Diffusion-weighted and multiphase contrast-enhanced MRI as surrogate markers of response to neoadjuvant sunitinib in metastatic renal cell carcinoma

TY - JOUR

T1 - Diffusion-weighted and multiphase contrast-enhanced MRI as surrogate markers of response to neoadjuvant sunitinib in metastatic renal cell carcinoma

AU - Bharwani, N.

AU - Miquel, M. E.

AU - Powles, T.

AU - Dilks, P.

AU - Shawyer, A.

AU - Sahdev, A.

AU - Wilson, P. D.

AU - Chowdhury, Simon

AU - Berney, D. M.

AU - Rockall, A. G.

PY - 2014/2/4

Y1 - 2014/2/4

N2 - Background: Current imaging criteria for categorising disease response in metastatic renal cell carcinoma (mRCC) correlate poorly with overall survival (OS) in patients on anti-angiogenic therapies. We prospectively assess diffusion-weighted and multiphase contrast-enhanced (MCE) MR imaging (MRI) as markers of outcome.Methods: Treatment-naive mRCC patients on a phase II trial using sunitinib completed an MRI substudy. Whole-tumour apparent diffusion coefficient (ADC) maps and histograms were generated, and mean ADC and AUC(low) (proportion of the tumour with ADC values lying below the 25th percentile of the ADC histogram) recorded. On MCE-MRI, regions of interest were drawn around the most avidly enhancing components to analyse enhancement parameters. Baseline (n = 26) and treatment-related changes in surviving patients (n = 20) were correlated with OS. Imaged metastases were also analysed.Results: Forty-seven per cent of the patients showed significant changes in whole-tumour mean ADC following therapy, but there was no correlation with outcome. Patients with a high baseline AUClow and greater-than-median AUClow increase had reduced OS (HR = 3.67 (95% confidence interval (CI) = 1.23-10.9), P = 0.012 and HR = 3.72 (95% CI = 0.98-14.21), P = 0.038, respectively). There was no correlation between MCE-MRI parameters and OS. Twenty-eight metastases were analysed and showed positive correlation with primary tumour mean ADC for individual patients (r = 0.607; P <0.001).Conclusion: Primary RCC ADC histogram analysis shows dynamic changes with sunitinib. Patients in whom the tumour ADC histogram demonstrated high baseline AUC(low) or a greater-than-median increase in AUC(low) with treatment had reduced OS.

AB - Background: Current imaging criteria for categorising disease response in metastatic renal cell carcinoma (mRCC) correlate poorly with overall survival (OS) in patients on anti-angiogenic therapies. We prospectively assess diffusion-weighted and multiphase contrast-enhanced (MCE) MR imaging (MRI) as markers of outcome.Methods: Treatment-naive mRCC patients on a phase II trial using sunitinib completed an MRI substudy. Whole-tumour apparent diffusion coefficient (ADC) maps and histograms were generated, and mean ADC and AUC(low) (proportion of the tumour with ADC values lying below the 25th percentile of the ADC histogram) recorded. On MCE-MRI, regions of interest were drawn around the most avidly enhancing components to analyse enhancement parameters. Baseline (n = 26) and treatment-related changes in surviving patients (n = 20) were correlated with OS. Imaged metastases were also analysed.Results: Forty-seven per cent of the patients showed significant changes in whole-tumour mean ADC following therapy, but there was no correlation with outcome. Patients with a high baseline AUClow and greater-than-median AUClow increase had reduced OS (HR = 3.67 (95% confidence interval (CI) = 1.23-10.9), P = 0.012 and HR = 3.72 (95% CI = 0.98-14.21), P = 0.038, respectively). There was no correlation between MCE-MRI parameters and OS. Twenty-eight metastases were analysed and showed positive correlation with primary tumour mean ADC for individual patients (r = 0.607; P <0.001).Conclusion: Primary RCC ADC histogram analysis shows dynamic changes with sunitinib. Patients in whom the tumour ADC histogram demonstrated high baseline AUC(low) or a greater-than-median increase in AUC(low) with treatment had reduced OS.

KW - renal cancer

KW - diffusion-weighted MRI

KW - multiphase contrast-enhanced MRI

KW - sunitinib

KW - PHASE-I

KW - COMPUTED-TOMOGRAPHY

KW - LIVER METASTASES

KW - INTERFERON-ALPHA

KW - TARGETED THERAPY

KW - SOLID TUMORS

KW - CANCER

KW - BIOMARKER

KW - SIZE

KW - INHIBITOR

U2 - 10.1038/bjc.2013.790

DO - 10.1038/bjc.2013.790

M3 - Article

SN - 0007-0920

VL - 110

SP - 616

EP - 624

JO - BJC: British Journal of Cancer

JF - BJC: British Journal of Cancer

IS - 3

ER -