Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls.

Bladder cancer (BC), predominantly comprising urothelial carcinomas (UCs), ranks as the tenth most common cancer worldwide. UCs with variant histology (variant UC), including squamous differentiation, glandular differentiation, plasmacytoid variant, micropapillary variant, sarcomatoid variant, and nested variant, accounting for 5-10% of cases, exhibit more aggressive and advanced tumor characteristics compared to pure UC. The Vesical Imaging-Reporting and Data System (VI-RADS), established in 2018, provides guidelines for the preoperative evaluation of muscle-invasive bladder cancer (MIBC) using multiparametric magnetic resonance imaging (mpMRI). This technique integrates T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE)-MRI, and diffusion-weighted imaging (DWI) to distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). VI-RADS has demonstrated high diagnostic performance in differentiating these two categories for pure UC. However, its accuracy in detecting muscle invasion in variant UCs is currently under investigation. These variant UCs are associated with a higher likelihood of disease recurrence and require precise preoperative assessment and immediate surgical intervention. This review highlights the potential value of mpMRI for different variant UCs and explores the clinical implications and prospects of VI-RADS in managing these patients, emphasizing the need for careful interpretation of mpMRI examinations including DCE-MRI, particularly given the heterogeneity and aggressive nature of variant UCs. Additionally, the review addresses the fundamental MRI reading procedures, discusses potential causes of diagnostic errors, and considers future directions in the use of artificial intelligence and radiomics to further optimize the bladder MRI protocol.

Imaging at the nexus: how state of the art imaging techniques can enhance our understanding of cancer and fibrosis.

Both cancer and fibrosis are diseases involving dysregulation of cell signaling pathways resulting in an altered cellular microenvironment which ultimately leads to progression of the condition. The two disease entities share common molecular pathophysiology and recent research has illuminated the how each promotes the other. Multiple imaging techniques have been developed to aid in the early and accurate diagnosis of each disease, and given the commonalities between the pathophysiology of the conditions, advances in imaging one disease have opened new avenues to study the other. Here, we detail the most up-to-date advances in imaging techniques for each disease and how they have crossed over to improve detection and monitoring of the other. We explore techniques in positron emission tomography (PET), magnetic resonance imaging (MRI), second generation harmonic Imaging (SGHI), ultrasound (US), radiomics, and artificial intelligence (AI). A new diagnostic imaging tool in PET/computed tomography (CT) is the use of radiolabeled fibroblast activation protein inhibitor (FAPI). SGHI uses high-frequency sound waves to penetrate deeper into the tissue, providing a more detailed view of the tumor microenvironment. Artificial intelligence with the aid of advanced deep learning (DL) algorithms has been highly effective in training computer systems to diagnose and classify neoplastic lesions in multiple organs. Ultimately, advancing imaging techniques in cancer and fibrosis can lead to significantly more timely and accurate diagnoses of both diseases resulting in better patient outcomes.

Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

Body oncologic imaging subspecialty training a curriculum based on the experience in a tertiary cancer center.

PURPOSE: To describe the structure of a dedicated body oncologic imaging fellowship program. To summarize the numbers and types of cross-sectional imaging examinations reported by fellows. METHODS: The curriculum, training methods, and assessment measures utilized in the program were reviewed and described. An educational retrospective analysis was conducted. Data on the number of examinations interpreted by fellows, breakdown of modalities, and examinations by disease management team (DMT) were collected. RESULTS: A total of 38 fellows completed the fellowship program during the study period. The median number of examinations reported per fellow was 2296 [interquartile range: 2148 - 2534], encompassing all oncology-relevant imaging modalities: CT 721 [646-786], MRI 1158 [1016-1309], ultrasound 256 [209-320] and PET/CT 176 [130-202]. The breakdown of examinations by DMT revealed variations in imaging patterns, with MRIs most frequently interpreted for genitourinary, musculoskeletal, and hepatobiliary cancers, and CTs most commonly for general staging or assessment of nonspecific symptoms. CONCLUSION: This descriptive analysis may serve as a foundation for the development of similar fellowship programs and the advancement of body oncologic imaging. The volume and diversity of examinations reported by fellows highlights the comprehensive nature of body oncologic imaging.

