Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma

<h4>Purpose</h4> To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. <h4>Method</h4> Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-...

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Autores principales:	Stephan Ursprung, Andrew N. Priest, Fulvio Zaccagna, Wendi Qian, Andrea Machin, Grant D. Stewart, Anne Y. Warren, Timothy Eisen, Sarah J. Welsh, Ferdia A. Gallagher, Tristan Barrett
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/311f38bdaa6b4af39cc2c5dfb6c7f495
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spelling	oai:doaj.org-article:311f38bdaa6b4af39cc2c5dfb6c7f4952021-11-04T06:19:42ZMultiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma1932-6203https://doaj.org/article/311f38bdaa6b4af39cc2c5dfb6c7f4952021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547646/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4> To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. <h4>Method</h4> 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. <h4>Results</h4> 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). <h4>Conclusions</h4> 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. <h4>Trial registration</h4> EudraCtNo: 2005-004502-82.Stephan UrsprungAndrew N. PriestFulvio ZaccagnaWendi QianAndrea MachinGrant D. StewartAnne Y. WarrenTimothy EisenSarah J. WelshFerdia A. GallagherTristan BarrettPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephan Ursprung Andrew N. Priest Fulvio Zaccagna Wendi Qian Andrea Machin Grant D. Stewart Anne Y. Warren Timothy Eisen Sarah J. Welsh Ferdia A. Gallagher Tristan Barrett Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
description	<h4>Purpose</h4> To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. <h4>Method</h4> 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. <h4>Results</h4> 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). <h4>Conclusions</h4> 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. <h4>Trial registration</h4> EudraCtNo: 2005-004502-82.
format	article
author	Stephan Ursprung Andrew N. Priest Fulvio Zaccagna Wendi Qian Andrea Machin Grant D. Stewart Anne Y. Warren Timothy Eisen Sarah J. Welsh Ferdia A. Gallagher Tristan Barrett
author_facet	Stephan Ursprung Andrew N. Priest Fulvio Zaccagna Wendi Qian Andrea Machin Grant D. Stewart Anne Y. Warren Timothy Eisen Sarah J. Welsh Ferdia A. Gallagher Tristan Barrett
author_sort	Stephan Ursprung
title	Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
title_short	Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
title_full	Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
title_fullStr	Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
title_full_unstemmed	Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
title_sort	multiparametric mri for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/311f38bdaa6b4af39cc2c5dfb6c7f495
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Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma

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