Muscle mass estimation on breast magnetic resonance imaging in breast cancer patients: comparison between psoas muscle area on computer tomography and pectoralis muscle area on MRI.

OBJECTIVES: To evaluate the correlation between psoas muscle area (TPA) on CT images and pectoralis muscle area (PMA) on MRI in breast cancer patients. METHODS: This retrospective study was institutional review board approved and women involved gave written informed consent. Twenty six patients with both body CT and breast MRI available were evaluated. Two radiologists calculated TPA on 1.25-mm and 5-mm body CT images. Two radiologists measured PMA on axial T1-weighted images. Statistical analysis included inter- and intra-reader agreement and correlation between TPA on CT and PMA on MRI. RESULTS: The Pearson r correlation coefficient was 0.70 (95% CI 0.41-0.81) and the coefficient of determination was 0.49. The inter-reader agreement was k = 0.85 and k = 0.79 for axial 1.25-mm and 5-mm CT images, respectively. The intra-reader agreement of reader 1 was k = 0.98 and k = 0.94 for 1.25-mm and 5-mm CT images, respectively. The intra-reader agreement of reader 2 was k = 0.95 and k = 0.94 for 1.25-mm and 5-mm CT images, respectively. On axial T1-weighted images, the inter-reader agreement for radiologists evaluating the PMA was k = 0.61. Intra-observer agreement of reader 1 and reader 2 for PMA estimation was good (0.62 and 0.64), respectively. CONCLUSION: The correlation between TPA on CT images and PMA on MRI was very good. Pectoralis muscle area on breast MRI could be useful to estimate muscle mass in women with breast cancer. KEY POINTS: • Pectoralis muscle area can be estimated on breast MRI • Total psoas area on CT and pectoralis muscle area on MRI are strongly correlated • Pectoralis muscle area on breast MRI could estimate the skeletal muscle mass.

Rapid review: radiomics and breast cancer.

PURPOSE: To perform a rapid review of the recent literature on radiomics and breast cancer (BC). METHODS: A rapid review, a streamlined approach to systematically identify and summarize emerging studies was done (updated 27 September 2017). Clinical studies eligible for inclusion were those that evaluated BC using a radiomics approach and provided data on BC diagnosis (detection or characterization) or BC prognosis (response to therapy, morbidity, mortality), or provided data on technical challenges (software application: open source, repeatability of results). Descriptive statistics, results, and radiomics quality score (RQS) are presented. RESULTS: N = 17 retrospective studies, all published after 2015, provided BC-related radiomics data on 3928 patients evaluated with a radiomics approach. Most studies were done for diagnosis and/or characterization (65%, 11/17) or to aid in prognosis (41%, 7/17). The mean number of radiomics features considered was 100. Mean RQS score was 11.88 ± 5.8 (maximum value 36). The RQS criteria related to validation, gold standard, potential clinical utility, cost analysis, and open science data had the lowest scores. The majority of studies n = 16/17 (94%) provided correlation with histological outcomes and staging variables or biomarkers. Only 4/17 (23%) studies provided evidence of correlation with genomic data. Magnetic resonance imaging (MRI) was used in most studies n = 14/17 (82%); however, ultrasound (US), mammography, or positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F FDG PET/CT) was also used. Much heterogeneity was found for software usage. CONCLUSIONS: The study of radiomics in BC patients is a new and emerging translational research topic. Radiomics in BC is frequently done to potentially improve diagnosis and characterization, mostly using MRI. Substantial quality limitations were found; high-quality prospective and reproducible studies are needed to further potential application.

Accuracy and reading time for six strategies using digital breast tomosynthesis in women with mammographically negative dense breasts.

OBJECTIVE: To compare six strategies using digital breast tomosynthesis in women with mammographically negative dense breasts. MATERIALS AND METHODS: This is a substudy of the 'ASTOUND' trial. 163 women who underwent tomosynthesis with synthetically reconstructed projection images (S-2D) inclusive of 13 (7.9%) cases diagnosed with breast cancer at histopathology after surgery were evaluated. Accuracy measures and screen-reading time of six reading strategies were assessed: (A) Single reading of S-2D alone, (B) single reading of tomosynthesis alone, (C) single reading of joint interpretation of tomosynthesis + S-2D, (D) double-reading of S-2D alone, (E) double reading of tomosynthesis alone, (F) double reading of joint interpretation of tomosynthesis + S-2D. RESULTS: The median age of the patients was 53 years (range, 36-88 years). The highest global accuracy was obtained with double reading of tomosynthesis + S2D (F) with an AUC of 0.979 (p<0.001) and a mean reading time of 154 s versus 34 s for the fastest strategy (single reading of S-2D alone). The AUCs for the other five strategies did not differ from each other. CONCLUSION: Double reading of tomosynthesis+ S2D had the best accuracy of six screen-reading strategies although it had the longest reading time. KEY POINTS: • Tomosynthesis acquisitions are progressively implemented with reconstructed synthesized 2D images • Double reading using S-2D plus tomosynthesis had the highest global accuracy (p<0.001). • Double reading of S-2D plus tomosynthesis increased reading time.

