Papers by Valeria Panebianco

European review for medical and pharmacological sciences, 2016
The aim of this study was to evaluate the accuracy of unenhanced whole-body MRI, including whole-... more The aim of this study was to evaluate the accuracy of unenhanced whole-body MRI, including whole-body Diffusion Weighted Imaging (DWI), used as a diagnostic modality to detect pathologic lymph nodes and skeletal metastases in patients with prostate cancer (PCa) undergoing restaging after primary treatment. 152 male patients with biochemical recurrence after radical prostatectomy (RP) or external beam radiation therapy (EBRT) underwent MRI at a 1.5 Tesla magnet with whole spinal sagittal T2-weighted, sagittal T1-weighted, sagittal STIR images, axial T1 and T2-weighted and STIR images of the pelvis and whole-body. 18Fcholine-PET/CT exam was used as the reference standard. MRI protocol including whole-body combined T1-weighted+T2-weighted+STIR+DWI showed a sensitivity (Se) of 99%, a specificity (Spe) of 98%, a positive predictive value (PPV) of 98%, a negative predictive value (NPV) of 96%, an accuracy of 98% and an area under the receiver operating characteristic curve (AUC) of 0.971...

European Journal of Radiology, 2016
To evaluate the potential added value of the intravoxel incoherent motion model to conventional m... more To evaluate the potential added value of the intravoxel incoherent motion model to conventional multiparametric magnetic resonance protocol in order to differentiate between healthy and neoplastic prostate tissue in the peripheral zone. Material and methods: Mono-exponential and bi-exponential fits were used to calculate ADC and IVIM parameters in 53 patients with peripheral zone biopsy proved tumor. Inferential statistics analysis was performed on T2, ADC and IVIM parameters (D, D*, f) comparing healthy and neoplastic tissues. Linear discriminant analysis was performed for the conventional parameters (T2 and ADC), the IVIM parameters (molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*), and perfusion fraction (f) and the combined T2-weighted imaging/DWI and IVIM parameters (T2, ADC, D, D* and f). A correlation with Gleason scores was achieved. Results: The values of T2, ADC and D were significantly lower in cancerous tissues (2749.82 ± 1324.67 ms, 0.76 ± 0.27 × 10 −3 mm 2 /s and 0.99 ± 0.38 × 10 −3 mm 2 /s respectively) compared to those found in the healthy tissues (3750.70 ± 1735.37 ms, 1.39 ± 0.48 × 10 −3 mm 2 /s and 1.77 ± 0.36 × 10 −3 mm 2 /s respectively); D* parameter was significantly increased in neoplastic compared to healthy tissue (15.56 ± 12.91 × 10 −3 mm 2 /s and 10.25 ± 10.52 × 10 −3 mm 2 /s respectively). The specificity, sensitivity and accuracy of the T2-weighted imaging/DWI and IVIM parameters were 100, 96 and 98%, respectively, compare to 88, 92 and 90% and 96, 92 and 94 for T2-weighted imaging/ADC and IVIM alone. Conclusions: IVIM parameters increase the specificity and sensitivity in the evaluation of peripheral zone prostate cancer. A statistical difference between low grade tumors and high grade tumors has been demostrated in that ADC, D and D* dataset; in particular, D has been found to have the highest significativity.
European journal of nuclear medicine and molecular imaging, 2015
Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (P... more Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

BJU International, 2012
What ' s known on the subject? and What does the study add? In clinical practice, we know that it... more What ' s known on the subject? and What does the study add? In clinical practice, we know that it is necessary to identify new biomarkers that can better detect prostate cancer (PC), at the same time as reducing the number of unnecessary biopsies. Recently, studies have suggested that the most relevant clinical scenario in which the prostate cancer antigen 3 (PCA3) score could be used comprises patients with a previous negative prostate biopsy and persistently elevated PSA levels. At the same time, although multiparametric MRI is not currently used as a fi rst approach for diagnosing PC, it can be useful for directing targeted biopsies, especially in those patients with elevated PSA levels and a previous negative TRUS-guided biopsy. Considering all of these aspects, the present study aimed to evaluate the role of multiparametric MRI as an additional diagnostic tool for improving the accuracy of the urinary PCA3 test in patients with increased PSA levels and a previous negative prostate biopsy.

