Involvement of radiologists in oncologic multidisciplinary team meetings: an international survey by the European Society of Oncologic Imaging.

OBJECTIVES: Multidisciplinary tumour boards (MTBs) play an increasingly important role in managing cancer patients from diagnosis to treatment. However, many problems arise around the organisation of MTBs, both in terms of organisation-administration and time management. In this context, the European Society of Oncologic Imaging (ESOI) conducted a survey among its members, aimed at assessing the quality and amount of involvement of radiologists in MTBs, their role in it and related issues. METHODS: All members were invited to fill in a questionnaire consisting of 15 questions with both open and multiple-choice answers. Simple descriptive analyses and graphs were performed. RESULTS: A total of 292 ESOI members in full standing for the year 2018 joined the survey. Most respondents (89%) declared to attend MT-Bs, but only 114 respondents (43.9%) review over 70% of exams prior to MTB meetings, mainly due to lack of time due to a busy schedule for imaging and reporting (46.6%). Perceived benefits (i.e. surgical and histological feedback (86.9%), improved knowledge of cancer treatment (82.7%) and better interaction between radiologists and referring clinicians for discussing rare cases (56.9%)) and issues (i.e. attending MTB meetings during regular working hours (71.9%) and lack of accreditation with continuing medical education (CME) (85%)) are reported. CONCLUSIONS: Despite the value and benefits of radiologists' participation in MTBs, issues like improper preparation due to a busy schedule and no counterpart in CME accreditation require efforts to improve the role of radiologists for a better patient care. KEY POINTS: • Most radiologists attend multidisciplinary tumour boards, but less than half of them review images in advance, mostly due to time constraints. • Feedback about radiological diagnoses, improved knowledge of cancer treatment and interaction with referring clinicians are perceived as major benefits. • Concerns were expressed about scheduling multidisciplinary tumour boards during regular working hours and lack of accreditation with continuing medical education.

Diagnostic Algorithm to Differentiate Benign Atypical Leiomyomas from Malignant Uterine Sarcomas with Diffusion-weighted MRI.

Background Improving the differentiation of uterine sarcomas from atypical leiomyomas remains a clinical challenge and is needed to avoid inappropriate surgery. Purpose To develop a diagnostic algorithm including diffusion-weighted MRI criteria to differentiate malignant uterine sarcomas from benign atypical leiomyomas. Materials and Methods This case-control retrospective study identified women with an atypical uterine mass at MRI between January 2000 and April 2017, with surgery or MRI follow-up after 1 year or longer. A diagnostic algorithm including T2-weighted MRI and diffusion-weighted imaging (DWI) signal and apparent diffusion coefficient (ADC) values was developed to predict for sarcoma. The training set consisted of 51 sarcomas and 105 leiomyomas. Two external validation sets were used to evaluate interreader reproducibility (16 sarcomas; 26 leiomyomas) and impact of reader experience (29 sarcomas; 30 leiomyomas). Wilson confidence intervals (CIs) were calculated for sensitivity and specificity. Results Evaluated were 156 women (median age, 50 years; interquartile range, 44-63 years). Predictive MRI criteria for malignancy were enlarged lymph nodes or peritoneal implants, high DWI signal greater than that in endometrium, and ADC less than or equal to 0.905 × 10-3 mm2/sec. Conversely, a global or focal area of low T2 signal intensity and a low or an intermediate DWI signal less than that in endometrium or lymph nodes allowed readers to confidently diagnose as benign a uterine mass demonstrating one or more of these signs (P < .001) in 100% cases in all three data sets. The sensitivities and specificities of the algorithm for diagnosis of malignancy were 98% (50 of 51 masses; 95% CI: 90%, 100%) and 94% (99 of 105 masses; 95% CI: 88%, 98%) in the training set; 88% (14 of 16 masses; 95% CI: 64%, 97%) and 100% (26 of 26 masses; 95% CI: 87%, 100%) in the validation set; and 83% (24 of 29 masses; 95% CI: 65%, 92%) and 97% (29 of 30 masses; 95% CI: 83%, 99%) for the less experienced reader, respectively. Conclusion A diagnostic algorithm with predictive features including lymphadenopathy, high diffusion-weighted imaging signal with reference to endometrium, and low apparent diffusion coefficient enabled differentiation of malignant sarcomas from atypical leiomyomas, and it may assist inexperienced readers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Méndez in this issue.

