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Purpose To investigate the diagnostic performance of sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and the incremental value of spine MRI to “predict” clinical disease activity in patients with axial spondyloarthritis (axSpA). Materials and methods This cross-sectional study included adult patients with known axSpA according to the SpondyloArthritis International Society (ASAS) classification criteria, radiological arm. MRI disease activity was scored semi-quantitatively for SIJ and total spine MRI in each patient. Two cut-off levels (≥ 1.3 and ≥ 2.1) for ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were considered for clinical disease activity categorization. MRI scores were first evaluated individually. Then, SIJ score was combined with the score from a spine segment (lumbar, cervical, thoracic or total spine) to build a bi-parametric model using a classification tree. Receiver operating characteristic (ROC) curves were constructed to evaluate the classification performance according to disease activity category of these models. Results Forty-four patients (30 men, 14 women; mean age, 37 years ± 10 [SD] [range: 17–64 years]) with a mean disease duration of 5 years ± 8 (SD) (range: 0–35 years) were included. Thirty-six patients (36/44; 82%) had ASDAS-CRP ≥ 1.3 and 27 patients (27/44; 61%) had ASDAS-CRP ≥ 2.1. The most frequently involved spinal segment was mid-thoracic (T7-T8). The SIJ MRI score was an informative model to identify active axSpA (AUC ≥ 0.7, regardless of the cut-off level on ASDAS-CRP). Performance of bi-parametric models based on “SIJ + thoracic spine” (for detecting patients with ASDAS-CRP ≥ 1.3) or “SIJ + total spine” (for detecting patients with ASDAS-CRP ≥ 2.1) outperformed that of the individual SIJ score (P Conclusion The combination of MRI of the SIJ and spine allows to accurately discriminate between active and inactive axSpA, outperforming SIJ MRI alone.

To compare the diagnostic performance of MRI and 18F-FDG-PET/CT in detecting bone marrow involvement (BMI) in patients with multiple myeloma (MM). This retrospective study was approved by our Institutional Review Board. Two radiologists and two nuclear medicine specialists independently and blindly reviewed 84 pairs of MRI and PET/CT scans obtained in 73 MM patients. Readers assessed the presence and patterns of BMI. The best valuable comparator (BVC) for BMI was established by a panel review of all baseline and follow-up imaging, and biological and pathological information. Intra- and inter-reader agreement and correlation between MRI and PET/CT were assessed using the prevalence-adjusted bias-adjusted kappa (k) coefficient. Diagnostic performance of MRI and PET/CT in detecting BMI was evaluated from ROC characteristics. Association between imaging and biological, pathological, and clinical findings was assessed using Wilcoxon rank-sum and chi-square tests. Intra- and inter-reader agreement was very good for MRI (k = 0.90 [0.81; 1.00] and 0.88 [0.78; 0.98]). Intra- and inter-reader agreement was good for PET/CT (k = 0.80 [0.69; 0.91] and 0.71 [0.56; 0.86]). The sensitivity of MRI to detect BMI (97% [90%; 100%]) was significantly superior to that of PET/CT (76% [64%; 85%]) (p

To determine the margins of non-inferiority of the sensitivity of CT and the sample size needed to test the non-inferiority of CT in comparison with MRI. During a 2-year period, elderly patients with suspected radiographically occult post-traumatic bone injuries were investigated by CT and MRI in two institutions. Four radiologists analyzed separately the CT and MRI examinations to detect post-traumatic femoral injuries. Their sensitivities at CT (SeCT) and MRI (SeMRI) were calculated with the reference being a best valuable comparator (consensus reading of the MRI and clinical follow-up). ROC analysis followed by an exact test (Newcombe’s approach) was performed to assess the 95% confidence interval (CI) for the difference SeCT–SeMRI for each reader. A sample size calculation was performed based on our observed results by using a one-sided McNemar’s test. Twenty-nine out of 102 study participants had a post-traumatic femoral injury. SeCT ranged between 83 and 93% and SeMRI ranged between 97 and 100%. The 95% CIs for (SeCT–SeMRI) were [− 5.3%, + 0.8%], (pR1 = 0.1250), [− 4.5%; + 1.2%] (pR2 = 0.2188), [− 3.4%; + 1.1%] (pR3 = 0.2500) to [− 3.8%; + 1.6%] (pR4 = 0.3750) according to readers, with a lowest limit for 95% CIs superior to a non-inferiority margin of (− 6%) for all readers. A population of 440 patients should be analyzed to test the non-inferiority of CT in comparison with MRI. CT and MRI are sensitive for the detection of radiographically occult femoral fractures in elderly patients after low-energy trauma. The choice between both these modalities is a compromise between the most available and the most sensitive technique. • The sensitivity of four separate readers to detect radiographically occult post-traumatic femoral injuries in elderly patients after low-energy trauma ranged between 83 and 93% at CT and between 97 and 100% at MRI according to a best valuable comparator including MRI and clinical follow-up. • CT is a valuable alternative method to MRI for the detection of post-traumatic femoral injuries in elderlies after low-energy trauma if a 6% loss in sensitivity can be accepted in comparison with MRI. • The choice between CT and MRI is a compromise between the most available and the most sensitive technique.

Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits in a standardized whole-body (WB)-MRI protocol., info:eu-repo/semantics/published

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone defects in rats by &micro, CT. We hypothesized that a preemptive running exercise would quicken bone healing. Twenty 5-week-old, male, Wistar rats were randomly allocated to one of the following groups (n = 10): sedentary control (SED) or continuous running (EX, 45 min/d, 5 d/week at moderate speed, for 8 consecutive weeks). A 2 mm diameter bone defect was then performed in the right tibia and femur. No exercise was performed during a 4 week-convalescence. Healing-tissue trabecular microarchitectural parameters were assessed once a week for 4 weeks using &micro, CT and plasma bone turnover markers measured at the end of the study protocol (time point T12). At T12, bone volume fraction (BV/TV, BV: bone volume, TV: tissue volume) of the healing tissue in tibiae and femurs from EX rats was higher compared to that in SED rats (p = 0.001). BV/TV in EX rats was also higher in tibiae than in femurs (p &lt, 0.01). The bone mineral density of the healing tissue in femurs from EX rats was higher compared to that in femurs from SED rats (p &lt, 0.03). N-terminal telopeptide of collagen type I in EX rats was decreased compared to SED rats (p &lt, 0.05), while no differences were observed for alkaline phosphatase and parathyroid hormone. The study provides evidence that preemptive moderate continuous running improves the healing of non-critical sized bone defects in male Wistar rats.

It is generally accepted that when metastases develop in a patient with biochemical recurrence of prostate cancer (PCa), they follow a centrifuge pattern of seeding from the pelvis and that most patients enter the disease as oligometastatic. In this study, we used whole-body magnetic resonance imaging (WB-MRI) to assess the anatomical distribution of oligo- and polymetastatic disease and the impact of the initial treatment on this distribution in patients. WB-MRI examinations of patients with a rising prostate-specific antigen (PSA) after radical treatment by surgery or/and radiotherapy were analyzed for disease recurrence. The patients were separated into three groups, based on the primary treatment: patients treated by radical prostatectomy without radiotherapy and with/without lymph node dissection (RP), patients treated only by radiotherapy or hormono-radiotherapy (RT) and patients treated with radical prostatectomy and adjuvant or salvage radiotherapy (RP + RT). Patients with ≤ 5 bone or/and node metastases were considered oligometastatic. Regional distributions of bone and lymph nodes metastases were reported using anatomical diagrams. Univariate and multivariable logistic regressions were performed to identify prognostic factors of relapse. The primary treatment (RP, RT, RP + RT), Gleason score, PSA at relapse, time between first diagnosis and recurrence did not influence the metastatic status (oligo vs. polymetastatic). Oligometastatic patients showed different distribution of bone metastases compared to the polymetastatic ones and the distribution of the oligometastatic disease was not influenced by the primary treatment. In this WB-MRI-based study, there was no evidence that the primary treatment influenced the metastatic status of the patient or the distribution of the oligometastatic disease.

To compare the diagnostic accuracy of DWI and STIR sequences in Whole body (WB) MRI of SpA patients. Twenty consecutive patients with confirmed active SpA and 20 controls were investigated with identical WB MRI protocols, including DWI and STIR images. Two observers recorded 'lesions' (high signal intensity foci on STIR and high b-value DWI) in 17 anatomical areas, making a 17-point 'area score' and a 40-point 'lesion score'. ROC performance, inter-observer agreement, correlation with clinical parameters and spine and sacro-iliac joints (SIJ) MRI scores were assessed. SpA patients had significantly higher lesion scores on DWI than on STIR (p

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

To compare the diagnostic accuracy of whole-body T1, short tau inversion recovery (STIR), high b-value diffusion-weighted imaging (DWI), and sequence combinations to detect bone involvement in prostate cancer (PCa) and multiple myeloma (MM) patients. We included 50 consecutive patients with PCa at high risk for metastasis and 47 consecutive patients with a histologically confirmed diagnosis of MM who received whole-body MRI at two institutions from January to December 2015. Coronal T1, STIR, and reconstructed coronal high b-values DWI were obtained for all patients. Two musculoskeletal radiologists read individual sequences, pairs of sequences (T1-DWI, T1-STIR, and STIR-DWI), and all combined (T1-STIR-DWI) to detect bone involvement. Receiver operating characteristic curve analysis was used to assess diagnostic performance according to a “best valuable comparator” combining baseline and 6-month imaging and clinical and biological data. Interobserver agreement was calculated. Interobserver agreement for individual and combined MRI sequences was very good in the PCa group and ranged from good to very good in the MM group (0.76–1.00). In PCa patients, T1-DWI, T1-STIR, and T1-STIR-DWI showed the highest performance (sensitivity = 100% [95% CI = 90.5–100%], specificity = 100% [75.3–100%]). In MM patients, the highest performance was achieved by T1-STIR-DWI (sensitivity = 100% [88.4–100%], specificity = 94.1% [71.3–100%]). T1-STIR-DWI significantly outperformed all sequences (p