European Radiology, 2017
Objectives Our goal is to determine the ability of multiparametric magnetic resonance imaging (mp... more Objectives Our goal is to determine the ability of multiparametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from nonmuscle invasive bladder cancer (NMIBC). Methods Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusionweighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + diffusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. Results A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. Conclusions MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. Key Points • A critical step in BCa staging is to differentiate NMIBC from MIBC. • Morphological and functional sequences are reliable techniques in differentiating NMIBC from MIBC. • Diffusion tensor imaging could be an additional tool in BCa staging.

Abdominal Radiology
Purpose The Vesical Imaging-Reporting and Data System (VI-RADS) criteria are expanding, providing... more Purpose The Vesical Imaging-Reporting and Data System (VI-RADS) criteria are expanding, providing fine differentiation of bladder wall layers involvement. We aimed to explore the feasibility of a novel categorical scoring, the Neoadjuvant chemotherapy VI-RADS (nacVI-RADS) for radiologic assessment of response (RaR), to define the spectrum of treatment response among patients with muscle invasive bladder cancer (MIBC). Methods Ten consecutive patients diagnosed with non-metastatic MIBC were prospectively enrolled and addressed to NAC and underwent mpMRI before staging resection and after the chemotherapy cycles. The follow-up MRI assessment was performed using the nacVI-RADS algorithm for evaluation of response to therapy. NacVI-RADS categorically define complete RaR, based on prior VI-RADS score, presence of residual disease, tumor size, and infiltration of the muscularis propria. Results NacVI-RADS categories were able to match all the final radical cystectomy pathology both for complete pT0 responders and for the patients defined as partial or minimal responders, who only showed some RaR inter-scoring class downstaging. Conclusion This report is the preliminary evidence of the feasibility of nacVI-RADS criteria. These findings might lead to possible paradigmatic shifts for cancer-specific survival risk assessment and to possibly drive the therapeutic decision through active surveillance programs, bladder-sparing modalities, or to the standard of care.
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome, Italy; Depart... more Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome, Italy; Department of Radiological Sciences, Oncology and Pathology, “Sapienza” University of Rome, Rome, Italy; Regina Elena National Cancer Institute, Rome, Italy; Department of Urology, Sapienza University of Rome, Rome, Italy; e Sapienza University of Rome, Rome, Italy E U RO P E AN URO LOGY 74 ( 2 018 ) 4 8 – 5 4

La radiologia medica
Purpose The aim of the study was to prospectively evaluate the agreement between chest magnetic r... more Purpose The aim of the study was to prospectively evaluate the agreement between chest magnetic resonance imaging (MRI) and computed tomography (CT) and to assess the diagnostic performance of chest MRI relative to that of CT during the follow-up of patients recovered from coronavirus disease 2019. Materials and methods Fifty-two patients underwent both follow-up chest CT and MRI scans, evaluated for ground-glass opacities (GGOs), consolidation, interlobular septal thickening, fibrosis, pleural indentation, vessel enlargement, bronchiolar ectasia, and changes compared to prior CT scans. DWI/ADC was evaluated for signal abnormalities suspicious for inflammation. Agreement between CT and MRI was assessed with Cohen’s k and weighted k. Measures of diagnostic accuracy of MRI were calculated. Results The agreement between CT and MRI was almost perfect for consolidation (k = 1.00) and change from prior CT (k = 0.857); substantial for predominant pattern (k = 0.764) and interlobular septal...

