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Combined Whole Body and Multiparametric Prostate Magnetic Resonance Imaging as a 1-Step Approach to the Simultaneous Assessment of Local Recurrence and Metastatic Disease after Radical Prostatectomy
Robertson, Nicola L; Sala, Evis; Benz, Matthias; Landa, Jonathan; Scardino, Peter; Scher, Howard I; Hricak, Hedvig; Vargas, Hebert A
PURPOSE:We report our initial experience with whole body and dedicated prostate magnetic resonance imaging as a single examination to assess local recurrence and metastatic disease in patients with suspected recurrent prostate cancer after radical prostatectomy. MATERIALS AND METHODS:In this institutional review board approved, retrospective, single center study 76 consecutive patients with clinically suspected recurrent prostate cancer following radical prostatectomy underwent combined whole body and dedicated prostate magnetic resonance imaging at a single session from October 2014 to January 2016. Scans were evaluated to detect disease in the prostate bed and regional nodes, and at distant sites. Comparison was made to other imaging tests, and prostate bed, node and bone biopsies performed within 90 days. RESULTS:F-fluorodeoxyglucose positron emission tomography/computerized tomography and subsequent negative bone biopsy. CONCLUSIONS:Combined whole body and dedicated prostate magnetic resonance imaging is feasible in a clinical practice setting. It can provide incremental information compared to standard imaging in men with suspected prostate cancer recurrence after radical prostatectomy.
PMCID:5639723
PMID: 28216327
ISSN: 1527-3792
CID: 5452222
The performance of PI-RADSv2 and quantitative apparent diffusion coefficient for predicting confirmatory prostate biopsy findings in patients considered for active surveillance of prostate cancer
Nougaret, Stephanie; Robertson, Nicola; Golia Pernicka, Jennifer; Molinari, Nicolas; Hötker, Andreas M; Ehdaie, Behfar; Sala, Evis; Hricak, Hedvig; Vargas, Hebert Alberto
PURPOSE:To assess the performance of the updated Prostate Imaging Reporting and Data System (PI-RADSv2) and the apparent diffusion coefficient (ADC) for predicting confirmatory biopsy results in patients considered for active surveillance of prostate cancer (PCA). METHODS:IRB-approved, retrospective study of 371 consecutive men with clinically low-risk PCA (initial biopsy Gleason score ≤6, prostate-specific antigen <10 ng/ml, clinical stage ≤T2a) who underwent 3T-prostate MRI before confirmatory biopsy. Two independent radiologists recorded the PI-RADSv2 scores and measured the corresponding ADC values in each patient. A composite score was generated to assess the performance of combining PI-RADSv2 + ADC. RESULTS:PCA was upgraded on confirmatory biopsy in 107/371 (29%) patients. Inter-reader agreement was substantial (PI-RADSv2: k = 0.73; 95% CI [0.66-0.80]; ADC: r = 0.74; 95% CI [0.69-0.79]). Accuracies, sensitivities, specificities, positive predicted value and negative predicted value of PI-RADSv2 were 85, 89, 83, 68, 95 and 78, 82, 76, 58, 91% for ADC. PI-RADSv2 accuracy was significantly higher than that of ADC for predicting biopsy upgrade (p = 0.014). The combined PI-RADSv2 + ADC composite score did not perform better than PI-RADSv2 alone. Obviating biopsy in patients with PI-RADSv2 score ≤3 would have missed Gleason Score upgrade in 12/232 (5%) of patients. CONCLUSION:PI-RADSv2 was superior to ADC measurements for predicting PCA upgrading on confirmatory biopsy.
PMCID:5537601
PMID: 28258355
ISSN: 2366-0058
CID: 5452232
Causes of Avascular Hypoechoic Testicular Lesions Detected at Scrotal Ultrasound: Can They Be Considered Benign?