To compare 3D T1-weighted fast spin echo (FSE) and 3D T1-weighted gradient echo (GE) mDixon as morphologic sequences to complement diffusion-weighted imaging (DWI) for the metastatic screening in prostate cancer (PCa) patients. Thirty PCa patients at high risk of metastases prospectively underwent both a 3D T1 FSE (14 min) and a rapid 3D T1 GEmDixon (1 min 20 s) sequences within a WB-MRI protocol. Two readers assessed the diagnostic performance of the FSE/Fat/in-phase (IP)/IP+Fat sequences in detecting bone and node metastases. The reference standard was established by a panel of four physicians on the basis of all baseline and follow-up imaging, biological and clinical information. The reproducibility of readings, predictive accuracy (Acc) from ROC curves analysis, and contrast-to-reference ratio (CRR) in lesions were assessed for each sequence. In bone and lymph nodes (per-region analysis), reproducibility was at least good for all sequences/readers, except for nodes in the common iliac/inguinal regions. In bone (per-organ analysis), Acc of FSE was superior to that of mDixon (difference + 4%, p < 0.0083). In nodes (per-organ analysis), Acc of Fat was superior to that of other sequences (difference + 4% to + 6% depending on reader, p < 0.0083). In the per-patient analysis, Acc of FSE was superior to that of mDixon (difference + 4% to + 6% depending on sequence, p < 0.0083). Fat images had higher CRR compared with FSE in the thoracic spine, the bony pelvis and lymph node metastases (p < 0.025). 3D T1 GEmDixon may replace 3D T1 FSE to complement DWI in WB-MRI for metastatic screening in PCa. It demonstrates an Acc ranging from + 4% to + 6% (nodes) to − 4% to − 6% (bone and patient staging) compared with FSE and considerably reduces the examination time, offering the perspective of acquiring WB-MRI examinations in less than 20 min. • The replacement of 3D T1 FSE by the 3D T1 GE mDixon as morphologic sequence to complement DWI drastically reduces the acquisition time of WB-MRI studies. • The 3D T1 GE mDixon sequence offers similar reproducibility of image readings compared with that of the 3D T1 FSE. • Differences in diagnostic accuracy are limited (+ 4%/+ 6% in favor of mDixon to detect node metastases; + 4%/+ 6% in favor of FSE to detect bone metastases/metastatic disease in a patient).

Aim We hypothesized that multiple-choice questions written by radiology residents (MCQresident) for their weekly case presentations during radiology staff meetings could be used along with multiple-choice questions written by radiology teachers (MCQteacher) for their annual evaluation. The current prospective study aimed at determining the educational characteristics of MCQresident and at comparing them with those of MCQteacher. Methods Fifty-one radiology residents of the first to the fifth year of training took the 2017 exam that contained 58 MCQresident and 63 of MCQteacher. The difficulty index, the discrimination power, and the distractor’s quality were calculated in the two series of MCQs and were compared by using Student t test. Two radiologists classified each MCQ according to Bloom’s taxonomy and frequencies of required skills of both MCQ series were compared. Results The mean ± SD difficulty index of MCQresident was statistically significantly higher than that of MCQteacher (0.81 ± 0.1 vs 0.64 ± 0.2; p < 0.0001). The mean ± SD discrimination index of MCQresident was statistically significantly higher than that of MCQteacher (0.34 ± 0.2 vs 0.23 ± 0.2; p = 0.0007). The mean number of non-functional distractors per MCQresident was statistically significantly higher than that per MCQteacher (1.36 ± 0.9 vs 0.86 ± 0.9; p = 0.0031). MCQresident required recalling skills more frequently than MCQteacher which required more advanced skills to obtain a correct answer. Conclusions Educational characteristics of MCQresident differ from those of MCQteacher. This study highlights the characteristics to optimize the writing of MCQs by radiology residents.

OBJECTIVES To determine the proportion of prostate cancer (PCa) patients with oligometastatic disease (≤3 synchronous lesions) using whole body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI/DWI). To determine the proportion of patients with nodal disease confined within currently accepted target areas for extended lymph node dissection (eLND) and pelvic external beam radiation therapy (EBRT). SUBJECTS AND METHODS Two radiologists reviewed WB-MRI/DWI studies in 96 consecutive newly diagnosed metastatic PCa patients; 46 patients with newly diagnosed castration naive PCa (mHNPC) and 50 patients with first appearance of metastasis during monitoring for non-metastatic castration resistant PCa (M0 to mCRPC). The distribution of metastatic deposits was assessed and the proportions of patients with oligometastatic disease and with LN metastases located within eLND and EBRT targets were determined. RESULTS Twenty-eight percent of mHNPC and 50% of mCPRC entered the metastatic disease with ≤3 sites. Bone metastases (BM) were identified in 68.8% patients; 71.7% of mHNPC and 66% mCRPC patients. Most commonly involved areas were iliac bones and lumbar spine. Enlarged lymph nodes (LN) were detected in 68.7% of patients; 69.6% of mHNPC and 68.0% of mCRPC. Most commonly involved areas were para-aortic, inter-aortico-cava, and external iliac areas. BM and LN were detected concomitantly in 41% of mHNPC and 34% of mCRPC. Visceral metastases were detected in 6.7%. Metastatic disease was confined to LN located within the accepted boundaries of eLND or pelvic EBRT target areas in only ≤25% and ≤30% of patients, respectively. CONCLUSIONS Non-invasive mapping of metastatic landing sites in PCa using WB-MRI/DWI shows that 28% of the mHNPC patients, and 52% of the mCRPC can be classified as oligometastatic, thus challenging the concept of metastatic targeted therapy. More than two thirds of metastatic patients have LN located outside the usually recommended targets of eLND and pelvic EBRT. Prophylactic or salvage treatments of these sole areas in patients with high-risk prostate cancer may not prevent the emergence of subsequent metastases. Prostate © 2016 Wiley Periodicals, Inc.

