Inguinal lymph node metastases from prostate cancer: clinical, pathology, and multimodality imaging considerations.

Objective: To investigate clinical, pathology, and imaging findings associated with inguinal lymph node (LN) metastases in patients with prostate cancer (PCa). Materials and Methods: This was a retrospective single-center study of patients with PCa who underwent imaging and inguinal LN biopsy between 2000 and 2023. We assessed the following aspects on multimodality imaging: inguinal LN morphology; extrainguinal lymphadenopathy; the extent of primary and recurrent tumors; and non-nodal metastases. Imaging, clinical, and pathology features were compared between patients with and without metastatic inguinal LNs. Results: We evaluated 79 patients, of whom 38 (48.1%) had pathology-proven inguinal LN metastasis. Certain imaging aspects- short-axis diameter, prostate-specific membrane antigen uptake on positron-emission tomography, membranous urethra involvement by the tumor, extra-inguinal lymphadenopathy, and distant metastases-were associated with pathology-proven inguinal LN metastases (p < 0.01 for all). Associations with long-axis diameter, fatty hilum, laterality, and uptake of other tracers on positronemission tomography were not significant (p = 0.09-1.00). The patients with metastatic inguinal LNs had higher prostate-specific antigen levels and more commonly had castration-resistant PCa (p < 0.01), whereas age, histological grade, and treatment type were not significant factors (p = 0.07-0.37). None of the patients had inguinal LN metastasis in the absence of locally advanced disease with membranous urethra involvement or distant metastasis. Conclusion: Several imaging, clinical, and pathology features are associated with inguinal LN metastases in patients with PCa. Isolated metastasis to inguinal LNs is extremely rare and unlikely to occur in the absence of high-risk imaging, clinical, or pathology features.

Objetivo: Investigar achados clinicopatológicos e de imagem associados a metástases linfonodais inguinais em pacientes com câncer de próstata (CaP). Materiais e Métodos: Estudo retrospectivo de uma única instituição de pacientes com CaP submetidos a exames de imagem e biópsia inguinal de linfonodos em 2000­2023. A imagem multimodalidade foi avaliada para morfologia inguinal do linfonodo, linfadenopatia fora da região inguinal, extensão do CaP primário/recorrente e sítios metastáticos não nodais. Características de imagem e clinicopatológicas foram comparadas entre pacientes com e sem linfonodos inguinais metastáticos pela patologia. Resultados: Entre 79 pacientes estudados, 38 (48,1%) apresentaram metástase inguinal de linfonodo comprovada patologicamente. Certos achados de imagem ­ diâmetro do eixo curto, captação do antígeno de membrana prostático específico na tomografia por emissão de pósitrons, envolvimento da uretra membranosa pelo tumor, linfadenopatia fora da região inguinal e metástases a distância ­ foram associados com metástases inguinais no linfonodo pela patologia (p < 0,01). Diâmetro de eixo longo, hilo gorduroso, lateralidade, captação em outros traçadores de tomografia por emissão de pósitrons não foram significativos (p = 0,09­1,00). Clinicopatologicamente, os pacientes com linfonodos inguinais metastáticos apresentaram maior antígeno prostático específico e foram mais resistentes à castração (p < 0,01); idade, grau histológico e tipo de tratamento não foram estatisticamente significantes (p = 0,07­0,37). Nenhum paciente apresentou metástase inguinal isolada no linfonodo na ausência de doença localmente avançada com envolvimento da uretra membranosa ou metástase a distância. Conclusão: Várias características de imagem e clinicopatológicas foram associadas a metástases em LNs inguinais em pacientes com CaP. A metástase isolada para os LNs inguinais é extremamente rara e é improvável que ocorra na ausência de características de imagem e clinicopatológicas de alto risco.

Utility of ADC Values for Differentiating Uterine Sarcomas From Leiomyomas: Systematic Review and Meta-Analysis.

