{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:33:48Z","timestamp":1784313228346,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005\u2010004502\u201082) single\u2010centre, single\u2010arm, single\u2010agent, Phase II trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Treatment\u2010na\u00efve patients with metastatic renal cell carcinoma (mRCC) received 50\u2009mg once daily sunitinib for 12\u2009days pre\u2010surgically, then post\u2010surgery on 4 week\u2010on, 2 week\u2010off, repeating 6\u2010week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast\u2010enhanced magnet resonance imaging (DCE\u2010MRI) and research blood sampling were performed at baseline and after 12\u2009days. Computed tomography imaging was performed at baseline and post\u2010surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE\u2010MRI of the tumour following pre\u2010surgery sunitinib, overall survival (OS), progression\u2010free survival (PFS), response duration, surgical morbidity\/mortality, and toxicity. Translational and imaging endpoints were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 14 patients received pre\u2010surgery sunitinib, 71% (10\/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7\u201384.8%). The median OS was 33.7\u2009months and median PFS was 15.7\u2009months. Amongst those achieving a PR or CR, the median response duration was 8.7\u2009months. No unexpected surgical complications, sunitinib\u2010related toxicities, or surgical delays occurred. Within the translational endpoints, pre\u2010surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation\u201031 (CD31), Ki67, circulating vascular endothelial growth factor\u2010C (VEGF\u2010C), and transfer constant (\n                      <jats:italic>\n                        K\n                        <jats:sup>Trans<\/jats:sup>\n                      <\/jats:italic>\n                      , measured using DCE\u2010MRI; all\n                      <jats:italic>P\u2009<\/jats:italic>\n                      &lt;\u20090.05). There was a trend for improved OS in patients with high baseline plasma VEGF\u2010C expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02). Reduction in radiological tumour volume after pre\u2010surgical sunitinib correlated with high percentage of solid tumour components at baseline (Spearman\u2019s coefficient \u03c1\u2009=\u20090.69,\n                      <jats:italic>P\u2009<\/jats:italic>\n                      =\u20090.02). Conversely, the percentage tumour volume reduction correlated with lower baseline percentage necrosis (coefficient = \u22120.51,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neoadjuvant studies such as the NeoSun can safely and effectively explore translational biological and imaging endpoints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.15600","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T05:39:57Z","timestamp":1632289197000},"page":"244-253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dynamic biomarker and imaging changes from a phase II study of pre\u2010 and post\u2010surgical sunitinib"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5690-2677","authenticated-orcid":false,"given":"Sarah J.","family":"Welsh","sequence":"first","affiliation":[{"name":"Department of Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"},{"name":"Department of Surgery Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"},{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Warren","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge UK"},{"name":"Department of Pathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9771-4290","authenticated-orcid":false,"given":"Andrew N.","family":"Priest","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Barrett","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge UK"},{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Ursprung","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge UK"},{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdia A.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge UK"},{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Zaccagna","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-9140","authenticated-orcid":false,"given":"Grant D.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Surgery Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"},{"name":"Cancer Research UK Cambridge Centre Urological Malignancies Programme University of Cambridge  Cambridge 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University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ingleson","sequence":"additional","affiliation":[{"name":"Department of Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mullin","sequence":"additional","affiliation":[{"name":"Department of Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony C. 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