Purpose To assess the distribution of bone lesions in patients with prostate cancer (PCa) and those with multiple myeloma (MM) using whole-body magnetic resonance imaging (MRI); and to assess the added value of four anatomical regions located outside the thoraco-lumbo-pelvic area to detect the presence of bone lesions in a patient-based perspective. Materials and methods Fifty patients (50 men; mean age, 67 ± 10 [SD] years; range, 59–87 years) with PCa and forty-seven patients (27 women, 20 men; mean age, 62.5 ± 9 [SD] years; range, 47–90 years) with MM were included. Three radiologists assessed bone involvement in seven anatomical areas reading all MRI sequences. Results In patients with PCa, there was a cranio-caudal increasing prevalence of metastases (22% [11/50] in the humeri and cervical spine to 60% [30/50] in the pelvis). When the thoraco-lumbo-pelvic region was not involved, the prevalence of involvement of the cervical spine, proximal humeri, ribs, or proximal femurs was 0% in patients with PCa and ≥ 4% (except for the cervical spine, 0%) in those with MM. Conclusion In patients with PCa, there is a cranio-caudal positive increment in the prevalences of metastases and covering the thoraco-lumbo-pelvic area is sufficient to determine the metastatic status of a patient with PCa. In patients with MM, there is added value of screening all regions, except the cervical spine, to detect additional lesions.

Whole-body coverage using MRI was developed almost 2 decades ago. The first applications focused on the investigation of the skeleton to detect neoplastic disease, mainly metastases from solid cancers, and involvement by multiple myeloma and lymphoma. But the extensive coverage of the whole musculoskeletal system, combined with the exquisite sensitivity of MRI to tissue alteration in relation to different pathologic conditions, mainly inflammation, has led to the identification of a growing number of indications outside oncology. Seronegative rheumatisms, systemic sclerosis, inflammatory diseases involving muscles or fascias, and multifocal osseous, vascular, or neurologic diseases represent currently validated or emerging indications of whole-body MRI (WB-MRI). We first illustrate the most valuable indications of WB-MRI in seronegative rheumatisms that include providing significant diagnostic information in patients with negative or ambiguous MRI of the sacroiliac joints and the lumbar spine, assessing disease activity in advanced (ankylosed) central disease, and evaluating the peripherally dominant forms of spondyloarthropathy. Then we review the increasing indications of WB-MRI in other rheumatologic and nonneoplastic disorders, underline the clinical needs, and illustrate the role of WB-MRI in the positive diagnosis and evaluation of disease burden, therapeutic decisions, and treatment monitoring.

Numerous imaging modalities are available for the diagnosis of bone metastases (BM) in patients with cancer. This paper reviews published studies comparing whole-body (wb) MRI to BS, PET or PET-CT to provide up-to-date evaluation of the diagnostic accuracy of wbMRI to detect BM. This review is based on a systematic search of the literature of studies evaluating the diagnostic performance of wbMRI for BM detection. Evidence synthesis was achieved via a classification tree, which provides an overview of the performance of the different imaging techniques and of the context in which these are assessed, and an evidence table to seek confirmation of the diagnostic value of the imaging techniques. Eligible studies (n = 23/301) included patients with cancer who underwent wbMRI for suspicion of BM or for systematic cancer staging, compared with at least one other imaging tool. The evidence supporting the superiority of wbMRI over BS for BM screening is strong. wbMRI with diffusion-weighted imaging (DWI) sequence has higher sensitivity than wbMRI alone. The respective accuracies of wbMRI and FDG PET-CT differ depending both on the type of analysis (lesion, region or patient-based) and primary cancer. wbMRI and PET-CT emerge as the techniques of choice for the diagnosis of BM. The inclusion of DWI in wbMRI protocols is of value to optimize the sensitivity but does not add in specificity. This indicates the importance of the anatomical sequences in those protocols. Further comparisons between wbMRI and DWI alone, 18F-NaF, 11C-Choline, PSMA PET-CT and PET-MRI systems remain necessary.

Purpose To develop and assess the diagnostic performance of a three-dimensional (3D) whole-body T1-weighted magnetic resonance (MR) imaging pulse sequence at 3.0 T for bone and node staging in patients with prostate cancer. Materials and Methods This prospective study was approved by the institutional ethics committee; informed consent was obtained from all patients. Thirty patients with prostate cancer at high risk for metastases underwent whole-body 3D T1-weighted imaging in addition to the routine MR imaging protocol for node and/or bone metastasis screening, which included coronal two-dimensional (2D) whole-body T1-weighted MR imaging, sagittal proton-density fat-saturated (PDFS) imaging of the spine, and whole-body diffusion-weighted MR imaging. Two observers read the 2D and 3D images separately in a blinded manner for bone and node screening. Images were read in random order. The consensus review of MR images and the findings at prospective clinical and MR imaging follow-up at 6 months were used as the standard of reference. The interobserver agreement and diagnostic performance of each sequence were assessed on per-patient and per-lesion bases. Results The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significantly higher with whole-body 3D T1-weighted imaging than with whole-body 2D T1-weighted imaging regardless of the reference region (bone or fat) and lesion location (bone or node) (P < .003 for all). For node metastasis, diagnostic performance (area under the receiver operating characteristic curve) was higher for whole-body 3D T1-weighted imaging (per-patient analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P = .006 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging), as was sensitivity (per-lesion analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging). Conclusion Whole-body MR imaging is feasible with a 3D T1-weighted sequence and provides better SNR and CNR compared with 2D sequences, with a diagnostic performance that is as good or better for the detection of bone metastases and better for the detection of lymph node metastases.