Background: Uterine sarcomas are rare; however, they display imaging features that overlap those of leiomyomas. The potential for undetected uterine sarcomas is clinically relevant because minimally invasive treatment of leiomyomas may lead to cancer dissemination. ADC values have shown potential for differentiating benign and malignant uterine masses. Objective: The purpose of this study was to perform a systematic review of the diagnostic performance of ADC values in differentiating uterine sarcomas from leiomyomas. Evidence acquisition: We searched three electronic databases (MEDLINE, EMBASE, and Cochrane databases) for studies distinguishing uterine sarcomas from leiomyomas using MRI, including ADC, with pathologic tissue confirmation or imaging follow-up as the reference standard. Data extraction and QUADAS-2 quality assessment were performed. Sensitivity and specificity were pooled using hierarchic models, including bivariate and hierarchic summary ROC models. Metaregression was used to assess the impact of various factors on heterogeneity. Evidence synthesis: Twenty-one studies met study inclusion criteria. Pooled sensitivity and specificity were 89% (95% CI, 82-94%) and 86% (95% CI, 78-92%), respectively. Area under the summary ROC curve was 94% (95% CI, 92-96%). Context of ADC interpretation (i.e., standalone vs part of multiparametric MRI [mpMRI]) was the only factor found to account significantly for heterogeneity (p = .01). Higher specificity (95% [95% CI, 92-99%] vs 82% [95% CI, 75-89%]) and similar sensitivity (94% [95% CI, 89-99%] vs 88% [95% CI, 82-93%]) were observed when ADC was evaluated among mpMRI features as compared with standalone ADC assessment. ADC cutoff values ranged (0.87-1.29 × 10-3 mm2/s) but were not associated with statistically different performance (p = .37). Pooled mean ADC values in sarcomas and leiomyomas were 0.904 × 10-3 mm2/s and 1.287 × 10-3 mm2/s, respectively. Conclusion: As part of mpMRI evaluation of uterine masses, mass ADC value less than 0.904 × 10-3 mm2/s may be a useful test-positive threshold for uterine sarcoma, consistent with a prior expert consensus statement. Institutional protocols may influence locally selected ADC values. Clinical Impact: Using ADC as part of mpMRI assessment improves detection of uterine sarcoma, which could influence candidate selection for minimally invasive treatments.

The Prevalence and Radiologic Features of Renal Cancers Associated with FLCN, BAP1, SDH, and MET Germline Mutations.

Purpose To investigate the prevalence of FLCN, BAP1, SDH, and MET mutations in an oncologic cohort and determine the prevalence, clinical features, and imaging features of renal cell carcinoma (RCC) associated with these mutations. Secondarily, to determine the prevalence of encountered benign renal lesions. Materials and Methods From 25 220 patients with cancer who prospectively underwent germline analysis with a panel of more than 70 cancer-predisposing genes from 2015 to 2021, patients with FLCN, BAP1, SDH, or MET mutations were retrospectively identified. Clinical records were reviewed for patient age, sex, race/ethnicity, and renal cancer diagnosis. If RCC was present, baseline CT and MRI examinations were independently assessed by two radiologists. Summary statistics were used to summarize continuous and categorical variables by mutation. Results A total of 79 of 25 220 (0.31%) patients had a germline mutation: FLCN, 17 of 25 220 (0.07%); BAP1, 22 of 25 220 (0.09%); SDH, 39 of 25 220 (0.15%); and MET, one of 25 220 (0.004%). Of these 79 patients, 18 (23%) were diagnosed with RCC (FLCN, four of 17 [24%]; BAP1, four of 22 [18%]; SDH, nine of 39 [23%]; MET, one of one [100%]). Most hereditary RCCs demonstrated ill-defined margins, central nonenhancing area (cystic or necrotic), heterogeneous enhancement, and various other CT and MR radiologic features, overlapping with the radiologic appearance of nonhereditary RCCs. The prevalence of other benign solid renal lesions (other than complex cysts) in patients was up to 11%. Conclusion FLCN, BAP1, SDH, and MET mutations were present in less than 1% of this oncologic cohort. Within the study sample size limits, imaging findings for hereditary RCC overlapped with those of nonhereditary RCC, and the prevalence of other associated benign solid renal lesions (other than complex cysts) was up to 11%. Keywords: Familial Renal Cell Carcinoma, Birt-Hogg-Dubé Syndrome, Carcinoma, Renal Cell, Paragangliomas, Urinary, Kidney © RSNA, 2024.

Clinical application of bladder MRI and the Vesical Imaging-Reporting and Data System.

