Repository logo
 

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

Published version
Peer-reviewed

Change log

Authors

Zaccagna, Fulvio 
Qian, Wendi 
Machin, Andrea 

Abstract

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 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.

Description

Funder: Cancer Research UK


Funder: Cancer Research UK Cambridge Centre


Funder: Cambridge Commonwealth, European and International Trust; funder-id: http://dx.doi.org/10.13039/501100003343


Funder: Mark Foundation For Cancer Research; funder-id: http://dx.doi.org/10.13039/100014599


Funder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester


Funder: NIHR Cambridge Biomedical Research Centre


Funder: Cambridge Experimental Cancer Medicine Centre


Funder: Cambridge Clinical Trials Unit


Funder: Addenbrooke’s Charitable Trust

Keywords

Research Article, Medicine and health sciences, Research and analysis methods, Biology and life sciences

Journal Title

PLOS ONE

Conference Name

Journal ISSN

1932-6203

Volume Title

16

Publisher

Public Library of Science