dc.contributor.author | Khan, K | |
dc.contributor.author | Rata, M | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Koh, D-M | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Hahne, JC | |
dc.contributor.author | Vlachogiannis, G | |
dc.contributor.author | Hedayat, S | |
dc.contributor.author | Marchetti, S | |
dc.contributor.author | Lampis, A | |
dc.contributor.author | Damavandi, MD | |
dc.contributor.author | Lote, H | |
dc.contributor.author | Rana, I | |
dc.contributor.author | Williams, A | |
dc.contributor.author | Eccles, SA | |
dc.contributor.author | Fontana, E | |
dc.contributor.author | Collins, D | |
dc.contributor.author | Eltahir, Z | |
dc.contributor.author | Rao, S | |
dc.contributor.author | Watkins, D | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Thomas, J | |
dc.contributor.author | Kalaitzaki, E | |
dc.contributor.author | Fotiadis, N | |
dc.contributor.author | Begum, R | |
dc.contributor.author | Bali, M | |
dc.contributor.author | Rugge, M | |
dc.contributor.author | Temple, E | |
dc.contributor.author | Fassan, M | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Braconi, C | |
dc.contributor.author | Valeri, N | |
dc.date.accessioned | 2017-07-05T10:58:51Z | |
dc.date.issued | 2018-08-01 | |
dc.identifier.citation | Gut, 2018, 67 (8), pp. 1484 - 1492 | |
dc.identifier.issn | 0017-5749 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/681 | |
dc.identifier.eissn | 1468-3288 | |
dc.identifier.doi | 10.1136/gutjnl-2017-314178 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1484 - 1492 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMJ PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Phenylurea Compounds | |
dc.subject | Pyridines | |
dc.subject | Magnetic Resonance Imaging | |
dc.subject | Treatment Outcome | |
dc.subject | Prospective Studies | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Biomarkers | |
dc.title | Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-23 | |
rioxxterms.versionofrecord | 10.1136/gutjnl-2017-314178 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Gut | |
pubs.issue | 8 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 67 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Gastrointestinal Cancers Clinical Trials | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Evolutionary Genomics & Modelling | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Gastrointestinal Cancer Biology and Genomics | |
icr.researchteam | Systems and Precision Cancer Medicine | |
icr.researchteam | Magnetic Resonance | |
dc.contributor.icrauthor | Hahne, Jens | |
dc.contributor.icrauthor | Hedayat-Husseyin, Somaieh | |
dc.contributor.icrauthor | Lampis, Andrea | |
dc.contributor.icrauthor | Lote, Hazel | |
dc.contributor.icrauthor | Fontana, Elisa | |
dc.contributor.icrauthor | Collins, David | |
dc.contributor.icrauthor | Braconi, Chiara | |
dc.contributor.icrauthor | Valeri, Nicola | |