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Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy
Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

Background: Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH). Objective: To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC). Design, setting, and participants: A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions. Intervention: The phase II trial assessed vascular endothelial growth factor-targeted therapy ± Src inhibition. Outcome measurements and statistical analysis: RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria. Results and limitations: In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39–2.92; p < 0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43–3.14; p < 0.001). Limitations include retrospective study design. Conclusions: RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required. Patient summary: We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.

Heterogeneity, Prognostic factor, Radiological response, Renal cell carcinoma, Vascular endothelial growth factor
Hall, Peter E.
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Shepherd, Scott T.C.
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Brown, Janet
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Larkin, James
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Jones, Robert
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Ralph, Christy
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Hawkins, Robert
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Chowdhury, Simon
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Boleti, Ekaterini
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Bahl, Amit
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Fife, Kate
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Webb, Andrew
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Crabb, Simon J.
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Geldart, Thomas
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Hill, Robert
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Dunlop, Joanna
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McLaren, Duncan
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Ackerman, Charlotte
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Wimalasingham, Akhila
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Beltran, Luis
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Nathan, Paul
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Powles, Thomas
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Hall, Peter E.
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Shepherd, Scott T.C.
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Brown, Janet
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Larkin, James
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Jones, Robert
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Ralph, Christy
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Hawkins, Robert
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Chowdhury, Simon
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Boleti, Ekaterini
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Bahl, Amit
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Fife, Kate
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Webb, Andrew
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Crabb, Simon J.
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Geldart, Thomas
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Hill, Robert
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Dunlop, Joanna
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McLaren, Duncan
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Ackerman, Charlotte
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Wimalasingham, Akhila
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Beltran, Luis
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Nathan, Paul
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Powles, Thomas
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Hall, Peter E., Shepherd, Scott T.C., Brown, Janet, Larkin, James, Jones, Robert, Ralph, Christy, Hawkins, Robert, Chowdhury, Simon, Boleti, Ekaterini, Bahl, Amit, Fife, Kate, Webb, Andrew, Crabb, Simon J., Geldart, Thomas, Hill, Robert, Dunlop, Joanna, McLaren, Duncan, Ackerman, Charlotte, Wimalasingham, Akhila, Beltran, Luis, Nathan, Paul and Powles, Thomas (2019) Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. European Urology Focus. (doi:10.1016/j.euf.2019.01.010).

Record type: Article

Abstract

Background: Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH). Objective: To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC). Design, setting, and participants: A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions. Intervention: The phase II trial assessed vascular endothelial growth factor-targeted therapy ± Src inhibition. Outcome measurements and statistical analysis: RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria. Results and limitations: In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39–2.92; p < 0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43–3.14; p < 0.001). Limitations include retrospective study design. Conclusions: RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required. Patient summary: We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.

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Accepted/In Press date: 16 January 2019
e-pub ahead of print date: 6 February 2019
Keywords: Heterogeneity, Prognostic factor, Radiological response, Renal cell carcinoma, Vascular endothelial growth factor

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Local EPrints ID: 428841
URI: https://eprints.soton.ac.uk/id/eprint/428841
PURE UUID: 2aced3ee-4275-4ae7-bed1-803f6adc749f

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Date deposited: 11 Mar 2019 17:30
Last modified: 13 Mar 2019 17:33

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Contributors

Author: Peter E. Hall
Author: Scott T.C. Shepherd
Author: Janet Brown
Author: James Larkin
Author: Robert Jones
Author: Christy Ralph
Author: Robert Hawkins
Author: Simon Chowdhury
Author: Ekaterini Boleti
Author: Amit Bahl
Author: Kate Fife
Author: Andrew Webb
Author: Simon J. Crabb
Author: Thomas Geldart
Author: Robert Hill
Author: Joanna Dunlop
Author: Duncan McLaren
Author: Charlotte Ackerman
Author: Akhila Wimalasingham
Author: Luis Beltran
Author: Paul Nathan
Author: Thomas Powles

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