Diagnostic work-up and risk stratification in patients with bladder cancer before and after treatment must be refined to optimize management and improve outcomes. MRI has been suggested as a non-invasive technique for bladder cancer staging and assessment of response to systemic therapy. The Vesical Imaging-Reporting And Data System (VI-RADS) was developed to standardize bladder MRI image acquisition, interpretation and reporting and enables accurate prediction of muscle-wall invasion of bladder cancer. MRI is available in many centres but is not yet recommended as a first-line test for bladder cancer owing to a lack of high-quality evidence. Consensus-based evidence on the use of MRI-VI-RADS for bladder cancer care is needed to serve as a benchmark for formulating guidelines and research agendas until further evidence from randomized trials becomes available.

Bridging Communication Gaps Between Radiologists, Referring Physicians, and Patients Through Standardized Structured Cancer Imaging Reporting: The Experience with Female Pelvic MRI Assessment Using O-RADS and a Simulated Cohort Patient Group.

RATIONALE AND OBJECTIVES: This study aimed to evaluate whether implementing structured reporting based on Ovarian-Adnexal Reporting and Data System (O-RADS) magnetic resonance imaging (MRI) in women with sonographically indeterminate adnexal masses improves communication between radiologists, referrers, and patients/caregivers and enhances diagnostic performance for determining adnexal malignancy. MATERIALS AND METHODS: We retrospectively analyzed prospectively issued MRI reports in 2019-2022 performed for characterizing adnexal masses before and after implementing O-RADS MRI; 56 patients/caregivers and nine gynecologic oncologists ("referrers") were surveyed about report interpretability/clarity/satisfaction; responses for pre- and post-implementation reports were compared using Fisher's exact and Chi-squared tests. Diagnostic performance was assessed using receiver operating characteristic curves. RESULTS: A total of 123 reports from before and 119 reports from after O-RADS MRI implementation were included. Survey response rates were 35.7% (20/56) for patients/caregivers and 66.7% (6/9) for referrers. For patients/caregivers, O-RADS MRI reports were clearer (p < 0.001) and more satisfactory (p < 0.001) than unstructured reports, but interpretability did not differ significantly (p = 0.14), as 28.0% (28/100) of postimplementation and 38.0% (38/100) of preimplementation reports were considered difficult to interpret. For referrers, O-RADS MRI reports were clearer, more satisfactory, and easier to interpret (p < 0.001); only 1.3% (1/77) were considered difficult to interpret. For differentiating benign from malignant adnexal lesions, O-RADS MRI showed area under the curve of 0.92 (95% confidence interval [CI], 0.85-0.99), sensitivity of 0.81 (95% CI, 0.58-0.95), and specificity of 0.91 (95% CI, 0.83-0.96). Diagnostic performance of reports before implementation could not be calculated due to many different phrases used to describe the likelihood of malignancy. CONCLUSION: Implementing standardized structured reporting using O-RADS MRI for characterizing adnexal masses improved clarity and satisfaction for patients/caregivers and referrers. Interpretability improved for referrers but remained limited for patients/caregivers.

Inguinal lymph node metastases from prostate cancer: clinical, pathology, and multimodality imaging considerations / Metástases de linfonodos inguinais de câncer de próstata: considerações clínicas, patológicas e de imagem multimodalidade

Abstract Objective: To investigate clinical, pathology, and imaging findings associated with inguinal lymph node (LN) metastases in patients with prostate cancer (PCa). Materials and Methods: This was a retrospective single-center study of patients with PCa who underwent imaging and inguinal LN biopsy between 2000 and 2023. We assessed the following aspects on multimodality imaging: inguinal LN morphology; extrainguinal lymphadenopathy; the extent of primary and recurrent tumors; and non-nodal metastases. Imaging, clinical, and pathology features were compared between patients with and without metastatic inguinal LNs. Results: We evaluated 79 patients, of whom 38 (48.1%) had pathology-proven inguinal LN metastasis. Certain imaging aspects— short-axis diameter, prostate-specific membrane antigen uptake on positron-emission tomography, membranous urethra involvement by the tumor, extra-inguinal lymphadenopathy, and distant metastases—were associated with pathology-proven inguinal LN metastases (p < 0.01 for all). Associations with long-axis diameter, fatty hilum, laterality, and uptake of other tracers on positronemission tomography were not significant (p = 0.09-1.00). The patients with metastatic inguinal LNs had higher prostate-specific antigen levels and more commonly had castration-resistant PCa (p < 0.01), whereas age, histological grade, and treatment type were not significant factors (p = 0.07-0.37). None of the patients had inguinal LN metastasis in the absence of locally advanced disease with membranous urethra involvement or distant metastasis. Conclusion: Several imaging, clinical, and pathology features are associated with inguinal LN metastases in patients with PCa. Isolated metastasis to inguinal LNs is extremely rare and unlikely to occur in the absence of high-risk imaging, clinical, or pathology features.

