Abstract
BackgroundAngiogenesis 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).MethodsAs 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).ResultsAt 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).ConclusionsDifferently from MVD, DCE-CT-derived BV and BF had prognostic impact and may better reflect angiogenesis in mRCC.Trial registrationNCT01274273
Highlights
Angiogenesis is prominent in metastatic renal cell carcinoma
The disease can be treated with immunotherapy: interferon-alpha (INF-α2b, IntronA: Merck & Co., Whitehouse Station, NJ) and interleukin-2 were first shown to be effective [6] followed by the checkpoint inhibitors nivolumab (Opdivo: Bristol Myers Squibb, New York, NY) and ipilimumab (Yervoy: Bristol Myers Squibb, New York, NY) [7]
A total of 13 (52%) patients were treated with interleukin 2 (IL-2) and IFN-α, and 12 (48%) patients were treated with IL-2, IFN-α, and bevacizumab
Summary
Angiogenesis is prominent in metastatic renal cell carcinoma (mRCC). Angiogenesis plays a crucial role in growth, metastasis, and progression in RCC [4]. Blocking angiogenesis by vascular endothelial growth factor (VEGF) receptor-targeted therapies sorafenib (Nexavar, Bayer, Leverkusen, Germany), sunitinib (Sutent: Pfizer, New York, NY), pazopanib (Votrient: Novartis Oncology, East Hanover, NJ/before 2015: GlaxoSmithKline, Research Triangle Park, NC), tivozanib (Fotivda: EUSA Pharma, Hempstead, UK), cabozantinib (Cabometyx: Ipsen Pharma, Paris, France), or anti-VEGF antibodies such as bevacizumab (Avastin: Genentech, Roche, South San Francisco, CA; all other countries: Basel, Switzerland), has been the mainstay of therapy for more than a decade in patients with metastatic RCC (mRCC) [5]. Immunotherapy combined with VEGF inhibitors has shown promising activity [8,9,10,11]
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