Dataset Information

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

ABSTRACT:

Background

The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification.

Objective

To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease.

Design, setting, and participants

Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa.

Intervention

Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients.

Outcome measurement and statistical analysis

Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication.

Results and limitations

A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up.

Conclusions

Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied.

Patient summary

Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed.

SUBMITTER: Parry MA

PROVIDER: S-EPMC6472613 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

Parry Marina A MA Srivastava Shambhavi S Ali Adnan A Cannistraci Alessio A Antonello Jenny J Barros-Silva João Diogo JD Ubertini Valentina V Ramani Vijay V Lau Maurice M Shanks Jonathan J Nonaka Daisuke D Oliveira Pedro P Hambrock Thomas T Leong Hui Sun HS Dhomen Nathalie N Miller Crispin C Brady Ged G Dive Caroline C Clarke Noel W NW Marais Richard R Baena Esther E

European urology oncology 20180905 1

<h4>Background</h4>The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification.<h4>Objective</h4>To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease.<h4>D ...[more]

PMID: 30929837

Similar Datasets

Project description:PurposeThe clinical utility of multiparametric magnetic resonance imaging (mpMRI) for the detection and localization of prostate cancer (PCa) has been evaluated and validated. However, the implementation of mpMRI into the clinical practice remains some burden of cost and availability for patients and society. We aimed to predict the results of prostate mpMRI using the clinical parameters and multivariable model to reduce unnecessary mpMRI scans.MethodsWe retrospectively identified 784 men who underwent mpMRI scans and subsequent prostate biopsy between 2016 and 2020 according to the inclusion criterion. The cohort was split into a training cohort of 548 (70%) patients and a validation cohort of 236 (30%) patients. Clinical parameters including age, prostate-specific antigen (PSA) derivates, and prostate volume (PV) were assessed as the predictors of mpMRI results. The mpMRI results were divided into groups according to the reports: "negative", "equivocal", and "suspicious" for the presence of PCa.ResultsUnivariate analysis showed that the total PSA (tPSA), free PSA (fPSA), PV, and PSA density (PSAD) were significant predictors for suspicious mpMRI (P < 0.05). The PSAD (AUC = 0.77) and tPSA (AUC = 0.74) outperformed fPSA (AUC = 0.68) and PV (AUC = 0.62) in the prediction of the mpMRI results. The multivariate model (AUC = 0.80) had a similar diagnostic accuracy with PSAD (P = 0.108), while higher than tPSA (P = 0.024) in predicting the mpMRI results. The multivariate model illustrated a better calibration and substantial improvement in the decision curve analysis (DCA) at a threshold above 20%. Using the PSAD with a 0.13 ng/ml2 cut-off could spare the number of mpMRI scans by 20%, keeping a 90% sensitivity in the prediction of suspicious MRI-PCa and missing three (3/73, 4%) clinically significant PCa cases. At the same sensitivity level, the multivariate model with a 32% cut-off could spare the number of mpMRI scans by 27%, missing only one (1/73, 1%) clinically significant PCa case.ConclusionOur multivariate model could reduce the number of unnecessary mpMRI scans without comprising the diagnostic ability of clinically significant PCa. Further prospective validation is required.

Project description:There is a growing need to localize prostate cancers on magnetic resonance imaging (MRI) to facilitate the use of image guided biopsy, focal therapy, and active surveillance follow up. Our goal was to develop a decision support system (DSS) for detecting and localizing peripheral zone prostate cancers by using machine learning approach to calculate a cancer probability map from multiparametric MR images (MP-MRI).This IRB approved Health Insurance Portability and Accountability Act compliant retrospective study consisted of 31 patients (mean age and serum prostate specific antigen of 60.4 and 6.62 ng∕ml, respectively) who had MP-MRI at 3 T followed by radical prostatectomy. Seven patients were excluded due to technical issues with their MP-MRI (e.g., motion artifact, failure to perform all sequences). Cancer and normal regions were identified in the peripheral zone by correlating them to whole mount histology slides of the excised prostatectomy specimens. To facilitate the correlation, tissue blocks matching the MR slices were obtained using a MR-based patient-specific mold. Segmented regions on the MP-MRI were correlated to histopathology and used as training sets for the learning system that generated the cancer probability maps. Leave-one-patient-out cross-validation on the cancer and normal regions was performed to determine the learning system's efficacy, an evolutionary strategies approach (also known as a genetic algorithm) was used to find the optimal values for a set of parameters, and finally a cancer probability map was generated.For the 24 patients that were used in the study, 225 cancer and 264 noncancerous regions were identified from the region maps. The efficacy of DSS was first determined without optimizing support vector machines (SVM) parameters, where a region having a cancer probability greater than or equal to 50% was considered as a correct classification. The nonoptimized system had an f-measure of 85% and the Kappa coefficient of 71% (Rater's agreement, where raters are DSS and ground truth histology). The efficacy of the DSS after optimizing SVM parameters using a genetic algorithm had an f-measure of 89% and a Kappa coefficient of 80%. Thus, after optimization of the DSS there was a 4% increase in the f-measure and a 9% increase in the Kappa coefficient.This DSS provides a cancer probability map for peripheral zone prostate tumors based on endorectal MP-MRI. These cancer probability maps can potentially aid radiologists in accurately localizing peripheral zone prostate cancers for planning targeted biopsies, focal therapy, and follow up for active surveillance.