Ma, Weining; Sarasohn, Debra; Zheng, Junting; Vargas, Hebert A; Bach, Ariadne
OBJECTIVE:The purposes of this study were to determine the cause of avascular hypoechoic lesions detected at scrotal ultrasound and to assess usefulness of sonographic and clinical features in differentiating benign from malignant etiologic factors. MATERIALS AND METHODS/METHODS:This retrospective study included 58 patients with avascular hypoechoic lesions detected at testicular ultrasound. The sonographic features recorded were lesion size and margins and presence of peripheral vascularity and focal calcifications. Also recorded were patient age, symptoms, risk factors, lesion palpability, and levels of serum tumor markers. The reference standard was pathologic results or at least 2-year stability documented with serial follow-up ultrasound studies. Features associated with malignant, including burnt-out, lesions and benign lesions were examined by Fisher exact test, Wilcox-on rank sum test, and the generalized estimating equations method for multivariable models. RESULTS:Sixty-three lesions were identified in 58 patients; 40 of the 63 (63.5%) were benign. Patients with malignant lesions had elevated serum tumor marker levels more often than patients who had benign lesions (26.1% versus 5.7%, p = 0.043). The clinical palpability of lesions and history of testicular cancer were not statistically significantly different between patients with malignant and those with benign lesions. Poorly defined margins of a lesion and focal calcification within the lesion were more often found in malignant lesions. Maximal size of a lesion and peripheral vascularity were not associated with either the benign or the malignant nature of a lesion. CONCLUSION/CONCLUSIONS:Although most avascular hypoechoic testicular lesions are benign, a substantial proportion are malignant. The ultrasound characteristics of a lesion, the patient's clinical presentation, and serum tumor marker status may be useful in differentiating malignant from benign lesions.
PMID: 28639925
ISSN: 1546-3141
CID: 5452272
Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making
Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I
PURPOSE/OBJECTIVE:A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). METHODS:Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. RESULTS:alterations were specifically enriched in CRPC. CONCLUSION/CONCLUSIONS:Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.
PMID: 28825054
ISSN: 2473-4284
CID: 5452312
Abdominal wall endometriosis: differentiation from other masses using CT features
Yarmish, Gail; Sala, Evis; Goldman, Debra A; Lakhman, Yulia; Soslow, Robert A; Hricak, Hedvig; Gardner, Ginger J; Vargas, H Alberto
PURPOSE:To assess the utility of morphologic and quantitative CT features in differentiating abdominal wall endometriosis (AWE) from other masses of the abdominal wall. METHODS:Retrospective IRB-approved study of 105 consecutive women from two institutions who underwent CT and biopsy/resection of abdominal wall masses. CTs were independently reviewed by two radiologists blinded to final histopathologic diagnoses. Associations between CT features and pathology were tested using Fisher's Exact Test. Sensitivity, specificity, positive, and negative predictive values were calculated. P values were adjusted for multiple variable testing. RESULTS:24.8% (26/105) of patients had histologically proven abdominal wall endometriosis. The other most common diagnoses included adenocarcinoma NOS (21%; 22/105), desmoid (14.3%; 15/105), and leiomyosarcoma (8.6%; 9/105). CT features significantly associated with endometriosis for both readers were location below the umbilicus (P = 0.0188), homogeneous density (P = 0.0188), and presence of linear infiltration irradiating peripherally from a central soft tissue nodule (i.e., "gorgon" sign) (P < 0.0001). The highest combined sensitivity (0.69, 95% CI: 0.48-0.86) and specificity (0.97, 95% CI: 0.91-1.00) for both readers occurred for patients having all three of these features present. Border type (P = 0.0199) was only significant for R2, peritoneal extension (P = 0.0188) was only significantly for R1, and the remainder of features were insignificant (P = 0.06-60). There was overlap in Hounsfield units on non-contrast CT (N = 26) between AWE (median: 45HU, range: 39-54) and other abdominal wall masses (median: 38.5HU, range: 15-58). CONCLUSION:CT features are helpful in differentiating AWE from other abdominal wall soft tissue masses. Such differentiation may assist decisions regarding possible biopsy and treatment planning.