Multiparametric optical and MR imaging demonstrate inhibition of tumor angiogenesis natural history by mural cell therapy.

PURPOSE: To determine whether functional imaging using MRI and fibered confocal fluorescence microscopy (FCFM) could be used to monitor cell therapy by mural progenitor cells (MPC). METHODS: Fifty mice bearing TC1 murine xenograft tumors were allocated into: control (n = 17), sham (phosphate buffer saline, n = 16), and MPC-treated (MPC, n = 17) groups. MRI was performed before (D0 ) and 7 days (D7 ) after injection measuring tumor size, R2 * under air, oxygen, and carbogen using blood oxygen level dependent (BOLD) and f (fraction linked to microcirculation), D* (perfusion related coefficient) and Dr (restricted diffusion coefficient) using diffusion-weighted sequences based on the IVIM (intravoxel incoherent motion) method. FCFM was performed at D7 measuring "index leakage" (capillary permeability). RESULTS: Tumor growth was significantly slowed down in the MPC-treated animals (P = 0.002) on D7 . R2 *air significantly decreased in controls between D0 and D7 (P = 0.03), reflecting a decrease in tumor oxygenation. ΔR2 *O2CO2 significantly increased in controls between D0 and D7 (P = 0.01) reflecting loss of vessel response to carbogen. D* significantly decreased in controls between D0 and D7 (P = 0.03). Finally, "index leakage" was lower in the MPC-treated tumors (P = 0,009). CONCLUSION: Treatment by MPC resulted in slowing down of tumor growth, capillary permeability decrease, and stabilization of tumor angiogenesis.

O-RADS MRI scoring system has the potential to reduce the frequency of avoidable adnexal surgery.

OBJECTIVE: To assess the potential impact of the O-RADS MRI score on the decision-making process for the management of adnexal masses. METHODS: EURAD database (prospective, European observational, multicenter study) was queried to identify asymptomatic women without history of infertility included between March 1st and March 31st 2018, with available surgical pathology or clinical findings at 2-year clinical follow-up. Blinded to final diagnosis, we stratified patients into five categories according to the O-RADS MRI score (absent i.e. non adnexal, benign, probably benign, indeterminate, probably malignant). Prospective management was compared to theoretical management according to the score established as following: those with presumed benign masses (scored O-RADS MRI 2 or 3) (follow-up recommended) and those with presumed malignant masses (scored O-RADS MRI 4 or 5) (surgery recommended). RESULTS: The accuracy of the score for assessing the origin of the mass was of 97.2 % (564/580, CI95% 0.96-0.98) and was of 92.0 % (484/526) for categorizing lesions with a negative predictive value of 98.1 % (415/423, CI95% 0.96-0.99). Theoretical management using the score would have spared surgery in 229 patients (87.1 %, 229/263) with benign lesions and malignancy would have been missed in 6 borderline and 2 invasive cases. In patients with a presumed benign mass using O-RADS MRI score, recommending surgery for lesions >= 100 mm would miss only 4/77 (4.8 %) malignant adnexal tumors instead of 8 (50 % decrease). CONCLUSION: The use of O-RADS MRI scoring system could drastically reduce the number of asymptomatic patients undergoing avoidable surgery.

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII.

PURPOSE: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. METHODS: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. RESULT: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. CONCLUSION: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. CRITICAL RELEVANCE STATEMENT: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. KEY POINTS: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score ( https://metricsscore.github.io/metrics/METRICS.html ) and a repository created to collect feedback from the radiomics community ( https://github.com/metricsscore/metrics ).