Resumo Objetivo: Investigar achados clinicopatológicos e de imagem associados a metástases linfonodais inguinais em pacientes com câncer de próstata (CaP). Materiais e Métodos: Estudo retrospectivo de uma única instituição de pacientes com CaP submetidos a exames de imagem e biópsia inguinal de linfonodos em 2000-2023. A imagem multimodalidade foi avaliada para morfologia inguinal do linfonodo, linfadenopatia fora da região inguinal, extensão do CaP primário/recorrente e sítios metastáticos não nodais. Características de imagem e clinicopatológicas foram comparadas entre pacientes com e sem linfonodos inguinais metastáticos pela patologia. Resultados: Entre 79 pacientes estudados, 38 (48,1%) apresentaram metástase inguinal de linfonodo comprovada patologicamente. Certos achados de imagem - diâmetro do eixo curto, captação do antígeno de membrana prostático específico na tomografia por emissão de pósitrons, envolvimento da uretra membranosa pelo tumor, linfadenopatia fora da região inguinal e metástases a distância - foram associados com metástases inguinais no linfonodo pela patologia (p < 0,01). Diâmetro de eixo longo, hilo gorduroso, lateralidade, captação em outros traçadores de tomografia por emissão de pósitrons não foram significativos (p = 0,09-1,00). Clinicopatologicamente, os pacientes com linfonodos inguinais metastáticos apresentaram maior antígeno prostático específico e foram mais resistentes à castração (p < 0,01); idade, grau histológico e tipo de tratamento não foram estatisticamente significantes (p = 0,07-0,37). Nenhum paciente apresentou metástase inguinal isolada no linfonodo na ausência de doença localmente avançada com envolvimento da uretra membranosa ou metástase a distância. Conclusão: Várias características de imagem e clinicopatológicas foram associadas a metástases em LNs inguinais em pacientes com CaP. A metástase isolada para os LNs inguinais é extremamente rara e é improvável que ocorra na ausência de características de imagem e clinicopatológicas de alto risco.

Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI.

BACKGROUND: Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role. METHODS: Consecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000-November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS). RESULTS: 61 patients (36 men and 25 women; median age 65 years, interquartile range 59-72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62-0.85) vs. 0.58 (95% CI, 0.45-0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1-79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4-93.6) vs. 38.9% (95% CI, 17.3-64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70-9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66-17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02-37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39-8.71; p = 0.014). CONCLUSION: BP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens.

Improving risk stratification of indeterminate adnexal masses on MRI: What imaging features help predict malignancy in O-RADS MRI 4 lesions?

PURPOSE: Ovarian-Adnexal Reporting and Data System (O-RADS) MRI uses a 5-point scale to establish malignancy risk in sonographically-indeterminate adnexal masses. The management of O-RADS MRI score 4 lesions is challenging, as the prevalence of malignancy is widely variable (5-90%). We assessed imaging features that may sub-stratify O-RADS MRI 4 lesions into malignant and benign subgroups. METHOD: Retrospective single-institution study of women with O-RADS MRI score of 4 adnexal masses between April 2021-August 2022. Imaging findings were assessed independently by 2 radiologists according to the O-RADS lexicon white paper. MRI and clinical findingswere compared between malignant and benign adnexal masses, and inter-reader agreement was calculated. RESULTS: Seventy-four women (median age 52 years, IQR 36-61) were included. On pathology, 41 (55.4%) adnexal masses were malignant. Patients with malignant masses were younger (p = 0.02) with higher CA-125 levels (p = 0.03). Size of solid tissue was greater in malignant masses (p = 0.01-0.04). Papillary projections and larger solid portion were more common in malignant lesions; irregular septations and predominantly solid composition were more frequent in benign lesions (p < 0.01). Solid tissue of malignant lesions was more often hyperintense on T2-weighted and diffusion-weighted imaging (p ≤ 0.03). Other imaging findings were not significantly different (p = 0.09-0.77). Inter-reader agreement was excellent-good for most features (ICC = 0. 662-0.950; k = 0. 650-0.860). CONCLUSION: Various MRI and clinical features differed between malignant and benign O-RADS MRI score 4 adnexal masses. O-RADS MRI 4 lesions may be sub-stratified (high vs low risk) based on solid tissue characteristics and CA-125 levels.