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Despite its indolent nature, CLL remains an incurable disease. Herein we aimed to monitor CLL disease engraftment and, progression/regression in a xenograft CLL mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Spleen contrast enhancement, quantified as percentage change in signal intensity upon USPIO administration, demonstrated a difference due to a reduced USPIO uptake, in the spleens of mice injected with CLL cells (NSG-CLL, n=71) compared to controls (NSG-CTR, n=17). These differences were statistically significant both after 2 and 4weeks from CLL cells injection. In addition comparison of mice treated with rituximab with untreated controls for changes in spleen iron uptake confirmed that it is possible to monitor treatment efficacy in this mouse model of CLL using USPIO-enhanced MRI. Further applications could include the preclinical in vivo monitoring of new therapies and the clinical evaluation of CLL patients.

Epigenetic Silencing of DKK3 in medulloblastoma.

Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK) 1-4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001). Since copy number aberrations targeting the DKK3 locus (11p15.3) are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively) excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA), a potent inhibitor of histone deacetylases (HDAC), was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation.

Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma.

About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array-CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN-) tumors; G2, stage 4 patients, ≤ 18 months of age, MYCN- tumors and favorable outcome and G3, Stage 4 patients, ≥ 19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E-05). Noteworthy, G3/MYCN- NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN- NBs than in MYCN-amplified G3 may also explain why patients ≥ 19 months have a poor outcome independently by MYCN status.

Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma.

The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.

MRI versus Mammography plus Ultrasound in Women at Intermediate Breast Cancer Risk: Study Design and Protocol of the MRIB Multicenter, Randomized, Controlled Trial.

In women at high/intermediate lifetime risk of breast cancer (BC-LTR), contrast-enhanced magnetic resonance imaging (MRI) added to mammography ± ultrasound (MX ± US) increases sensitivity but decreases specificity. Screening with MRI alone is an alternative and potentially more cost-effective strategy. Here, we describe the study protocol and the characteristics of enrolled patients for MRIB feasibility, multicenter, randomized, controlled trial, which aims to compare MRI alone versus MX+US in women at intermediate breast cancer risk (aged 40-59, with a 15-30% BC-LTR and/or extremely dense breasts). Two screening rounds per woman were planned in ten centers experienced in MRI screening, the primary endpoint being the rate of cancers detected in the 2 arms after 5 years of follow-up. From July 2013 to November 2015, 1254 women (mean age 47 years) were enrolled: 624 were assigned to MX+US and 630 to MRI. Most of them were aged below 50 (72%) and premenopausal (45%), and 52% used oral contraceptives. Among postmenopausal women, 15% had used hormone replacement therapy. Breast and/or ovarian cancer in mothers and/or sisters were reported by 37% of enrolled women, 79% had extremely dense breasts, and 41% had a 15-30% BC-LTR. The distribution of the major determinants of breast cancer risk profiles (breast density and family history of breast and ovarian cancer) of enrolled women varied across centers.

Manganese-enhanced MRI (MEMRI) in breast and prostate cancers: Preliminary results exploring the potential role of calcium receptors.

PROCEDURES: To preliminary assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models. METHODS: NOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptor's status was carried out after the MR images acquisition by immunohistochemistry on excised tumours. RESULTS: Manganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (p<0.01), whereas TRPV6 expression levels appeared not relevant to the Mn uptake. CONCLUSION: Our preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors.

Transcribed-Ultra Conserved Region expression is associated with outcome in high-risk neuroblastoma.

BACKGROUND: Neuroblastoma is the most common, pediatric, extra-cranial, malignant solid tumor. Despite multimodal therapeutic protocols, outcome for children with a high-risk clinical phenotype remains poor, with long-term survival still less than 40%. Hereby, we evaluated the potential of non-coding RNA expression to predict outcome in high-risk, stage 4 neuroblastoma. METHODS: We analyzed expression of 481 Ultra Conserved Regions (UCRs) by reverse transcription-quantitative real-time PCR and of 723 microRNAs by microarrays in 34 high-risk, stage 4 neuroblastoma patients. RESULTS: First, the comparison of 8 short- versus 12 long-term survivors showed that 54 UCRs were significantly (P < 0.0491) over-expressed in the former group. For 48 Ultra Conserved Region (UCRs) the expression levels above the cut-off values defined by ROC curves were strongly associated with good-outcome (OS: 0.0001

Evaluation of body Computed Tomography-determined sarcopenia in breast cancer patients and clinical outcomes: A systematic review.