MRI is a very attractive approach for tumour detection and oncological staging with its absence of ionizing radiation, high soft tissue contrast and spatial resolution. Less than 10 years ago the use of Whole Body MRI (WB-MRI) protocols was uncommon due to many limitations, such as the forbidding acquisition times and limited availability. This decade has marked substantial progress in WB-MRI protocols. This very promising technique is rapidly arising from the research world and is becoming a commonly used examination for tumour detection due to recent technological developments and validation of WB-MRI by multiple studies and consensus papers. As a result, WB-MRI is progressively proposed by radiologists as an efficient examination for an expanding range of indications. As the spectrum of its uses becomes wider, radiologists will soon be confronted with the challenges of this technique and be urged to be trained in order to accurately read and report these examinations. The aim of this review is to summarize the validated indications of WB-MRI and present an overview of its most recent advances. This paper will briefly discuss how this examination is performed and which are the recommended sequences along with the future perspectives in the field.

Background Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT). Methods LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dualinput one-compartmental model. Results Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively. Conclusions LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is the standard for local prostate cancer (PCa) staging. Whole-body MRI (wbMRI) has shown capabilities for metastatic screening. This study assesses the feasibility and value of an all-in-one AJCC TNM staging of PCa during a unique MRI session combining mpMRI and wbMRI. METHODS: Thirty consecutive patients with "high-risk" PCa prospectively underwent mpMRI of the prostate and wbMRI, in addition to (99m) Tc bone scan (BS), completed with standard X-rays (±TXR) and contrast enhanced CT for distant staging. For the statistical analysis, a "best valuable comparator" (BVC) combining a panel review of all available baseline and follow-up imaging, biological, and clinical data was used to adjudicate lymph node and bone metastatic status. RESULTS: Prostate mpMRI was analyzed using ESUR guidelines. Sensitivity of BS ± TXR combined with CT and of wbMRI for detecting metastases (bones or nodes) was 85% and 100%, respectively, and specificity was 88% and 100%, respectively. For the overall staging of the patients as being either N0M0 or having disease extension beyond the prostate, wbMRI was superior to the combination of BS and CT (improvement in all ROC characteristics and of AUC by 13.6% (95% CI: +0.7% to +26.5%, P = 0.039)). The main limitation is the limited number of patients. CONCLUSIONS: AJCC M and N staging using wbMRI is feasible during the same imaging session as mpMRI performed for T staging, in less then one hour. wbMRI outperforms BS ± TXR and abdomino-pelvic CT work up for discriminating subsets of patients with or without distant spread of the cancer.

To investigate the safety and activity of cetuximab in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN).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.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 (P0.0001). 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).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.

Beyond lesion detection and characterisation, and disease staging, the quantification of the tumour load and assessment of response to treatment are daily expectations in oncology. Bone lesions have been considered “non-measurable” for years as opposed to lesions involving soft tissues and “solid” organs like the lungs or liver, for which response evaluation criteria are used in every day practice. This is due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques available for bone assessment, i.e. skeletal scintigraphy (SS), radiographs and computed tomography (CT). This paper reviews the possibilities and limitations of these techniques and highlights the possibilities of positron emission tomography (PET), but mainly concentrates on magnetic resonance imaging (MRI). Practical morphological and quantitative approaches are proposed to evaluate the treatment response of bone marrow lesions using “anatomical” MRI. Recent developments of MRI, i.e. dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered. • MRI offers improved evaluation of skeletal metastases and their response to treatment. • This new indication for MRI has wide potential impact on radiological practice. • MRI helps meet the expectations of the oncological community. • We emphasise the practical aspects, with didactic cases and illustrations.

Multiparametric Magnetic Resonance Imaging (mp-MRI) is the current standard of reference for the local staging of prostate cancer (PCa). On the other hand, despite the low sensitivity and specificity of Technetium Bone Scanning (BS) for the detection of bone metastases (BM) and of Body Computed Tomography CT for the detection of lymph node metastases (LNM), these techniques are routinely used, in the current clinical practice. Nevertheless, whole Body MRI (WB-MRI) and Positron Emission Tomography Computed Tomography (PET-CT) are emerging as robust tools for the staging of oncologic patients, including those with (PCa). The available techniques (BS, WB-MRI, PET, CT) for the detection of BM in oncologic patients were compared and showed striking center differences in terms of anatomic sequences and planes used. This heterogeneity and the long acquisition time of WB-MRI protocols – due to the addition of multiple anatomic sequences in different planes – questioned whether a single three dimensional (3D) sequence could replace the multiple anatomic sequences used for node and bone staging of PCa. We demonstrated that WB-MRI is a credible tool for the detection of bone and node metastasis. The second question addressed the possibility to obtain a complete TNM staging of PCa in a single MRI session. A WB-MRI protocol was developed to enable complete, T (local), N (regional) and M (distant) staging of PCa in a single session, in less than an hour. This ‘all-in-one’ protocol proved to be as efficient as the sum of exams currently in use for the staging of PCa (ie: mp-MRI of the prostate for ‘T’ staging, Thoraco-abdominal CT for ‘N’ staging and bone scintigraphy for ‘M’ staging).

Objective To assess the multirater agreement of the modified Outerbridge system for the grading of predefined areas of femorotibial cartilage at CT arthrography with multiple readers, with varying experience. Design Five readers with varying experience (two junior radiologists, three musculoskeletal radiologists including two experts in cartilage imaging) separately analyzed 962 cartilage sectors from pre-divided knee CT arthrograms with femorotibial osteoarthritis (Kellgren/Lawrence = 3). Each cartilage area was graded twice by each reader, at a three-month interval, according to the modified 5-grade Outerbridge system. Interobserver and intraobserver agreement were assessed. After the second reading, 121 areas exhibiting the highest interobserver disagreement were reviewed in consensus to determine the sources of disagreement. Results The global interobserver agreement was fair (k = 0.35), and increased with the grade (from k = 0.14 to k = 0.76 from grade 0–4). The intraobserver agreement varied with the readers’ experience from moderate (k = 0.59) to almost perfect (k = 0.92). The majority of cases of disagreement (44%) was due to difficulties in assessing the normal variations of cartilage thickness, including diffuse cartilage thinning (23%) and normal variants of cartilage thickness (22%). 32% of cases of disagreement were due to retrospectively avoidable interpretation errors. Conclusions The multirater agreement of the modified Outerbridge system is only fair when readers of different level of experience are taken into account, and interobserver agreement increases with readers’ experience. However, interobserver agreement is substantial for grade 4 lesions. We report normal variations of cartilage thickness that may improve observer agreement in reporting cartilage lesions.

