Benjamin M. Yeh

Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study

PURPOSE Identifying suitable markers of biologic activity is important when assessing novel compounds such as angiogenesis inhibitors to optimize the dose and schedule of therapy. Here we present the pharmacodynamic response to acute dosing of AG-013736 measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). PATIENTS AND METHODS Thirty-six patients with advanced solid tumors were treated with various doses of AG-013736. In addition to standard measures of objective disease response and pharmacokinetic analysis, DCE-MRI scans were acquired at baseline and repeated at cycle 1--day 2 after the scheduled morning dose of the AG-013736 in 26 patients. Indicators of a vascular response, such as the volume transfer constant (K(trans)) and initial area under the curve (IAUC), were calculated to assess the effect of treatment on tumor vascular function. RESULTS Evaluable vascular response data were obtained in 17 (65%) of 26 patients. A linear correlation was found in which the percentage change from baseline to day 2 in K(trans) and IAUC was inversely proportional to AG-013736 exposure. Using a conservative a priori assumption that a > or = 50% decrease in K(trans) was indicative of an objective vascular response, a 50% decrease in K(trans) was achieved and corresponded to a plasma AUC(0-24) of > 200 ng . h/mL. CONCLUSION A sufficient decrease in tumor vascular parameters was observed at a dose chosen for additional phase II testing by conventional toxicity criteria. In addition, the day 2 vascular response measured using DCE-MRI seems to be a useful indicator of drug pharmacology, and additional research is needed to determine if it is a suitable marker for predicting clinical activity.

Dual-Energy and Low-kVp CT in the Abdomen

OBJECTIVE The purpose of this article is to discuss the influence of tube potential on CT images and explore the potential impact of dual-energy CT on imaging of the abdomen and pelvis. CONCLUSION Low peak tube voltage (kVp) settings provide high conspicuity of contrast materials at CT but may result in high image noise, particularly in larger patients. Material decomposition at dual-energy CT can differentiate renal stones by their composition, quantify tissue iron stores, improve the detection of pathologic hyperenhancement, and reduce contrast material and radiation dose compared with conventional CT. Further clinical research and technique refinement will be needed as the usage of these exciting technologies spreads.

Characterization of cystic pancreatic masses: Relative accuracy of CT and MRI

OBJECTIVE The objective of our study was to determine the role and relative accuracy of CT and MRI in the characterization of cystic pancreatic masses. MATERIALS AND METHODS We retrospectively identified 58 patients with histopathologically proven cystic pancreatic masses at our institution who underwent preoperative CT (n = 40), MRI (n = 6), or both (n = 12). Two radiologists independently recorded their leading diagnoses with levels of diagnostic certainty (0-100%), their estimates of overall likelihood of malignancy (0-100%), and the morphologic characteristics of the tumors. Data were analyzed to determine relative accuracy in the diagnosis of malignancy, relationship between diagnostic certainty and accuracy, and frequency of malignancy in unilocular thin-walled cysts smaller than 4 cm. RESULTS Twenty-one (36%) of 58 masses were malignant. CT and MRI were equally accurate in establishing the diagnosis of malignancy (area under the receiver operating characteristic curve [A(z)] = 0.91 and 0.85 for reviewers 1 and 2 at MRI vs 0.82 and 0.76 at CT, respectively; p > 0.05). The leading diagnosis given by reviewers 1 and 2 was correct in 46% (32/70) and 43% (30/70) of the studies, respectively. When reviewer diagnostic certainty was 90% or more, the corresponding values were not significantly (p > 0.05) improved at 55% (12/22) and 48% (10/21), respectively. Two (15%) of 13 unilocular thin-walled cysts smaller than 4 cm were frankly malignant. CONCLUSION CT and MRI are reasonably and similarly accurate in the characterization of cystic pancreatic masses as benign or malignant; limitations include a substantial rate of misdiagnosis even when reviewer certainty is high and a moderate frequency of malignancy in small morphologically benign-appearing cysts.

