{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:15:50Z","timestamp":1772165750957,"version":"3.50.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2\u2009day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion\/permeability parameter,\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sup>trans<\/jats:sup>\n                      , increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2\u2009day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01\u20131.20,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker,\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sup>trans<\/jats:sup>\n                      , offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-021-08097-9","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T16:02:58Z","timestamp":1617292978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-7972","authenticated-orcid":false,"given":"Reem D.","family":"Mahmood","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tine","family":"Descamps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saifee","family":"Mullamitha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nerissa","family":"Mescallado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Backen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross A.","family":"Little","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P. B.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoff J. M.","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Dive","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon C.","family":"Jayson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"8097_CR1","volume-title":"Bowel Cancer statistics [internet]","author":"UK CR","year":"2016","unstructured":"UK CR. Bowel Cancer statistics [internet]. 2016. Available from: https:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/statistics-by-cancer-type\/bowel-cancer"},{"key":"8097_CR2","unstructured":"Office for National Statistics. Cancer survival in England - adults diagnosed [Internet]. Available from: https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/healthandsocialcare\/conditionsanddiseases\/datasets\/cancersurvivalratescancersurvivalinenglandadultsdiagnosed."},{"issue":"8","key":"8097_CR3","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","volume":"27","author":"E Van Cutsem","year":"2016","unstructured":"Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386\u2013422. https:\/\/doi.org\/10.1093\/annonc\/mdw235 Available from: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0923753419347544.","journal-title":"Ann Oncol"},{"key":"8097_CR4","unstructured":"National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Colon Cancer. 2019."},{"issue":"23","key":"8097_CR5","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa032691","volume":"350","author":"H Hurwitz","year":"2004","unstructured":"Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus Irinotecan, fluorouracil, and Leucovorin for metastatic colorectal Cancer. N Engl J Med. 2004;350(23):2335\u201342. https:\/\/doi.org\/10.1056\/NEJMoa032691.","journal-title":"N Engl J Med"},{"issue":"11","key":"8097_CR6","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/S1470-2045(13)70154-2","volume":"14","author":"D Cunningham","year":"2013","unstructured":"Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077\u201385. Available from: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1470204513701542. https:\/\/doi.org\/10.1016\/S1470-2045(13)70154-2.","journal-title":"Lancet Oncol"},{"issue":"3\u20134","key":"8097_CR7","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1159\/000163850","volume":"75","author":"F Kabbinavar","year":"2008","unstructured":"Kabbinavar F, Irl C, Zurlo A, Hurwitz H. Bevacizumab improves the overall and progression-free survival of patients with metastatic colorectal Cancer treated with 5-fluorouracil-based regimens irrespective of baseline risk. Oncology. 2008;75(3\u20134):215\u201323. Available from: https:\/\/www.karger.com\/Article\/FullText\/163850. https:\/\/doi.org\/10.1159\/000163850.","journal-title":"Oncology"},{"issue":"12","key":"8097_CR8","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1200\/JCO.2007.14.9930","volume":"26","author":"LB Saltz","year":"2008","unstructured":"Saltz LB, Clarke S, D\u00edaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013\u20139. https:\/\/doi.org\/10.1200\/JCO.2007.14.9930.","journal-title":"J Clin Oncol"},{"issue":"13","key":"8097_CR9","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/S1470-2045(15)00122-9","volume":"16","author":"C Cremolini","year":"2015","unstructured":"Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306\u201315. Available from: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1470204515001229. https:\/\/doi.org\/10.1016\/S1470-2045(15)00122-9.","journal-title":"Lancet Oncol"},{"issue":"18_suppl","key":"8097_CR10","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.1200\/jco.2007.25.18_suppl.4000","volume":"25","author":"E Van Cutsem","year":"2007","unstructured":"Van Cutsem E, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J, et al. Randomized phase III study of irinotecan and 5-FU\/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. J Clin Oncol. 