TY - JOUR T1 - <strong>Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study</strong> JF - Gut JO - Gut DO - 10.1136/gutjnl-2017-314178 SP - gutjnl-2017-314178 AU - Khurum Khan AU - Mihaela Rata AU - David Cunningham AU - Dow-Mu Koh AU - Nina Tunariu AU - Jens C Hahne AU - George Vlachogiannis AU - Somaieh Hedayat AU - Silvia Marchetti AU - Andrea Lampis AU - Mahnaz Darvish Damavandi AU - Hazel Lote AU - Isma Rana AU - Anja Williams AU - Suzanne A Eccles AU - Elisa Fontana AU - David Collins AU - Zakaria Eltahir AU - Sheela Rao AU - David Watkins AU - Naureen Starling AU - Jan Thomas AU - Eleftheria Kalaitzaki AU - Nicos Fotiadis AU - Ruwaida Begum AU - Maria Bali AU - Massimo Rugge AU - Eleanor Temple AU - Matteo Fassan AU - Ian Chau AU - Chiara Braconi AU - Nicola Valeri Y1 - 2017/07/31 UR - http://gut.bmj.com/content/early/2017/07/31/gutjnl-2017-314178.abstract N2 - 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, &gt;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. ER -