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Table S3. Toxicities (any level) occurring in at least two patients, grouped by CTCAE v4.0 categories. For patients with more than one adverse event per category, only the highest-grade event was counted.

Patient Demographics.

Supplementary Methods File

Purpose:This was a multicenter, histology-agnostic, single-arm prospective phase II trial of therapeutic activity of everolimus, an oral mTORC1 inhibitor, in patients with advanced solid tumors that harbored TSC1/TSC2 or MTOR mutations.Patients and Methods:Patients with tumors with inactivating TSC1/TSC2 or activating MTOR 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:Between November 2015 and October 2018, 30 patients were enrolled at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Tumors harbored TSC1 (13/30), TSC2 (15/30), concurrent TSC1 and TSC2 (1/30), or MTOR (1/30) mutations. The most common treatment-related adverse event of any grade was mucositis (8/30, 27%); 1 patient had fatal pneumonitis. Partial responses were seen in 2 patients [7%; 95% confidence interval (CI), 1%–22%]. Median progression-free survival was 2.3 months (95% CI, 1.8–3.7 months) and median overall survival (OS) was 7.3 months (95% CI, 4.5–12.7 months). There was no clear association between other genomic alterations and response. Of the 2 patients with objective response, 1 had upper tract urothelial carcinoma with biallelic inactivation of TSC1 and high tumor mutation burden, and the other had uterine carcinoma with biallelic TSC2-inactivating mutations and PEComa-like pathologic features.Conclusions:Everolimus therapy had a disappointing ORR (7%) in this pan-cancer, mutation-selected, basket study.See related commentary by Kato and Cohen, p. 3807

Purpose: To investigate whether tumor volume derived from apparent diffusion coefficient (ADC) maps (VolumeADC) and tumor mean ADC value (ADCmean) are independent predictors of prostate tumor Gleason score (GS).Experimental Design: Tumor volume and GS were recorded from whole-mount histopathology for 131 men (median age, 60 years) who underwent endorectal diffusion-weighted MRI for local staging of prostate cancer before prostatectomy. VolumeADC and ADCmean were derived from ADC maps and correlated with histopathologic tumor volume and GS. Univariate and multivariate analyses were performed to evaluate prediction of tumor aggressiveness. Areas under receiver-operating characteristics curves (AUC) were calculated to evaluate the performance of VolumeADC and ADCmean in discriminating tumors of GS 6 and GS ≥7.Results: Histopathology identified 116 tumor foci >0.5 mL. VolumeADC correlated significantly with histopathologic tumor volume (ρ = 0.683). The correlation increased with increasing GS (ρ = 0.453 for GS 6 tumors; ρ = 0.643 for GS 7 tumors; ρ = 0.980 for GS ≥8 tumors). Both VolumeADC (ρ = 0.286) and ADCmean (ρ = −0.309) correlated with GS. At univariate analysis, both VolumeADC (P = 0.0325) and ADCmean (P = 0.0033) could differentiate GS = 6 from GS ≥7 tumor foci. However, at multivariate analysis, only ADCmean (P = 0.0156) was a significant predictor of tumor aggressiveness (i.e., GS 6 vs. GS ≥7). For differentiating GS 6 from GS ≥7 tumors, AUCs were 0.644 and 0.704 for VolumeADC and ADCmean, respectively, and 0.749 for both parameters combined.Conclusion: In patients with prostate cancer, ADCmean is an independent predictor of tumor aggressiveness, but VolumeADC is not. The latter parameter adds little to the ADCmean in predicting tumor GS. Clin Cancer Res; 20(14); 3705–11. ©2014 AACR.

The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a College of American Pathologists–accredited and Clinical Laboratory Improvement Amendments–certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTC) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified on the basis of the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of the second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients. Cancer Res; 77(20); 5687–98. ©2017 AACR.

