Genome instability triggered by the V(D)J recombination by-product

A newly identified process by which mistargeted V(D)J recombination could cause genome instability in childhood leukemia has been discovered. In this mechanism, called cut-and-run, the excised DNA by-products of V(D)J recombination are re-bound by the recombinase proteins and erroneously trigger double-strand breaks at multiple locations throughout the genome. Many of these breakpoints co-localize with known chromosome alterations in acute lymphoblastic leukemia (ALL)

Prostate MRI quality: a critical review of the last 5 years and the role of the PI-QUAL score

There is increasing interest in the use of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer pathway. The European Association of Urology (EAU) and the British Association of Urological Surgeons (BAUS) now advise mpMRI prior to biopsy, and the Prostate Imaging Reporting and Data System (PI-RADS) recommendations set out the minimal technical requirements for the acquisition of mpMRI of the prostate.The widespread and swift adoption of this technique has led to variability in image quality. Suboptimal image acquisition reduces the sensitivity and specificity of mpMRI for the detection and staging of clinically significant prostate cancer.This critical review outlines the studies aimed at improving prostate MR quality that have been published over the last 5 years. These span from the use of specific MR sequences, magnets and coils to patient preparation. The rates of adherence of prostate mpMRI to technical standards in different cohorts across the world are also discussed.Finally, we discuss the first standardised scoring system (i.e., Prostate Imaging Quality, PI-QUAL) that has been created to evaluate image quality, although further iterations of this score are expected in the future

Understanding PI-QUAL for prostate MRI quality: a practical primer for radiologists

Prostate magnetic resonance imaging (MRI) of high diagnostic quality is a key determinant for either detection or exclusion of prostate cancer. Adequate high spatial resolution on T2-weighted imaging, good diffusion-weighted imaging and dynamic contrast-enhanced sequences of high signal-to-noise ratio are the prerequisite for a high-quality MRI study of the prostate. The Prostate Imaging Quality (PI-QUAL) score was created to assess the diagnostic quality of a scan against a set of objective criteria as per Prostate Imaging-Reporting and Data System recommendations, together with criteria obtained from the image. The PI-QUAL score is a 1-to-5 scale where a score of 1 indicates that all MR sequences (T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced sequences) are below the minimum standard of diagnostic quality, a score of 3 means that the scan is of sufficient diagnostic quality, and a score of 5 implies that all three sequences are of optimal diagnostic quality. The purpose of this educational review is to provide a practical guide to assess the quality of prostate MRI using PI-QUAL and to familiarise the radiologist and all those involved in prostate MRI with this scoring system. A variety of images are also presented to demonstrate the difference between suboptimal and good prostate MR scans

Sequential prostate MRI reporting in men on active surveillance: initial experience of a dedicated PRECISE software program

BACKGROUND AND OBJECTIVES: There is interest in using sequential multiparametric magnetic resonance imaging (mpMRI) to assess men on active surveillance (AS) for prostate cancer. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations propose standardised reporting mpMRI data for these men. This includes accurate size measurements of lesions over time, but such approach is time consuming for the radiologist and there is a strong need of dedicated tools to report serial scans in a systematic manner. We present the results from an initial validation cohort using dedicated PRECISE reporting software to allow automated comparison between sequential scans on AS. MATERIALS AND METHODS: We retrospectively analysed baseline and follow-up scans of 20 men randomised to 6 months of daily dutasteride (n = 10) or placebo (n = 10) from the MAPPED trial. Men underwent 3T mpMRI at baseline and after 6 months, and a dedicated radiologist reported the scans using both a widespread commercially-available platform (Osirix®) and a semi-automated dedicated PRECISE reporting tool (MIM®). Tumour volume by planimetry in all sequences and conspicuity on diffusion-weighted imaging were assessed. Reporting time was recorded, and we used the Wilcoxon test for statistical analysis. RESULTS: Median tumour volumes and conspicuity were similar using both approaches. The reporting time of the follow-up scan was quicker using the PRECISE reporting workflow both in the whole population (12'33″ vs 10'52″; p = 0.005) and in the dutasteride arm (15'50″ vs 12'59″; p = 0.01). A structured report including clinical and imaging data was generated according to the PRECISE recommendations and a comparison table between lesion characteristics at baseline and follow-up scans was also included. CONCLUSION: We conclude that a dedicated PRECISE reporting tool for sequential scans in men on AS results in a significant reduction in the reporting time and allows the radiologist to easily compare scans over time. This tool will help with our understanding of the natural history of mpMRI changes during AS