MR Imaging and CT of the Biliary Tract

Magnetic resonance (MR) imaging and computed tomography (CT) can be useful in the diagnosis of biliary disease, with both modalities allowing detailed evaluation of the biliary tract. Careful interrogation of the images is critical, regardless of modality. The identification of dilated bile ducts necessitates evaluation for strictures or filling defects, which is best performed with thin-section imaging. Smooth, concentric short-segment strictures favor a benign cause, whereas abrupt, eccentric long-segment strictures favor a malignancy. At MR imaging, extrabiliary entities such as crossing vessels or metallic clip artifact may mimic strictures and should not be mistaken for disease. A stone is the most common biliary filling defect and may occur in the absence of dilated ducts. Stones commonly have a lamellated, geometric shape and are found in a dependent portion of the duct. Identification of bile duct wall thickening raises concern for cholangitis or malignancy. Improved diagnosis of biliary disease can be achieved with a knowledge of the benefits and limitations of modern MR and CT cholangiographic techniques, including the use of biliary-excreted contrast material and of various postprocessing techniques. Familiarity with the radiologic appearances of the duct lumen, wall, and surrounding structures is also important for accurate image interpretation. The rapidly evolving technology for both MR imaging and CT of the biliary tract will continue to present radiologists with opportunities as well as challenges.

A Phase II Trial of Erlotinib in Combination with Bevacizumab in Patients with Metastatic Breast Cancer

Purpose: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. Experimental Design: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of ≥26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. Results: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. Conclusions: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.

Pulmonary Embolism Detection with Dual-Energy CT: Experimental Study of Dual-Source CT in Rabbits

PURPOSE To evaluate feasibility and added value of dual-energy computed tomography (CT) in diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS This institutional animal experimental committee-approved study was performed in accordance with animal care guidelines. Eight New Zealand rabbits underwent standard unenhanced and contrast material-enhanced dual-source CT. Gelatin sponge particles were injected into the pulmonary artery, and rabbits underwent contrast-enhanced dual-source CT pulmonary angiography, from which blood-flow (BF) and fusion images were created. Immediately after dual-source CT, rabbits were sacrificed, their lungs were removed and fixed in 10% formalin, and detailed pathologic determination of location and number of lung lobes with PE was performed. Two rabbits were excluded: One died during the procedure. In the other, the catheter tip was retained in the left inferior pulmonary artery. This caused marked postembolization CT image artifacts in adjacent regions. Six rabbits were included in final analysis. Two radiologists without knowledge of pathologic results evaluated five pulmonary lobes in each rabbit and recorded whether PE was present. Pathologic results served as the reference standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the techniques were calculated. Weighted kappa values were calculated to evaluate agreement between modalities. RESULTS Pathologic analysis revealed PE in 18 of 30 pulmonary lobes. Conventional CT angiography was used to correctly identify PE in 12 lobes and absence of emboli in 18 lobes, which corresponded to sensitivity, specificity, PPV, and NPV of 67%, 100%, 100%, and 67%, respectively. A kappa value of 0.65 indicated good correlation with pathologic findings. On BF images, segments with an embolic region showed low perfusion compared with segments with a normal pulmonary region. BF images and fused images correctly showed PE in 16 of 18 pulmonary lobes and absence of emboli in 11 of 12 lobes, which corresponded to sensitivity, specificity, PPV, and NPV of 89%, 92%, 94%, and 85%, respectively, in detection of PE. A kappa value of 0.80 indicated good correlation with pathologic findings. CONCLUSION Dual-source CT can depict normal and abnormal blood perfusion distribution in a rabbits lung. Abnormal pulmonary blood distribution, as shown at dual-source CT, improves detection of acute PE in rabbits.