Fig S1. A. Treatment duration and clinical events for four subjects with clinical benefit. In the swimmer plot, patients are deceased at last follow-up unless indicated by the arrowhead. Abbreviations: LMS - leiomyosarcoma; UTUC - upper tract urothelial carcinoma; SCC - squamous cell carcinoma. B-C. Kaplan Meier curves for progression-free survival (B) and overall survival (C).

Results of receiver operating characteristic (ROC) analysis for the identification of tumors with a Gleason score {greater than or equal to} 7. A model combining mean tumor ADC value (ADCmean) and tumor volume derived from ADC maps (VolumeADC) performed only slightly better than ADCmean alone. (Note: AUC = area under ROC curve.)

Lesion Characteristics.

BACKGROUND: It is unknown how the imperfect accuracy of MRI for local staging of prostate cancer relates to oncologic outcomes. PURPOSE: To analyze how staging discordances between MRI and histopathologic evaluation relate to recurrence and survival after radical prostatectomy. MATERIALS AND METHODS: Health Insurance Portability and Accountability Act–compliant retrospective analysis of preprostatectomy T2-weighted prostate MRI (January 2001 to December 2006). Extraprostatic extension and seminal vesicle invasion were assessed by using five-point Likert scales; scores of 4 or higher were classified as positive. Biochemical recurrence (BCR), metastases, and prostate cancer–specific mortality rates were estimated with Kaplan-Meier and Cox models. RESULTS: A total of 2160 patients (median age, 60 years; interquartile range, 55–64 years) were evaluated. Among patients with histopathologic extraprostatic (pT3) disease (683 of 2160; 32%), those with organ-confined disease at MRI (384 of 683; 56%) experienced better outcomes than those with concordant extraprostatic disease at MRI and pathologic analysis: 15-year risk for BCR, 30% (95% CI: 22, 40) versus 68% (95% CI: 60, 75); risk for metastases, 14% (95% CI: 8.4, 24) versus 32% (95% CI: 26, 39); risk for prostate cancer–specific mortality, 3% (95% CI: 1, 6) versus 15% (95% CI: 9.5, 23) (P < .001 for all comparisons). Among patients with histopathologic organ-confined disease (pT2) (1477 of 2160; 68%), those with extraprostatic disease at MRI (102 of 1477; 7%) were at higher risk for BCR (27% [95% CI: 19, 37] vs 10% [95% CI: 8, 14]; P < .001), metastases (19% [95% CI: 6, 48] vs 3% [95% CI: 1, 6]; P < .001), and prostate cancer–specific mortality (2% [95% CI: 1, 9] vs 1% [95% CI: 0, 5]; P = .009) than those with concordant organ-confined disease at MRI and pathologic analysis. At multivariable analyses, tumor extent at MRI (hazard ratio range, 4.1–5.2) and histopathologic evaluation (hazard ratio range, 3.6–6.7) was associated with the risk for BCR, metastases, and prostate cancer–specific mortality (P < .001 for all analyses). CONCLUSION: The local extent of prostate cancer at MRI is associated with oncologic outcomes after prostatectomy, independent of pathologic tumor stage. This might inform a strategy on how to integrate MRI into a clinical staging algorithm. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gottlieb in this issue.

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.