A Modified Newcastle-Ottawa Scale for Assessment of Study Quality in Genetic Urological Research

Our modification of the traditional Newcastle-Ottawa scale enables urological researchers to effectively appraise and communicate the quality of genetic-based research in urology

Tumour growth rates of prostate cancer during active surveillance: is there a difference between MRI-visible low and intermediate-risk disease?

OBJECTIVES: The aim of this study was to evaluate the changes in lesion volume on serial multiparametric magnetic resonance (mpMRI) during active surveillance for prostate cancer. METHODS: A total of 160 patients with a targeted biopsy-confirmed visible lesion on mpMRI, stratified by low- and intermediate-risk disease (Gleason Grade Group 1 vs Gleason Grade Group 2), were analysed. The % change per year was calculated using the formula: [(final volume/initial volume) exp (1/interval between scans in years)]-1. RESULTS: There was no significant difference in the annual median percentage change between Gleason Grade Group 1 (18%) and Gleason Grade Group 2 (23%) disease (p = 0.16), and between ≤ 10% (23%) and > 10% (22%) of Gleason pattern 4 (p = 0.78).Assuming a spherical lesion, these changes corresponded to annual increases in mean tumour diameter of 6% and 7% for Gleason Grade Group 1 and Gleason Grade Group 2 respectively, which may be less than the interscan variability of serial mpMRI. CONCLUSION: In an active surveillance cohort, we did not see a significant difference in the annual growth rate of Gleason Grade Group 1 and 2 tumours. ADVANCES IN KNOWLEDGE: In patients on active surveillance, the measured growth rates for visible tumours in Gleason Grade Groups 1 and 2 were similar. The annual growth rate was small in most cases and this may have implications for the MRI follow-up interval in active surveillance

Inter-reader agreement of the PI-QUAL score for prostate MRI quality in the NeuroSAFE PROOF trial

Objectives: The Prostate Imaging Quality (PI-QUAL) score assesses the quality of multiparametric MRI (mpMRI). A score of 1 means all sequences are below the minimum standard of diagnostic quality, 3 implies that the scan is of sufficient diagnostic quality, and 5 means that all three sequences are of optimal diagnostic quality. We investigated the inter-reader reproducibility of the PI-QUAL score in patients enrolled in the NeuroSAFE PROOF trial. Methods: We analysed the scans of 103 patients on different MR systems and vendors from 12 different hospitals. Two dedicated radiologists highly experienced in prostate mpMRI independently assessed the PI-QUAL score for each scan. Interobserver agreement was assessed using Cohen’s kappa with standard quadratic weighting (κw) and percent agreement. Results: The agreement for each single PI-QUAL score was strong (κw = 0.85 and percent agreement = 84%). A similar agreement (κw = 0.82 and percent agreement = 84%) was observed when the scans were clustered into three groups (PI-QUAL 1–2 vs PI-QUAL 3 vs PI-QUAL 4–5). The agreement in terms of diagnostic quality for each single sequence was highest for T2-weighted imaging (92/103 scans; 89%), followed by dynamic contrast-enhanced sequences (91/103; 88%) and diffusion-weighted imaging (80/103; 78%). Conclusion: We observed strong reproducibility in the assessment of PI-QUAL between two radiologists with high expertise in prostate mpMRI. At present, PI-QUAL offers clinicians the only available tool for evaluating and reporting the quality of prostate mpMRI in a systematic manner but further refinements of this scoring system are warranted