PMCID:5507191
PMID: 28004137
ISSN: 2366-0058
CID: 5452202
A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early-stage Metastatic Prostate Cancer
O'Shaughnessy, Matthew J; McBride, Sean M; Vargas, Hebert Alberto; Touijer, Karim A; Morris, Michael J; Danila, Daniel C; Laudone, Vincent P; Bochner, Bernard H; Sheinfeld, Joel; Dayan, Erica S; Bellomo, Lawrence P; Sjoberg, Daniel D; Heller, Glenn; Zelefsky, Michael J; Eastham, James A; Scardino, Peter T; Scher, Howard I
OBJECTIVE:To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with non-castrate metastatic prostate cancers that are incurable with single modality therapy. MATERIALS AND METHODS:Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary end point was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. RESULTS:Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval: 3%-38%) achieved the primary end point, which persisted for 5, 6, 27+ , and 46+ months. All patients meeting the primary end point had been classified with M1b disease at presentation. CONCLUSION:A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The end point of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and to shift the paradigm from palliation to cure.
PMID: 27888148
ISSN: 1527-9995
CID: 5452182
Validation of 3D volumetric-based renal function prediction calculator for nephron sparing surgery
Corradi, Renato; Kabra, Aashish; Suarez, Melissa; Oppenheimer, Jacob; Okhunov, Zhamshid; White, Hugh; Nougaret, Stephanie; Vargas, Hebert A; Landman, Jaime; Coleman, Jonathan; Liss, Michael A
OBJECTIVE:To evaluate a recently published volume-based renal function prediction calculator intended to be used in small renal mass surgical counseling. METHODS:Retrospective data collection included three-dimensional calculation of renal mass and parenchyma of patients who have undergone extirpative therapy. The predicted glomerular filtration rate (GFR) was calculated using the online calculator. The predicted GFR was compared with the actual 6-month GFR. The Pearson correlation coefficient, paired t test and root-mean-square error (RMSE) are utilized for statistical analysis. RESULTS:(P < .001, paired t test). The predicted GFR was highly correlated with the actual postoperative GFR at 6 months (Pearson correlation, r = .65, P < .001). RMSE of the validation cohort was 16.87. CONCLUSIONS:The predictive tool to determine renal function benefit of nephron sparing surgery compared to radical nephrectomy online calculator effectively predicts GFR and could potentially be used to help urologists and patients discuss renal function prior to extirpative renal surgery.
PMCID:5589462
PMID: 28161843
ISSN: 1573-2584
CID: 5452212
Rationale for Modernising Imaging in Advanced Prostate Cancer
Padhani, Anwar R; Lecouvet, Frederic E; Tunariu, Nina; Koh, Dow-Mu; De Keyzer, Frederik; Collins, David J; Sala, Evis; Fanti, Stefano; Vargas, H Alberto; Petralia, Giuseppe; Schlemmer, Heinz Peter; Tombal, Bertrand; de Bono, Johann
CONTEXT:To effectively manage patients with advanced prostate cancer (APC), it is essential to have accurate, reproducible, and validated methods for detecting and quantifying the burden of bone and soft tissue metastases and for assessing their response to therapy. Current standard of care imaging with bone and computed tomography (CT) scans have significant limitations for the assessment of bone metastases in particular. OBJECTIVE:We aimed to undertake a critical comparative review of imaging methods used for diagnosis and disease monitoring of metastatic APC from the perspective of their availability and ability to assess disease presence, extent, and response of bone and soft tissue disease. EVIDENCE ACQUISITION:An expert panel of radiologists, nuclear medicine physicians, and medical physicists with the greatest experience of imaging in advanced prostate cancer prepared a review of the practicalities, performance, merits, and limitations of currently available imaging methods. EVIDENCE SYNTHESIS:Meta-analyses showed that positron emission tomography (PET)/CT with different radiotracers and whole-body magnetic resonance imaging (WB-MRI) are more accurate for bone lesion detection than CT and bone scans (BSs). At a patient level, the pooled sensitivities for bone disease by using choline (CH)-PET/CT, WB-MRI, and BS were 91% (95% confidence interval [CI], 83-96%), 97% (95% CI, 91-99%), and 79% (95% CI, 73-83%), respectively. The pooled specificities for bone metastases detection using CH-PET/CT, WB-MRI, and BS were 99% (95% CI, 93-100%), 95% (95% CI, 90-97%), and 82% (95% CI, 78-85%), respectively. The ability of PET/CT and WB-MRI to assess therapeutic benefits is promising but has not been comprehensively evaluated. There is variability in the cost, availability, and quality of PET/CT and WB-MRI. CONCLUSIONS:Standardisation of acquisition, interpretation, and reporting of WB-MRI and PET/CT scans is required to assess the performance of these techniques in clinical trials of treatment approaches in APC. PATIENT SUMMARY:PET/CT and whole-body MRI scans have the potential to improve detection and to assess response to treatment of all states of advanced prostate cancer. Consensus recommendations on quality standards, interpretation, and reporting are needed but will require validation in clinical trials of established and new treatment approaches.