Sarcomatoid renal cell carcinoma: MRI features and their association with survival.

OBJECTIVE: To evaluate MRI features of sarcomatoid renal cell carcinoma (RCC) and their association with survival. METHODS: This retrospective single-center study included 59 patients with sarcomatoid RCC who underwent MRI before nephrectomy during July 2003-December 2019. Three radiologists reviewed MRI findings of tumor size, non-enhancing areas, lymphadenopathy, and volume (and percentage) of T2 low signal intensity areas (T2LIA). Clinicopathological factors of age, gender, ethnicity, baseline metastatic status, pathological details (subtype and extent of sarcomatoid differentiation), treatment type, and follow-up were extracted. Survival was estimated using Kaplan-Meier method and Cox proportional-hazards regression model was used to identify factors associated with survival. RESULTS: Forty-one males and eighteen females (median age 62 years; interquartile range 51-68) were included. T2LIAs were present in 43 (72.9%) patients. At univariate analysis, clinicopathological factors associated with shorter survival were: greater tumor size (> 10 cm; HR [hazard ratio] = 2.44, 95% CI 1.15-5.21; p = 0.02), metastatic lymph nodes (present; HR = 2.10, 95% CI 1.01-4.37; p = 0.04), extent of sarcomatoid differentiation (non-focal; HR = 3.30, 95% CI 1.55-7.01; p < 0.01), subtypes other than clear cell, papillary, or chromophobe (HR = 3.25, 95% CI 1.28-8.20; p = 0.01), and metastasis at baseline (HR = 5.04, 95% CI 2.40-10.59; p < 0.01). MRI features associated with shorter survival were: lymphadenopathy (HR = 2.24, 95% CI 1.16-4.71; p = 0.01) and volume of T2LIA (> 3.2 mL, HR = 4.22, 95% CI 1.92-9.29); p < 0.01). At multivariate analysis, metastatic disease (HR = 6.89, 95% CI 2.79-16.97; p < 0.01), other subtypes (HR = 9.50, 95% CI 2.81-32.13; p < 0.01), and greater volume of T2LIA (HR = 2.51, 95% CI 1.04-6.05; p = 0.04) remained independently associated with worse survival. CONCLUSION: T2LIAs were present in approximately two thirds of sarcomatoid RCCs. Volume of T2LIA along with clinicopathological factors were associated with survival.

Fat-containing adnexal masses on MRI: solid tissue volume and fat distribution as a guide for O-RADS Score assignment.

PURPOSE: To explore ways to improve O-RADS MRI scoring for fat-containing adnexal masses, by investigating methods for quantifying solid tissue volume and fat distribution and evaluating their associations with malignancy. METHODS: This retrospective, single-center study included patients with fat-containing adnexal masses on MRI during 2008-2021. Two radiologists independently reviewed overall size (Sizeoverall), size of any solid tissue (Sizeanysolid), size of solid tissue that was not Rokitansky nodule (Sizenon-Rokitansky), and fat distribution. Wilcoxon test, Fisher-exact test, and ROC curve analysis were performed. Reference standard was pathology or follow-up > 24 months. RESULTS: 188 women (median age 35 years) with 163 benign and 25 malignant lesions were included. Sizeoverall (R1, 9.9 cm vs 5.9 cm; R2, 12.4 cm vs 6.0 cm), Sizeanysolid (R1, 5.1 cm vs 1.2 cm; R2, 3.2 cm vs 0.0 cm), Sizenon-Rokitansky (R1, 5.1 cm vs 0.0 cm; R2, 3.1 cm vs 0.0 cm), and fat distribution differed significantly between malignant and benign lesions (p < 0.01). Area under ROC curve was greatest using Sizenon-Rokitansky (R1, 0.83; R2, 0.86) vs Sizeoverall (R1, 0.78; R2, 0.81) or Sizeanysolid (R1, 0.79; R2, 0.81), though differences were non-significant (p = 0.48-0.93). Cutoffs for Sizenon-Rokitansky (R1, ≥ 1.2 cm; R2, ≥ 1.0 cm) yielded sensitivity and specificity of 0.72 and 0.93 (R1) and 0.76 and 0.95 (R2). Among immature teratomas, 85.7% displayed scattered fat. CONCLUSION: Overall size, size of (any or non-Rokitansky-nodule) solid tissue, and fat distribution differed between benign and malignant fat-containing adnexal masses. Incorporating these would constitute simple and practical approaches to refining O-RADS MRI scoring.

