Abstract 3241: Cell-free DNA fragmentomes for treatment response monitoring in patients with metastatic colorectal cancer: the DOLPHIN study
Authors: Denise E. van Steijn, Jamie Medina, Lorenzo Rinaldi, Adria Closa, Lana Meiqari, Erica Peters, Alissa Konicki, Frederieke H. van der Baan, Mariska Bierkens, Haoyue Wang, Marjolein J. Greuter, Birgit I. Lissenberg-Witte, Veerle M. Coupé, Marie V. Coignet, Victor E. Velculescu, Daan van den Broek, Gerrit A. Meijer, Max J. Lahaye, Manon N.G. Braat, Jeanine M. Roodhart, Nicholas C. Dracopoli, Geraldine R. Vink, Niels F. Kok, Remond J. Fijneman
Journal: Cancer Research (2025)

Abstract Accurate monitoring of treatment response in patients with metastatic colorectal cancer (mCRC) is essential for optimizing therapeutic strategies. Current response evaluation relies on imaging-based assessment of tumor size changes. However, this approach is limited by suboptimal sensitivity for detecting lymph node and peritoneal metastases, as well as inter-reader variability. Circulating tumor DNA (ctDNA) is indicative of the number of neoplastic cells and could have clinical value to CT imaging for assessment of treatment response. A mutation- and tumor-independent ctDNA assay was recently developed, demonstrating its potential for longitudinal assessment of treatment response: the DELFI-tumor fraction (DELFI-TF) score. The DOLPHIN study aims to investigate the added clinical value of the DELFI-TF score compared to CT imaging for treatment response monitoring in patients with mCRC. DOLPHIN is a prospective, observational, multi-center substudy of the Prospective Dutch ColoRectal Cancer cohort (PLCRC). Clinical data, images, and blood samples from 400 patients receiving systemic therapy in 11 hospitals in the Netherlands are being collected. Blood samples are drawn longitudinally in conjunction with routine CT imaging. The plasma cfDNA fragmentomes will be assessed using the DELFI-TF. DELFI-TF is a locked and validated machine learning model that quantifies tumor burden uses using cell-free DNA (cfDNA) fragmentomes data derived from low-coverage whole genome sequencing. Droplet digital PCR (ddPCR) ctDNA testing will be used as a reference for patients with confirmed RAS/BRAF mutations. The primary objective is to evaluate the association between ctDNA changes and clinical response. Secondary objectives include analyzing the association between ctDNA changes and RECIST criteria (I), correlation with serum carcinoembryonic antigen (CEA) levels at specified points during systemic therapy (II), lead time of ctDNA-testing versus CT imaging for detecting disease progression (III), the prognostic value of longitudinal ctDNA-testing (IV). Until November 2024, 385 patients have been enrolled, with the anticipated inclusion target of 400 patients expected to be reached by December 2024. A comprehensive overview of the DOLPHIN study population will be presented at the conference. Application of DELFI-TF and ddPCR ctDNA testing on the initial cohort of collected samples is scheduled to commence in early 2025. The DOLPHIN study will assess the clinical validity of the DELFI-TF in monitoring treatment response and investigate whether longitudinal ctDNA-testing can complement or partially replace imaging-based treatment response monitoring. These findings could pave the way for ctDNA-guided decision-making, supporting and enhancing accurate assessment of therapeutic effectiveness and therapeutic decision-making for patients with mCRC. Citation Format: Denise E. van Steijn, Jamie Medina, Lorenzo Rinaldi, Adria Closa, Lana Meiqari, Erica Peters, Alissa Konicki, Frederieke H. van der Baan, Mariska Bierkens, Haoyue Wang, Marjolein J. Greuter, Birgit I. Lissenberg-Witte, Veerle M. Coupé, Marie V. Coignet, Victor E. Velculescu, Daan van den Broek, Gerrit A. Meijer, Max J. Lahaye, Manon N.G. Braat, Jeanine M. Roodhart, Nicholas C. Dracopoli, Geraldine R. Vink, Niels F. Kok, Remond J. Fijneman. Cell-free DNA fragmentomes for treatment response monitoring in patients with metastatic colorectal cancer: the DOLPHIN study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3241.