Background It is unknown how body fat distribution modulates the cardiometabolic risk of testicular cancer survivors after cisplatin-based chemotherapy. Methods For 455 patients enrolled in the Platinum Study at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified on prechemotherapy computed tomography. The VAT-to-SAT ratio was calculated as a quantitative measure of central adiposity. Endpoints were incidence of new posthemotherapy cardiometabolic disease (new antihypertensive, lipid-lowering, or diabetes medication), and postchemotherapy Framingham risk scores. Cox models and linear regression with interaction terms were applied. Postchemotherapy body fat distribution was analyzed in 108 patients. All statistical tests were 2-sided. Results The baseline median age was 31 years (interquartile range [IQR] = 26-39 years), body mass index (BMI) was 26 kg/m2 (IQR = 24-29 kg/m2), and the VAT-to-SAT ratio was 0.49 (IQR = 0.31-0.75). The median follow-up was 26 months (IQR = 16-59 months). Higher prechemotherapy VAT-to-SAT ratios inferred a higher likelihood of new cardiometabolic disease among patients with a BMI of 30 kg/m2 or greater (age-adjusted hazard ratio = 3.14, 95% confidence interval = 1.02 to 9.71, P = .047), but not other BMI groups. The prechemotherapy VAT-to-SAT ratio was associated with postchemotherapy Framingham risk scores in univariate regression analysis (exp(β)-estimate: 2.10, 95% confidence interval = 1.84 to 2.39, P Conclusions In testicular cancer survivors, central adiposity is associated with increased cardiometabolic risk after cisplatin-based chemotherapy, particularly in obese or young men. Weight gain after chemotherapy occurs preferentially in the visceral compartment, providing insight into the pathogenesis of cardiovascular disease in this population.

Purpose:This was a multicenter, histology-agnostic, single-arm prospective phase II trial of therapeutic activity of everolimus, an oral mTORC1 inhibitor, in patients with advanced solid tumors that harbored TSC1/TSC2 or MTOR mutations.Patients and Methods:Patients with tumors with inactivating TSC1/TSC2 or activating MTOR 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:Between November 2015 and October 2018, 30 patients were enrolled at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Tumors harbored TSC1 (13/30), TSC2 (15/30), concurrent TSC1 and TSC2 (1/30), or MTOR (1/30) mutations. The most common treatment-related adverse event of any grade was mucositis (8/30, 27%); 1 patient had fatal pneumonitis. Partial responses were seen in 2 patients [7%; 95% confidence interval (CI), 1%–22%]. Median progression-free survival was 2.3 months (95% CI, 1.8–3.7 months) and median overall survival (OS) was 7.3 months (95% CI, 4.5–12.7 months). There was no clear association between other genomic alterations and response. Of the 2 patients with objective response, 1 had upper tract urothelial carcinoma with biallelic inactivation of TSC1 and high tumor mutation burden, and the other had uterine carcinoma with biallelic TSC2-inactivating mutations and PEComa-like pathologic features.Conclusions:Everolimus therapy had a disappointing ORR (7%) in this pan-cancer, mutation-selected, basket study.See related commentary by Kato and Cohen, p. 3807

RATIONALE: New biomarkers for metastatic prostate cancer are needed. The aim of this study was to evaluate the prognostic value of FDG-PET whole body tumor burden parameters in patients with metastatic prostate cancer who received first line abiraterone or enzalutamide therapy. METHODS: Retrospective study of patients with metastatic castration-sensitive (mCSPC, n = 25) and metastatic castration-resistant prostate cancer (mCRPC, n = 71) who underwent 18F-FDG-PET/CT within 90 days 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 months (IQR: 37.7, 66.8); the median OS for patients with mCRPC and mCSPC was 27.8 and 76.1 months (p

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:18F-FDG PET/CT has clinical utility in patients with UrC-ADC by identifying metastatic disease not appreciated on anatomic imaging, leading to changes in staging and patient management.

OBJECTIVE To examine a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer and to determine the likelihood of residual extensive disease. METHODS We retrospectively analyzed data from 98 patients with unilateral prostate cancer on biopsy with detailed tumor maps from whole-mount slides and preoperative magnetic resonance imaging data. These patients met the focal therapy consensus meeting inclusion criteria (prostate-specific antigen

