Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.

Follow-up imaging of anal cancer after treatment.

Anal cancer treatment response assessment can be challenging with both magnetic resonance imaging (MRI) and clinical evaluation considered essential. MRI, in particular, has shown to be useful for the assessment of treatment response, the detection of recurrent disease in follow up and surveillance, and the evaluation of possible post-treatment complications as well as complications from the tumor itself. In this review, we focus on the role of imaging, mainly MRI, in anal cancer treatment response assessment. We also describe the treatment complications that can occur, and the imaging findings associated with those complications.

Paraneoplastic Syndromes from Head to Toe: Pathophysiology, Imaging Features, and Workup.

Patients often have symptoms due to the mass effect of a neoplasm on surrounding tissues or the development of distant metastases. However, some patients may present with clinical symptoms that are not attributable to direct tumor invasion. In particular, certain tumors may release substances such as hormones or cytokines or trigger an immune cross-reactivity between malignant and normal body cells, resulting in characteristic clinical features that are broadly referred to as paraneoplastic syndromes (PNSs). Recent advances in medicine have improved the understanding of the pathogenesis of PNSs and enhanced their diagnosis and treatment. It is estimated that 8% of patients with cancer develop a PNS. Diverse organ systems may be involved, most notably the neurologic, musculoskeletal, endocrinologic, dermatologic, gastrointestinal, and cardiovascular systems. Knowledge of various PNSs is necessary, as these syndromes may precede tumor development, complicate the patient's clinical presentation, indicate tumor prognosis, or be mistaken for metastatic spread. Radiologists should be familiar with the clinical presentations of common PNSs and the selection of appropriate imaging examinations. Many of these PNSs have imaging features that can assist with arriving at the correct diagnosis. Therefore, the key radiographic findings associated with these PNSs and the diagnostic pitfalls that can be encountered during imaging are important, as their detection can facilitate early identification of the underlying tumor, reveal early recurrence, and enable monitoring of the patient's response to therapy. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Multilevel Approach to Support Diversity, Equity and Inclusion in Radiology.

Integrating diversity into healthcare systems has its challenges and advantages. Academic medicine strives to expand the diversity of the healthcare workforce. The Association of University Radiologists (AUR) put together a task force to review the concept of Diversity, Equity and Inclusion (DEI) as it pertains to Radiology and to propose strategies for better integrating DEI in Radiology. We present several measures aimed at the trainee, leadership, management and professional society levels to empower DEI in Radiology.

Primary sclerosing cholangitis: review for radiologists.

Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.

Testicular Germ Cell Tumors: Classification, Pathologic Features, Imaging Findings, and Management.

Testicular germ cell tumors (TGCTs) demonstrate a wide variety of histopathologic, genetic, pathogenetic, and immunocytochemical characteristics and various clinical-biologic profiles and prognoses. Most TGCTs arise from an intratubular precursor cell referred to as germ cell neoplasia in situ (GCNIS), which is an embryonic germ cell with the potential to differentiate into a plethora of embryonic and extraembryonic lineages. Advances in pathologic examination and genetics paved the way for the 2016 World Health Organization (WHO) classification system, which recognizes two pathogenetically distinct groups of TGCTs. Although postpubertal tumors originate from GCNIS, almost all prepubertal tumors belong to the non-GCNIS category. Molecular testing for chromosome 12p amplification helps to distinguish the two tumor categories. Imaging techniques such as US, CT, MRI, and fluorine 18 (18F)-fluorodeoxyglucose PET/CT are pivotal to the diagnosis and staging, evaluation of complications and treatment response, and long-term surveillance of TGCTs. In addition, select MRI findings may help to differentiate a seminoma from a nonseminomatous mixed TGCT. Accurate diagnosis of TGCTs has therapeutic and prognostic implications. Although seminomas show exquisite response to chemotherapy and radiation therapy, postpubertal teratomas are highly resistant to both. The 2016 WHO classification system introduced changes in the diagnosis and management of TGCTs, including the development of new treatment and follow-up guidelines. Radiologists play an essential role in the optimal treatment of patients with TGCTs. Online supplemental material is available for this article. ©RSNA, 2021.

Comprehensive review of imaging features of sex cord-stromal tumors of the ovary.

Sex cord-stromal tumors of the ovary (SCST) are uncommon ovarian tumors arising from sex cord and/or stromal cells of the ovaries. They may be nonfunctional and asymptomatic or functional presenting with hyperestrogenic, hyperandrogenic or cushingoid symptoms. They present in a wide age group of women, mostly in early stages and follow a nonaggressive clinical course after surgical resection. They differ from more prevalent epithelial ovarian tumors which tend to present in older women in advanced stages with poor prognosis. Some of SCSTs are associated with clinical syndromes. We will review imaging features on ultrasound, computed tomography and magnetic resonance imaging, epidemiology and clinical presentations of these tumors.

A review of anatomy, pathology, and disease spread in the perisplenic region.

The perisplenic region is a complex anatomical area involving multiple peritoneal and subperitoneal structures, which influence the presentation and behavior of various pathologic processes. This review is a comprehensive resource for perisplenic anatomy and pathology with associated clinical presentations and imaging findings. Understanding the pathophysiologic intricacies of the perisplenic region assists the radiologist in building a helpful differential diagnosis and recognizing predictable disease patterns.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?

Immunotherapy (IO) has altered the therapeutic landscape for multiple cancers. There are emerging data from retrospective studies on a subset of patients who do not benefit from IO, instead experiencing rapid progression with dramatic acceleration of disease trajectory, termed 'hyperprogressive disease' (HPD). The incidence of HPD ranges from 4% to 29% from the studies reported. Biological basis and mechanisms of HPD are currently being elucidated, with one theory involving the Fc region of antibodies. Another group has shown EGFR and MDM2/MDM4 amplifications in patients with HPD. This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease. Thus, prospective studies are urgently needed to confirm the underlying biology, predict patients who are susceptible to HPD, and determine the modality of therapy post progression.

