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Correlation Between Imaging-Based Intermediate Endpoints and Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: Analysis of 28 Randomized Trials Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria in 16,511 Patients

Woo, Sungmin; Suh, Chong Hyun; Wibmer, Andreas G; Becker, Anton S; Teo, Min Yuen; Gönen, Mithat; Hricak, Hedvig; Scher, Howard I; Morris, Michael J; Vargas, Hebert Alberto
INTRODUCTION/BACKGROUND:Radiographic progression-free survival (rPFS) based on Prostate Cancer Working Group 2 (PCWG2) has been increasingly used as a meaningful imaging-based intermediate endpoint (IBIE) for overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). In randomized phase III trials, rPFS showed good correlation with OS at the individual trial level. We aimed to assess the correlation between the hazard ratios (HR) of IBIE and OS among PCWG2-based randomized trials. MATERIALS AND METHODS:PubMed and EMBASE databases were systematically searched for randomized trials evaluating systemic treatments on mCRPC using PCWG2 up to April 15, 2020. Hazard ratios for OS and IBIEs were extracted and their correlation was assessed using weighted linear regression. Subgroup analyses were performed according to various clinical settings: prior chemotherapy, drug category, type of IBIE (rPFS vs. composite IBIE, latter defined as progression by imaging and one or a combination of PSA, pain, skeletal-related events, and performance status), and publication year. RESULTS: = 0.32-0.91). CONCLUSION:IBIEs in the era of PCWG2 correlate well with OS in randomized trials for systemic drugs in patients with mCRPC. PCWG2-based rPFS should be used instead of a composite IBIE that includes PSA and other clinical variables.
PMCID:8816823
PMID: 34903480
ISSN: 1938-0682
CID: 5452952

Prognostic Utility of MRI Features in Intradiverticular Bladder Tumor

Woo, Sungmin; Ghafoor, Soleen; Becker, Anton S; Hricak, Hedvig; Goh, Alvin C; Vargas, Hebert Alberto
BACKGROUND:Intradiverticular bladder tumors (IDBT) are rare but clinically important, as they are difficult to assess endoscopically due to limited anatomic access and risk of perforation. MRI may be helpful in assessing IDBT and providing relevant staging and prognostic information. PURPOSE:To assess MRI findings of IDBT and their relationship with overall survival. METHODS:This retrospective study included 31 consecutive patients with IDBT undergoing MRI from 2008 to 2018 identified through electronic medical records and PACS database search. Two radiologists independently assessed the following MRI features: size (>3 vs ≤3 cm), diverticular neck involvement, Vesical Imaging-Reporting and Data System (VI-RADS) score (>3 vs ≤3), perivesical fat infiltration, additional tumors and suspicious pelvic lymph nodes. Overall survival was estimated using Kaplan-Meier analysis; and the relationship with clinicopathological and MRI features was determined using the Cox proportional-hazards regression model. Inter-reader agreement was assessed using intraclass correlation coefficients (ICC) and Cohen's kappa (K). RESULTS:Median follow-up was 1044 days (interquartile range, 474-1952 days). Twenty-six (83.9%) patients underwent surgical treatment with or without neoadjuvant chemotherapy. On MRI, greater tumor size (>3 cm), diverticular neck involvement, perivesical extension, and suspicious lymph nodes were associated with lower overall survival (HR = 3.6-8.1 and 4.3-6.3 for the 2 radiologists, p ≤ 0.03). Other clinicopathological or MRI findings were not associated with survival (p = 0.27-0.65). Inter-reader agreement was excellent for tumor size (ICC = 0.991; 95% CI 0.982-0.996), fair for VI-RADS (K = 0.52, 95% CI, 0.22-0.82), and moderate for others (K = 0.61-0.79). CONCLUSION:In patients with IDBT, several MRI features were significantly associated with overall survival. Utilizing all available clinicopathological and imaging information may improve estimation of prognosis.
PMCID:8096867
PMID: 33162319
ISSN: 1878-4046
CID: 5452792

Comparison of PI-RADS Versions 2.0 and 2.1 for MRI-based Calculation of the Prostate Volume

