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: 2005-004...

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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/20515c19e0624629b73c35ebcbaccf68
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spelling	oai:doaj.org-article:20515c19e0624629b73c35ebcbaccf682021-12-02T20:13:31ZMultiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.1932-620310.1371/journal.pone.0258988https://doaj.org/article/20515c19e0624629b73c35ebcbaccf682021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258988https://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, p e0258988 (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/20515c19e0624629b73c35ebcbaccf68
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Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

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