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

PURPOSE: To determine whether diffusion-weighted imaging (DWI) characteristics could predict the effectiveness of uterine arterial embolization in treatment of fibroids. METHODS: This retrospective study included 17 women (27 fibroids) who underwent uterine arterial embolization for fibroids. MR imaging (1.5 T) was performed before, 1 week and 6 months after uterine arterial embolization. The volume, T2 signal, T1 signal, enhancement after contrast media injection, DWI signal (b = 500 s/mm(2) ) and apparent diffusion coefficient (ADC) were assessed for fibroids. RESULTS: DWI signal or ADC, whether before or 1 week after the procedure, did not show a statistical relationship to success of uterine arterial embolization. On the 1-week follow-up, 22% of fibroids enhanced vs. 85% on baseline, P < 0.0001 and DW signal intensity increased. ADC values in fibroids decreased between baseline and 1-week (1.61 vs. 1.53 × 10(-3) mm(2) /s, P = 0.13). On 6-months, ADC continued to decrease compared with baseline (1.27 × 10(-3) mm(2) /s, P = 0.002), but with a lower signal on DWI. No changes were observed in myometrium ADC at any time point. CONCLUSION: Our study demonstrated that DWI and ADC reflected early and delayed changes in fibroids after embolization; however, we were not able to demonstrate a statistically significant relationship with outcome.

New insights into the management of renal cell cancer.

Kidney cancer is composed of several bio-histological entities. The most frequent type, clear-cell carcinoma, is not homogenous regarding gene mutations or transcriptomic profiles, but the biologic classifications are not yet mature. Therefore, biologically driven strategies of treatment have not yet been developed in the clinical setting. The choice of first-line agent currently depends on the prognostic criteria published by Motzer et al. [J Clin Oncol 1999;17:2530-2540] and recently by Heng et al. [J Clin Oncol 2009;27:5794-5799], with anti-vascular endothelial growth factor (VEGF) therapies for good- or intermediate-prognosis groups and anti-mammalian target of rapamycin (mTOR) for poor-risk patients. In the past years, biological changes leading to resistance to targeted agents have been widely investigated. Discoveries resulted in the development of second-generation VEGF receptor tyrosine kinase inhibitors, characterized by an improved potency and selectivity. Besides, co-inhibition of signalling pathways mediating resistance to anti-VEGF are being developed targeting fibroblast growth factor and c-Met. Dual mTOR/phosphatidylinositol 3-kinase inhibitors have greater efficacy than rapalogs in preclinical models and are being investigated in early clinical trials. In conclusion, the changing landscape in the biology and treatment of kidney cancer offers new opportunities for clinicians to treat patients, but, due to relatively high costs, the use of targeted therapies will likely be strongly controlled by health authorities.

Signal-to-noise ratio improvement in dynamic contrast-enhanced CT and MR imaging with automated principal component analysis filtering.

PURPOSE: To develop a new automated filtering technique and to evaluate its ability to compensate for the known low contrast-to-noise ratio (CNR) in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) and computed tomographic (CT) data, without substantial loss of information. MATERIALS AND METHODS: Clinical data acquisition for this study was approved by the institutional review board. Principal component analysis (PCA) was combined with the fraction of residual information (FRI) criterion to optimize the balance between noise reduction efficiency and information conservation. The PCA FRI filter was evaluated in 15 DCE MR imaging data sets and 15 DCE CT data sets by two radiologists who performed visual analysis and quantitative assessment of noise reduction after filtering. RESULTS: Visual evaluation revealed a substantial noise reduction while conserving information in 90% of MR imaging cases and 87% of CT cases for image analysis and in 93% of MR imaging cases and 90% of CT cases for signal analysis. Efficient denoising enabled improvement in structure characterization in 60% of MR imaging cases and 77% of CT cases. After filtering, CNR was improved by 2.06 ± 0.89 for MR imaging (P < .01) and by 5.72 ± 4.82 for CT (P < .01). CONCLUSION: This PCA FRI filter demonstrates noise reduction efficiency and information conservation for both DCE MR data and DCE CT data. FRI analysis enabled automated optimization of the parameters for the PCA filter and provided an optional visual control of residual information losses. The robust and fast PCA FRI filter may improve qualitative or quantitative analysis of DCE imaging in a clinical context. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100231/-/DC1.

Diagnostic Accuracy of Four Levels of Manual Compression Applied in Supersonic Shear Wave Elastography of the Breast.

