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dc.contributor.authorUrsprung, Stephan
dc.contributor.authorPriest, Andrew N
dc.contributor.authorZaccagna, Fulvio
dc.contributor.authorQian, Wendi
dc.contributor.authorMachin, Andrea
dc.contributor.authorStewart, Grant
dc.contributor.authorWarren, Anne
dc.contributor.authorEisen, Tim
dc.contributor.authorWelsh, Sarah
dc.contributor.authorGallagher, Ferdia
dc.contributor.authorBarrett, Tristan
dc.date.accessioned2021-10-15T23:31:10Z
dc.date.available2021-10-15T23:31:10Z
dc.date.issued2021
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329443
dc.description.abstractPURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). CONCLUSIONS: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. TRIAL REGISTRATION: EudraCtNo: 2005-004502-82.
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAll rights reserved
dc.titleMultiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.
dc.typeArticle
prism.issueIdentifier10
prism.publicationDate2021
prism.publicationNamePLoS One
prism.startingPagee0258988
prism.volume16
dc.identifier.doi10.17863/CAM.76891
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.1371/journal.pone.0258988
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021
dc.contributor.orcidUrsprung, Stephan [0000-0003-2476-178X]
dc.contributor.orcidPriest, Andrew N [0000-0002-9771-4290]
dc.contributor.orcidStewart, Grant [0000-0003-3188-9140]
dc.contributor.orcidWarren, Anne [0000-0002-1170-7867]
dc.contributor.orcidEisen, Tim [0000-0001-9663-4873]
dc.contributor.orcidWelsh, Sarah [0000-0001-5690-2677]
dc.contributor.orcidGallagher, Ferdia [0000-0003-4784-5230]
dc.contributor.orcidBarrett, Tristan [0000-0002-1180-1474]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (C12912/A27150)
pubs.funder-project-idCancer Research UK (C19212/A29082)
cam.issuedOnline2021-10-26
cam.orpheus.successTue Feb 01 19:02:03 GMT 2022 - Embargo updated*
cam.orpheus.counter2
rioxxterms.freetoread.startdate2021-10-26


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