Biomedicines
The MRI of the prostate is the gold standard for the detection of clinically significant prostate... more The MRI of the prostate is the gold standard for the detection of clinically significant prostate cancer (csPCa). Nonetheless, MRI still misses around 11% of clinically significant disease. The aim was to comprehensively integrate tissue and circulating microRNA profiling, MRI biomarkers and clinical data to implement PCa early detection. In this prospective cohort study, 76 biopsy naïve patients underwent MRI and MRI directed biopsy. A sentinel sample of 15 patients was selected for a pilot molecular analysis. Weighted gene coexpression network analysis was applied to identify the microRNAs drivers of csPCa. MicroRNA–target gene interaction maps were constructed, and enrichment analysis performed. The ANOVA on ranks test and ROC analysis were performed for statistics. Disease status was associated with the underexpression of the miRNA profiled; a correlation was found with ADC (r = −0.51, p = 0.02) and normalized ADC values (r = −0.64, p = 0.002). The overexpression of miRNAs from ...

Cancers
Background: To develop an international, multi-site nomogram for side-specific prediction of extr... more Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e...

Cancers
The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperati... more The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen’s Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evalu...
Translational Andrology and Urology

npj Systems Biology and Applications
Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very... more Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very controversial topics in the urological community. PCa is the second most common cancer in men worldwide and it is universally acknowledged as a complex disease, with a multi-factorial etiology. The pathway of PCa diagnosis has changed dramatically in the last few years, with the multiparametric magnetic resonance (mpMRI) playing a starring role with the introduction of the “MRI Pathway”. In this scenario the basic tenet of network medicine (NM) that sees the disease as perturbation of a network of interconnected molecules and pathways, seems to fit perfectly with the challenges that PCa early detection must face to advance towards a more reliable technique. Integration of tests on body fluids, tissue samples, grading/staging classification, physiological parameters, MR multiparametric imaging and molecular profiling technologies must be integrated in a broader vision of “disease” and it...

European Urology
Background: Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preop... more Background: Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended in most of high-risk non-muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient's stratification for such recommendation exist. Objective: To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT. Design, setting, and participants: Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of 3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes. Intervention: Multiparametric MRI of the bladder before TURBT. Outcome measurements and statistical analysis: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter-and intrareader variability. Results and limitations: A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at y These authors contributed equally. z These are co-last authors.

European Radiology
Objectives To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting an... more Objectives To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Methods Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement. Results Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPVand NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731). Conclusions VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good. Key Points • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness.

Abdominal Radiology
PurposeTo validate a novel consensus method, called target-in-target, combining human analysis of... more PurposeTo validate a novel consensus method, called target-in-target, combining human analysis of mpMRI with automated CAD system analysis, with the aim to increasing the prostate cancer detection rate of targeted biopsies.MethodsA cohort of 420 patients was enrolled and 253 patients were rolled out, due to exclusion criteria. 167 patients, underwent diagnostic 3T MpMRI. Two expert radiologists evaluated the exams adopting PI-RADSv2 and CAD system. When a CAD target overlapped with a radiologic one, we performed the biopsy in the overlapping area which we defined as target-in-target. Targeted TRUS-MRI fusion biopsy was performed in 63 patients with a total of 212 targets. The MRI data of all targets were quantitatively analyzed, and diagnostic findings were compared to pathologist’s biopsy reports.ResultsCAD system diagnostic performance exhibited sensitivity and specificity scores of 55.2% and 74.1% [AUC = 0.63 (0.54 ÷ 0.71)] , respectively. Human readers achieved an AUC value, in ROC analysis, of 0.71 (0.63 ÷ 0.79). The target-in-target method provided a detection rate per targeted biopsy core of 81.8 % vs. a detection rate per targeted biopsy core of 68.6 % for pure PI-RADS based on target definitions. The higher per-core detection rate of the target-in-target approach was achieved irrespective of the presence of technical flaws and artifacts.ConclusionsA novel consensus method combining human reader evaluation with automated CAD system analysis of mpMRI to define prostate biopsy targets was shown to improve the detection rate per biopsy core of TRUS-MRI fusion biopsies. Results suggest that the combination of CAD system analysis and human reader evaluation is a winning strategy to improve targeted biopsy efficiency.

