L. Fournier

Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent

Macromolecular contrast-enhanced functional CT was performed to characterize early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with chemically induced primary liver tumors ranging pathologically from hyperplasia to HCC and 15 control rats were investigated. Two dynamic CT scans using an experimental macromolecular contrast agent were performed on a single slice 11 and 18 weeks after tumor induction followed by pathological examination. A deconvolution mathematical model was applied, yielding the hepatic perfusion index (HPI), mean transit time (MTT), liver distribution volume (LDV) and arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC. On the first scans, HCC at an early pathological stage had a low FP (−30%, P=0.002) but a normal arterial-portal balance. On the scan contemporary to pathology, HCC perfusion parameters showed an inversion of the arterial-portal balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (−69%, P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even though only one (7%) was visible to the eye. Perfusion-CT allowed early detection of HCC. This technique could contribute in the detection and characterization of liver lesions in clinical studies.

Dynamic optical breast imaging : A novel technique to detect and characterize tumor vessels

PURPOSE To prospectively determine the diagnostic accuracy of optical absorption imaging in patients with Breast Imaging Reporting and Data System (BI-RADS) 3-5 breast lesions. MATERIALS AND METHODS Forty-six patients with BI-RADS classification 3 (11%), 4 (44%) or 5 (44%) lesions, underwent a novel optical imaging examination using red light to illuminate the breast. Pressure was applied on the breast, and time-dependent curves of light absorption were recorded. Curves that consistently increased or decreased over time were classified as suspicious for malignancy. All patients underwent a core or surgical biopsy. RESULTS Optical mammography showed a statistical difference in numbers of suspect pixels between benign (N=12) and malignant (N=35) lesions (respectively 1325 vs. 3170, P=0.002). In this population, optical imaging had a sensitivity of 74%, specificity of 92%, and diagnostic accuracy of 79%. The optical signal did not vary according to any other parameter including breast size or density, age, hormonal status or histological type of lesions. CONCLUSION Optical imaging is a low-cost, non-invasive technique, yielding physiological information dependent on breast blood volume and oxygenation. It appears to have a good potential for discriminating benign from malignant lesions. Further studies are warranted to define its potential role in breast cancer imaging.

Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations

CONTEXT The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. OBJECTIVE To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. EVIDENCE ACQUISITION Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. EVIDENCE SYNTHESIS A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. CONCLUSIONS Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques.

Magnetic Targeting of Rhodamine-Labeled Superparamagnetic Liposomes to Solid Tumors: In Vivo Tracking by Fibered Confocal Fluorescence Microscopy

Polyethylene glycol (PEG)ylated and rhodamine-labeled liposomes loaded with maghemite nanocrystals provide a novel nanoscaled hybrid system for magnetic targeting to solid tumors in possible combination with double in vivo imaging by fluorescence microscopy and magnetic resonance imaging (MRI). Human prostate adenocarcinoma tumors implanted in mice were used as a system model. A magnetic field gradient was produced at the tumor level by external apposition of a magnet. Noninvasive fibered confocal fluorescence microscopy was successfully used to track the liposomes in vivo within organs and tumor blood vessels. Active targeting to the magnet-exposed tumors was clearly shown, in agreement with previous MRI studies. The liposomes were driven and accumulated within the microvasculature through a process that preserved vesicle structure and content.

Response of renal cell carcinoma pancreatic metastasis to sunitinib treatment: a retrospective analysis.

PURPOSE Pancreatic metastasis accounts for 2% of metastatic renal cell carcinoma cases. Surgical management is typically recommended because of the limited value of immunotherapy as an effective treatment. Sunitinib recently showed clinical efficacy in patients with advanced renal cell carcinoma. We report a series of patients with pancreatic metastasis treated with sunitinib. MATERIALS AND METHODS We retrospectively studied a population of 15 adults with pancreatic metastasis of renal cell carcinoma at 1 center in France and at 2 in the United States who were treated with sunitinib between 2005 and 2007. Sunitinib monotherapy was given at a dose of 50 mg orally in 6-week cycles, consisting of 4 weeks of treatment followed by 2 weeks of rest. All clinical and radiological data were analyzed. RESULTS At a median followup of 20 months the overall tumor response using Response Evaluation Criteria in Solid Tumors was 34%. Median time to relapse was 20 months. Two deaths were noted and median survival was not attained. Responses in the pancreatic metastasis were seen in 28% of patients and were stable in 72%. The main grade 3 and 4 adverse events were diarrhea in 7% of cases and fatigue in 7%. Only grade 1 increased lipase was noted in 27% of patients and no increase in amylase was noted. CONCLUSIONS Sunitinib is effective in patients with pancreatic metastasis. This raises the question of whether patients with metastatic renal cell carcinoma limited to the pancreas may derive greater clinical benefit from anti-angiogenic agents, rather than from aggressive surgical resection. However, surgery remains the only potential cure in patients with isolated pancreatic metastasis.

Radiological evaluation of response to treatment: Application to metastatic renal cancers receiving anti-angiogenic treatment

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject.

Imagerie de la réponse aux traitements en cancérologie.

Resume L’imagerie en oncologie a un role primordial pour guider le therapeute dans ses choix de traitements. Nous aborderons des nouvelles techniques permettant de predire et d’evaluer la reponse aux traitements en cancerologie. La methode de reference d’evaluation des traitements est basee sur la mesure de la taille des lesions. L’imagerie fonctionnelle ne s’interesse pas a la taille de la lesion, mais a une caracteristique physiologique ou moleculaire, dont les modifications apparaissent plus precocement en reponse au traitement. L’imagerie dynamique de la microcirculation suit la biodistribution d’un agent de contraste et analyse la vascularisation tumorale. L’imagerie par resonance magnetique ponderee en diffusion permet de distinguer l’eau libre de l’eau restreinte dans les tissus, refletant ainsi la cellularite tumorale. La spectroscopie par RMN detecte la quantite relative de differents composants chimiques dans les tissus normaux et tumoraux. La tomographie par emission de positons (TEP) au 18FDG fournit une information sur le metabolisme tissulaire. La captation du FDG est proportionnelle a l’activite proliferative et au nombre de cellules viables dans une tumeur. Les etudes testant ces techniques sont cependant preliminaires et la communaute medicale doit aborder une reflexion sur leur role dans l’evaluation de la reponse au traitement en oncologie en pratique quotidienne.

Diffusion-weighted imaging for evaluation of uterine arterial embolization of fibroids.

To determine whether diffusion‐weighted imaging (DWI) characteristics could predict the effectiveness of uterine arterial embolization in treatment of fibroids.

Rein et produits de contraste iodés et gadolinés

UNLABELLED In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged. LEARNING OBJECTIVES to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.

Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multi-vendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology.Key Points• Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials.• Establishing “precision” of the measurement in the multicentre context is essential.• A repository with traceable data of known provenance promotes further research.