Purpose: To prospectively assess the utility of perfusion computed tomography (CT) for differentiating minimal from intermediate fibrosis in treatment-naive patients with chronic hepatitis C virus (HCV) infection. Materials and Methods: This study was approved by the Institutional Review Board, and informed consent was obtained. Fifty-two patients with treatment-naive HCV infection underwent perfusion CT and percutaneous liver biopsy on the same day. Portal vein, arterial, and total liver perfusion; mean transit time; and distribution volumes for the right and left liver lobes were measured. Liver samples were scored for fibrosis, and fibrosis area was determined. Differences in quantitative perfusion parameters between patients with minimal fibrosis (score of F1) and those with intermediate fibrosis (score of F2 or F3) were tested. Results: In patients with intermediate fibrosis (F2 and F3) compared with those with minimal fibrosis (F1), the portal venous perfusion (87 mL . min(-1) . 100 mL(-1) +/- 27 [standard deviation] vs 138 mL . min(-1) . 100 mL(-1) +/- 112, P = .042) and total liver perfusion (107 mL . min(-1) . 100 mL(-1) +/- 31 vs 169 mL . min(-1) . 100 mL(-1) +/- 137, P = .02) were significantly decreased, and the mean transit time was significantly increased (16 seconds +/- 4 vs 13 seconds +/- 5, P = .025). At multivariate analysis, only the mean transit time was an independent factor (odds ratio, 1.18; 95% confidence interval: 1.02, 1.37; P = .030). Receiver operating characteristic curve analysis showed that a mean transit time threshold of 13.4 seconds allowed discrimination between minimal and intermediate fibrosis with a sensitivity of 71% and a specificity of 65%. Conclusion: The results of this study show that perfusion changes occur early during fibrosis in chronic HCV infection and can be detected with perfusion CT. Perfusion CT may help to discriminate minimal from intermediate fibrosis. Mean transit time appears to be the most promising perfusion parameter for differentiating between fibrosis stages, although the large amount of overlap in the measured parameters limits the clinical utility of this test at present. (C) RSNA, 2010

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 (Ktrans) 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 Ktrans 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.

PURPOSE: To assess which MRI-derived kinetic parameters reflect decreased transvascular and interstitial transport when low- and high-molecular-weight agents are used in rat hepatocellular carcinomas. MATERIALS AND METHODS: Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA, gadoterate) and two high-molecular-weight contrast agents of 6.47 kDa (P792, gadomelitol) and 52 kDa (P717, carboxymethyldextran Gd-DOTA) was performed in rats with chemically induced hepatocellular carcinomas. The data were analyzed with the Kety compartmental model, the extended Kety compartmental model in which it is assumed that the tissue voxels contain a vascular component, and the St Lawrence and Lee distributed-parameter model. RESULTS: The extravascular extracellular space accessible to the contrast agent v(e) and the extraction fraction E decreased with increasing molecular weight of the contrast agent. In contrast, the volume transfer constant Ktrans did not differ significantly when low- or high-molecular-weight agents were used. CONCLUSION: In this animal model the results suggest that the accessible extravascular extracellular space and the extraction fraction are more sensitive indicators of decreased transvascular and interstitial transport with high-molecular-weight agents than the volume transfer constant, which is a lumped representation of blood flow and permeability. J. Magn. Reson. Imaging 2008;28:906-914. (c) 2008 Wiley-Liss, Inc.

Although myxoma is extremely rare, it represents the most common primary benign cardiac tumor, accounting for 50% of cases [1]. Echocardiography is the first in line imaging modality but it has a limited tissue characterization ability, hampering to establish the diagnosis of myxoma presenting atypically [2]. Therefore, cardiac magnetic resonance (CMR) is increasingly used in the diagnostic patient work up. Because of its rarity, our knowledge of the imaging characteristics of myxoma at CMR, is limited to case reports and small patient series. In this study, we report the CMR features of a consecutive patient cohort (n = 35, 17 men, 64 years (26–86 years)) with histologically confirmed myxomas obtained at two tertiary hospitals from 2005 to 2015.

Background. Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN). Methods. Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow Fp, extravascular space ve, vascular space vp, and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points. Results. Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion. Conclusions. Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome.

BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

The purpose of this article is to evaluate and compare the prevalence and measurement values of CT signs of femoroacetabular impingement (FAI) in asymptomatic hips without CT signs of osteoarthritis between two age groups: younger than 40 years and older than 60 years.We prospectively included patients undergoing thoracoabdominopelvic MDCT for nonorthopedic indications with asymptomatic hips and excluded hips with signs of osteoarthritis seen on CT. Two age groups including 75 hips each were enrolled (40 years old: mean age, 31 years; 15 women;60 years old: mean age, 66 years; 21 women). Two observers independently performed the image analysis. Prevalences and quantitative values of the cam (alpha angle and femoral head-neck offset) and pincer (acetabular version angle, acetabular index, lateral center-edge angle, crossover sign, and posterior wall sign) FAI morphotypes were compared using both difference and equivalence tests. Intraobserver agreement was assessed.The prevalence of CT signs of FAI were high and showed great variation depending on the signs and cutoff values, in both groups (9-63% for cam; 3-50% for pincer). The prevalence and measurement values of CT signs of the cam morphotype were equivalent between the two age groups. The prevalence and measurement values of CT signs of the pincer morphotype were statistically equivalent between the age groups except for the acetabular version angle, lateral center-edge angle, and crossover sign for which no statistical difference was found, but statistical equivalence was not reached. Interobserver and intraobserver agreement were moderate to almost perfect (κ = 0.72-0.89; intraclass correlation coefficient, 0.42-0.94).The prevalence and measurement values of most CT signs of FAI morphotypes were high and equivalent between the two age groups of patients with asymptomatic nonosteoarthritic hips.

Imaging has multiple roles in oncology. Besides lesion detection and characterization, disease staging, the quantification of the tumor load and the evaluation of response to therapy are of critical importance for the patient and for the clinician, both in primary and metastatic cancers. The assessment of the response to treatment of bone lesions has been considered difficult or impossible even for most prestigious cancer authorities, compared to lesions involving soft tissues or other organs like the lungs or liver, for which response evaluation criteria exist (Eisenhauer et al. 45:228–247, 2009; Therasse et al. 92:205–216, 2000). This is mainly due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques that have been available for years for the assessment of bone lesions, i.e. bone scintigraphy (BS), radiographs and X-ray computed tomography (CT). This chapter first summarizes the possibilities and limitations of the aforementioned techniques. It illustrates the capabilities of “modern” imaging modalities, i.e. positron emission tomography (PET) and most importantly magnetic resonance imaging (MRI). Practical morphologic as well as functional observations that can be made using MRI at primary diagnosis are emphasized as well as the evaluation of response of bone marrow lesions to treatment. Technical advances in MRI, which further refine the capabilities of this modality for early evaluation of the response, including dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered.

The MR appearance of the normal marrow shows important variations not only with age and gender but also among individuals of the same age range and sex. On the contrary, marrow distribution and signal intensity patterns show little variation among similar bones of the same subject. Focal alterations in signal intensity can be observed as normal findings, reflecting local variations in the amount of normal expected medullary space components (including fat, hematopoietic or bone cells and vessels). Several variations from the normal age-related expected appearance have been recognized including focal or diffuse red marrow hyperplasia, enchondromas, hemangiomas, and marrow changes related to the presence of notochordal cells. Important limitations in the characterization potentials of MR imaging should also be kept in mind.

To assess the performance of parameters used in conventional magnetic resonance imaging (MRI), perfusion-weighted MR imaging (PWI) and visual texture analysis, alone and in combination, to differentiate a single brain metastasis (MET) from glioblastoma multiforme (GBM).In a retrospective study of 50 patients (41 GBM and 14 MET) who underwent T2/FLAIR/T1(post-contrast) imaging and PWI, morphological (circularity, surface area), perfusion (rCBV in the ring-like tumor area, rCBV in the peritumoral area, percentage of signal intensity recovery at the end of first pass) and texture parameters in the peritumoral area were estimated. Statistical differences and performances were assessed using Wilcoxon's test and receiver operating characteristic curves, respectively. Multiparametric classification of tumors was performed using k-means clustering.Significant statistical differences in circularity, surface area, rCBVs, percentage of signal intensity recovery and texture parameters (energy, entropy, homogeneity, correlation, inverse differential moment, sum average) were observed between MET and GBM (P0.05). Moderate-to-good classification performances were found with these parameters. Clustering based on rCBV and texture parameters (contrast, sum average) differentiated MET from GBM with a sensitivity of 92% and a specificity of 71%.Combining perfusion and visual texture parameters within a statistical classifier significantly improved the differentiation of a single brain MET and GBM.

PURPOSE:: To assess if 1.5T MRI can be used to study the transport to the liver, the intrahepatic distribution and engraftment of iron-oxide labelled hepatocytes in cyclophosphamide-treated and untreated mice. MATERIALS AND METHODS:: Hepatocytes were isolated from C57bl/6 mice and were labelled with 1.63 mum iron-oxide particles. Seventeen mice were pretreated with cyclophosphamide to disrupt the sinusoidal endothelium and 15 were left untreated. Seven days after splenic injection of the labelled hepatocytes, T2*-weighted gradient-echo images at 1.5T were acquired. The hepatic transport, distribution and engraftment of the labelled hepatocytes were assessed with signal intensity (SI) and T2* measurements, electron paramagnetic resonance (EPR), texture analysis and histology. RESULTS:: Lower hepatic SI (P = 0.005), lower T2* (P = 0.033) and larger number of particles at histology (P = 0.006) suggested increased transport to the liver of labelled hepatocytes in cyclophosphamide-treated mice versus untreated mice. At histology, most particles were located in Kupffer cells. Particles distribution was heterogeneous. No difference between both groups was observed at texture analysis. CONCLUSION:: MRI is useful to assess the transport to the liver and intrahepatic distribution of transplanted labelled hepatocytes. The preferential location of iron-oxide particles within Kupffer cells after seven days limits the value of MRI for assessing hepatocyte engraftment. J. Magn. Reson. Imaging 2010;32:367-375. (c) 2010 Wiley-Liss, Inc.