PURPOSE: To investigate the diagnostic accuracy of applying four levels of manual pressure in Shear Wave Elastography (SWE) of the breast and to assess inter-rater reliability. MATERIALS AND METHODS: Single-center prospective preliminary study including patients receiving ultrasound examination of breast lesions as part of routine clinical practice. SWE was performed on 60 breast masses (26 benign and 34 malignant) in 54 patients by a breast fellowship trained radiologist. Stiffness values were compared between benign and malignant masses at four levels of manual compression: none, mild, moderate, and marked. Accuracy of SWE was assessed using receiving operating characteristics analysis at each level. In 18 patients, a second radiologist repeated the SWE acquisitions to evaluate reproducibility. Reproducibility was assessed using intraclass correlation coefficient. RESULTS: Without compression, we observed no significant difference in stiffness (p > 0.99) between benign and malignant lesions, and SWE demonstrated low accuracy (area under the curve = 0.64). Stiffness was higher in malignant lesions at all levels of compression (p < 0.001). SWE demonstrated good accuracy at all three levels of compression (from area under the curve = 0.71 to 0.84 across Emax and Emean), with high interobserver agreement. CONCLUSION: This preliminary study suggests that not using compression during SWE for breast lesion characterization offers suboptimal results. On the contrary, application of compression yields high diagnostic performance with good interobserver agreement and, as such, should be included in routine clinical practice.

Bone Metastases Are Measurable: The Role of Whole-Body MRI and Positron Emission Tomography.

Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone lesions, which can change in morphology due to treatment effects and/or secondary bone remodeling. Hence, morphological imaging is regarded unsuitable for response assessment of bone metastases and in the current Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) guideline bone metastases are deemed unmeasurable. Nevertheless, the advent of functional and molecular imaging modalities such as whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography (PET) has improved the ability for follow-up of bone metastases, regardless of their morphology. Both these modalities not only have improved sensitivity for visual detection of bone lesions, but also allow for objective measurements of bone lesion characteristics. WB-MRI provides a global assessment of skeletal metastases and for a one-step "all-organ" approach of metastatic disease. Novel MRI techniques include diffusion-weighted imaging (DWI) targeting highly cellular lesions, dynamic contrast-enhanced MRI (DCE-MRI) for quantitative assessment of bone lesion vascularization, and multiparametric MRI (mpMRI) combining anatomical and functional sequences. Recommendations for a homogenization of MRI image acquisitions and generalizable response criteria have been developed. For PET, many metabolic and molecular radiotracers are available, some targeting tumor characteristics not confined to cancer type (e.g. 18F-FDG) while other targeted radiotracers target specific molecular characteristics, such as prostate specific membrane antigen (PSMA) ligands for prostate cancer. Supporting data on quantitative PET analysis regarding repeatability, reproducibility, and harmonization of PET/CT system performance is available. Bone metastases detected on PET and MRI can be quantitatively assessed using validated methodologies, both on a whole-body and individual lesion basis. Both have the advantage of covering not only bone lesions but visceral and nodal lesions as well. Hybrid imaging, combining PET with MRI, may provide complementary parameters on the morphologic, functional, metabolic and molecular level of bone metastases in one examination. For clinical implementation of measuring bone metastases in response assessment using WB-MRI and PET, current RECIST1.1 guidelines need to be adapted. This review summarizes available data and insights into imaging of bone metastases using MRI and PET.

Metastatic renal carcinoma: evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT.

PURPOSE: To determine whether tumor perfusion parameters assessed by using dynamic contrast material-enhanced computed tomography (CT) could help predict and detect response in patients receiving antiangiogenic therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained. In two phase-III trials involving 51 patients with metastatic renal cell carcinoma (38 men, 13 women; age range, 30-80 years) receiving antiangiogenic drugs (sorafenib [n = 10], sunitinib [n = 22]), a placebo (n = 12), or interferon alfa (n = 7), serial dynamic contrast-enhanced CT was performed, during 90 seconds before and after injection of 80 mL of iobitridol. Perfusion parameters of a target metastatic tumor (tumor blood flow [TBF], tumor blood volume [TBV], mean transit time, and vascular permeability-surface area product) were calculated. Values before and after treatment were compared by using a Wilcoxon signed rank test, and relative changes in groups were compared by using the Wilcoxon rank sum test. Results were compared with Response Evaluation Criteria in Solid Tumors response and with progression-free and overall survival by using Kaplan-Meier curves. RESULTS: Among patients receiving antiangiogenic drugs, baseline perfusion parameters were higher in responders than in stable patients (TBF = 245.3 vs 119.5 mL/min/100 mL, P = .04; TBV = 15.5 vs 8.2 mL/100 mL, P = .02) but were not significantly predictive of survival. After the first cycle of treatment, there was a significant decrease in TBF (162.5 vs 76.7 mL/min/100 mL, P = .0002) and TBV (9.1 vs 3.9 mL/100 mL, P < .0001) in patients receiving antiangiogenic treatment. CONCLUSION: Renal carcinoma perfusion parameters determined with dynamic contrast-enhanced CT can help predict biologic response to antiangiogenic drugs before beginning therapy and help detect an effect after a single cycle of treatment.

Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) Score for Risk Stratification of Sonographically Indeterminate Adnexal Masses.

Importance: Approximately one-quarter of adnexal masses detected at ultrasonography are indeterminate for benignity or malignancy, posing a substantial clinical dilemma. Objective: To validate the accuracy of a 5-point Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for risk stratification of adnexal masses. Design, Setting, and Participants: This multicenter cohort study was conducted between March 1, 2013, and March 31, 2016. Among patients undergoing expectant management, 2-year follow-up data were completed by March 31, 2018. A routine pelvic MRI was performed among consecutive patients referred to characterize a sonographically indeterminate adnexal mass according to routine diagnostic practice at 15 referral centers. The MRI score was prospectively applied by 2 onsite readers and by 1 reader masked to clinical and ultrasonographic data. Data analysis was conducted between April and November 2018. Main Outcomes and Measures: The primary end point was the joint analysis of true-negative and false-negative rates according to the MRI score compared with the reference standard (ie, histology or 2-year follow-up). Results: A total of 1340 women (mean [range] age, 49 [18-96] years) were enrolled. Of 1194 evaluable women, 1130 (94.6%) had a pelvic mass on MRI with a reference standard (surgery, 768 [67.9%]; 2-year follow-up, 362 [32.1%]). A total of 203 patients (18.0%) had at least 1 malignant adnexal or nonadnexal pelvic mass. No invasive cancer was assigned a score of 2. Positive likelihood ratios were 0.01 for score 2, 0.27 for score 3, 4.42 for score 4, and 38.81 for score 5. Area under the receiver operating characteristic curve was 0.961 (95% CI, 0.948-0.971) among experienced readers, with a sensitivity of 0.93 (95% CI, 0.89-0.96; 189 of 203 patients) and a specificity of 0.91 (95% CI, 0.89-0.93; 848 of 927 patients). There was good interrater agreement among both experienced and junior readers (κ = 0.784; 95% CI, 0.743-0824). Of 580 of 1130 women (51.3%) with a mass on MRI and no specific gynecological symptoms, 362 (62.4%) underwent surgery. Of them, 244 (67.4%) had benign lesions and a score of 3 or less. The MRI score correctly reclassified the mass origin as nonadnexal with a sensitivity of 0.99 (95% CI, 0.98-0.99; 1360 of 1372 patients) and a specificity of 0.78 (95% CI, 0.71-0.85; 102 of 130 patients). Conclusions and Relevance: In this study, the O-RADS MRI score was accurate when stratifying the risk of malignancy in adnexal masses.

In-vivo NIR autofluorescence imaging of rat mammary tumors.

We investigate in vivo detection of mammary tumors in a rat model using autofluorescence imaging in the red and far-red spectral regions. The objective was to explore this method for non-invasive detection of malignant tumors and correlation between autofluorescence properties of tumors and their pathologic status. Eighteen tumor-bearing rats, bearing eight benign and seventeen malignant tumors were imaged. Autofluorescence images were acquired using spectral windows centered at 700-nm, 750-nm and 800-nm under laser excitation at 632.8-nm and 670- nm. Intensity in the autofluorescence images of malignant tumors under 670-nm excitation was higher than that of the adjacent normal tissue. whereas intensity of benign tumors was lower compared to normal tissue.

Supersonic Shear Wave Elastography of Response to Anti-cancer Therapy in a Xenograft Tumor Model.