PURPOSE To determine if radiomic measures of tumor heterogeneity derived from baseline contrast-enhanced computed tomography (CE-CT) are associated with durable clinical benefit and time to off-treatment in patients with recurrent ovarian cancer (OC) enrolled in prospective immunotherapeutic trials. MATERIALS AND METHODS This retrospective study included 75 patients with recurrent OC who were enrolled in prospective immunotherapeutic trials (n = 74) or treated off-label (n = 1) and had baseline CE-CT scans. Disease burden (total tumor volume, number of disease sites), radiomic measures of intertumor heterogeneity (cluster-site entropy, cluster-site dissimilarity), and intratumor heterogeneity of the largest lesion (Haralick texture features) were computed. Associations of clinical, conventional imaging, and radiomic measures with durable clinical benefit and time to off-treatment were examined. RESULTS In univariable analysis, fewer disease sites, lower intertumor heterogeneity (lower cluster-site entropy, lower cluster-site dissimilarity), and lower intratumor heterogeneity of the largest lesion (higher energy) were significantly associated with durable clinical benefit ( P ≤ .031). More disease sites, presence of pleural disease and/or distant metastases, higher intertumor heterogeneity (higher cluster-site entropy, higher cluster-site dissimilarity), and higher intratumor heterogeneity of the largest lesion (higher Contrastlargest-lesion) were significantly associated with shorter time to off-treatment ( P ≤ .034). In multivariable analysis, higher Energylargest-lesion (indicator of lower intratumor heterogeneity; P = .006; odds ratio, 1.41) and fewer disease sites ( P = .003; odds ratio, 1.64) remained significant indicators of durable clinical benefit (multivariable model C-index, 0.821). Higher cluster-site dissimilarity (indicator of higher intertumor heterogeneity) was a modest but single independent indicator of shorter time to off-treatment ( P = .004; hazard ratio, 1.19; C-index, 0.6). CONCLUSION Fewer disease sites and lower intra- and intertumor heterogeneity modeled from the baseline CE-CT may indicate better response of OC to immunotherapy.

The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation.Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series.Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra.A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer.

INTRODUCTION AND OBJECTIVE:Prostate cancers with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) and high tumor mutational burden (TMB-H) are rare but recognized as molecular...

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: Twenty-eight phase II-III randomized trials (16,511 patients) were included. Correlation between OS and IBIE was good (R2=0.57, 95%CI 0.35–0.78). Trials using rPFS showed substantially higher correlation than those using a composite IBIE (R2=0.58, 95%CI 0.32–0.82 vs 0.00, 95%CI -0.01–0.01). Correlations between OS and IBIE in other subgroups were at least moderate in nearly all subgroups (R2=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.

Acknowledging the increasing number of studies describing the use of whole-body MRI for cancer screening, and the increasing number of examinations being performed in patients with known cancers, an international multidisciplinary expert panel of radiologists and a geneticist with subject-specific expertise formulated technical acquisition standards, interpretation criteria, and limitations of whole-body MRI for cancer screening in individuals at higher risk, including those with cancer predisposition syndromes. The Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) proposes a standard protocol for individuals at higher risk, including those with cancer predisposition syndromes. ONCO-RADS emphasizes structured reporting and five assessment categories for the classification of whole-body MRI findings. The ONCO-RADS guidelines are designed to promote standardization and limit variations in the acquisition, interpretation, and reporting of whole-body MRI scans for cancer screening. Published under a CC BY 4.0 license Online supplemental material is available for this article.

Mucinous adenocarcinoma of the urachal remnant is a nonurothelial malignancy that may be asymptomatic until locally advanced or metastatic. We describe a 37-year-old woman with invasive ductal breast carcinoma who underwent 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) computed tomography (CT) demonstrating a non-FDG avid pelvic mass, initially suspected to represent a pedunculated uterine fibroid. Magnetic resonance imaging revealed a mixed solid-cystic mass separate from the uterus, suspicious for urachal neoplasm, confirmed as mucinous adenocarcinoma on histopathology. Urachal tumors may not be FDG-avid and represent a potential pitfall on FDG PET/CT.

OBJECTIVE: The purpose of this article is to perform a systematic review and meta-analysis regarding the diagnostic test accuracy of MRI for detecting extramural venous invasion (EMVI) in patients with colorectal cancer. MATERIALS AND METHODS: PubMed and EMBASE were searched up to November 9, 2018. We included diagnostic accuracy studies that used MRI for EMVI detection in patients with colorectal cancer, using pathologic analysis as the reference standard. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies–2 tool. Sensitivity and specificity were pooled and plotted in a hierarchic summary ROC plot. Metaregression analysis using several clinically relevant covariates was performed. RESULTS: Fourteen studies (n = 1751 patients) were included. Study quality was moderate in general. Pooled sensitivity was 0.61 (95% CI, 0.49–0.71), and pooled specificity was 0.87 (95% CI, 0.79–0.92). There was substantial heterogeneity according to the Cochran Q test (p < 0.01) and Higgins I(2) heterogeneity index (98% and 95% for sensitivity and specificity, respectively). Publication bias was present (p = 0.01). Higher rates of advanced T category, use of high-resolution MRI, and use of antispasmodic drugs were shown to significantly affect heterogeneity (p < 0.01). Location of primary tumor, preoperative treatment status, study design, definition of reference standard, magnetic field strength, and use of functional MRI were not statistically significant (p = 0.17–0.92). CONCLUSION: MRI shows moderate sensitivity and good specificity for the detection of EMVI in colorectal cancer. The use of high-resolution MRI may improve diagnostic performance.

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include 68Ga-prostate-specific membrane antigen HBED-CC ( 68Ga-PSMA), 18F-DCFPyL, 18F-fluorome-thylcholine ( 18F-FCH), and 18F-dihydrotestosterone ( 18F-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 68Ga-PSMA scans, 50 18F-DCFPyL scans, 68 18F-FCH scans, and 27 18F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUV max, SUV mean, SUV peak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For 68Ga-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%–35.2%; P 5 0.001–0.024). For 18F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P 5 0.001–0.003). The least variable 18F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%–24.2%; P 5 0.001–0.012). For 18F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%–23.6%; P 5 0.001–0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for 68Ga-PSMA and 18F-DCFPyL and the liver for 18F-FCH and 18F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.

The management of advanced prostate cancer has changed substantially with the availability of multiple effective novel treatments, which has led to improved disease survival. In the era of personalized cancer treatments, more precise imaging may help physicians deliver better care. More accurate local staging and earlier detection of metastatic disease, accurate identification of oligometastatic disease, and optimal assessment of treatment response are areas where modern imaging is rapidly evolving and expanding. Next-generation imaging modalities, including whole-body MRI and molecular imaging with combined PET and CT and combined PET and MRI using novel radiopharmaceuticals, create new opportunities for imaging to support and refine management pathways in patients with advanced prostate cancer. This article demonstrates the potential and challenges of applying next-generation imaging to deliver the clinical promise of treatment breakthroughs.

Pelvic pain is common in both reproductive age and postmenopausal women, and the major etiologies change throughout the life cycle. Chronic pain is defined as lasting for at least 6 months. There are many gastrointestinal and urinary disorders associated with chronic pain in this age group, which are not discussed in this guideline. Pain may be localized to the deep pelvis, with potential causes including pelvic congestion syndrome, intraperitoneal adhesions, hydrosalpinx, chronic inflammatory disease, or cervical stenosis. Ultrasound is the initial imaging modality of choice, while CT and MRI may be appropriate for further characterization of sonographic findings. Alternatively, pain may be localized to the vagina, vulva, or perineum, with potential causes including vaginal atrophy, vaginismus, vaginal or vulvar cysts, vulvodynia, or pelvic myofascial pain. Imaging is primarily indicated in context of an abnormal physical exam and ultrasound is the initial modality of choice, while MRI may be appropriate for further characterization in select cases. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

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 p p p 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.

