RT Journal Article SR Electronic T1 Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP gutjnl-2017-314178 DO 10.1136/gutjnl-2017-314178 A1 Khurum Khan A1 Mihaela Rata A1 David Cunningham A1 Dow-Mu Koh A1 Nina Tunariu A1 Jens C Hahne A1 George Vlachogiannis A1 Somaieh Hedayat A1 Silvia Marchetti A1 Andrea Lampis A1 Mahnaz Darvish Damavandi A1 Hazel Lote A1 Isma Rana A1 Anja Williams A1 Suzanne A Eccles A1 Elisa Fontana A1 David Collins A1 Zakaria Eltahir A1 Sheela Rao A1 David Watkins A1 Naureen Starling A1 Jan Thomas A1 Eleftheria Kalaitzaki A1 Nicos Fotiadis A1 Ruwaida Begum A1 Maria Bali A1 Massimo Rugge A1 Eleanor Temple A1 Matteo Fassan A1 Ian Chau A1 Chiara Braconi A1 Nicola Valeri YR 2017 UL http://gut.bmj.com/content/early/2017/07/31/gutjnl-2017-314178.abstract AB Objective Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection.Design Patients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (Ktrans), enhancing fraction (EF) and their product KEF (summarised median values of Ktrans× EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal RAS mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies.Results Twenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07–1.04), p=0.06).Conclusions Combining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications.