Denis Rommel

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.

Substitution of 11C-methionine PET by perfusion MRI during the follow-up of treated high-grade gliomas: Preliminary results in clinical practice.

PURPOSE Our aim was to compare perfusion magnetic resonance imaging (MRI) and positron emission tomography (PET) using carbon-11 labelled methionine (MET) in gliomas and their value in differentiating tumour recurrence from necrosis. MATERIALS AND METHODS We retrospectively reviewed 28 patients with a high-grade glioma. A total of 33MR perfusions and MET-PET were ultimately analysable for comparison between the relative cerebral blood volume (rCBV) and MET-PET examinations. Intra- and interobserver reproducibility was assessed and diagnostic value of rCBV compared to MET-PET and histology was assessed by the area under the receiver operating characteristic (ROC) curve. RESULTS ROC curve analysis showed that rCBV had at least equal performances in differentiating tumour recurrence and necrosis than MET-PET. Cut-off value of rCBV for differentiating tumour from necrosis was 182% with a sensitivity of 81.5% and a specificity of 100%. CONCLUSION In clinical practice, perfusion MRI could replace MET-PET for differentiating necrosis from tumour recurrence.

Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck.

BACKGROUND To investigate the safety and activity of cetuximab in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Cetuximab was administered for 2 weeks before surgery to 33 treatment-naïve patients selected for primary surgical treatment. Tumour biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography ((18)FDG-PET) and imaging were carried out at baseline and before surgery. The primary aim of the study was safety and the secondary aims included metabolical, radiological and pathological tumour response. Five untreated patients were included as controls. RESULTS Cetuximab given 24 h before surgery was safe. Ninety percent of patients had (18)FDG-PET partial response (EORTC guideline) in the cetuximab group versus 0% in the control group. Delta maximal standardized uptake values (ΔSUVmax) were correlated with tumour cellularity on the surgical specimens (P < 0.0001). For patients with ΔSUVmax less than -25% or less than -50%, Ki67 was significantly decreased by cetuximab (P = 0.01 and 0.003). Cetuximab induced down-regulation of pEGFR (P = 0.0004) and pERK (P = 0.003). CONCLUSIONS Short-course pre-operative administration of cetuximab is safe and shows a high rate of (18)FDG-PET response. (18)FDG-PET response was correlated with residual tumour cellularity suggesting that (18)FDG-PET deserves further investigation as a potential early marker of cetuximab activity in SCCHN.

Gliomatosis cerebri, imaging findings of 12 cases.

BACKGROUND AND PURPOSE We report 12 cases of Gliomatosis cerebri (GC), a rare brain neoplasm, to define its semeiologic criteria. Literature was reviewed to clarify its physiopathology. PATIENTS AND METHODS From 1997 to 2008, 12 histologically proven cases with GC were retrospectively reviewed. Of the 12 patients, nine were male. The mean age was of 54 years. Were performed CT-Scan (n=6), MRI (n=12), diffusion and perfusion weighted images (n=12 and n=4), MR Spectroscopy (n=3), a FDG and a Methionin PET-Scan (n=2 and n=3 respectively). RESULTS Primary diagnosis was missed in six cases. Most frequent clinical signs were seizure and mental changes. Imaging criteria were: area of high signal intensity on FLAIR and T2-weighted images, involving three or more contiguous lobes with conserved architecture. Frequently a bilateral widespread invasion with involvment of the corpus callosum or the anterior white commissure or both was observed. At diagnosis and in the classical form (type I) of GC, no significant contrast enhancement and decreased rCBV were observed. Focal enhancement and increased rCBV were observed in the focal mass in type II GC. MR Spectroscopy showed an increase of the Cho/Cr ratio and a decrease in the NAA/Cr one. FDG PET showed in type I a decreased avidity for the FDG whereas in type II a increased avidity was observed. MET-PET showed an increased avidity for the tracer in a GC type II and a slight avidity in a GC type I. CONCLUSION GC is a rare brain entity. Primary diagnosis is often missed. The imaging findings of GC I, a WHO grade III tumor, should be known and include classical MRI but also PWI, MRS and scintigraphic findings.

Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions.

Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images.

Early (72-Hour) detection of radiotherapy-induced changes in an experimental tumor model using diffusion-weighted imaging, diffusion tensor imaging, and Q-space imaging parameters : A comparative study.

To assess and compare the potential of various diffusion‐related magnetic resonance imaging (MRI) parameters to detect early radiotherapy (RT)‐induced changes in tumors.

Lateral sacral artery aneurysm: case report and review of the literature

OBJECTIVE AND IMPORTANCE:We report the third case of an aneurysm of the lateral sacral artery (AnLSA). In all cases, because of an incorrect preoperative diagnosis, the surgeons were confronted with severe and unexpected hemorrhaging, and surgery was aborted without effective treatment. Our purpose is to present the preoperative features of AnLSA and its treatment modalities. CLINICAL PRESENTATION:A 54-year-old man had a medical history of renal transplantation on his left external iliac artery. He complained of acute lumbar pain associated with cauda equina syndrome, which resolved within a few hours. At that time, a magnetic resonance imaging (MRI) scan revealed an intracanal hematoma extending from S1 to T12. Six weeks later, a second MRI scan demonstrated an oval-shaped intracanal mass behind the vertebral body of S1 with intense gadolinium enhancement. INTERVENTION:An anterior epidural mass was found. An incision into this mass resulted in significant arterial hemorrhaging. Transparietal embolization with a cotton compress and closure of the aneurysm wall were performed. The postoperative clinical status was stable, and a delayed angiographic study suggested a diagnosis of aneurysm of the right LSA, a branch of the internal iliac artery. Its pathophysiology was explained by the development of a high-flow transpelvic shunt from the right iliac artery territory to the left, to maintain the renal graft blood flow that had initially been reduced by stenosis of the left common iliac artery. Six weeks later, a new MRI scan demonstrated that the AnLSA had increased in size. The lesion was then excluded endovascularly by injection of glue. CONCLUSION:A medical history of renal transplantation with MRI scans showing an anterior epidural mass behind S1 or a spontaneous spinal epidural hematoma are features that must evoke a diagnosis of AnLSA. Treatment is mandatory and is best achieved by embolization. Surgery based on angiographic findings is indicated if the lesion is responsible for a compressive hematoma.