Backgound Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a subtype of RCC that is increasingly recognized pathologically. The aim of this study was to evaluate the imaging features of FH-RCC on computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG PET), and to determine the pre-operative diagnostic potential of imaging. Methods This single-site retrospective study included patients with histologically confirmed FH-RCC or with a renal cancer and known germline FH mutation; imaging of the renal mass before treatment with contrast-enhanced CT, contrast-enhanced MRI, or FDG PET/CT between October 2007 and May 2019. Clinical information, pathological data, and imaging features were analyzed and reported descriptively. Results Sixteen patients with sixteen tumors were included (median age 46 years, interquartile range 38–53 years; 31 % female). Almost all tumors were unifocal (15/16, 94 %). Most tumors had infiltrative margins (14/16, 88 %); few were circumscribed (2/16, 12 %). A large cystic tumor component (> 75 % of tumor volume) was seen in 8/16 (50 %) of tumors. Involvement of renal sinus fat was seen in 13/16 (81 %) of tumors, involvement of the hilar collecting system in 8/16 (50 %), and renal vein tumor thrombus in 6/16 (38 %). All 12 tumors (100 %) imaged with MRI had heterogenous tumor enhancement and heterogenous T2 signal. Of those patients that had diffusion-weighted imaging, 11/11 (100 %) of tumors had diffusion restriction in the solid portions of the tumor. Of the patients who had PET, 3/3 (100 %) tumors showed high metabolic activity with mean maximum standardized uptake value (SUVmax) of 16.4 (range 9.6–21.9). Patients presented with retroperitoneal nodal metastases in 69 % of cases and distant metastases in 75 %. Of those four patients without metastatic disease at presentation, three (75 %) developed metastases within 4 years of diagnosis. Conclusions In our study, the majority of tumors (≥ 75 %) were unifocal, had an infiltrative margin, invaded the renal sinus fat, and presented with distant metastases. On MRI, most tumors had heterogenous T2 signal and diffusion restriction in their solid components. The small number of cases that had PET imaging showed high metabolic activity.

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&rsquo, s Kappa [&kappa, ] 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 evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean &kappa, estimate was 0.83 (95%CI: 0.78&ndash, 0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p &lt, 0.001, I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader&rsquo, s experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007, p= 0.003 and 0.036, SE: 0.009, p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.

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 due to 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.

New biomarkers for metastatic prostate cancer are needed. The aim of this study was to evaluate the prognostic value of (18)F-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 (18)F-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 (18)F-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, (18)F-FDG PET WB TLG is independently associated with OS and might be used as a quantitative prognostic imaging biomarker.

Purpose Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown promise for detecting nodal and distant prostate cancer (PCa) metastases. However, its performance for local tumor staging is not as well established. The purpose of this study was to review the diagnostic performance of PSMA-PET for determining seminal vesical invasion (SVI) and extraprostatic extension (EPE). Methods Pubmed and Embase databases were searched until January 12, 2020. Studies assessing accuracy of PSMA-PET in determining SVI and EPE were included. Study quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity were calculated using hierarchical summary receiver operating characteristics modeling. Heterogeneity was explored using meta-regression analyses for anatomical imaging component (MRI vs CT) and by testing for a threshold effect. Results Twelve studies (615 patients) were included. Pooled sensitivity and specificity were 0.68 (95% CI 0.53-0.81) and 0.94 (95% CI 0.90-0.96) for SVI and 0.72 (95% CI 0.56-0.84) and 0.87 (95% CI 0.72-0.94) for EPE. Meta-regression analyses showed that for SVI, PET/MRI demonstrated greater sensitivity than PET/CT (0.87 [95% CI 0.75-0.98] vs 0.60 [95% CI 0.47-0.74]; p = 0.02 for joint model) while specificity was comparable (0.91 [95% CI 0.84-0.97] vs. 0.96 [95% CI 0.93-0.99]) but not for EPE (p = 0.08). A threshold effect was present for studies assessing EPE (correlation coefficient = 0.563 [95% CI, −0.234-0.908] between sensitivity and false-positive rate). Conclusion PSMA-PET has moderate sensitivity and excellent specificity for assessing local tumor extent in patients with PCa. PET/MRI showed potential for greater sensitivity than PET/CT in assessing SVI.

