infrastructure organizes accrual of colorectal cancer patients in more than 50 hospitals in the Netherlands, among which 25 hospitals that accrue patients for PROVENC3. If informed consent is provided, blood is collected at baseline, post-surgery, post-ACT and every six months up to 3 years, and shipped to a central location. Tumor-informed detection of mutations in ctDNA will be performed by combined analysis of targeted sequencing of a panel of &gt;30 genes in cfDNA (PGDx elio plasma test) and a panel of &gt;500 genes in DNA from formalin-fixed paraffin-embedded tumor tissue (PGDx elio tissue complete assay). The clinical, pathological, and molecular data will be handled according to the FAIR (findable, accessible, interoperable and reusable) principles and integrated in cBioPortal.
Results and future directions: Around 125 patients and 400 blood samples included to date. Once sequencing data are obtained we will determine: 1) the proportion of ctDNA-positive and ctDNA-negative patients after surgery and the corresponding recurrence rates; 2) the prognostic value of ctDNA pre-surgery; and 3) the lead time between ctDNA detection and recurrence. Ultimately, the results of this study will be used to model and design an ethically acceptable and cost-effective ctDNA-guided interventional trial, to reduce futile ACT and its associated side-effects in stage III colon cancer patients.
Citation Format: Carmen Rubio Alarcón, Dave E. van der Kruijssen, Lana Meiqari, Linda J. Bosch, John K. Simmons, Victor E. Velculescu, Daan van den Broek, Cornelis J. Punt, Veerle M. Coupé, Miriam Koopman, Gerrit A. Meijer, Geraldine R. Vink, Remond J. Fijneman. Liquid biopsy cell-free circulating tumor DNA as prognostic biomarker for stage III colon cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3096.