Background : Only a subset of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies (windows studies) in treatment-naive patients are crucial to better characterize the molecular pathways involved in treatment response or resistance. Methods : Cetuximab (C) (400mg/m2 first wk followed by 250mg/m2/wk) was given pre-operatively during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0) to 20 treatment-naive SCCHN pts selected for primary curative surgery. As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. The aims of the study were (i) safety, (ii) C activity by FDG-PET (Po = 0.10, P1 = 0.35, a = 0.05 and b= 0.10) and (iii) translational research. We compared pathologic changes in surgical specimens of the C group with control specimens and correlated these results with microarray analysis performed on paired biopsies in the C group. Results : C infusion given 24 hrs before surgery was safe. 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group vs 0% in the controls. 52% had a ΔSUVmax decrease of >50%. In surgical specimens we detected modifications of the peritumoral environment. By immunochemistry, we found more fibrosis arranged in a compact manner in the C group than in the non-treated samples (histological score) (p = 0.04). Genome-wide expression analysis (Affymetrix HG U133 Plus 2.0) of the paired biopsies taken in the tumor center before and after C supports this histological observation. Results show a significant increase in expression (Student's T test p = 0.02; n = 20) of a previously published stroma signature (Finak et al., Breast Cancer Res 2006) after C. A trend was also observed between this stroma signature score and the fibrosis histological score. Conclusions : Pre-operative study with C is safe. Our findings suggest that C induces quantitative modifications in the microenvironment of the tumor. We are currently investigating other components of the peri-tumoral environment (inflammation and vascularization).

5519 Background: Only a minority of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies are crucial to better characterize the molecular pathways involved in treatment response or resistance. Targeted agents (TA) are often investigated in unselected end-stage cancer pts, making difficult optimal translational research. One way to resolve this issue is to perform “window” studies where a TA is given during the incompressible period between the diagnosis and surgery. Methods: We conducted a phase I/II study: cetuximab (C) was given pre-operatively to treatment-naïve SCCHN pts selected for primary curative surgery. C (400mg/m2 first wk followed by 250mg/m2/wk) was given during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0). Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. In the phase I, we investigated the safety of preoperative C by progressively reducing the delay between the last dose of C and surgery (minimum delay : 24 hrs ; 3+3 phase 1 design). The aims of the phase II were (i) safety, (ii) C activity by FDG-PET (Po=0.10, P1=0.35, a=0.05 and b= 0.10). As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Results: The phase 1 study (n=18) demonstrated that C infusion given 24 hrs before surgery was safe. Safety was confirmed in the phase II (n=20). 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group and 0% in the controls. 52% had a ΔSUVmax decrease of >50%. 2 pts evaluable by CT/MRI had a PR (RECIST). Then, we compared the pre-and post treatment biopsies by immunochemistry. For the whole group, C did not reduce Ki67 (p=0.1) and did not seem to induce apoptosis (caspase). However, for pts with ΔSUVmax decrease > 25% or > 50%, Ki67 was decreased (p=0.04 and 0.006). C induced downregulation of pEGFR (p=0.0004) and pERK (p=0.007) but not pAKT/AKT (Histoscore). Conclusions: Pre-operative study with C is safe. Our findings suggest that the main downstream molecular pathway blocked by C in SCCHN is the RAS/RAF/ERK. Further analyses are ongoing to better characterize molecular response and escape mechanisms.

6024 Background: Up to 90% of head and neck squamous cell carcinoma (HNSCC) express the vascular endothelial growth factor (VEGF) or the VEGF receptors (VEGFR) 1–3. Angiogenic factors could have prognostic implication making anti-angiogenic therapies an attractive treatment modality. Sunitinib inhibits multiple tyrosine kinase receptors including VEGFR1–3 and PDGFR. Methods: Palliative HNSCC in PD after platinum therapy received sunitinib 37.5 mg/day continuously. The primary endpoint was the disease control rate (SD, PR, CR) at 6–8 wks. A two-stage design was used (Simon; a = 0.15,b = 0.10, H0 = 10%, H1 = 25%) meaning that at least 6 patients out of 37 should achieve a SD. Dynamic contrast enhanced (DCE) magnetic resonance (MR) perfusion-weighted imaging before and 6 wks after treatment initiation was performed on a 3T system. Results: 37 pts (M/F:28/9;PS 0/1:5/32) were included.11 pts were not evaluable by imaging due to rapid clinical PD (7 pts) or toxicity (4 pts) and were considered in PD.PR was found in 1 pts, SD in 18, and PD in 18 (RECIST). Among the SD, 6 had a minor response and 5 had an unconfirmed PR (maximum % reduction in sum of the largest diameters: 2%, 4%, 7%, 10%, 16%, 17%, 30%, 45%, 48%, 65%, 73%). PR could not be confirmed due to PD within 4 wks (3 pts) or treatment termination due to toxicity (2 pts). 4 pts had MR DCE monitoring. In 3, a significant decrease in the volume transfer constant Ktrans measuring the tumor perfusion and endothelial permeability was found during sunitinib treatment. The main Gr3–4 toxicities (N pts) were fatigue (12), tumor bleedings (2), LVEF decrease (2), hypertension (2). Gr5 tumor bleedings occurred in 4 pts. Other local complications included apparition/worsening of tumor skin ulceration or tumor fistula in 15 pts. Conclusions: This trial met its primary endpoint with modest activity of sunitinib in HNSSC. The rate of complications (i.e., fatal bleedings) outlines the importance of a better patient selection. DCE-MRI may be useful to predict response. No significant financial relationships to disclose.