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Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
PURPOSE: 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 t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547646/ https://www.ncbi.nlm.nih.gov/pubmed/34699525 http://dx.doi.org/10.1371/journal.pone.0258988 |
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author | Ursprung, Stephan Priest, Andrew N. Zaccagna, Fulvio Qian, Wendi Machin, Andrea Stewart, Grant D. Warren, Anne Y. Eisen, Timothy Welsh, Sarah J. Gallagher, Ferdia A. Barrett, Tristan |
author_facet | Ursprung, Stephan Priest, Andrew N. Zaccagna, Fulvio Qian, Wendi Machin, Andrea Stewart, Grant D. Warren, Anne Y. Eisen, Timothy Welsh, Sarah J. Gallagher, Ferdia A. Barrett, Tristan |
author_sort | Ursprung, Stephan |
collection | PubMed |
description | PURPOSE: 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 R(2)* (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(-6)mm(2)/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 K(trans) 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. |
format | Online Article Text |
id | pubmed-8547646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85476462021-10-27 Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma Ursprung, Stephan Priest, Andrew N. Zaccagna, Fulvio Qian, Wendi Machin, Andrea Stewart, Grant D. Warren, Anne Y. Eisen, Timothy Welsh, Sarah J. Gallagher, Ferdia A. Barrett, Tristan PLoS One Research Article PURPOSE: 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 R(2)* (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(-6)mm(2)/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 K(trans) 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. Public Library of Science 2021-10-26 /pmc/articles/PMC8547646/ /pubmed/34699525 http://dx.doi.org/10.1371/journal.pone.0258988 Text en © 2021 Ursprung et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ursprung, Stephan Priest, Andrew N. Zaccagna, Fulvio Qian, Wendi Machin, Andrea Stewart, Grant D. Warren, Anne Y. Eisen, Timothy Welsh, Sarah J. Gallagher, Ferdia A. Barrett, Tristan Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547646/ https://www.ncbi.nlm.nih.gov/pubmed/34699525 http://dx.doi.org/10.1371/journal.pone.0258988 |
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