Adrenal cortical carcinoma: pathology, genomics, prognosis, imaging features, and mimics with impact on management.

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Most tumors are either metastatic or locally invasive at the time of diagnosis. Differentiation between ACC and other adrenal masses depends on clinical, biochemical, and imaging factors. This review will discuss the genetics, pathological, and imaging feature of ACC.

Chronic Spontaneous Pneumoperitoneum with Pneumatosis Cystoides Intestinalis of the Small and Large Intestine.

Pneumoperitoneum can be an alarming radiological finding and a manifestation of a surgical emergency that warrant urgent intervention, or it can be a manifestation of chronic benign condition that can be managed conservatively. The sequela of misdiagnosing pneumoperitoneum due to surgical abdomen as a chronic benign pneumoperitoneum can be life-threatening and misdiagnosing chronic spontaneous pneumoperitoneum due to chronic condition as surgical emergency will lead to unnecessary surgical interventions. Diagnosis of chronic spontaneous pneumoperitoneum can be challenging to the unwary healthcare-providers. We present a case of chronic pneumoperitoneum secondary to pneumatosis cystoides intestinalis that has been managed conservatively.

Potential Application of Dual-Energy CT in Gynecologic Cancer: Initial Experience.

OBJECTIVE: The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer. CONCLUSION: DECT has the potential to improve diagnostic performance, may improve the ability to differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.

Ovarian Cancer, the Revised FIGO Staging System, and the Role of Imaging.

OBJECTIVE: It is now recognized that ovarian cancer includes a heterogeneous group of malignant epithelial tumors originating from the ovaries, fallopian tubes, or peritoneum. This development has prompted the International Federation of Gynecology and Obstetrics (FIGO) to issue a revised staging system that can provide prognostic information and guidance on personalized management of ovarian cancer. CONCLUSION: We review the epidemiology of ovarian cancer, the new FIGO staging system, and the role of imaging in the assessment, staging, and follow-up of ovarian cancer.

STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.

BACKGROUND: Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. METHODS: Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). RESULTS: Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. CONCLUSIONS: For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

Diffusion-weighted MRI in pediatric inflammatory bowel disease.

OBJECTIVE: Pediatric patients with inflammatory bowel disease (IBD) commonly need repetitive imaging to assess disease activity and complications. Recently, MR enterography has become a first-line radiologic study in children with IBD because of improved image quality, excellent soft-tissue contrast resolution, and lack of ionizing radiation. The purpose of this article is to describe the use of diffusion-weighted imaging (DWI) in MR enterography and the evaluation of pediatric IBD. CONCLUSION: Several contemporary publications have shown that DWI can be useful for assessing both pediatric and adult patients with IBD as an important adjunct pulse sequence. Specifically, DWI can be used to identify abnormal bowel segments, assess disease inflammatory activity, and detect and characterize a variety of extraintestinal IBD-related manifestations and complications.

Diagnostic approach to hereditary renal cell carcinoma.

OBJECTIVE: The purpose of this article is to discuss the histopathologic features, genetics, clinical presentation, and imaging of hereditary renal cancer syndromes. CONCLUSION: Hereditary renal cell carcinoma syndromes can be diagnosed with a pattern-based approach focused on the predominant histologic renal cell carcinoma subtype and associated renal and extrarenal features of each syndrome.

Uncommon pancreatic tumors and pseudotumors.

A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators" are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management.

Primary hepatic angiosarcoma: multi-institutional comprehensive cancer centre review of multiphasic CT and MR imaging in 35 patients.

OBJECTIVE: To assess the imaging features of primary hepatic angiosarcoma on multiphasic CT and MR. METHODS: Multi-institutional review identified 35 adults (mean age, 57.1 years; 22M/13F) with pathologically proven hepatic angiosarcoma and pretreatment multiphasic CT (n = 33) and/or MR (n = 7). RESULTS: Multifocal hepatic involvement was seen in all 35 cases, with at least 10 lesions in 74.3% (26/35). Mean size of the dominant mass was 8.9 ± 4.7 cm (range, 2.6-20 cm). Individual nodules were typically circumscribed. Arterial-phase foci of hypervascular enhancement without washout were seen in 89.7% (26/29). Heterogeneously expanding foci of enhancement generally followed blood pool in 88.6% (31/35). Progressive centripetal (n = 16) or diffuse "flash-fill" (n = 4) enhancement pattern resembling cavernous haemangiomas predominated in 20 cases, whereas a "reverse haemangioma" centrifugal pattern predominated in 11 cases. Rapid interval growth was seen in 24 (96.0%) of 25 cases with serial imaging. Vascular invasion was not seen in any case. Underlying cirrhotic morphology was seen in 42.3% (15/35). CONCLUSION: Primary hepatic angiosarcomas typically manifest as aggressive multifocal tumors containing small heterogeneous hypervascular foci that progressively expand and follow blood pool. The appearance can mimic cavernous haemangiomas, but distinction is generally possible. In the setting of cirrhosis, lack of tumour washout and vascular invasion argue against multifocal hepatocellular carcinoma. KEY POINTS: • Hepatic angiosarcoma manifests on CT and MR as rapidly progressive multifocal tumours • Multiphasic imaging demonstrates hypervascular foci that progressively expand and follow blood pool • Enhancement pattern can resemble cavernous haemangiomas or show a "reverse" centrifugal pattern • Lack of tumour washout of hypervascular lesions argues against multifocal hepatocellular carcinoma • Careful assessment of the cross-sectional imaging findings may suggest the diagnosis.