PURPOSE: Sarcopenia has been considered a poor prognostic factor in various malignant diseases. However, the studies that evaluated the association between CT-determined sarcopenia and outcome in breast cancer patients reported different results. Therefore, the aim of the present study is to perform a systematic review of the current literature on the evaluation of body CT-determined sarcopenia in breast cancer patients, focusing on the correlation with outcome values. METHODS: Two reviewers evaluated independently all studies dealing with CT-determined sarcopenia in breast cancer women from major medical libraries up to 24 April 2019. The keywords used for database searching were: "sarcopenia" or "muscles" or "muscle weight" or "body composition" and "breast neoplasms" or "breast cancer" and "computed tomography". Studies reporting clinical outcome values were finally compared. RESULTS: Of the n = 191 studies identified, a total of n = 15 articles were included in the systematic review. In all studies, sarcopenia was assessed at the level of the third lumbar vertebra (L3) on CT; n = 14/15 studies were retrospective. N = 13/15 studies evaluated the impact of sarcopenia on clinical outcomes. Among these studies, n = 8/13 studies concluded that sarcopenia is an important risk factor for poor prognosis in breast cancer and n = 5/13 studies concluded that body composition changes are not associated with poor prognosis. CONCLUSIONS: Most studies concluded that sarcopenia assessed on CT is an important prognostic risk factor in breast cancer patients. High-quality prospective studies to strongly confirm and assess the impact of sarcopenia evaluated on CT and breast cancer outcome are needed.

Local recurrence of soft tissue sarcoma: a radiomic analysis.

Background To perform a radiomics analysis in local recurrence (LR) surveillance of limb soft tissue sarcoma (STS) Patients and methods This is a sub-study of a prospective multicenter study with Institutional Review Board approval supported by ESSR (European Society of Musculoskeletal Radiology). radiomics analysis was done on fast spin echo axial T1w, T2w fat saturated and post-contrast T1w (T1wGd) 1.5T MRI images of consecutively recruited patients between March 2016 and September 2018. Results N = 11 adult patients (6 men and 5 women; mean age 57.8 ± 17.8) underwent MRI to exclude STS LR: a total of 33 follow-up events were evaluated. A total of 198 data-sets per patients of both pathological and normal tissue were analyzed. Four radiomics features were significantly correlated to tumor size (p < 0.02) and four radiomics features were correlated with grading (p < 0.05). ROC analysis showed an AUC between 0.71 (95%CI: 0.55-0.87) for T1w and 0.96 (95%CI: 0.87-1.00) for post-contrast T1w. Conclusions radiomics features allow to differentiate normal tissue from pathological tissue in MRI surveillance of local recurrence of STS. radiomics in STS evaluation is useful not only for detection purposes but also for lesion characterization.

Background parenchymal enhancement assessment: Inter- and intra-rater reliability across breast MRI sequences.

OBJECTIVE: To evaluate inter- and intra-rater reliability of background parenchymal enhancement (BPE) assessment across breast MRI sequences. MATERIALS AND METHODS: Institutional review board approval was obtained and the requirement for consent was waived. Three radiologists qualitatively categorized BPE on 150 breast MRI using a four-point scale (minimal, mild, moderate or marked) according to BI-RADS category system. According to MR-sequence used for the assessment of BPE, inter-rater and intra-rater reliability across a simulated reading strategy with four options was performed: (1) initial contrast-enhanced (CE) fat-suppressed T1-weighted images (2) initial CE subtracted images (3) maximum-intensity-projection (MIP) of the first CE subtracted images (4) combination of initial CE fat-suppressed T1-weighted, initial CE subtracted and MIP images. Raters repeated BPE assessment of 45 breast MRI four weeks after the initial assessment. Gwet's AC1 index with ordinal weights was used to assess reliabilities. RESULTS: Gwet's index for the reliability among the three raters was 0.68 (0.63-0.74) using initial contrast-enhanced fat-suppressed T1 weighted images, 0.74 (0.69-0.80) using subtracted images, 0.80 (0.76-0.83) using MIP, 0.80 (0.77-0.84) using a combination of the initial contrast-enhanced fat-suppressed T1 weighted, initial contrast-enhanced subtracted and MIP images. Test-retest reliability was 0.81 (0.60-1.00) for rater 1, 0.77 (0.55-0.98) for rater 2, 0.79 (0.59-0.99) for rater 3 using the combination of initial contrast-enhanced fat-suppressed T1 weighted, initial contrast-enhanced subtracted and MIP images. CONCLUSIONS: Overall, the combination of all CE MRI images showed the highest reliability of BPE assessment. However, MIP showed a high reliability with lower reading time compared to the combination of all CE MRI images.