Ghafoor, Soleen; Becker, Anton S; Woo, Sungmin; Causa Andrieu, Pamela I; Stocker, Daniel; Gangai, Natalie; Hricak, Hedvig; Vargas, Hebert Alberto
RATIONALE AND OBJECTIVES:Prostate gland volume (PGV) should be routinely included in MRI reports of the prostate. The recently updated Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 includes a change in the recommended measurement method for PGV compared to version 2.0. The purpose of this study was to evaluate the agreement of MRI-based PGV calculations with the volumetric manual slice-by-slice prostate segmentation as a reference standard using the linear measurements per PI-RADS versions 2.0 and 2.1. Furthermore, to assess inter-reader agreement for the different measurement approaches, determine the influence of an enlarged transition zone on measurement accuracy and to assess the value of the bullet formula for PGV calculation. MATERIALS AND METHODS:Ninety-five consecutive treatment-naive patients undergoing prostate MRI were retrospectively analyzed. Prostates were manually contoured and segmented on axial T2-weighted images. Four different radiologists independently measured the prostate in three dimensions according to PI-RADS v2.0 and v2.1, respectively. MRI-based PGV was calculated using the ellipsoid and bullet formulas. Calculated volumes were compared to the reference manual segmentations using Wilcoxon signed-rank test. Inter-reader agreement was calculated using intraclass correlation coefficient (ICC). RESULTS:Inter-reader agreement was excellent for the ellipsoid and bullet formulas using PI-RADS v2.0 (ICC 0.985 and 0.987) and v2.1 (ICC 0.990 and 0.994), respectively. The median difference from the reference standard using the ellipsoid formula derived PGV was 0.4 mL (interquartile range, -3.9 to 5.1 mL) for PI-RADS v2.0 (p = 0.393) and 2.6 mL (interquartile range, -1.6 to 7.3 mL) for v2.1 (p < 0.001) with a median difference of 2.2 mL. The bullet formula overestimated PGV by a median of 13.3 mL using PI-RADS v2.0 (p < 0.001) and 16.0 mL using v2.1 (p < 0.001). In the presence of an enlarged transition zone the PGV tended to be higher than the reference standard for PI-RADS v2.0 (median difference of 4.7 mL; p = 0.018) and for v2.1 (median difference of 5.7 mL, p < 0.001) using the ellipsoid formula. CONCLUSION:Inter-reader agreement was excellent for the calculated PGV for both methods. PI-RADS v2.0 measurements with the ellipsoid formula yielded the most accurate volume estimates. The differences between PI-RADS v2.0 and v2.1 were statistically significant although small in absolute numbers but may be of relevance in specific clinical scenarios like prostate-specific antigen density calculation. These findings validate the use of the ellipsoid formula and highlight that the bullet formula should not be used for prostate volume estimation due to systematic overestimation.
PMID: 32814644
ISSN: 1878-4046
CID: 5452742

BJR female genitourinary oncology special feature: introductory editorial [Editorial]

Nougaret, Stephanie; Vargas, Hebert Alberto; Sala, Evis
PMCID:9327764
PMID: 34415200
ISSN: 1748-880x
CID: 5452922

Emergency room imaging in pediatric patients with cancer: analysis of the spectrum and frequency of imaging modalities and findings in a tertiary cancer center and their relationship with survival

Woo, Sungmin; Araji, Abdallah; El Amine, Mohammad Ali; Gangai, Natalie; Acquafredda, Elizabeth; Price, Anita P; Trippett, Tanya M; Hricak, Hedvig; Vargas, Hebert Alberto; Behr, Gerald G
BACKGROUND:To assess the spectrum and frequency of modalities used for emergency room (ER) imaging and their findings in pediatric cancer patients and assess their relationship with survival. METHODS:Consecutive pediatric cancer patients that underwent imaging during an ER visit at our tertiary cancer center over a 5-year period were retrospectively analyzed. Imaging findings were considered positive when they were relevant to the ER presenting complaint. Imaging positivity was correlated with inpatient admission. Overall survival (OS) was assessed with Kaplan-Meier curves and uni- and multi-variate Cox proportional hazards model was used to identify significant factors associated with OS. RESULTS:Two hundred sixty-one patients (135 males and 126 females; median age 11 years [interquartile range 5-16 years] with 348 visits and a total of 406 imaging studies were included. Common chief complaints were related to the chest (100 [28.7 %]) and fever (99 [28.4 %]). ER imaging was positive in 207 visits (59.5 %), commonly revealing increased metastases (50 [14.4 %]), pneumonia (47 [13.5 %]), and other lung problems (12 [2.9 %]). Positive ER imaging was associated with inpatient admission (69.3 % [133/192] vs. 40.4 % [63/156], p < 0.01). Multivariate survival analysis showed that positive ER imaging (hazard ratio [HR] = 2.35 [95% CI 1.44-3.83, p < 0.01), admission (HR = 1.86 [95% CI 1.17-3.00], p < 0.01), number of ER visits (HR = 3.08 [95% CI 1.62-5.83], p < 0.01 for ≥ 3 visits) were associated with poorer survival. CONCLUSIONS:Imaging was able to delineate the cause for ER visits in children with cancer in over half of the cases. Positive ER imaging was associated with admission and worse survival.
PMCID:8400759
PMID: 34454626
ISSN: 1470-7330
CID: 5452932

Quantification of Metastatic Prostate Cancer Whole-Body Tumor Burden with 18F-FDG PET Parameters and Associations with Overall Survival After First-Line Abiraterone or Enzalutamide: A Single-Center Retrospective Cohort Study