Our objective was to evaluate the impact of (18)F-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 (18)F-FDG PET/CT, rate of detection of the primary malignancy and metastases on (18)F-FDG PET/CT, Mayo stage after (18)F-FDG PET/CT, and change in patient management were determined. Results: Of 21 patients with UrC-ADC before (18)F-FDG PET/CT, Mayo staging was I/II in 8, III in 3, and IV in 10. (18)F-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: (18)F-FDG PET/CT has clinical utility in patients with UrC-ADC by identifying metastatic disease not appreciated on anatomic imaging, leading to changes in staging and patient management.

Visual Abstract, 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.

Objectives To investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC). Methods This retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values Results Four proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p p = 0.047, τ = 0.326). Conclusion This study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins. Key Points • CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC. • CT imaging traits correlate with protein abundance in patients with HGSOC.

To review the diagnostic performance of contemporary imaging modalities for determining local disease extent and nodal metastasis in patients with newly diagnosed cervical cancer. Pubmed and Embase databases were searched for studies published from 2000 to 2019 that used ultrasound (US), CT, MRI, and/or PET for evaluating various aspects of local extent and nodal metastasis in patients with newly diagnosed cervical cancer. Sensitivities and specificities from the studies were meta-analytically pooled using bivariate and hierarchical modeling. Of 1311 studies identified in the search, 115 studies with 13,999 patients were included. MRI was the most extensively studied modality (MRI, CT, US, and PET were evaluated in 78, 12, 9, and 43 studies, respectively). Pooled sensitivities and specificities of MRI for assessing all aspects of local extent ranged between 0.71–0.88 and 0.86–0.95, respectively. In assessing parametrial invasion (PMI), US demonstrated pooled sensitivity and specificity of 0.67 and 0.94, respectively—performance levels comparable with those found for MRI. MRI, CT, and PET performed comparably for assessing nodal metastasis, with low sensitivity (0.29–0.69) but high specificity (0.88–0.98), even when stratified to anatomical location (pelvic or paraaortic) and level of analysis (per patient vs. per site). MRI is the method of choice for assessing any aspect of local extent, but where not available, US could be of value, particularly for assessing PMI. CT, MRI, and PET all have high specificity but poor sensitivity for the detection of lymph node metastases. • Magnetic resonance imaging is the method of choice for assessing local extent. • Ultrasound may be helpful in determining parametrial invasion, especially in lower-resourced countries. • Computed tomography, magnetic resonance imaging, and positron emission tomography perform similarly for assessing lymph node metastasis, with high specificity but low sensitivity.

Accurate staging of bladder cancer (BC) is critical, with local tumor staging directly influencing management decisions and affecting prognosis. However, clinical staging based on clinical examination, including cystoscopy and transurethral resection of bladder tumor (TURBT), often understages patients compared to final pathology at radical cystectomy and lymph node (LN) dissection, mainly due to underestimation of the depth of local invasion and the presence of LN metastasis. MRI has now become established as the modality of choice for the local staging of BC and can be additionally utilized for the assessment of regional LN involvement and tumor spread to the pelvic bones and upper urinary tract (UUT). The recent development of the Vesical Imaging-Reporting and Data System (VI-RADS) recommendations has led to further improvements in bladder MRI, enabling standardization of image acquisition and reporting. Multiparametric magnetic resonance imaging (mpMRI) incorporating morphological and functional imaging has been proven to further improve the accuracy of primary and recurrent tumor detection and local staging, and has shown promise in predicting tumor aggressiveness and monitoring response to therapy. These sequences can also be utilized to perform radiomics, which has shown encouraging initial results in predicting BC grade and local stage. In this article, the current state of evidence supporting MRI in local, regional, and distant staging in patients with BC is reviewed. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:649-667.