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.

Advances in CAR T Cell Therapy for Non-Small Cell Lung Cancer.

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

Improving Radiology Oncologic Imaging Trainee Case Diversity through Automatic Examination Assignment: Retrospective Study from a Tertiary Cancer Center.

In a retrospective single-center study, the authors assessed the efficacy of an automated imaging examination assignment system for enhancing the diversity of subspecialty examinations reported by oncologic imaging fellows. The study aimed to mitigate traditional biases of manual case selection and ensure equitable exposure to various case types. Methods included evaluating the proportion of "uncommon" to "common" cases reported by fellows before and after system implementation and measuring the weekly Shannon Diversity Index to determine case distribution equity. The proportion of reported uncommon cases more than doubled from 8.6% to 17.7% in total, at the cost of a concurrent 9.0% decrease in common cases from 91.3% to 82.3%. The weekly Shannon Diversity Index per fellow increased significantly from 0.66 (95% CI: 0.65, 0.67) to 0.74 (95% CI: 0.72, 0.75; P < .001), confirming a more balanced case distribution among fellows after introduction of the automatic assignment. © RSNA, 2023 Keywords: Computer Applications, Education, Fellows, Informatics, MRI, Oncologic Imaging.

Advances in PET/CT Imaging for Breast Cancer.

One out of eight women will be affected by breast cancer during her lifetime. Imaging plays a key role in breast cancer detection and management, providing physicians with information about tumor location, heterogeneity, and dissemination. In this review, we describe the latest advances in PET/CT imaging of breast cancer, including novel applications of 18F-FDG PET/CT and the development and testing of new agents for primary and metastatic breast tumor imaging and therapy. Ultimately, these radiopharmaceuticals may guide personalized approaches to optimize treatment based on the patient's specific tumor profile, and may become a new standard of care. In addition, they may enhance the assessment of treatment efficacy and lead to improved outcomes for patients with a breast cancer diagnosis.

Imaging the Side Effects of CAR T Cell Therapy: A Primer for the Practicing Radiologist.

Chimeric antigen receptor (CAR) T cell therapy is a revolutionary form of immunotherapy that has proven to be efficacious in the treatment of many hematologic cancers. CARs are modified T lymphocytes that express an artificial receptor specific to a tumor-associated antigen. These engineered cells are then reintroduced to upregulate the host immune responses and eradicate malignant cells. While the use of CAR T cell therapy is rapidly expanding, little is known about how common side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) present radiographically. Here we provide a comprehensive review of how side effects present in different organ systems and how they can be optimally imaged. Early and accurate recognition of the radiographic presentation of these side effects is critical to the practicing radiologist and their patients so that these side effects can be promptly identified and treated.

Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.

More than Just Skin-Deep: A Review of Imaging's Role in Guiding CAR T-Cell Therapy for Advanced Melanoma.

Advanced melanoma is one of the deadliest cancers, owing to its invasiveness and its propensity to develop resistance to therapy. Surgery remains the first-line treatment for early-stage tumors but is often not an option for advanced-stage melanoma. Chemotherapy carries a poor prognosis, and despite advances in targeted therapy, the cancer can develop resistance. CAR T-cell therapy has demonstrated great success against hematological cancers, and clinical trials are deploying it against advanced melanoma. Though melanoma remains a challenging disease to treat, radiology will play an increasing role in monitoring both the CAR T-cells and response to therapy. We review the current imaging techniques for advanced melanoma, as well as novel PET tracers and radiomics, in order to guide CAR T-cell therapy and manage potential adverse events.

The Clinical Utility of Molecular Imaging in COVID-19: An Update.