Bilateral anterior fornix infarction: the “amnestic syndrome of the subcallosal artery”

A 74-year-old, left-handed female patient developed an awakening sudden anterograde amnesia with headache. The memory of events occurring in the last 3 months was also lost. She had a prior medical history of right mastectomy several years ago and chronic arterial hypertension treated with bisoprolol and ramipril. On admission, her blood pressure was 150/80 mmHg. The neurological examination was otherwise normal. Cranial computerized tomography and EEG were unremarkable. A transient global amnesia was first suspected. However, the memory disturbances persisted the day after admission and brain magnetic resonance imaging (MRI) revealed a bilateral acute infarction of both anterior columns of the fornix and posterior part of the corpus callosum genu (Fig. 1). AngioMRI showed an anterior cerebral artery stenosis (A1 segment) with absent anterior communicating artery (ACoA). Ultrasound Doppler of the cervical arteries, transoesophagal echocardiography, and 24 h Holter-ECG were normal. Blood tests revealed a mild hypercholesterolemia. The neuropsychological testing was performed on day 5. A working memory deficit affecting the phonological loop was associated with verbal anterograde amnesia (encoding deficit) and reduced capacities on visual long term memory. Recognition memory was preserved. There was no other attention, executive, language, or gestual disorder. Signs of callosal disconnection syndrome (such as lefthand ideomotor apraxia, agraphia, tactile anomia, or alien hand) were not found. She was treated with a low dose of aspirin (80 mg/day) and clopidogrel (75 mg/day). 3 months later, the episodic memory disorders did not significantly improve. Infarction of both anterior fornix and posterior part of the corpus callosum genu results in acute episodic memory disorder with preserved recognition memory. This rare entity is also known as ‘‘the amnestic syndrome of the subcallosal artery’’. It is the result of an acute infarction in the territory of the subcallosal arteries, which are perforating branches originating from the anterior communicating artery (ACoA). Only a few cases have been reported in the literature (Table 1), mostly in a context of small vessel disease [1, 2, 4–6], but also in cardio-embolic disease [3] and giantcell arteritis [7]. Similar infarctions can also occur secondarily to ACoA aneurysm rupture or embolization [8, 9]. The lesions are usually bilateral and almost always exclusively involving the anterior columns of the fornix. Infarction can extend to other neural structures, such as the anterior corpus callosum, septal nuclei and anterior cingulum [9]. Unilateral anterior fornix infarction may also lead to anterograde amnesia [10]. The fornix is an important component of the classic Papez circuit. This white matter bundle is a major efferent pathway connecting the hippocampus with other limbic and diencephalic structures, ending in the homolateral hypothalamic mammillary body. It plays an important role in the formation and consolidation of declarative memory. Lesions of the fornix impair recall process by interruption of the hippocampo–anterior thalamic memory pathway. They do not affect recognition memory depending on the perirhinal medial system [2, 3, 9]. Diffusion tensor tractography can identify partial or complete disruption of the corpus callosum genu and fornix anterior columns projection fibers and so help to predict the outcome in fornix infarction [5, 8]. & Matthieu Pierre Rutgers M.Rutgers@cliniquesdeleurope.be

Congenital Horner Syndrome with Heterochromia Iridis Associated with Ipsilateral Internal Carotid Artery Hypoplasia

Background Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. Case Report We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). Conclusions CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT.

Enhanced choline metabolism in a rodent rhabdomyosarcoma model: correlation between RT-PCR and translational 3 T H-MRS.

PURPOSE To investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model. MATERIALS AND METHODS Twenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour. After euthanasia, cubic centimetre tissue specimens corresponding to Proton magnetic resonance spectroscopy (H-MRS) VOIs were frozen in liquid nitrogen. Out of 89 H-MRS voxels, only 39 with a corresponding tissue specimen suitable for biochemical processing were included in the analysis. RNA was extracted from all the 39 samples and reverse-transcribed into cDNA. Choline kinase α and β gene expression as well as genes of the transmembrane transporters OCT1, OCT2, OCT3, CTL1, CTL3, CTL4 and CHT1 were studied using reverse transcriptase polymerase chain reaction. The expression level of each gene (ΔCt), was normalized referred to that of the RPL19 gene. The Spearman rank correlation coefficient was used to analyse variables. RESULTS There was no overexpression of genes coding for kinases; however, significant correlation was observed between kinase α sub-type and the tCho peak (P=.002; r=0.51). OCT1 was the most overexpressed transporter gene. Less overexpressed CTL1 gene was significantly correlated with the tCho peak (P=.02; r=0.38). CONCLUSION Choline transporters seem to play a predominant role in the increase in total choline concentration at the gene expression level in our model.