Breast cancer Ki-67 expression prediction by digital breast tomosynthesis radiomics features.

BACKGROUND: To investigate whether quantitative radiomic features extracted from digital breast tomosynthesis (DBT) are associated with Ki-67 expression of breast cancer. MATERIALS AND METHODS: This is a prospective ethically approved study of 70 women diagnosed with invasive breast cancer in 2018, including 40 low Ki-67 expression (Ki-67 proliferation index <14%) cases and 30 high Ki-67 expression (Ki-67 proliferation index ≥ 14%) cases. A set of 106 quantitative radiomic features, including morphological, grey/scale statistics, and texture features, were extracted from DBT images. After applying least absolute shrinkage and selection operator (LASSO) method to select the most predictive features set for the classifiers, low versus high Ki-67 expression was evaluated by the area under the curve (AUC) at receiver operating characteristic analysis. Correlation coefficient was calculated for the most significant features. RESULTS: A combination of five features yielded AUC of up to 0.698. The five most predictive features (sphericity, autocorrelation, interquartile range, robust mean absolute deviation, and short-run high grey-level emphasis) showed a statistical significance (p ≤ 0.001) in the classification. Thirty-four features were significantly (p ≤ 0.001) correlated with Ki-67, and five of these had a correlation coefficient of > 0.5. CONCLUSION: The present study showed that quantitative radiomic imaging features of breast tumour extracted from DBT images are associated with breast cancer Ki-67 expression. Larger studies are needed in order to further evaluate these findings.

Differentiating diffuse from focal pattern on Computed Tomography in multiple myeloma: Added value of a Radiomics approach.

PURPOSE: Focal pattern in multiple myeloma (MM) seems to be related to poorer survival and differentiation from diffuse to focal pattern on computed tomography (CT) has inter-reader variability. We postulated that a Radiomic approach could help radiologists in differentiating diffuse from focal patterns on CT. METHODS: We retrospectively reviewed imaging data of 70 patients with MM with CT, PET-CT or MRI available before bone marrow transplant. Two general radiologist evaluated, in consensus, CT images to define a focal (at least one lytic lesion >5 mm in diameter) or a diffuse (lesions <5 mm, not osteoporosis) pattern. N = 104 Radiomics features were extracted and evaluated with an open source software. RESULTS: The pathological group included: 22 diffuse and 39 focal patterns. After feature reduction, 9 features were different (p < 0.05) in the diffuse and focal patterns (n = 2/9 features were Shape-based: MajorAxisLength and Sphericity; n = 7/9 were Gray Level Run Length Matrix (Glrlm)). AUC of the Radiologists versus Reference Standard was 0.64 (95 % CI: (0.49-0.78) p = 0.20. AUC of the best 4 features (MajorAxisLength, Median, SizeZoneNonUniformity, ZoneEntropy) were: 0.73 (95 % CI: 0.58-0.88); 0.71 (95 % CI: 0.54-0.88); 0.79 (95 % CI: 0.66-0.92); 0.68 (95 % CI: 0.53-0.83) respectively. CONCLUSION: A Radiomics approach improves radiological evaluation of focal and diffuse pattern of MM on CT.

An exploratory radiomics analysis on digital breast tomosynthesis in women with mammographically negative dense breasts.

PURPOSE: To compare Digital Breast Tomosynthesis (DBT) for cancers and normal screens in women with dense breasts and negative mammography using a Radiomics approach. MATERIALS AND METHODS: A substudy (N = 40) of the 'Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts (ASTOUND)' trial was done based on 20 women who had DBT-detected, histology-proven, breast cancer and 20 controls matched for age and density. Using a Radiomics approach normal and pathological breast parenchyma were evaluated, and correlations among Radiomics features and clinical and prognostic parameters were investigated. RESULTS: The median age of the patients was 50 years (range 39-70 years). After Radiomics feature number reduction, 3 of 6 (50%) selected features differed between controls and cancers (Skewness (0.002); Entropy (p.004); 90percentile (p.006)). Three Radiomics features (Energy, Entropy and Dissimilarity) significantly correlated to tumor size (r = -0.15,r = 0.49,r = 0.51), but not with prognostic factors. Entropy correlated with Estrogen Receptor status (r = -0,46; p.004). CONCLUSION: Radiomics features in patients with dense breasts and negative mammography appear to differ between cancerous and normal breast tissue, with evidence of correlation with tumor size and estrogen receptors. This new information warrants further evaluation in larger studies and could contribute to improved understanding of breast cancer through imaging, and may support tailored screening and treatments.