Internal Medicine Journal
INTRODUCTION Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal heredi... more INTRODUCTION Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. The aim of this study was to identify and quantify in ADPKD, through a novel MR protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the function renal. MATERIAL AND METHODS 15 ADPKD patients undergone to renal MRI 3Tesla at T0 and revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima media thickness (IMT), ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS Our study showed a significant negative correlation between total kidney volume and estimated glomerular filtration rate (eGFR) during observational observation (p<0.02). Moreover, we showed a negative correlation between eGFR with Total Fibrotic Volume (TFV) (p<0.04) and Total Perfusion Volume/Total kidney Volume(<0.02). Moreover TFV was correlated positively with PAC (p<0.05), insulin values (p<0.05), ABI (p <0.05) and LVMI(p<0.01). CONCLUSIONS The MRI 3Tesla, despite the high costs, could be considered an useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger group are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies.

European Urology
Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sens... more Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csPCa). Nevertheless, the clinical utility of negative mpMRI (nMRI) is less clear. Objective: To assess outcomes of men with nMRI and clinical follow-up after 7 yr of activity at a reference center. Design, setting, and participants: All mpMRI performed from January 2010 to May 2015 were reviewed. We selected all patients with nMRI and divided them in group A (naïve patients) and group B (previous negative biopsy). All patients without a diagnosis of PCa had a minimum follow-up of 2 yr and at least two consecutive nMRI. Patients with positive mpMRI were also identified to assess their biopsy outcomes. Outcome measurements and statistical analysis: A Kaplan-Meier analysis was performed to assess both any-grade PCa and csPCa diagnosis-free survival probabilities. Univariable and multivariable Cox regression models were fitted to identify predictors of csPCa diagnosis. Results and limitations: We identified 1545 men with nMRI, and 1255 of them satisfied the inclusion criteria; 659 belonged to group A and 596 to group B. Any-grade PCa and csPCa diagnosis-free survival probabilities after 2 yr of follow-up were 94% and 95%, respectively, in group A; in group B, they were 96%. After 48 mo of follow-up, any-grade PCa diagnosis-free survival probability was 84% in group A and 96% in group B (log rank p < 0.001). Diagnosis-free survival probability for csPCa was unchanged after 48 mo of follow-up. On multivariable Cox regression analysis, increasing age (p = 0.005) was an independent predictor of lower csPCa diagnosis probability, while increasing prostate-specific antigen (PSA) and PSA density (<0.001) independently predicted higher csPCa diagnosis probability. The prevalence of and positive predictive value for csPCa were 31.6% and 45.5%, respectively. Limitations include limited follow-up and the inability to calculate true csPCa prevalence in the study population. Conclusions: mpMRI is highly reliable to exclude csPCa. Nevertheless, systematic biopsy should be recommended even after nMRI, especially in younger patients with high or raising PSA levels. Patient summary: It is a matter of debate whether patients with negative multiparametric magnetic resonance imaging (mpMRI) of the prostate could obviate the need to perform a systematic biopsy. In this report, we looked at the outcomes of patients with negative mpMRI and midterm clinical followup at a reference center. We found mpMRI to be highly reliable to exclude significant prostate cancer; nonetheless, systematic biopsy must still be recommended after negative mpMRI in patients with high clinical suspicion of prostate cancer.

International journal of urology : official journal of the Japanese Urological Association, Jan 20, 2018
We aimed to review the current state-of-the-art imaging methods used for primary and secondary st... more We aimed to review the current state-of-the-art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and positron-emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta-analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross-sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high-risk patients, but is still sugge...
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Papers by Valeria Panebianco