Faculty Bibliography

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.

The aim of this work is to develop a data-driven quantitative dynamic contrast-enhanced (DCE) MRI technique using Golden-angle RAdial Sparse Parallel (GRASP) MRI with high spatial resolution and high flexible temporal resolution and pharmacokinetic (PK) analysis with an arterial input function (AIF) estimated directly from the data obtained from each patient. DCE-MRI was performed on 13 patients with gynecological malignancy using a 3-T MRI scanner with a single continuous golden-angle stack-of-stars acquisition and image reconstruction with two temporal resolutions, by exploiting a unique feature in GRASP that reconstructs acquired data with user-defined temporal resolution. Joint estimation of the AIF (both AIF shape and delay) and PK parameters was performed with an iterative algorithm that alternates between AIF and PK estimation. Computer simulations were performed to determine the accuracy (expressed as percentage error [PE]) and precision of the estimated parameters. PK parameters (volume transfer constant [K^trans ], fractional volume of the extravascular extracellular space [v_e ], and blood plasma volume fraction [v_p ]) and normalized root-mean-square error [nRMSE] (%) of the fitting errors for the tumor contrast kinetic data were measured both with population-averaged and data-driven AIFs. On patient data, the Wilcoxon signed-rank test was performed to compare nRMSE. Simulations demonstrated that GRASP image reconstruction with a temporal resolution of 1 s/frame for AIF estimation and 5 s/frame for PK analysis resulted in an absolute PE of less than 5% in the estimation of K^trans and v_e , and less than 11% in the estimation of v_p . The nRMSE (mean ± SD) for the dual temporal resolution image reconstruction and data-driven AIF was 0.16 ± 0.04 compared with 0.27 ± 0.10 (p < 0.001) with 1 s/frame using population-averaged AIF, and 0.23 ± 0.07 with 5 s/frame using population-averaged AIF (p < 0.001). We conclude that DCE-MRI data acquired and reconstructed with the GRASP technique at dual temporal resolution can successfully be applied to jointly estimate the AIF and PK parameters from a single acquisition resulting in data-driven AIFs and voxelwise PK parametric maps.

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.

MRI is used in the evaluation of ovarian and adnexal lesions. MRI can further characterize lesions seen on ultrasound to help decrease the number of false-positive lesions and avoid unnecessary surgery in benign lesions. Currently, the reporting of ovarian and adnexal findings on MRI is inconsistent because of the lack of standardized descriptor terminology. The development of uniform reporting descriptors can lead to improved interpretation agreement and communication between radiologists and referring physicians. The Ovarian-Adnexal Reporting and Data Systems MRI Committee was formed under the direction of the ACR to create a standardized lexicon for adnexal lesions with the goal of improving the quality and consistency of imaging reports. This white paper describes the consensus process in the creation of a standardized lexicon for ovarian and adnexal lesions for MRI and the resultant lexicon.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50-0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67-0.79). Patients were treated with ¹⁷⁷Lu-PSMA therapy in five, chemotherapy in three, ²²³Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

Our objective was to evaluate the impact of ¹⁸F-FDG PET CT on the management of urachal adenocarcinoma (UrC-ADC). Methods: A retrospective analysis of patients with UrC-ADC from 2001 to 2019 at Memorial Sloan Kettering was performed. Mayo stage before ¹⁸F-FDG PET/CT, rate of detection of the primary malignancy and metastases on ¹⁸F-FDG PET/CT, Mayo stage after ¹⁸F-FDG PET/CT, and change in patient management were determined. Results: Of 21 patients with UrC-ADC before ¹⁸F-FDG PET/CT, Mayo staging was I/II in 8, III in 3, and IV in 10. ¹⁸F-FDG PET/CT detected previously unidentified metastases in 8 (38%) of 21 patients, resulting in upstaging of disease in 3 (14%) patients and a change in treatment in 4 (19%) patients. Conclusion:

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 SUV_max (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.

With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of γ-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy. Methods: GT3 was loaded into liposomes using passive loading. ⁶⁴Cu-GT3-Nano and ³H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. The radioprotection efficacy of GT3-Nano was assessed after acute ¹³⁷Cs whole-body irradiation at a sublethal (4 Gy), a lethal (9 Gy), or a single high-dose administration of ¹⁵³Sm-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP). Flow cytometry and fluorescence microscopy were used to analyze hematopoietic cell population dynamics and the cellular site of GT3-Nano localization in the spleen and bone marrow, respectively. Results: Bone marrow uptake and retention (percentage injected dose per gram of tissue) at 24 h was 6.98 ± 2.34 for ⁶⁴Cu-GT3-Nano and 7.44 ± 2.52 for ³H-GT3-Nano. GT3-Nano administered 24 h before or after 4 Gy of total-body irradiation (TBI) promoted rapid and complete hematopoietic recovery, whereas recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9-Gy TBI. Flow cytometry of the bone marrow indicated that progenitor bone marrow cells MPP2 and CMP were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating the marrow-suppressive effects of sublethal and lethal TBI in mice. GT3-Nano can facilitate rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent ¹⁵³Sm-EDTMP.