Thierry Duprez

Phase II Study of Sunitinib in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: GORTEC 2006-01

PURPOSE To assess the efficacy and toxicity of sunitinib monotherapy in palliative squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Thirty-eight patients with SCCHN having evidence of progressive disease (PD) were treated with sunitinib 37.5 mg/d given continuously until PD or unacceptable toxicity. The primary end point was the rate of disease control, defined as stable disease (SD) or partial response (PR) at 6 to 8 weeks after treatment initiation (two-stage design, Simon). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed in a subset of patients before and 6 to 8 weeks after treatment. The volume transfer constant of the contrast agent (K(trans)) was used to measure changes in the microcirculation blood flow and endothelial permeability of the tumor. Results A PR was observed in one patient, SD in 18, and PD in 19 (Response Evaluation Criteria in Solid Tumors [RECIST]), resulting in a disease control rate of 50%. Among the 18 patients with SD, there were five unconfirmed PRs and six additional minor responses. A significant decrease in K(trans) was seen in three of the four patients who received DCE-MRI monitoring. Grade 5 head and neck bleeds occurred in four patients. Local complications, including the appearance or worsening of tumor skin ulceration or tumor fistula, were recorded in 15 patients. CONCLUSION Sunitinib demonstrated modest activity in palliative SSCHN. The severity of some of the complications highlights the importance of improved patient selection for future studies with sunitinib in head and neck cancer. Sunitinib should not be used outside clinical trials in SSCHN.

Usefulness of Magnetic Resonance–Derived Quantitative Measurements of Cerebral Blood Flow and Volume in Prediction of Infarct Growth in Hyperacute Stroke

Background and Purpose The identification of the tissue at risk for infarction remains challenging in stroke patients. In this study, we evaluated the value of quantitative cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements in the prediction of infarct growth in hyperacute stroke. Methods Fluid-attenuated inversion recovery (FLAIR), diffusion-weighted (DW), and gradient-echo echo-planar perfusion-weighted (PW) sequences were obtained in 66 patients within 6 hours of stroke onset; ischemia was confirmed on follow-up FLAIR images. We delineated the following: (1) the initial infarct on DW images, (2) the area of hemodynamic disturbance on mean transit time (MTT) maps, and (3) the final infarct on follow-up FLAIR images. MTT, CBF, and CBV were calculated in the following areas: area of initial infarct (INF), area of infarct growth (IGR, final minus initial infarct), the hemodynamically disturbed area that remained viable (OLI, hemodynamic disturbance minus final infarct), and all contralateral mirror regions. Results Compared with mirror regions, the MTT in abnormal areas was always prolonged. The respective mean±SD CBF and CBV values were as follows: for INF, 28±16 mL/min per 100 g and 6.9±2.7%; for IGR, 36±20 mL/min per 100 g and 8.9±3.1%; for OLI, 50±17 mL/min per 100 g and 11.2±3%; and for mirror regions, 64±23 mL/min per 100 g and 8.7±2.5%. The CBV and CBF values were significantly different between all abnormal areas (except for the CBF between INF and IGR). In the area of DW/PW mismatch, a combined CBF or CBV threshold of 35 or 8.2, respectively, predicted evolution to infarction with a sensitivity of 81% and a specificity of 76%. Conclusions Quantitative measurements of CBF and CBV in hyperacute stroke may help to predict infarct growth and to select the subjects who will benefit from thrombolysis.

Whole brain quantitative CBF, CBV, and MTT measurements using MRI bolus tracking: implementation and application to data acquired from hyperacute stroke patients.

A robust whole brain magnetic resonance (MR) bolus tracking technique based on indicator dilution theory, which could quantitatively calculate cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) on a regional basis, was developed and tested. T2*‐weighted gradient‐echo echoplanar imaging (EPI) volumes were acquired on 40 hyperacute stroke patients after gadolinium diethylene triamine pentaacetic acid (Gd‐DTPA) bolus injection. The thalamus, white matter (WM), infarcted area, penumbra, and mirror infarcted and penumbra regions were analyzed. The calculation of the arterial input function (AIF) needed for absolute quantification of CBF, CBV, and MTT was shown to be user independent. The CBF values (ml/min/100 g units) and CBV values (% units, in parentheses) for the thalamus, WM, infarct, mirror infarct, penumbra, and mirror penumbra (averaged over all patients) were 69.8 ± 22.2 (9.0 ± 3.0 SD); 28.1 ± 6.9 (3.9 ± 1.2); 34.4 ± 22.4 (7.1 ± 2.7); 60.3 ± 20.7 (8.2 ± 2.3); 50.2 ± 17.5 (10.4 ± 2.4); and 64.2 ± 17.0 (9.5 ± 2.3), respectively, and the corresponding MTT values (in seconds) were 8.0 ± 2.1; 8.6 ± 3.0; 16.1 ± 8.9; 8.6 ± 2.9; 13.3 ± 3.5; and 9.4 ± 3.2. The infarct and penumbra CBV values were not significantly different from their corresponding mirror values, whereas the CBF and MTT values were (P < 0.01). Quantitative measurements of CBF, CBV, and MTT were calculated on a regional basis on data acquired from hyperacute stroke patients, and the CBF and MTT values showed greater sensitivity to areas with perfusion defects than the CBV values. J. Magn. Reson. Imaging 2000;12:400–410.

Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss.

Objective: The study aimed to investigate whether the degree of postinfectious olfactory loss is reflected in volume of the olfactory bulb (OB).

Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell.

Objective: The aims of this study were to evaluate olfactory function with orthonasal and retronasal testing in patients with posttraumatic olfactory loss and to investigate the relation between residual olfactory function and olfactory bulb (OB) volume.

Whole brain quantitative CBF and CBV measurements using MRI bolus tracking: comparison of methodologies.

Three different deconvolution techniques for quantifying cerebral blood flow (CBF) from whole brain T*2‐weighted bolus tracking images were implemented (parametric Fourier transform P‐FT, parametric single value decomposition P‐SVD and nonparametric single value decomposition NP‐SVD). The techniques were tested on 206 regions from 38 hyperacute stroke patients. In the P‐FT and P‐SVD techniques, the tissue and arterial concentration time curves were fit to a gamma variate function and the resulting CBF values correlated very well (CBFP‐FT = 1.02 • CBFP‐SVD, r2= 0.96). The NP‐SVD CBF values (i.e., original unfitted curves were used) correlated well with the P‐FT CBF values only when a sufficient number of time series volumes were acquired to minimize tracer time curve truncation (CBFP‐FT × 0.92 • CBFNP‐SVD, r2= 0.88). The correlation between the fitted CBV and the unfitted CBV values was also maximized in regions with minimal tracer time curve truncation (CBVfit = 1.00 • CBVunfit, r2= 0.89). When a sufficient number of time series volumes could not be acquired (due to scanner limitations) to avoid tracer time curve truncation, the P‐FT and P‐SVD techniques gave more reliable estimates of CBF than the NP‐SVD technique. Magn Reson Med 43:559–564, 2000.

Resolution of early diffusion-weighted and FLAIR MRI abnormalities in a patient with TIA

Article abstract We report a patient with a clinical history and neurologic examination consistent with acute stroke. Diffusion-weighted and fast fluid-attenuated inversion recovery MRI obtained 4 hours after stroke onset detected focal abnormalities suggestive of acute ischemic brain damage. The neurologic deficit and the imaging abnormalities both resolved completely at follow-up. This patient illustrates complete resolution of early changes observed with diffusion-weighted MRI at the hyperacute phase in a TIA.

Fast FLAIR sequence for detecting major vascular abnormalities during the hyperacute phase of stroke : a comparison with MR angiography

Abstract In the hyperacute phase of stroke, occluded vessels can be seen as high signal on fast-FLAIR images or as absence of flow-related enhancement in maximum-intensity projection (MIP) MR angiography (MRA). To compare these techniques, we examined 53 patients within 6 h of a stroke, using a standardised MRI protocol including fast-FLAIR and 3D time-of-flight TOF MR to detect vessel occlusion or reduced flow corresponding to the suspected ischaemic territory. Brain infarcts were confirmed on MRI after 1–5 days in 41 cases (77 %). The overall accuracy of 3D-TOF MRA was 68 % and sensitivity, specificity, positive and negative predictive values were 67 %, 71 %, 87 %, and 43 % respectively. Values for the fast-FLAIR sequence were: 65 %, 85 %, 93 % and 44 %, with an overall accuracy of 70 %. The fast-FLAIR sequence was thus able to show occluded vessels or reduced flow with about the same accuracy as 3D-TOF MRA and enabled better prediction of the ischaemic area.

High signal in cerebrospinal fluid mimicking subarachnoid haemorrhage on FLAIR following acute stroke and intravenous contrast medium

Abstract We describe five cases of high signal in the cerebrospinal fluid (CSF) on fast-FLAIR images 24–48 h after onset of stroke. All the patients had undergone perfusion-weighted MRI within 6 h of the onset of the symptoms. The CSF was far brighter than the cortical gyri. The high signal was diffusely around both cerebral hemispheres in two cases and around one hemisphere in two others; it was focal, around the acute ischaemic lesion, in one. CT was normal in all cases. The CSF high signal was transient, decreasing in extent and intensity with time and resolving completely within 3–6 days. It was not associated with worsening of the clinical state or poor outcome. Our explanation of this phenomena is hypothetical: we speculate that it could be due to disruption of the blood-brain barrier resulting in leakage of protein, gadolinium chelates, or both in to the subarachnoid space. It should not be confused with subarachnoid haemorrhage.

Diffusion-weighted MRI postoperative assessment of an epidermoid tumour in the cerebellopontine angle.

Abstract Cerebellopontine angle epidermoid tumour generally has a typical appearance with conventional MRI sequences. The lesion is irregular in shape and gives slightly higher signal than cerebrospinal fluid on T1- and T2-weighted images, with a characteristic marbled inner pattern on T1-weighted images. Diffusion-weighted imaging (DWI) can be useful for the diagnosis of an atypical epidermoid tumour. Our case report illustrates the usefulness of DWI for postoperative assessment of residual foci of tumour. The specific appearance of an epidermoid tumour is illustrated, with emphasis on apparent diffusion coefficient (ADC) measurements.