A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2).

BACKGROUND: Increased risk of breast cancer (BC) and increased risk of an interval BC at mammography screening are associated with high mammographic density. Adjunct imaging detects additional BCs not detected at mammography screening in women with dense breasts. AIM: The aim is to estimate the incremental cancer detection rate (CDR) and false-positive recall for each of tomosynthesis and ultrasound, as adjunct screening modalities in women with mammography-negative dense breasts. METHODS: A multicentre prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2) recruited asymptomatic women attending Italian breast screening services. All participants had independently interpreted tomosynthesis and ultrasound. Outcomes were ascertained from excision histopathology or completed assessment. Paired binary data were compared using McNemar's test. RESULTS: We recruited 5300 screening participants with median age of 50 (interquartile range 43-79) years who had negative mammography and dense breasts (April 2015-September 2017). Adjunct screening detected 29 additional BCs (27 invasive, 2 in situ): 12 detected on both tomosynthesis and ultrasound, 3 detected only on tomosynthesis, 14 detected only on ultrasound. Incremental CDR for tomosynthesis (+15 cancers) was 2.83/1000 screens (95% confidence interval [CI]: 1.58-4.67) versus ultrasound (+26 cancers) with an incremental CDR of 4.90/1000 screens (95% CI: 3.21-7.19), P = 0.015. Mean size of these cancers was 14.2 mm (standard deviation: 7.8 mm), and six had nodal metastases. Incremental false-positive recall was 1.22% (95% CI: 0.91%-1.49%) and differed significantly between tomosynthesis (0.30%) and ultrasound (1.0%), P < 0.001. CONCLUSIONS: Ultrasound detected more BCs but caused more false positives than tomosynthesis, underscoring trade-offs in screening outcomes when adjunct imaging is used for screening dense breasts.

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence.

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rß1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rß1 chain when cocultured with activated T cells or CD40L+ cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.

Evaluation of background parenchymal enhancement on breast MRI: a systematic review.

OBJECTIVE: To perform a systematic review of the methods used for background parenchymal enhancement (BPE) evaluation on breast MRI. METHODS: Studies dealing with BPE assessment on breast MRI were retrieved from major medical libraries independently by four reviewers up to 6 October 2015. The keywords used for database searching are "background parenchymal enhancement", "parenchymal enhancement", "MRI" and "breast". The studies were included if qualitative and/or quantitative methods for BPE assessment were described. RESULTS: Of the 420 studies identified, a total of 52 articles were included in the systematic review. 28 studies performed only a qualitative assessment of BPE, 13 studies performed only a quantitative assessment and 11 studies performed both qualitative and quantitative assessments. A wide heterogeneity was found in the MRI sequences and in the quantitative methods used for BPE assessment. CONCLUSION: A wide variability exists in the quantitative evaluation of BPE on breast MRI. More studies focused on a reliable and comparable method for quantitative BPE assessment are needed. Advances in knowledge: More studies focused on a quantitative BPE assessment are needed.

Radiological clinical trials: Proposal of a problem-finding questionnaire to improve study success.

AIM: To develop a survey to help define the main problems in radiological clinical trials. METHODS: Since 2006, we have managed seven different radiological clinical trials recruiting patients in academic and non-academic centres. We developed a preliminary questionnaire using a four-round Delphi approach to identify problems occurring in radiological clinical trials run at our centre. We investigated the recruitment experience, involvement of all multi-disciplinary team members and main obstacles to completing the projects. A final round of Delphi processes elucidated solutions to the identified problems. RESULTS: Among 19/20 (95%) respondents, 10 (53%) were young physicians (under 35 years old), and the respondents included non-faculty members, fellows, residents, and undergraduate students. Ninety-four percent (18/19) of respondents showed interest in conducting clinical trials. On a scale of 1 to 10, the problems with higher/worse scores (8-9) were related to technical or communication problems. The most frequent problems across all studies were technical problems related to clinical trial equipment, insufficient willingness to participate, obstacles to understanding the design of electronic-case report form and extra work. CONCLUSION: The developed questionnaire identified the main recurring problems in radiological clinical trials as perceived by end-users and helped define possible solutions that are mostly related to having dedicated clinical trial research staff.