Late adverse events to iodinated contrast media in patients treated with IL-2: a safety report from the Danish Renal Carcinoma Group (DaRenCa) study - 1.

BACKGROUND: A higher incidence of late adverse events (LAEs) to iodinated contrast media in interleukin-2 (IL-2)-treated patients has been reported. PURPOSE: To assess the incidence of LAEs after administration of iodinated contrast media in patients with metastatic renal cell carcinoma (mRCC) treated with IL-2. MATERIAL AND METHODS: Patients were randomized to treatment with IL-2 and interferon-α with/without bevacizumab in the Danish Renal Carcinoma Group study - 1. Patients underwent a computed tomography (CT) scan at baseline, at one month, at three months, and every third month until RECIST 1.1 defined progression. LAEs due to iodinated contrast media were systematically registered according to the Common Terminology Criteria for Adverse Events classification. RESULTS: In total, 89 patients were included and underwent a total of 507 contrast-enhanced CT scans. An overall incidence of 46 (9.1%) LAEs was observed in 38 of 89 (42.7%) patients; 3 LAEs at baseline (3.4% of all baseline scans), 39 (13.9%) LAEs during IL-2-based therapies, and 4 (2.9%) LAEs after termination of IL-based therapies. There was no difference in progression-free survival, overall survival, and treatment response in patients experiencing LAEs compared to patients without LAEs (P = 0.2, P = 0.5, and P = 0.6, respectively). CONCLUSION: Patients with mRCC demonstrated a higher incidence of LAEs after administration of iodinated contrast during ongoing IL-2 therapy, indicating that iodinated contrast media may cause a recall phenomenon of IL-2 toxicities in patients with mRCC. Treatment with IL-2 should not be a contraindication for contrast-enhanced scans in patients with mRCC but expertise and vigilance are required.

Early reduction in spectral dual-layer detector CT parameters as favorable imaging biomarkers in patients with metastatic renal cell carcinoma.

OBJECTIVES: To associate the early change in DL-CT parameters and HU with survival outcomes and treatment response in patients with metastatic renal cell carcinoma (mRCC). METHODS: DL-CT scans were performed at baseline and after 1 month of checkpoint immunotherapy or tyrosine kinase inhibitor therapy. Scans were reconstructed to conventional CT and DL-CT series, and used for assessment of HU, iodine concentration (IC), and the effective atomic number (Zeffective) in the combined RECISTv.1.1 target lesions. The relative changes, defined as ΔIC(combined), ΔZeffective(combined), and ΔHU(combined), were associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The reduction in the sum of diameters of target lesions ≥ 30% after 1 month was associated with OS, PFS, and ORR. RESULTS: Overall, 115 and 104 mRCC patients were included at baseline and 1 month, respectively. Median IC(combined) decreased from 2.3 to 1.2 mg/ml (p < 0.001), Zeffective(combined) from 8.5 to 8.0 (p < 0.001), and HU(combined) from 86.0 to 64.00 HU (p < 0.001). After multivariate adjustments, the largest reductions in ΔIC(combined) (HR 0.47, 95% CI: 0.24-0.94, p = 0.033) and ΔZeffective(combined) (HR = 0.43, 95% CI: 0.21-0.87, p = 0.019) were associated with favorable OS; the largest reduction in ΔZeffective(combined) was associated with higher response (OR = 2.79, 95% CI: 1.12-6.94, p = 0.027). The largest reduction in ΔHU(combined) was solely associated with OS in univariate analysis (HR 0.45, 95% CI: 0.23-0.91). Reduction in SOD ≥ 30% at 1 month was not associated with outcomes (p > 0.075). CONCLUSIONS: Early reductions at 1 month in ΔIC(combined) and ΔZeffective(combined) are associated with favorable outcomes in patients with mRCC. This information may reassure physicians and patients about treatment strategy. KEY POINTS: • Early reductions following 1 month of therapy in spectral dual-layer detector CT-derived iodine concentration and the effective atomic number (Zeffective) are independent biomarkers for better overall survival in patients with metastatic renal cell carcinoma. • Early reduction after 1 month of therapy in the effective atomic number (Zeffective) is an independent imaging biomarker for better treatment response metastatic renal cell carcinoma.

Baseline blood volume identified by dynamic contrast-enhanced computed tomography as a new independent prognostic factor in metastatic renal cell carcinoma.

BACKGROUND: Preliminary data showed prognostic impact of contrast-enhanced computed tomography (DCE-CT) identified Blood Volume (BV) in patients with metastatic renal cell carcinoma (mRCC). BV as an independent prognostic factor remains to be assessed. MATERIALS AND METHODS: DCE-CT identified BV was prospectively quantified in patients with mRCC receiving first line therapies, adjusted for International mRCC Database Consortium (IMDC) individual features and treatments, and associated with overall survival (OS), progression-free survival (PFS) and objective response (ORR), using Cox and logistic regression, respectively. RESULTS: 105 patients with mRCC were included. Median baseline BV was 32.87 mL × 100 g-1 (range 9.52 to 92.87 mL × 100 g-1). BV above median was associated with IMDC favorable risk category (P = 0.004), metastasis free interval ≥ 1 year (P = 0.007), male gender (P = 0.032), normal hemoglobin (P = 0.040) and normal neutrophils (P = 0.007), whereas low BV was associated with poor risk IMDC features (P < 0.05). 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 independent favorable for OS (HR 0.49, 95% CI 0.30-0.78, P = 0.003) and PFS (HR 0.64; 95% CI 0.42-0.97, P = 0.036). BV as a continuous variable was also associated with OS in the multivariate analysis (HR 0.98, 95% CI 0.96-1.00, P = 0.017). The estimated concordance index (c-index) was 0.688 using IMDC score and 0.701 when BV was added. CONCLUSIONS: DCE-CT identified Blood Volume is a new, independent prognostic factor in mRCC, which may improve the prognostic accuracy of IMDC.