Risk stratification of prostate cancer utilizing apparent diffusion coefficient value and lesion volume on multiparametric MRI

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136035/1/jmri25363_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136035/2/jmri25363.pd

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147814/1/bju14515_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147814/2/bju14515.pd

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation

Histones shape chromatin structure and the epigenetic landscape. H1, the most diverse histone in the human genome, has 11 variants. Due to the high structural similarity between the H1s, their unique functions in transferring information from the chromatin to mRNA-processing machineries have remained elusive. Here, we generated human cell lines lacking up to five H1 subtypes, allowing us to characterize the genomic binding profiles of six H1 variants. Most H1s bind to specific sites, and binding depends on multiple factors, including GC content. The highly expressed H1.2 has a high affinity for exons, whereas H1.3 binds intronic sequences. H1s are major splicing regulators, especially of exon skipping and intron retention events, through their effects on the elongation of RNA polymerase II (RNAPII). Thus, H1 variants determine splicing fate by modulating RNAPII elongation.The research was funded by the Israel Science Foundation (ISF 671/18, ISF 142/13, and ISF 2417/20); the Israel Cancer Research Foundation (ICRF PG-18-105, PG-20-104); and the United States – Israel Binational Science Foundation (BSF 2017086). V.R.R. was supported by Edmond J. Safra Bioinformatics Center fellowship at Tel Aviv University.Peer reviewe

Multi-parametric MRI of the prostate: Factors predicting extracapsular extension at the time of radical prostatectomy

Objective: Extracapsular extension (ECE) of prostate cancer is a poor prognostic factor associated with progression, recurrence after treatment, and increased prostate cancer-related mortality. Accurate staging prior to radical prostatectomy is crucial in avoidance of positive margins and when planning nerve-sparing procedures. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has shown promise in this regard, but is hampered by poor sensitivity. We sought to identify additional clinical variables associated with pathologic ECE and determine our institutional accuracy in the detection of ECE amongst patients who went on to radical prostatectomy. Methods: mpMRI studies performed between the years 2012 and 2014 were cross-referenced with radical prostatectomy specimens. Predictive properties of ECE as well as additional clinical and biochemical variables to identify pathology-proven prostate cancer ECE were analyzed. Results: The prevalence of ECE was 32.4%, and the overall accuracy of mpMRI for ECE was 84.1%. Overall mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for detection of ECE were 58.3%, 97.8%, 93.3%, and 81.5%, respectively. Specific mpMRI characteristics predictive of pathologic ECE included primary lesion size ((20.73 ± 9.09) mm, mean ± SD, p < 0.001), T2 PIRADS score (p = 0.009), overall primary lesion score (p < 0.001), overall study suspicion score (p = 0.003), and MRI evidence of seminal vesicle invasion (SVI) (p = 0.001). Conclusion: While mpMRI is an accurate preoperative assessment tool for the detection of ECE, its overall sensitivity is poor, likely related to the low detection rate of standard protocol MRI for microscopic extraprostatic disease. The additional mpMRI findings described may also be considered in surgical margin planning prior to radical prostatectomy

Role of multi-parametric MRI of the prostate for screening and staging: Experience with over 1500 cases