Wibmer, Andreas G; Morris, Michael J; Gonen, Mithat; Zheng, Junting; Hricak, Hedvig; Larson, Steven; Scher, Howard I; Vargas, Hebert Alberto
New biomarkers for metastatic prostate cancer are needed. The aim of this study was to evaluate the prognostic value of 18F-FDG PET whole-body tumor burden parameters in patients with metastatic prostate cancer who received first-line abiraterone or enzalutamide therapy. Methods: This was a retrospective study of patients with metastatic castration-sensitive prostate cancer (mCSPC, n = 25) and metastatic castration-resistant prostate cancer (mCRPC, n = 71) who underwent 18F-FDG PET/CT within 90 d before first-line treatment with abiraterone or enzalutamide at a tertiary-care academic cancer center. Whole-body tumor burden on PET/CT was quantified as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and correlated with overall survival (OS) probabilities using Kaplan-Meier curves and Cox models. Results: The median follow-up in survivors was 56.3 mo (interquartile range, 37.7-66.8 mo); the median OSs for patients with mCRPC and mCSPC were 27.8 and 76.1 mo, respectively (P < 0.001). On univariate analysis, the OS probability of mCRPC patients was significantly associated with plasma levels of alkaline phosphatase (hazard ratio [HR], 1.90; P < 0.001), plasma levels of lactate dehydrogenase (HR, 1.01; P < 0.001), hemoglobin levels (HR, 0.80; P = 0.013), whole-body SUVmax (HR, 1.14; P < 0.001), the number of 18F-FDG-avid metastases (HR, 1.08; P < 0.001), whole-body metabolic tumor volume (HR, 1.86; P < 0.001), and TLG (HR, 1.84; P < 0.001). On multivariable analysis with stepwise variable selection, hemoglobin levels (HR, 0.81; P = 0.013) and whole-body TLG (HR, 1.88; P < 0.001) were independently associated with OS. In mCSPC patients, no significant association was observed between these variables and OS. Conclusion: In patients with mCRPC receiving first-line treatment with abiraterone or enzalutamide, 18F-FDG PET WB TLG is independently associated with OS and might be used as a quantitative prognostic imaging biomarker.
PMCID:8833874
PMID: 33419944
ISSN: 1535-5667
CID: 5452822

Defining the index lesion for potential salvage partial or hemi-gland ablation after radiation therapy for localized prostate cancer

Chesnut, Gregory T; Tin, Amy L; Sivaraman, Arjun; Takeda, Toshikazu; Lee, Taehyoung; Fainberg, Jonathan; Benfante, Nicole; Sjoberg, Daniel D; Vargas, Hebert Alberto; Fine, Samson W; Scardino, Peter T; Eastham, James A; Coleman, Jonathan A; Touijer, Karim A; Zelefsky, Michael J; Ehdaie, Behfar
BACKGROUND:Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. OBJECTIVE:To evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens. DESIGN, SETTING, AND PARTICIPANTS:Men who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Primary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides. RESULTS AND LIMITATIONS:Of 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%-89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men. CONCLUSIONS:In men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.
PMCID:8542418
PMID: 33583697
ISSN: 1873-2496
CID: 5452842

Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel

Becker, Anton S; Perez-Johnston, Rocio; Chikarmane, Sona A; Chen, Melissa M; El Homsi, Maria; Feigin, Kimberly N; Gallagher, Katherine M; Hanna, Ehab Y; Hicks, Marshall; Ilica, Ahmet T; Mayer, Erica L; Shinagare, Atul B; Yeh, Randy; Mayerhoefer, Marius E; Hricak, Hedvig; Vargas, H Alberto
Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.
PMID: 33625298
ISSN: 1527-1315
CID: 5452872

Phase II Clinical Trial of Everolimus in a Pan-Cancer Cohort of Patients with mTOR Pathway Alterations

Adib, Elio; Klonowska, Katarzyna; Giannikou, Krinio; Do, Khanh T; Pruitt-Thompson, Solida; Bhushan, Ketki; Milstein, Matthew I; Hedglin, Jennifer; Kargus, Katherine E; Sholl, Lynette M; Tsuji, Junko; Hyman, David M; Sisk, Anne; Shapiro, Geoffrey I; Vargas, Hebert A; Harding, James J; Voss, Martin H; Iyer, Gopa; Kwiatkowski, David J
PURPOSE:mutations. PATIENTS AND METHODS:mutations identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. Patients were treated with everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Whole-exome sequencing was performed to identify co-occurring genomic alterations. RESULTS:-inactivating mutations and PEComa-like pathologic features. CONCLUSIONS:.
PMID: 33727259
ISSN: 1557-3265
CID: 5452882

Radiomics and radiogenomics in ovarian cancer: a literature review

Nougaret, S; McCague, Cathal; Tibermacine, Hichem; Vargas, Hebert Alberto; Rizzo, Stefania; Sala, E
Ovarian cancer remains one of the most lethal gynecological cancers in the world despite extensive progress in the areas of chemotherapy and surgery. Many studies have postulated that this is because of the profound heterogeneity that underpins response to therapy and prognosis. Standard imaging evaluation using CT or MRI does not take into account this tumoral heterogeneity especially in advanced stages with peritoneal carcinomatosis. As such, newly emergent fields in the assessment of tumor heterogeneity have been proposed using radiomics to evaluate the whole tumor burden heterogeneity as opposed to single biopsy sampling. This review provides an overview of radiomics, radiogenomics, and proteomics and examines the use of these newly emergent fields in assessing tumor heterogeneity and its implications in ovarian cancer.
PMID: 33174120
ISSN: 2366-0058
CID: 5452802