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Purpose Dynamic contrast–enhanced (DCE) MRI-extracted parameters measure tumor microvascular physiology and are usually calculated from an intratumor region of interest (ROI). Optimal ROI delineation is not established. The valid clinical use of DCE-MRI requires that the variation for any given parameter measured within a tumor be less than that observed between tumors in different patients. This work evaluates the impact of tumor ROI selection on the assessment of intra- and interpatient variability. Method and Materials Head and neck cancer patients received initial targeted therapy (TT) treatment with erlotinib and/or bevacizumab, followed by radiotherapy and concurrent cisplatin with synchronous TT. DCE-MRI data from Baseline and the end of the TT regimen (Lead-In) were analyzed to generate the vascular transfer function (K trans ), the extracellular volume fraction (v e ), and the initial area under the concentration time curve (iAUC 1 min ). Four ROI sampling strategies were used: whole tumor or lymph node (Whole), the slice containing the most enhancing voxels (SliceMax), three slices centered in SliceMax (Partial), and the 5% most enhancing contiguous voxels within SliceMax (95Max). The average coefficient of variation (aCV) was calculated to establish intrapatient variability among ROI sets and interpatient variability for each ROI type. The average ratio between each intrapatient CV and the interpatient CV was calculated (aRCV). Results Baseline primary/nodes aRCVs for different ROIs not including 95Max were, for all three MR parameters, in the range of 0.14–0.24, with Lead-In values between 0.09 and 0.2, meaning a low intrapatient vs. interpatient variation. For 95Max, intrapatient CVs approximated interpatient CVs, meaning similar data dispersion and higher aRCVs (0.6–1.27 for baseline) and 0.54–0.95 for Lead-In. Conclusion Distinction between different patient’s primary tumors and/or nodes cannot be made using 95Max ROIs. The other three strategies are viable and equivalent for using DCE-MRI to measure head and neck cancer physiology.

RATIONALE: Early detection of tumor response to therapy is a key goal. Finding measurement algorithms capable of early detection of tumor response could individualize therapy treatment as well as reduce the cost of bringing new drugs to market. On an individual basis, the urgency arises from the desire to prevent continued treatment of the patient with a high-cost and/or high-risk regimen with no demonstrated individual benefit and rapidly switch the patient to an alternative efficacious therapy for that patient. In the context of bringing new drugs to market, such algorithms could demonstrate efficacy in much smaller populations, which would allow phase 3 trials to achieve statistically significant decisions with fewer subjects in shorter trials. MATERIALS AND METHODS: This consensus-based article describes multiple, image modality-independent means to assess the relative performance of algorithms for measuring tumor change in response to therapy. In this setting, we describe specifically the example of measurement of tumor volume change from anatomic imaging as well as provide an overview of other promising generic analytic methods that can be used to assess change in heterogeneous tumors. To support assessment of the relative performance of algorithms for measuring small tumor change, data sources of truth are required. RESULTS: Very short interval clinical imaging examinations and phantom scans provide known truth for comparative evaluation of algorithms. CONCLUSIONS: For a given category of measurement methods, the algorithm that has the smallest measurement noise and least bias on average will perform best in early detection of true tumor change.

This article describes methods and issues that are specific to the assessment of change in tumor characteristics as measured using quantitative magnetic resonance (MR) techniques and how this relates to the establishment of quantitative MR imaging (MRI) biomarkers of patient response to therapy. The initial focus is on the various sources of bias and variance in the measurement of microvascular parameters and diffusion parameters as such parameters are being used relatively commonly as secondary or exploratory end points in current phase 1/2 clinical trails of conventional and targeted therapies. Several ongoing initiatives that seek to identify the magnitude of some of the sources of measurement variations are then discussed. Finally, resources being made available through the National Cancer Institute Reference Image Database to Evaluate Response (RIDER) project that might be of use in investigations of quantitative MRI biomarker change analysis are described. These resources include 1) data from phantom-based assessment of system response, including short-term (1 hour) and moderate-term (1 week) contrast response and relaxation time measurement, 2) data obtained from repeated dynamic contrast agent-enhanced MRI studies in intracranial tumors, and 3) data obtained from repeated diffusion MRI studies in both breast and brain. A concluding section briefly discusses issues that must be addressed to allow the transition of MR-based imaging biomarker measures from their current role as secondary/exploratory end points in clinical trials to primary/surrogate markers of response and, ultimately, in clinical application.

Repeat imaging data sets performed on patients with cancer are becoming publicly available. The potential utility of these data sets for addressing important questions in imaging biomarker development is vast. In particular, these data sets may be useful to help characterize the variability of quantitative parameters derived from imaging. This article reviews statistical analysis that may be performed to use results of repeat imaging to 1) calculate the level of change in parameter value that may be seen in individual patients to confidently characterize that patient as showing true parameter change, 2) calculate the level of change in parameters value that may be seen in individual patients to confidently categorize that patient as showing true lack of parameter change, 3) determine if different imaging devices are interchangeable from the standpoint of repeatability, and 4) estimate the numbers of patients needed to precisely calculate repeatability. In addition, we recommend a set of statistical parameters that should be reported when the repeatability of continuous parameters is studied.

The advent of diffusion-weighted MR imaging and diffusion tensor MR imaging has had little impact on brain tumor detection. Diffusion-weighted imaging has been effective in characterizing specific types of masses, particularly in distinguishing epidermoids from arachnoid cysts, and cystic tumors from intracerebral abscesses. Presurgical planning using tractography with diffusion tensor MR imaging, and perhaps the evaluation of tumor response to chemotherapy and radiation therapy with diffusion-weighted imaging, may become important applications in the near future.