Project description:Background: To develop a radiomics model based on multiparametric MRI (mpMRI) for preoperative prediction of extraprostatic extension (EPE) in patients with prostate cancer (PCa). Methods: Ninety-five pathology-confirmed PCa patients with 115 lesions (49 positive and 66 negative) were retrospectively enrolled. A 3.0T MR scanner was used to perform T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE). Radiomics features extracted from T2WI, DWI, apparent diffusion coefficient (ADC), and DCE were used to build a radiomics model. Patients' clinical and pathological variables were also obtained to build a clinical model. The radiomics model and clinical model were further integrated to build a combined nomogram. All lesions were randomly divided into the training group (82 lesions) and the validation group (33 lesions). A least absolute shrinkage and selection operator (LASSO) regression algorithm was applied to build the radiomics model. The diagnostic performance of different models was assessed by calculating the area under the curve (AUC) and compared using the Delong test. The calibration curve and decision curve analyses were used to assess the calibration and clinical usefulness of the radiomics model. Results: The AUC values for the radiomics model in the training and validation group were 0.919 and 0.865, respectively, with a good calibration performance. The decision curve analysis confirmed the clinical utility of the radiomics model. The accuracy, sensitivity, and specificity were 81.8, 71.4, and 89.5% in the validation group. In the validation group, the radiomics model outperformed the clinical model (AUC = 0.658, P = 0.020), and was comparable with the combined nomogram (AUC = 0.857, P = 0.644). Conclusion: The radiomics model based on mpMRI could different EPE and non-EPE lesions with satisfactory diagnostic performance, and this model might assist in predicting EPE before prostatectomy.

Project description:Background:Current magnetic resonance imaging (MRI) of pancreatic disease is qualitative in nature. Quantitative imaging offers several advantages, including increased reproducibility and sensitivity to detect mild or diffuse disease. The role of multiparametric mapping MRI in characterizing various tissue types in pancreatic disease such as chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) has rarely been evaluated. Purpose:To evaluate the feasibility of multiparametric mapping [T1, T2, and apparent diffusion coefficient (ADC)] in defining tissue characteristics that occur in CP and PDAC to improve disease diagnosis. Materials and Methods:Pancreatic MRI was performed in 17 patients with PDAC undergoing therapy, 7 patients with CP, and 29 healthy volunteers with no pancreatic disease. T1 modified Look-Locker Inversion Recovery (T1 MOLLI), T2-prepared gradient-echo, and multi-slice single-shot echo-planar diffusion weighted imaging (SS-EPI DWI) sequences were used for data acquisition. Regions of interest (ROIs) of pancreas in PDAC, CP, and control subjects were outlined by an experienced radiologist. One-way analysis of variance (ANOVA) was used to compare the difference between groups and regions of the pancreas, and Tukey tests were used for multiple comparison testing within groups. Receiver operator characteristic (ROC) curves were analyzed, and the areas under the curves (AUCs) were calculated using single parameter and combined parameters, respectively. Results:T1, T2, and ADC values of the entire pancreas among PDAC, CP, and control subjects; and between upstream and downstream portions of the pancreas in PDAC patients were all significantly different (p < 0.05). The AUC values were 0.90 for T1, 0.55 for T2, and 0.71 for ADC for independent prediction of PDAC. By combining T1, T2, and ADC, the AUC value was 0.94 (sensitivity 91.54%, specificity 85.81%, 95% CI: 0.92-0.96), which yielded higher accuracy than any one parameter only (p < 0.001). Conclusion:Multiparametric mapping MRI is feasible for the evaluation of the differences between PDAC, CP, and normal pancreas tissues. The combination of multiple parameters of T1, T2, and ADC provides a higher accuracy than any single parameter alone in tissue characterization of the pancreas.

Dataset Information

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

Background

Objective

Design, setting, and participants

Intervention

Outcome measurement and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets