Dataset Information

Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis.

ABSTRACT: Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction.

SUBMITTER: Morrison G

PROVIDER: S-EPMC8910093 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis.

Morrison Gareth G Buckley Jonathan J Ostrow Dejerianne D Varghese Bino B Cen Steven Y SY Werbin Jeffrey J Ericson Nolan N Cunha Alexander A Lu Yi-Tsung YT George Thaddeus T Smith Jeffrey J Quinn David D Duddalwar Vinay V Triche Timothy T Goldkorn Amir A

International journal of molecular sciences 20220225 5

Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluoresc ...[more]

PMID: 35269713

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Project description:To determine the evolution of prostatic multi-parametric magnetic resonance imaging (mp-MRI) signal following transrectal ultrasound (TRUS)-guided biopsy.Local ethical permission and informed written consent was obtained from all the participants (n=14, aged 43-69, mean 64 years). Patients with a clinical suspicion of prostate cancer (PSA range 2.2-11.7, mean 6.2) and a negative (PIRAD 1-2/5) pre-biopsy mp-MRI (pre-contrast T1, T2, diffusion-weighted and dynamic-contrast-enhanced MRI) who underwent 10-core TRUS-guided biopsy were recruited for additional mp-MRI examinations performed at 1, 2 and 6 months post biopsy. We quantified mp-MRI peripheral zone (PZ) and transition zone (TZ) normalized T2 signal intensity (nT2-SI); T1 relaxation time (T10); diffusion-weighted MRI, apparent diffusion coefficient (ADC); dynamic contrast-enhanced MRI, maximum enhancement (ME); slope of enhancement (SoE) and area-under-the-contrast-enhancement-curve at 120 s (AUC120). Significant changes in mp-MRI parameters were identified by analysis of variance with Dunnett's post testing.Diffuse signal changes were observed post-biopsy throughout the PZ. No significant signal change occurred following biopsy within the TZ. Left and right PZ mean nT2-SI (left PZ: 5.73, 5.16, 4.90 and 5.12; right PZ: 5.80, 5.10, 4.84 and 5.05 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) and mean T10 (left PZ: 1.02, 0.67, 0.78, 0.85; right PZ: 1.29, 0.64, 0.78, 0.87 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) were reduced significantly (P<0.05) from pre-biopsy values for up to 6 months post biopsy. Significant changes (P<0.05) of PZ-ME and AUC120 were observed at 1 month but resolved by 2 months post biopsy. PZ ADC did not change significantly following biopsy (P=0.23-1.0). There was no significant change of any TZ mp-MRI parameter at any time point following biopsy (P=0.1-1.0).Significant PZ (but not TZ) T2 signal changes persist up to 6 months post biopsy, whereas PZ and TZ ADC is not significantly altered as early as 1 month post biopsy. Caution must be exercised when interpreting T1- and T2-weighted imaging early post biopsy, whereas ADC images are more likely to maintain clinical efficacy.

Project description:Objectives: To develop and validate a predictive model for discriminating clinically significant prostate cancer (csPCa) from clinically insignificant prostate cancer (ciPCa). Methods: This retrospective study was performed with 159 consecutively enrolled pathologically confirmed PCa patients from two medical centers. The dataset was allocated to a training group (n = 54) and an internal validation group (n = 22) from one center along with an external independent validation group (n = 83) from another center. A total of 1,188 radiomic features were extracted from T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images derived from DWI for each patient. Multivariable logistic regression analysis was performed to develop the model, incorporating the radiomic signature, ADC value, and independent clinical risk factors. This was presented using a radiomic nomogram. The receiver operating characteristic (ROC) curve was utilized to assess the predictive efficacy of the radiomic nomogram in both the training and validation groups. The decision curve analysis was used to evaluate which model achieved the most net benefit. Results: The radiomic signature, which was made up of 10 selected features, was significantly associated with csPCa (P < 0.001 for both training and internal validation groups). The area under the curve (AUC) values of discriminating csPCa for the radiomics signature were 0.95 (training group), 0.86 (internal validation group), and 0.81 (external validation group). Multivariate logistic analysis identified the radiomic signature and ADC value as independent parameters of predicting csPCa. Then, the combination nomogram incorporating the radiomic signature and ADC value demonstrated a favorable classification capability with the AUC of 0.95 (training group), 0.93 (internal validation group), and 0.84 (external validation group). Appreciable clinical utility of this model was illustrated using the decision curve analysis for the nomogram. Conclusions: The nomogram, incorporating radiomic signature and ADC value, provided an individualized, potential approach for discriminating csPCa from ciPCa.

Dataset Information

Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis.

Publications

Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis.

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