The novel pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in Wuhan, China in late 2019 with Coronavirus disease 2019 (COVID-19) declared a global pandemic in March 2020. Primarily involving the lungs, conventional imaging with chest radiography and CT can play a complementary role to RT-PCR in the initial diagnosis, and also in follow up of select patients. As a broader understanding of the multi-systemic nature of COVID-19 has evolved, a potential role for molecular imaging has developed, that may detect functional changes in advance of standard cross-sectional imaging. In this review, we highlight the evolving role of molecular imaging such as fluorine-18 (18F) fluorodeoxyglucose (FDG) with PET/CT and PET/MRI in the evaluation of both pulmonary and extra-pulmonary COVID-19, ventilation and perfusion scan with SPECT/CT for thromboembolic disease, long term follow-up of COVID-19 infection, and COVID-19 vaccine-related complications.

Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer.

Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05; 95% confidence interval (CI), 1.74-2.42; P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63; 95% CI, 0.52-0.76; P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy.

Programmatic Implementation of a Custom Subspecialized Oncologic Imaging Workflow Manager at a Tertiary Cancer Center.

PURPOSE: To evaluate whether a custom programmatic workflow manager reduces reporting turnaround times (TATs) from a body oncologic imaging workflow at a tertiary cancer center. METHODS: A custom software program was developed and implemented in the programming language R. Other aspects of the workflow were left unchanged. TATs were measured over a 12-month period (June-May). The same prior 12-month period served as a historical control. Median TATs of magnetic resonance imaging (MRI) and computed tomography (CT) examinations were compared with a Wilcoxon test. A chi-square test was used to compare the numbers of examinations reported within 24 hours and after 72 hours as well as the proportions of examinations assigned according to individual radiologist preferences. RESULTS: For all MRI and CT examinations (124,507 in 2019/2020 and 138,601 in 2020/2021), the median TAT decreased from 4 (interquartile range: 1-22 hours) to 3 hours (1-17 hours). Reports completed within 24 hours increased from 78% (124,127) to 89% (138,601). For MRI, TAT decreased from 22 (5-49 hours) to 8 hours (2-21 hours), and reports completed within 24 hours increased from 55% (14,211) to 80% (23,744). For CT, TAT decreased from 3 (1-19 hours) to 2 hours (1-13 hours), and reports completed within 24 hours increased from 84% (82,342) to 92% (99,922). Delayed reports (with a TAT > 72 hours) decreased from 17.0% (4,176) to 2.2% (649) for MRI and from 2.5% (2,500) to 0.7% (745) for CT. All differences were statistically significant (P < .001). CONCLUSION: The custom workflow management software program significantly decreased MRI and CT report TATs.

Translating Molecules into Imaging-The Development of New PET Tracers for Patients with Melanoma.

Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information. Thus, they can be used to assess prognosis, tumor heterogeneity, and identify instances of treatment failure. Numerous agents tested preclinically and clinically demonstrate promising results with high tumor-to-background ratios in both primary and metastatic melanoma tumors. Here, we detail the development and testing of multiple molecular targeted PET-imaging agents, including agents for general oncological imaging and those specifically for PET imaging of melanoma. Of the numerous radiopharmaceuticals evaluated for this purpose, several have made it to clinical trials and showed promising results. Ultimately, these agents may become the standard of care for melanoma imaging if they are able to demonstrate micrometastatic disease and thus provide more accurate information for staging. Furthermore, these agents provide a more accurate way to monitor response to therapy. Patients will be able to receive treatment based on tumor uptake characteristics and may be able to be treated earlier for lesions that with traditional imaging would be subclinical, overall leading to improved outcomes for patients.

Value of MRI in evaluating urachal carcinoma: A single center retrospective study.