Purpose: Our purpose was to show the computed tomography (CT) and magnetic resonance (MR) imaging features of vertex epidural hematomas (EDHs) and emphasize pitfalls in the diagnosis of this entity. Subjects and methods: The neuroradiologic studies of four patients (CT in four, MR imaging and MR venography in one) were evaluated for EDH shape, size and appearance. Results: EDHs were biconvex in three patients and crescentic in one patient. CT appearances included a collection that was hyperdense (two patients), generally isodense with a few regions of hyperdensity (one patient) and mixed hyperdense and hypodense (one patient). MR imaging findings in one patient consisted of hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. Inferior displacement of the superior sagittal sinus was seen in two patients. Diagnosis of a small vertex EDH was difficult on routine axial CT in one patient, but apparent on MR imaging and MR venography. Conclusions: Small vertex EDHs can be difficult to diagnose on routine CT. MR imaging or thin section CT should be performed to exclude the diagnosis in patients with trauma to the skull vertex.

As intracranial MR angiography becomes more widely used and spatial resolution improves, anomalies at the Circle of Willis which have been previously well described on angiographic studies and anatomic dissections will become more frequently appreciated by MR angiography. Recognition of these variants is important to avoid confusion of the anomalies with aneurysms, evaluate collateral pathways in the intracerebral circulation, and enhance pre-operative planning in patients undergoing surgery at the skull base. In this review, we illustrate several of the more common types of anomalies at the Circle of Willis and discuss the possible clinical significance of each.

We present a female with premature birth, polyhydramnios, congenital apnea, cranial nerve palsies, orofacial and limb anomalies. Neuroimaging revealed calcifications along the vental margin of the caudal fourth ventricle. Neuropathologic findings at postmortem examination were consistent with brainstem tegmental necrosis and olivary hypoplasia, a rare lethal entity that should be considered in the differential diagnosis of congenital apnea.

Background There is no effective therapy for recurrent GBM pts following progression on the vascular endothelial growth factor (VEGF)-targeting agent bevacizumab (BV), with historical series reporting progression-free survival at 6 months (PFS-6) of only 2%. Several mechanisms of tumor adaptation following anti-VEGF therapy have been proposed, including upregulation of alternative angiogenic cytokines. We therefore performed a single-arm phase 2 study to evaluate lenvatinib (L), an oral tyrosine kinase inhibitor targeting FGFR1-4, PDGFRβ, VEGFR1-3, RET, and KIT, in pts with recurrent GBM progressing on BV. Methods 32 pts with recurrent GBM (≤2 prior progressions) and progression on BV received L 24 mg once daily in 28-day cycles until PD or unacceptable toxicity. Dynamic contrast-enhanced MRI was performed before and after 1 day of L on a subset of pts (n = 16). Response was assessed using Response Assessment in Neuro-Oncology criteria. Primary endpoint was PFS-6. This cohort has completed enrollment; 1 pt is still ongoing. Results Median age was 52 y, 56% were male, and 19% had a KPS Conclusions Lenvatinib has modest activity and a similar toxicity profile when compared with other tyrosine kinase inhibitors. Further study of VEGF therapy failure mechanisms as well as biomarkers of outcome is needed. Disclosure D.A. Reardon: D. Reardon discloses reimbursement for serving as an advisory board member for Genentech/Roche and Schering/Merck in the past year. E. Pan: E. Pan has been reimbursed as an advisory board member for Genentech in the past year. He has also been on the Speakers' Bureau for Genentech, Merck, and Sigma Tau in the past year. J. Fan: J. Fan is an Eisai employee. J. Mink: J. Mink is an employee of Eisai. D.P. Barboriak: D. Barboriak discloses receiving imaging core lab support from Eisai Pharmaceuticals, ACRIN, NIBIB / RSNA QIBA Member of GE Medical Systems Neuro MRI advisory board Pulse sequence support from Siemens Healthcare. J.J. Vredenburgh: J.J. Vredenburgh received financial compensation from Genentech/Roche for Speakers Bureau participation and consultation. A. Desjardins: A. Desjardins received financial compensation from Genentech/Roche for Speakers Bureau participation. J.P. O'Brien: J. P. O'Brien is an employee of Eisai. P.Y. Wen: P. Wen discloses research support from Eisai. All other authors have declared no conflicts of interest.

and OS for the entire cohort were 88.0%, 69.5%, and 78.4%, respectively. Of the 85 patients, there were 7 locoregional failures (LRF), 13 distant failures (DF), 4 LRF and DF, and 4 deaths from intercurrent illness. Among the 16 patients with locoregional ordistantfailure,mediantimefromendofradiotherapytofirstfailurewas9.8months.OnCoxproportionalhazardsregressionanalysis, an increase in integrated SUV of 209.2 SUV$ml (difference between the 75th and 25th percentiles) was associated with a statistically significant increased hazard of recurrence (2.2-fold, p\0.0001), even after controlling for Karnofsky performance status (2.0-fold, p = 0.0007), and of death (1.7-fold, p = 0.0037). An increase in MTV was also associated with increased hazard of progression (1.9-fold, p = 0.002) and of death (2.1-fold, p = 0.001). We did not find a significant relationship between maximum SUV and DFS or OS. Conclusions: High metabolic tumor burden as measured by MTV or integrated SUV are adverse prognostic factors for disease recurrence and death in head and neck cancer. MTV and integrated SUV retained significance after controlling for KPS, another significant adverse prognostic factor in this cohort. These metabolic parameters are potentially valuable tools for risk stratification and guiding treatment in future clinical trials.

A group of 38 patients with a second revascularization procedure was studied for factors which may have contributed to the reappearance of angina after the first operation. Our data indicate that these patients usually have the first operation at an earlier age and had fewer bypasses at that time. In addition, they had inadequate control of the plasma triglyceride and cholesterol levels.