Abstract

BackgroundData on functional imaging parameters such as blood volume (BV) in metastatic renal cell carcinoma (mRCC) is limited. We assessed the association of baseline BV with survival outcome adjusted for baseline clinical factor in patients with mRCC. MethodsBV was quantified using dynamic contrast-enhanced computed tomography in patients from two prospective studies; Angiogenesis Inhibitor Study (AIS) with pazopanib, sunitinib and temsirolimus and the Danish Renal Cancer Group Study-1 (Darenca-1) with interleukin-2, interferon alpha with or without bevacizumab. Data were analyzed using an Advanced Perfusion and Permeability Application softwareprogram, Phillips. BV was evaluated as a binary (above/below median) and as a continuous variable adjusted for treatment, gender, and individual IMDC factors. Association was evaluated using chi squared test for clinical factors, Cox regression for overall survival (OS) and progression-free survival (PFS), and logistic regression for objective response rate (ORR). ResultsAmong 122 included patients, 105 patients had technically feasible scans and were included in the final analysis (AIS, N=29 and Darenca-1, N=76). Median BV was 32.87mL * 100g-1 (range 9.52 to 92.87). BV above median was associated with IMDC favorable risk group (p=0.004), metastasis free interval > 1 year (p=0.007) and male gender (p=0.032). BV below median was associated with anemia (p=0.040) and neutrophilia (p=0.007). Patients with high vs. low baseline BV had longer PFS (12.5 vs. 5.6 months, p=0.015) and longer OS (42.2 vs. 22.4 months, p=0.001), respectively. In multivariate analysis, high baseline BV remained an independent favorable prognostic factor (OS: HR 0.49, 95% CI 0,30-0,78, p=0.003, PFS: HR 0.64; 95% CI 0,42-0,97, p=0.040). BV analyzed as a continuous variable was also associated with OS in multivariate analysis (HR 0.98, 95% CI 0,96-1,00, p=0,017). No association was found between BV and ORR (OR 1.56; 95% CI 0,67-3,63, p=0.3). ConclusionsHigh baseline BV, obtained using functional imaging, is a new independent favorable prognostic factor associated with longer PFS and OS in patients with mRCC. Further research in functional imaging is encouraged. Clinical trial identificationNCT01274273 (Darenca-1 Study). Legal entity responsible for the studyAuthors. FundingPhillips Healthcare provided the software used for DCE-CT analysis Roche and Novartis supported the clinical part of the study financially - but were however not invovled in the imaging analysis. DisclosureA. Drljevic-Nielsen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: BMS. F. Donskov: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Ipsen. All other authors have declared no conflicts of interest.

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