Objective: Contemporary prostate cancer (PCa) screening modalities such as prostate specific antigen (PSA) and digital rectal examination (DRE) are limited in their ability to predict the detection of clinically significant disease. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has been explored as a staging modality for PCa. Less is known regarding its utility as a primary screening modality. We examined our experience with mpMRI as both a screening and staging instrument. Methods: mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography (TRUS) biopsy findings. Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant (Gleason score ≥7) disease. Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy. mpMRI studies were also cross-referenced with RP specimens. Statistical analyses determined predictive ability of extracapsular extension (ECE), seminal vesicle involvement (SVI), and pathologic evidence of clinically significant disease (Gleason score ≥7). Results: Four hundred biopsy naïve or prior negative biopsy patients had positive mpMRI studies. Overall sensitivity, specificity, positive and negative predictive values were 94%, 37%, 58%, and 87%, respectively and 95%, 31%, 42%, and 93%, respectively for overall cancer detection and Gleason score ≥7 disease. In patients with no prior biopsy history, mpMRI sensitivity, specificity, positive and negative predictive values were 94%, 36%, 65%, and 82%, for all cancers, and 95%, 30%, 50%, and 89% for Gleason score≥7 lesions, respectively. In those with prior negative biopsy sensitivity, specificity, positive and negative predictive values were 94%, 37%, 52%, and 90% for all cancers, and 96%, 32%, 36%, and 96% for Gleason score ≥7 lesions, respectively. Seventy-four patients underwent radical prostatectomy (RP) after mpMRI. Lesion size on mpMRI correlated with the presence of Gleason score ≥7 cancers (p = 0.005). mpMRI sensitivity, specificity, positive and negative predictive values were 84%, 39%, 81%, and 44% respectively, for Gleason ≥7 cancer. For ECE and SVI, sensitivity and specificity were 58% and 98% and 44% and 97%, respectively. Conclusion: mpMRI is an accurate predictor of TRUS biopsy and RP outcomes. mpMRI has significant potential to change PCa management, particularly in the screening population, in whom a significant proportion may avoid TRUS biopsy. Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms

Comparison of Multiparametric MRI Scoring Systems and the Impact on Cancer Detection in Patients Undergoing MR US Fusion Guided Prostate Biopsies.

Multiple scoring systems have been proposed for prostate MRI reporting. We sought to review the clinical impact of the new Prostate Imaging Reporting and Data System v2 (PI-RADS) and compare those results to our proposed Simplified Qualitative System (SQS) score with respect to detection of prostate cancers and clinically significant prostate cancers.All patients who underwent multiparametric prostate MRI (mpMRI) had their images interpreted using PI-RADS v1 and SQS score. PI-RADS v2 was calculated from prospectively collected data points. Patients with positive mpMRIs were then referred by their urologists for enrollment in an IRB-approved prospective phase III trial of mpMRI-Ultrasound (MR/TRUS) fusion biopsy of suspicious lesions. Standard 12-core biopsy was performed at the same setting. Clinical data were collected prospectively.1060 patients were imaged using mpMRI at our institution during the study period. 341 participants were then referred to the trial. 312 participants underwent MR/TRUS fusion biopsy of 452 lesions and were included in the analysis. 202 participants had biopsy-proven cancer (64.7%) and 206 (45.6%) lesions were positive for cancer. Distribution of cancer detected at each score produced a Gaussian distribution for SQS while PI-RADS demonstrates a negatively skewed curve with 82.1% of cases being scored as a 4 or 5. Patient-level data demonstrated AUC of 0.702 (95% CI 0.65 to 0.73) for PI-RADS and 0.762 (95% CI 0.72 to 0.81) for SQS (p< 0.0001) with respect to the detection of prostate cancer. The analysis for clinically significant prostate cancer at a per lesion level resulted in an AUC of 0.725 (95% CI 0.69 to 0.76) and 0.829 (95% CI 0.79 to 0.87) for the PI-RADS and SQS score, respectively (p< 0.0001).mpMRI is a useful tool in the workup of patients at risk for prostate cancer, and serves as a platform to guide further evaluation with MR/TRUS fusion biopsy. SQS score provided a more normal distribution of scores and yielded a higher AUC than PI-RADS v2. However until our findings are validated, we recommend reporting of detailed sequence-specific findings. This will allow for prospectively collected data to be utilized in determining the impact of ongoing changes to these scoring systems as our understanding of mpMRI interpretation evolves

5-point scale: Overall SQS Score and PI-RADS use the same terminology for grading.

<p>5-point scale: Overall SQS Score and PI-RADS use the same terminology for grading.</p

PI-RADS Scoring System.

<p>PI-RADS Scoring System.</p