2007;25(18_suppl):4000. https:\/\/doi.org\/10.1200\/jco.2007.25.18_suppl.4000.","journal-title":"J Clin Oncol"},{"issue":"14","key":"8097_CR11","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1056\/NEJMoa0805019","volume":"360","author":"E Van Cutsem","year":"2009","unstructured":"Van Cutsem E, K\u00f6hne C-H, Hitre E, Zaluski J, Chang Chien C-R, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408\u201317. https:\/\/doi.org\/10.1056\/NEJMoa0805019.","journal-title":"N Engl J Med"},{"issue":"31","key":"8097_CR12","doi-asserted-by":"publisher","first-page":"4697","DOI":"10.1200\/JCO.2009.27.4860","volume":"28","author":"J-Y Douillard","year":"2010","unstructured":"Douillard J-Y, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with Infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697\u2013705. https:\/\/doi.org\/10.1200\/JCO.2009.27.4860.","journal-title":"J Clin Oncol"},{"issue":"19","key":"8097_CR13","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.1200\/JCO.2009.27.7723","volume":"28","author":"NC Tebbutt","year":"2010","unstructured":"Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian gastrointestinal trials group randomized phase III MAX study. J Clin Oncol. 2010;28(19):3191\u20138. https:\/\/doi.org\/10.1200\/JCO.2009.27.7723.","journal-title":"J Clin Oncol"},{"issue":"9","key":"8097_CR14","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1038\/bjc.2012.416","volume":"107","author":"A Greystoke","year":"2012","unstructured":"Greystoke A, Dean E, Saunders MP, Cummings J, Hughes A, Ranson M, et al. Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancertle. Br J Cancer. 2012;107(9):1518\u201324. https:\/\/doi.org\/10.1038\/bjc.2012.416.","journal-title":"Br J Cancer"},{"issue":"3","key":"8097_CR15","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/sj.bjc.6605175","volume":"101","author":"LC Scott","year":"2009","unstructured":"Scott LC, Evans TRJ, Cassidy J, Harden S, Paul J, Ullah R, et al. Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response. Br J Cancer. 2009;101(3):410\u20137. Available from: http:\/\/www.nature.com\/articles\/6605175. https:\/\/doi.org\/10.1038\/sj.bjc.6605175.","journal-title":"Br J Cancer"},{"issue":"11","key":"8097_CR16","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1056\/NEJMoa1305275","volume":"369","author":"J-Y Douillard","year":"2013","unstructured":"Douillard J-Y, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab\u2013FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023\u201334. https:\/\/doi.org\/10.1056\/NEJMoa1305275.","journal-title":"N Engl J Med"},{"issue":"15_suppl","key":"8097_CR17","doi-asserted-by":"publisher","first-page":"3506","DOI":"10.1200\/jco.2014.32.15_suppl.3506","volume":"32","author":"F Ciardiello","year":"2014","unstructured":"Ciardiello F, Lenz H-J, Kohne C-H, Heinemann V, Tejpar S, Melezinek I, et al. Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with\/without cetuximab. J Clin Oncol. 2014;32(15_suppl):3506. https:\/\/doi.org\/10.1200\/jco.2014.32.15_suppl.3506.","journal-title":"J Clin Oncol"},{"issue":"15_suppl","key":"8097_CR18","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1200\/jco.2014.32.15_suppl.3505","volume":"32","author":"C Bokemeyer","year":"2014","unstructured":"Bokemeyer C, Kohne C-H, Ciardiello F, Lenz H-J, Heinemann V, Klinkhardt U, et al. Treatment outcome according to tumor RAS mutation status in OPUS study patients with metastatic colorectal cancer (mCRC) randomized to FOLFOX4 with\/without cetuximab. J Clin Oncol. 2014;32(15_suppl):3505. https:\/\/doi.org\/10.1200\/jco.2014.32.15_suppl.3505.","journal-title":"J Clin Oncol"},{"issue":"3","key":"8097_CR19","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrclinonc.2012.2","volume":"9","author":"JPB O\u2019Connor","year":"2012","unstructured":"O\u2019Connor JPB, Jackson A, Parker GJM, Roberts C, Jayson GC. Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies. Nat Rev Clin Oncol. 2012;9(3):167\u201377. Available from: http:\/\/www.nature.com\/articles\/nrclinonc.2012.2. https:\/\/doi.org\/10.1038\/nrclinonc.2012.2.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"8097_CR20","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1097\/RCT.0b013e318230d905","volume":"35","author":"M Anzidei","year":"2011","unstructured":"Anzidei M, Napoli A, Zaccagna F, Cartocci G, Saba L, Menichini G, et al. Liver metastases from colorectal cancer treated with conventional and antiangiogenetic chemotherapy. J Comput Assist Tomogr. 2011;35(6):690\u20136. Available from: https:\/\/insights.ovid.com\/crossref?an=00004728-201111000-00006. https:\/\/doi.org\/10.1097\/RCT.0b013e318230d905.","journal-title":"J Comput Assist Tomogr"},{"issue":"21","key":"8097_CR21","doi-asserted-by":"publisher","first-page":"6674","DOI":"10.1158\/1078-0432.CCR-09-0731","volume":"15","author":"JPB O\u2019Connor","year":"2009","unstructured":"O\u2019Connor JPB, Carano RAD, Clamp AR, Ross J, Ho CCK, Jackson A, et al. Quantifying Antivascular effects of monoclonal antibodies to vascular endothelial growth factor: insights from imaging. Clin Cancer Res. 2009;15(21):6674\u201382. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-0731.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"8097_CR22","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.2214\/AJR.06.0601","volume":"188","author":"D-M Koh","year":"2007","unstructured":"Koh D-M, Scurr E, Collins D, Kanber B, Norman A, Leach MO, et al. Predicting response of colorectal hepatic metastasis: value of pretreatment apparent diffusion coefficients. Am J Roentgenol. 2007;188(4):1001\u20138. https:\/\/doi.org\/10.2214\/AJR.06.0601.","journal-title":"Am J Roentgenol"},{"issue":"1","key":"8097_CR23","doi-asserted-by":"publisher","first-page":"4672","DOI":"10.1038\/s41467-018-07174-1","volume":"9","author":"GC Jayson","year":"2018","unstructured":"Jayson GC, Zhou C, Backen A, Horsley L, Marti-Marti K, Shaw D, et al. Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer. Nat Commun. 