Growth rate of hepatocellular carcinoma : Evaluation with serial computed tomography or magnetic resonance imaging

Objective: To evaluate the growth rate of untreated hepatocellular carcinoma (HCC) by calculating tumor volume doubling time (TVDT) on serial computed tomography (CT) or magnetic resonance imaging (MRI) and to predict TVDT based on initial tumor size. Methods: Sixteen untreated HCCs in 11 patients with cirrhosis who underwent serial CT or MRI at our institution were retrospectively identified. Two independent readers recorded bidimensional measurements for all tumors, which were used to determine tumor volume (TV). Growth rate was expressed as TVDT. A mathematic model was used to predict TVDT based on baseline tumor size. Results: Mean baseline and follow-up TVs were 10.5 cm3 (range: 0.7-243.6 cm3) and 22.0 cm3 (range: 2.5-870.8 cm3), respectively. Mean duration of follow-up was 176 days (range: 76-472 days). Mean TVDT was 127 days (95% confidence interval: 80, 203; range: 17.5-541.4 days). Expected TVDT could be expressed as TVDT = 114 × (baseline volume) 0.14 (P < 0.002). Conclusion: The results of this study suggest a preferred interval follow-up of approximately 4.5 months (127 days) for HCC screening. Small HCCs show a tendency toward faster growth and may require shorter follow-up to demonstrate progression.

CT Radiation Dose: What Can You Do Right Now in Your Practice?

OBJECTIVE The purpose of this article is to review reasonable measures that community radiologists can realistically implement as a response to the current increased public concern regarding CT radiation risk. CONCLUSION Potential measures include provision of patient information material, review of CT protocols and indications, promotion of alternative studies, use of decision support software, automatic tube current modulation, bismuth shields, improved image reconstruction algorithms, empowerment of technologists to adjust protocols, and calculation of radiation dose for possible reporting.

Risk of Injury to Adjacent Organs with Lower-pole Fluoroscopically Guided Percutaneous Nephrostomy: Evaluation with Prone, Supine, and Multiplanar Reformatted CT

PURPOSE To assess the risk of injury to organs near the kidney during lower-pole fluoroscopically guided percutaneous nephrostomy by evaluation of prone, supine, and multiplanar reformatted computed tomography (CT). MATERIALS AND METHODS Eighty-three patients who underwent prone and supine CT examinations were identified retrospectively. The expected path of nephrostomy tube placement to the lower-pole calyx was simulated on prone and supine axial images and multiplanar CT reformations. Intervening organs along this path were considered at risk for injury and were recorded for each kidney (N = 166). RESULTS The risk of organ injury as determined on multiplanar reformatted prone images (n = 5) and supine images (n = 0) was significantly less (P < .05) than determined on axial prone images (n = 25) or supine images (n = 10). The colon was the only organ identified to be at risk for injury during the simulated lower-pole percutaneous nephrostomy placement; spleen and liver were not seen along the nephrostomy path on axial or multiplanar reformatted images. CONCLUSION Lower-pole fluoroscopically guided percutaneous nephrostomy carries a low risk of visceral injury, and the risk of injury is overestimated by evaluation of axial CT images alone compared with oblique parasagittal reformations.

Predicting Strangulated Small Bowel Obstruction: An Old Problem Revisited

BackgroundDiagnosing intestinal strangulation complicating a small bowel obstruction (SBO) remains a considerable challenge. Despite decades of experience and numerous studies, no clinical indicators have been identified that reliably predict this life-threatening condition. Our goal was to determine which clinical indicators in patients with SBO can be used to independently predict the presence of strangulated intestine.MethodsMedical records were reviewed for 192 adult patients operated on for acute SBO over an 11-year period (1996–2006). Seventy-two preoperative clinical, laboratory, and radiologic findings at admission were examined. Data from patients with strangulated intestine were compared to data from patients without bowel compromise. Likelihood ratios were generated for each significant parameter in a multivariate logistic regression analysis.ResultsForty-four patients had bowel strangulation requiring bowel resection, and 148 had no strangulation. The most significant independent predictor of bowel strangulation was the computed tomography (CT) finding of reduced wall enhancement, with a sensitivity and specificity of 56% and 94% [likelihood ratio (LR) 9.3]. Elevated white blood cell (WBC) count and guarding were moderately predictive (LR 1.7 and 2.8).ConclusionRegression analysis of multiple preoperative criteria demonstrates that reduced wall enhancement on CT, peritoneal signs, and elevated WBC are the only variables independently predictive of bowel strangulation in patients with SBO.