OBJECTIVES: Urachal carcinomas (UrC) are rare non-urothelial bladder neoplasms, however the potential role for MR imaging in UrC has not been well established. Our objective was to assess the value of magnetic resonance imaging (MRI) in primary and recurrent UrC. METHODS AND MATERIALS: This retrospective single-center study included all patients with UrC that underwent MRI between January 2005 and May 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. For primary UrC, tumor location, size, morphology, invasion of peritoneum and/or local structures other than bladder and concordance between Mayo stage on MRI and pathology were assessed. MRI performed for recurrent UrC evaluated the pattern of recurrence. The reference standard was histopathological analysis. RESULTS: Ninety-six patients with UrC were identified of which 17 were included (9 men and 8 women, median age 50 years [IQR 42-62]). At initial MR staging (n = 10), all primary UrC were located at the bladder dome with median longest axis dimension of 6.0 cm. Most (70%) were mixed solid-and-cystic. Invasion of the peritoneum and/or local structures other than bladder was identified in 30%. Concordance between consensus MRI Mayo stage and final pathologic Mayo stage was 90%. At MR restaging (n = 7), UrC recurrence was most commonly seen at the bladder dome (71%). Overall, MRI showed a sensitivity of 85% and specificity of 50% for detecting recurrent tumor. CONCLUSION: MRI demonstrates value in evaluation of disease extent in primary and recurrent UrC, with high concordance between Mayo stage at MRI and pathology, and in the detection of local recurrences.

Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival.

OBJECTIVES: Plasmacytoid urothelial carcinomas (PUC) of the bladder are rare variants known for diffuse and infiltrative spread, however their magnetic resonance imaging (MRI) features are not well established. We aimed to evaluate MRI features of PUC of the bladder and their association with survival. METHODS AND MATERIALS: This retrospective single-center study included 41 patients with pathologically-proven bladder PUC of the bladder that underwent pre-treatment MRI between January 2000 and March 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. On MRI, tumor extent, size, Vesical Imaging-Reporting and Data System (VI-RADS) scores (≥4, muscle-invasive; 5, extravesical extension [EVE]), pelvic peritoneal spread (PPS), hydronephrosis, pelvic adenopathy and clinicopathological factors of age, gender, pathological stage, and treatment type were extracted. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with survival. RESULTS: Thirty-two men and 9 women (median age 70 years, IQR 64-76) were included. Most were muscle-invasive (n = 30 [73.2%]). On MRI, most tumors were diffuse (n = 28 [68.3%]), >5 cm (n = 30 [73.2%]), VI-RADS 4 to 5 (n = 36 [87.8%]) with features of EVE and (n = 31 [75.6%]) and PPS (n = 25 [61.0%]). Variables associated with survival were: Larger tumors (>5 cm; hazard ratio [HR] = 5.0; 95% confidence interval [CI] 1.6-15.5; P < 0.01), diffuse extent (HR = 4.0; 95% CI 1.4-11.2; P = 0.01), EVE (HR = 4.5; 95% CI 1.5-13.6; P < 0.01), PPS (HR = 3.0; 95% CI 1.2-7.4; P = 0.01), hydronephrosis (HR = 13.7; 95% CI 3.1-60.9; P < 0.01), pathologic stage (≥pT3 vs. pT1; HR = 5.6; 95% CI 1.3-22.0; P = 0.02), and margin positivity (HR = 4.4 [95% CI 1.2-16.4], P = 0.03). CONCLUSION: PUCs of the bladder are commonly large, diffuse VI-RADS score 4 to 5 tumors with MRI features of EVE and PPS. These features and pathological stage were associated with survival.

Malignant perivascular epithelioid cell tumor of the ileum on 18F-fluorodeoxyglucose positron emission tomography/ computed tomography with pathological correlation.

A 75-year-old woman presented with a 1-month history of abdominal pain. Contrast-enhanced computed tomography (CT) demonstrated a large solid mass in the left lower abdominal quadrant, suspicious for malignancy. Staging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT imaging demonstrated intense FDG uptake in the mass with no evidence of metastatic disease. Complete surgical resection was performed, and histopathological analysis confirmed a malignant perivascular epithelioid cell tumor of the ileum.