Management of regorafenib-related toxicities: a review.

Regorafenib (Stivarga, BAY 73-4506; Bayer Pharma AG, Berlin, Germany) is an oral multikinase inhibitor that targets the angiogenic tumor microenvironment and oncogenic kinases including vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR1, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), RAF, KIT, RET and BRAF. Its antiangiogenic effect is greater than that of its related drug, sorafenib. Regorafenib has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (mCRC) in patients who have failed treatment with fluoropyrimidine, oxaliplatin and irinotecan based chemotherapy, an anti-VEGF therapy and, if KRAS wild type, an anti-EGFR therapy. The FDA based this approval on data from the CORRECT trial, which showed the efficacy of regorafenib compared with placebo. The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension and fatigue. This review discusses the efficacy data, and the incidence and management of regorafenib's toxicities.

Decreased incidence of NSF in patients on dialysis after changing gadolinium contrast-enhanced MRI protocols.

PURPOSE: To retrospectively determine the incidence of nephrogenic systemic fibrosis (NSF) in patients on dialysis administered either a lower dose high-relaxivity linear gadolinium-chelate, gadobenate dimeglumine (MultiHance, MH), compared to a standard dose linear gadolinium chelate, gadodiamide (Omniscan, OM). MATERIALS AND METHODS: This study was Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved. As per institution standardized contrast-enhanced magnetic resonance imaging (MRI) protocols, patients on dialysis were imaged using either MH, between 2/2007 to 9/2008, or OM between 10/2003 and 1/2007. Rates of NSF were compared using 95% score-based confidence intervals (CI). The Wilcoxon rank sum test was used to test similarity/difference between contrast doses given to each patient group. RESULTS: Overall, 312 patients on dialysis received OM and eight (2.6%) developed NSF (95% CI: 1.30%-4.98%). In all, 784 patients on dialysis received MH at a mean cumulative dose of 0.11 mmol/kg (0.05-0.75 mmol/kg) and no cases of NSF were identified (upper 95% confidence bound of 0.45%). The mean cumulative dose of OM was 0.16 mmol/kg (0.1-0.9 mmol/kg) for all patients and 0.28 mmol/kg (0.1-0.8 mmol/kg) for the patients with NSF. The median OM dose was greater in patients who developed NSF (P = 0.03), and was greater than the median MH dose (P < 0.005). CONCLUSION: NSF incidence in at-risk patients receiving contrast-enhanced MRI can be reduced after changing contrast administration protocols that includes changing the type and dose of contrast agent.

On improving temporal and spatial resolution of 3D contrast-enhanced body MR angiography with parallel imaging.

Use of a parallel imaging technique to improve temporal and spatial resolution at three-dimensional contrast-enhanced magnetic resonance (MR) angiography was investigated. Thirty experiments were performed in five groups of healthy subjects. In groups 1-3, the technique was used to improve imaging speed by a factor of two or four while maintaining spatial resolution. Contrast agent concentration was two to four times higher than at standard MR angiography, to take advantage of the faster imaging speed. In groups 4 and 5, the technique was used to double spatial resolution in the phase-encoding direction while maintaining imaging speed and contrast agent concentration. At a two to four times faster imaging speed, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) almost equaled those at standard MR angiography, likely a result of increased contrast agent concentration. The use of parallel imaging to achieve higher spatial resolution was also proved feasible, but with substantial reduction in SNR and CNR.

Low-density pheochromocytoma on CT: a mimicker of adrenal adenoma.

OBJECTIVE: Attenuation values on CT of less than 10 H are considered characteristic of adrenal adenomas. Adrenal pheochromocytomas can infrequently contain fat that could result in low attenuation on CT. The purpose of our study was to determine if pheochromocytomas could be confused with adenomas by virtue of their attenuation values on unenhanced CT. MATERIALS AND METHODS: CT attenuation and size of nine adrenal nodules producing pheochromocytoma syndrome were measured on unenhanced CT in nine patients. For five patients who received IV contrast material, washout profiles were also calculated. RESULTS: Two of the nine patients had adrenal lesions with attenuation values of less than 10 H; one had a pheochromocytoma with an attentuation of 9.0 H, and the other had a medullary hyperplasia with an attenuation of 1.8 H. These two nodules showed evidence of microscopic fat at histologic examination. No macroscopic fat was seen on the CT scans. The remaining seven patients had lesions with attenuation values exceeding 10 H (mean value, 25.6 H; range, 1.8-41 H). Mean diameter of the nine tumors (including the hyperplastic nodule) was 3.2 cm (range, 0.8-6.7 cm; SD, +/- 2.3 cm). The two low-attenuation lesions also mimicked adenomas by displaying more than 60% contrast washout on 10-min-delayed contrast-enhanced scans, unlike the other three pheochromocytomas for which we had washout data. CONCLUSION: On CT, pheochromocytomas may have attenuation values less than 10 H and also may display more than 60% washout of contrast agents on delayed scanning. Adrenal pheochromocytomas should be included with adenomas in the differential diagnosis both for masses with low attenuation on unenhanced CT and for lesions exhibiting a high percentage of contrast washout.