Oncologically Relevant Findings Reporting and Data System (ONCO-RADS): Guidelines for the Acquisition, Interpretation, and Reporting of Whole-Body MRI for Cancer Screening.

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.

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

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.

Clinical Utility of 18F-FDG PET/CT for Staging and Treatment Planning in Urachal Adenocarcinoma.

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.

γ-Tocotrienol-Loaded Liposomes for Radioprotection from Hematopoietic Side Effects Caused by Radiotherapeutic Drugs.

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.

Accelerating Prostate Diffusion-weighted MRI Using a Guided Denoising Convolutional Neural Network: Retrospective Feasibility Study.

PURPOSE: To investigate the feasibility of accelerating prostate diffusion-weighted imaging (DWI) by reducing the number of acquired averages and denoising the resulting image using a proposed guided denoising convolutional neural network (DnCNN). MATERIALS AND METHODS: Raw data from the prostate DWI scans were retrospectively gathered between July 2018 and July 2019 from six single-vendor MRI scanners. There were 103 datasets used for training (median age, 64 years; interquartile range [IQR], 11), 15 for validation (median age, 68 years; IQR, 12), and 37 for testing (median age, 64 years; IQR, 12). High b-value diffusion-weighted (hb DW) data were reconstructed into noisy images using two averages and reference images using all 16 averages. A conventional DnCNN was modified into a guided DnCNN, which uses the low b-value DW image as a guidance input. Quantitative and qualitative reader evaluations were performed on the denoised hb DW images. A cumulative link mixed regression model was used to compare the readers' scores. The agreement between the apparent diffusion coefficient (ADC) maps (denoised vs reference) was analyzed using Bland-Altman analysis. RESULTS: Compared with the original DnCNN, the guided DnCNN produced denoised hb DW images with higher peak signal-to-noise ratio (32.79 ± 3.64 [standard deviation] vs 33.74 ± 3.64), higher structural similarity index (0.92 ± 0.05 vs 0.93 ± 0.04), and lower normalized mean square error (3.9% ± 10 vs 1.6% ± 1.5) (P < .001 for all). Compared with the reference images, the denoised images received higher image quality scores from the readers (P < .0001). The ADC values based on the denoised hb DW images were in good agreement with the reference ADC values (mean ADC difference ranged from -0.04 to 0.02 × 10-3 mm2/sec). CONCLUSION: Accelerating prostate DWI by reducing the number of acquired averages and denoising the resulting image using the proposed guided DnCNN is technically feasible. Supplemental material is available for this article. © RSNA, 2020.

Overview of VI-RADS in Bladder Cancer.

OBJECTIVE. The purpose of this article is to review the natural history and management of bladder cancer, with insight into MRI applications for the assessment of muscle invasiveness of bladder cancer using the newly developed Vesical Imaging Reporting and Data System (VI-RADS) score. CONCLUSION. Multiparametric MRI and the VI-RADS score have been consistently validated across several different institutions as appropriate tools for local staging of bladder cancer and have been proven to contribute to the diagnostic workup and management of urinary bladder cancer.

MRI of Bladder Cancer: Local and Nodal Staging.

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.

Extensive disease among potential candidates for hemi-ablative focal therapy for prostate cancer.

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 <15 ng/mL, clinical stage T1c-T2a and Gleason score 3 + 3 or 3 + 4 on needle biopsy), and underwent radical prostatectomy between 2000 and 2014. Extensive disease was defined as having Gleason pattern 4/5 in bilateral lobes, any extraprostatic extension, seminal vesicle invasion or lymph node invasion. Both lobes of the prostate were scored on magnetic resonance imaging. Preoperative characteristics including biopsy and magnetic resonance imaging data were used to predict extensive disease. RESULTS: Among our cohort of 98 patients, 40% (95% CI 30-50%) had extensive disease. A total of 33% (95% CI 24-43%) had Gleason pattern 4/5 in both lobes with a median Gleason pattern 4/5 tumor volume in the biopsy negative lobe of 0.06 cm3 , 17 patients had pathological tumor stage ≥3 and one patient had lymph node invasion. CONCLUSIONS: An important number of patients meeting the focal therapy consensus meeting inclusion criteria can present extensive disease. Further studies using targeted biopsies might provide more accurate information about the selection of focal therapy candidates.