Prognostic value of DCE-CT-derived blood volume and flow compared to core biopsy microvessel density in patients with metastatic renal cell carcinoma

Aska Drljevic-Nielsen, Finn Rasmussen, Patricia Switten Nielsen, Christina Stilling, Kennet Thorup, Jill Rachel Mains, Hans Henrik Torp Madsen, Frede Donskov, Aska Drljevic-Nielsen, Finn Rasmussen, Patricia Switten Nielsen, Christina Stilling, Kennet Thorup, Jill Rachel Mains, Hans Henrik Torp Madsen, Frede Donskov

Abstract

Background: Angiogenesis is prominent in metastatic renal cell carcinoma (mRCC). We compared two angiogenesis assessment methods: dynamic contrast-enhanced computed tomography (DCE-CT)-derived blood volume (BV) and blood flow (BF) and core biopsy microvessel density (MVD).

Methods: As planned in DaRenCa Study-1 study, DCE-CT and core biopsy were performed from the same tumour/metastasis at baseline. MVD was assessed by CD34 immunostaining in tumour (CD34-indexT) or tumour including necrosis (CD34-indexTN). BV and BF were assessed using the DCE-CT software. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier analysis. Spearman coefficient (rho) tested the correlation between MVD and BV, BF, or CT density (HU).

Results: At baseline, 25 patients had analysable scans and tissue. BVdeconv, BVPatlak, and BFdeconv > median were associated with favourable OS (43.2 versus 14.6 months, p = 0.002; 31.6 versus 20.2 months, p = 0.015; and 31.6 versus 24.5 months, p = 0.019). CD34-indexT and CD34-indexTN did not correlate with age (p = 0.543), sex (p = 0.225), treatment (p = 0.848), International mRCC Database Consortium category (p = 0.152), synchronous versus metachronous metastatic disease (p = 0.378), or tumour volume (p = 0.848). CD34-indexT or CD34-indexTN > median was not associated with PFS (p = 0.441 and p = 0.854, respectively) or OS (p = 0.987 and p =0.528, respectively). CD34-indexT or CD34-indexTN was not correlated with BV, BF, or HU (rho 0.20-0.26).

Conclusions: Differently from MVD, DCE-CT-derived BV and BF had prognostic impact and may better reflect angiogenesis in mRCC.

Trial registration: NCT01274273.

Keywords: Blood volume; Carcinoma (renal cell); Microvascular density; Prognosis; Tomography (x-ray computed).

Conflict of interest statement

A. Drljevic-Nielsen reports receiving research grants from Ipsen, the Maersk Foundation, and the Health Research Foundation of Central Denmark Region, and conference travels from Pfizer and Ipsen. F. Donskov reports receiving research grants from Ipsen, Pfizer, MSD, and the Health Research Foundation of Central Denmark Region. JR. Mains reports receiving research grants from the Memorial Foundation of Eva and Henry Fraenkel and the Health Research Foundation of Central Denmark Region and conference travels from Pfizer. No potential conflicts of interest were disclosed by C. Stilling, P. Switten Nielsen, F. Rasmussen, and K. Thorup.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
A heterogeneous metastasis in the right iliac bone (purple arrow) at baseline presented on (a) CE-CT, (b) BVdeconv map, and (c) the corresponding BVdeconv histogram. The histogram depicts a large BV range, illustrating the intratumoural heterogeneity. BVdeconv Blood volume (deconvolution), CE-CT Contrast-enhanced computed tomography, No. Number
Fig. 2
Fig. 2
A retroperitoneal metastasis marked with a white circle depicted on (a) a contrast-enhanced CT at peak arterial enhancement with the corresponding functional imaging colour maps, (b) BVdeconv, (c) BVPatlak, and (d) BFdeconv. BVdeconv histogram for the entire target lesion at baseline is shown in e, while f represents the CD34 immunostaining from the same retroperitoneal metastasis with microvessels (arrow) stained brown. BVdeconv Blood volume (deconvolution), BVPatlak Blood volume (Patlak), BFdeconv Blood flow (deconvolution)
Fig. 3
Fig. 3
Kaplan-Meier curves for overall survival for high versus low (a) BVdeconv, (b) BVPatlak, (c) BFdeconv, and (d) CD34-index in tumor, respectively, demonstrating favourable survival outcome for high BVdeconv, BVPatlak, and BFdeconv, whereas CD34-index was not associated to survival outcome. BVdeconv Blood volume (deconvolution), BVPatlak Blood volume (Patlak), BFdeconv Blood flow (deconvolution)
Fig. 4
Fig. 4
Plots illustrating no correlation between CD34-index in tumor outlines and (a) BFdeconv, (b) BVPatlak, (c) BVdeconv, and (d) HU, respectively at baseline. BVdeconv Blood volume (deconvolution), BVPatlak Blood volume (Patlak), BFdeconv Blood flow (deconvolution), HU Hounsfield units

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