2018;9(1):4672 Available from: http:\/\/www.nature.com\/articles\/s41467-018-07174-1.","journal-title":"Nat Commun"},{"issue":"2","key":"8097_CR24","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/bjc.2016.194","volume":"115","author":"C Zhou","year":"2016","unstructured":"Zhou C, Clamp A, Backen A, Berzuini C, Renehan A, Banks RE, et al. Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab. Br J Cancer. 2016;115(2):228\u201335. Available from: http:\/\/www.nature.com\/articles\/bjc2016194. https:\/\/doi.org\/10.1038\/bjc.2016.194.","journal-title":"Br J Cancer"},{"issue":"17","key":"8097_CR25","doi-asserted-by":"publisher","first-page":"4549","DOI":"10.1158\/1078-0432.CCR-13-3248","volume":"20","author":"A Backen","year":"2014","unstructured":"Backen A, Renehan AG, Clamp AR, Berzuini C, Zhou C, Oza A, et al. The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in Bevacizumab-treated patients with ovarian Cancer. Clin Cancer Res. 2014;20(17):4549\u201358. https:\/\/doi.org\/10.1158\/1078-0432.CCR-13-3248.","journal-title":"Clin Cancer Res"},{"issue":"2","key":"8097_CR26","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228\u201347 Available from: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959804908008733.","journal-title":"Eur J Cancer"},{"issue":"1","key":"8097_CR27","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/s12885-016-2276-3","volume":"16","author":"G Li","year":"2016","unstructured":"Li G, Wang Z, Xu J, Wu H, Cai S, He Y. The prognostic value of lactate dehydrogenase levels in colorectal cancer: a meta-analysis. BMC Cancer. 2016;16(1):249. https:\/\/doi.org\/10.1186\/s12885-016-2276-3.","journal-title":"BMC Cancer"},{"issue":"6","key":"8097_CR28","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/S0959-8049(02)00811-0","volume":"39","author":"M Duffy","year":"2003","unstructured":"Duffy M, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, et al. Clinical utility of biochemical markers in colorectal cancer. Eur J Cancer. 2003;39(6):718\u201327. Available from: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959804902008110. https:\/\/doi.org\/10.1016\/S0959-8049(02)00811-0.","journal-title":"Eur J Cancer"},{"issue":"11","key":"8097_CR29","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1038\/bjc.2013.649","volume":"109","author":"SKM Spencer","year":"2013","unstructured":"Spencer SKM, Pommier AJC, Morgan SR, Barry ST, Robertson JD, Hoff PM, et al. Prognostic\/predictive value of 207 serum factors in colorectal cancer treated with cediranib and\/or chemotherapy. Br J Cancer. 2013;109(11):2765\u201373. Available from: http:\/\/www.nature.com\/articles\/bjc2013649. https:\/\/doi.org\/10.1038\/bjc.2013.649.","journal-title":"Br J Cancer"},{"issue":"2","key":"8097_CR30","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1177\/172460080301800209","volume":"18","author":"P Lissoni","year":"2003","unstructured":"Lissoni P, Rovelli F, Malugani F, Brivio F, Fumagalli L, Gardani GS. Changes in circulating VEGF levels in relation to clinical response during chemotherapy for metastatic cancer. Int J Biol Markers. 2003;18(2):152\u20135. Available from: http:\/\/www.biological-markers.com\/article\/changes-in-circulating-vegf-levels-in-relation-to-clinical-response-during-chemotherapy-for-metastatic-cancer-art005450. https:\/\/doi.org\/10.1177\/172460080301800209.","journal-title":"Int J Biol Markers"},{"issue":"3","key":"8097_CR31","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1200\/JCO.2009.24.8252","volume":"28","author":"S Kopetz","year":"2010","unstructured":"Kopetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY, et al. Phase II trial of Infusional fluorouracil, Irinotecan, and Bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol. 2010;28(3):453\u20139. https:\/\/doi.org\/10.1200\/JCO.2009.24.8252.","journal-title":"J Clin Oncol"},{"key":"8097_CR32","unstructured":"UK Legislation. The medicines for human use (clinical trials) regulations 2004 [Internet]. 2004 [cited 2020 May 12]. Available from: http:\/\/www.legislation.gov.uk\/uksi\/2004\/1031\/pdfs\/uksi_20041031_en.pdf."}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-021-08097-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12885-021-08097-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-021-08097-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T16:03:26Z","timestamp":1617293006000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-021-08097-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["8097"],"URL":"https:\/\/doi.org\/10.1186\/s12885-021-08097-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-44821\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-44821\/v1","asserted-by":"object"}]},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]},"assertion":[{"value":"19 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This trial was performed with local ethics committee approval from the NRES Committee North West - Liverpool East, under the NHS Health Research Authority (11\/NW\/0118) [\n                      \n                      ]. Local research and development department approval was obtained and laboratory work was carried out in accordance with the principles of Good Clinical Laboratory Practice (World Health Organization 2009). All patients gave written informed consent to participate in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"GJMP is a director and shareholder in Bioxydyn Limited, a company with an interest in advanced MRI biomarkers.No other competing interests","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"354"}}