Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma
Stewart, Grant D.
Welsh, Sarah J.
Gallagher, Ferdia A.
Public Library of Science
MetadataShow full item record
Ursprung, S., Priest, A. N., Zaccagna, F., Qian, W., Machin, A., Stewart, G. D., Warren, A. Y., et al. (2021). Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma. PLOS ONE, 16 (10) https://doi.org/10.1371/journal.pone.0258988
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
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.
Research Article, Medicine and health sciences, Research and analysis methods, Biology and life sciences
External DOI: https://doi.org/10.1371/journal.pone.0258988
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329981