PMID: 28753774
ISSN: 2405-4569
CID: 5455492
Renal Masses Detected on FDG PET/CT in Patients With Lymphoma: Imaging Features Differentiating Primary Renal Cell Carcinomas From Renal Lymphomatous Involvement
Nicolau, Carlos; Sala, Evis; Kumar, Anita; Goldman, Debra A; Schoder, Heiko; Hricak, Hedvig; Vargas, Hebert Alberto
OBJECTIVE:F-FDG PET/CT features of solid renal masses detected in patients with lymphoma and to evaluate the ability of PET/CT to differentiate renal cell carcinoma (RCC) from renal lymphomatous involvement. MATERIALS AND METHODS/METHODS:of the tumor to that of the normal liver, and the ratio of the SUVmean of the tumor to that of the normal liver. Renal mass size and margins (well defined vs infiltrative) and the presence of calcifications were evaluated on CT. Renal biopsy results were used as the reference standard. Relationships between imaging parameters and histopathologic findings were assessed. RESULTS:lower than 5.26 g/mL (median, 2.91 g/mL). No statistically significant differences in mass size or margins were found between RCCs and renal lymphoma. CONCLUSION/CONCLUSIONS:PET/CT features may be useful for differentiating RCCs from renal involvement in patients with lymphoma with solid renal masses.
PMCID:5548005
PMID: 28095016
ISSN: 1546-3141
CID: 5496702
Prostate cancer bone metastases on staging prostate MRI: prevalence and clinical features associated with their diagnosis
Vargas, Hebert Alberto; Schor-Bardach, Rachel; Long, Niamh; Kirzner, Anna N; Cunningham, Jane D; Goldman, Debra A; Moskowitz, Chaya S; Sosa, Ramon E; Sala, Evis; Panicek, David M; Hricak, Hedvig
PURPOSE:Bone lesions on prostate MRI often raise concern about metastases. This study aimed to evaluate the prevalence of bone metastases on staging prostate MRI and evaluate associations between their MRI features and clinical/pathologic characteristics. METHODS:Retrospective, IRB-approved study of 3765 patients undergoing prostate MRI for newly diagnosed PCa between 2000 and 2014. The reference standard to calculate the prevalence of bone metastases was bone biopsy and/or ≥1-year follow-up after MRI. In a subsample of 228 patients, the MRI characteristics of bone lesions were recorded by two radiologists independently. Associations between MRI and clinical/pathologic findings, including National Comprehensive Cancer Network (NCCN) risk categories, were calculated. RESULTS:57/3765 patients (1.5%, 95% CI 1.2-2.0%) had bone metastases. No patient with NCCN low-risk PCa (Gleason < 7, PSA < 10 ng/mL, cT1-2a) had bone metastases. In the subsample, ≥1 bone lesion was present on MRI in 74% (95% CI 0.67-0.79) and 72% (95% CI 0.66-0.78) of patients (R1 and R2). Larger lesion diameter (OR 1.33/1.19; p < 0.001 for both readers) and the absence of intralesional fat (OR 0.07/0.11; p = 0.004/0.002 for R1/R2) were significantly associated with bone metastases. CONCLUSION:Bone lesions are common in prostate MRI, but only rarely represent metastases. MRI should be interpreted in the context of clinical features that influence the likelihood of metastatic disease.
PMCID:5247358
PMID: 27480976
ISSN: 2366-0058
CID: 5452142