Our objective was to determine if supersonic shear wave elastography (SSWE) can detect changes in stiffness of a breast cancer model under therapy. A human invasive carcinoma was implanted in 22 mice. Eleven were treated with an anti-angiogenic therapy and 11 with glucose for 24 d. Tumor volume and stiffness were assessed during 2 wk before treatment and 0, 7, 12, 20 and 24 d after the start of therapy using SSWE. Pathology was assessed after 12 and 24 d of treatment. We found that response to therapy was associated with early softening of treated tumors only, resulting in a significant difference from non-treated tumors after 12 d of treatment (p = 0.03). On pathology, large areas of necrosis were observed at 12 d in treated tumors. Although treatment was still effective, treated tumors subsequently stiffened during a second phase of the treatment (days 12-24), with a small amount of necrosis observed on pathology on day 24. In conclusion, SSWE was able to measure changes in the stiffness of tumors in response to anti-cancer treatment. However, stiffness changes associated with good response to treatment may change over time, and increased stiffness may also reflect therapy efficacy.

Initial computed tomography imaging experience using a new macromolecular iodinated contrast medium in experimental breast cancer.

OBJECTIVE: The objective of this study was to evaluate computed tomography (CT) enhancement characteristics for a new iodinated macromolecular contrast medium (MMCM), PEG12000-Gen4-triiodo, for angiographic effect and for assessment of abnormal vascular permeability in cancer. MATERIALS AND METHODS: Time persistence of angiographic effect was evaluated on rat CT images acquired over 30 minutes using the iodinated polyethyleneglycol- (PEG) based macromolecule. Dynamic CT imaging after PEG12000-Gen4-triiodo-enhancement in tumor-bearing rats was used to quantitatively estimate plasma volume and microvascular transendothelial permeability for both tumor and normal soft tissue. Using identical doses of iodine, 300 mg iodine/kg, blood curves for this MMCM and iohexol were compared. RESULTS: Serial whole-body CT angiograms using PEG12000-Gen4-triiodo showed diagnostic vascular detail through 20 minutes, and the blood enhancement curve was higher and more persistent than with small-molecular iohexol. Permeability estimates were significantly (P<0.02; paired t test) higher in tumors (48.2+/-18.1 microL/min-1 100 mL) than in muscle (2.5+/-5.7 microL/min-1 100 mL). CONCLUSIONS: Use of PEG-based MMCM for experimental CT allowed for a persistent angiographic enhancement and for quantitative estimation of tumor microvascular characteristics.

Magnetic resonance imaging detects early changes in microvascular permeability in xenograft tumors after treatment with the matrix metalloprotease inhibitor Prinomastat.

Macromolecular contrast medium-enhanced magnetic resonance imaging was applied to monitor the effect of matrix metalloprotease (MMP) inhibition on microvascular characteristics of human breast cancers implanted in athymic rats. Twice-daily intraperitoneal administration of Prinomastat over 1.5 days induced significant declines in MRI-assayed microvascular permeabilities (p<0.05); but this leak suppression effect had extinguished by the 10(th) day of MMP treatment using the same dose and time schedule. Results demonstrate that Prinomastat produces a rapid but transient decrease in tumor vascular permeability. Contrast-enhanced MRI using macromolecular contrast medium may prove useful as a biomarker for the dynamic MMP biological effect in cancers.

Prognostic factors in patients with advanced renal cell carcinoma treated with VEGF-targeted agents.

The medical treatment of metastatic renal cell carcinoma (mRCC) has undergone a paradigm shift during the last decade with the approval of five drugs targeting vascular endothelial growth factor (VEGF) or its receptors (bevacizumab, sunitinib, sorafenib, pazopanib and axitinib) and of two drugs inhibiting the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway (temsirolimus and everolimus). Median survival has now reached 2 years in mRCC patients receiving first-line targeted treatment. A considerable body of work was conducted on the identification of prognostic factors of survival in the earlier era of immunotherapy of mRCC. The current challenge is to pursue this work on biomarkers of prognosis for targeted therapy and, even more importantly, to identify predictive factors of response to such therapy. This review provides an overview of recent key work on prognostic and predictive factors in patients with advanced clear cell RCC treated with VEGF-targeted agents.