PURPOSE: To study the risk of metastatic prostate cancer development in men with Grade Group 2 disease being managed with active surveillance (AS) at Memorial Sloan Kettering Cancer Center. MATERIALS AND METHODS: 219 men with Grade Group 2 prostate cancer were managed with AS between 2000–2017. Biopsy was performed every 2–3 years or upon changes in magnetic resonance imaging, prostate-specific antigen (PSA) level, or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. RESULTS: The median age at diagnosis was 67 years (IQR 61, 72), the median PSA was 5 ng/mL (IQR 4, 7), and most patients (69%) had non-palpable disease. During follow-up, 64 men received treatment: 36/64 (56%) radical prostatectomy; 20/64 (31%) radiotherapy; 3/64 (5%) hormone therapy; and 5/64 (8%) focal therapy. Of the 36 patients who underwent radical prostatectomy, 32/36 (89%) had Grade Group 2 disease on pathology and 4/36 (11%) had Grade Group 3. Treatment-free survival was 61% (95% CI 52%–70%) at 5 years and 49% (95% CI 37%–60%) at 10 years. Three men experienced biochemical recurrence, no men developed distant metastasis, and no men died of prostate cancer during the follow-up. The median follow-up was 3.1 years (IQR 1.9, 4.9). CONCLUSIONS: AS appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer managed at a tertiary cancer center. Definitive conclusions await further follow-up.

The question referred to in the title of this article is a relatively common situation when performing prostate MRI in some healthcare settings. Moreover, the answer is not always straightforward. The decisions on type of receiver coil for prostate MRI and whether or not an endorectal coil (ERC) should be used is based on several factors. These relate to the patient (e.g., body habitus, presence of metallic devices in the pelvis), the focus of the exam (diagnosis, staging, recurrence), and characteristics of the MRI system (e.g., magnetic field strength and hardware components including coil design and number of elements/channels available in the surface coil). Historically, the combined use of an ERC and a surface coil was the optimal combination for maximizing the signal-to-noise ratio (SNR), particularly for low-strength magnetic fields (1.5T). However, there are several disadvantages associated with the use of an ERC, and several studies have advocated equivalent clinical performance of modern MRI systems for diagnosis and staging of prostate cancer (PCa), either with ERC or surface alone. Accordingly, there is a wide variation in the precise imaging technique across institutions. This article focuses on the most relevant aspects of the decision of whether to use an ERC for PCa MR imaging.

Objective To report a case of pelvic angiosarcoma in a 27-year-old man with Li-Fraumeni Syndrome (LFS) and evaluate the presentation and timeline of genitourinary (GU) tract involvement in LFS patients. Methods We retrospectively identified 39 LFS patients treated at our institution between 2000 and 2014; 7 (18%) had experienced a GU malignancy or an LFS-related malignancy involving the GU tract. Clinical characteristics, including dates of onset of first GU tract malignancies; pathologic findings; multimodal management; and familial history of LFS were reviewed. Results Median age at first malignancy was 14.0 years (interquartile range [IQR] 5.5-24.0). There was a slight male predominance (4 of 7). Median time between first malignancy and the malignancy involving the GU tract was 10.1 years (IQR 8.0-19.5). Six of the 7 patients (86%) had a form of sarcoma involving the GU tract; 1 developed adrenocortical carcinoma. The cancer pedigree of all patients showed LFS-associated malignancies in family members. Multimodal management included surgical resection in 6 patients with adjuvant chemotherapy or radiotherapy in 1 patient each. One patient received chemotherapy only. Following diagnosis of malignancy involving the GU tract, 5 of the 7 patients developed additional primary malignancies. At a median follow-up of 4.7 years (IQR 3.0-12.1), 2 patients are alive, 3 died of disease, and 1 died of unknown cause. One patient was lost at follow-up. Conclusion Continued follow-up of LFS cancer patients aimed at the determination of optimal screening, management, and surveillance protocols is recommended and may result in longer survival expectations.