Clinical Factors Associated with Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed with Radical Prostatectomy including PSA <0.5 ng/mL.

PURPOSE: There is limited data on PSMA PET/CT for work-up of recurrence after radical prostatectomy (RP) at low PSA values. We evaluated a PSMA PET/CT cohort of post-RP patients, focusing on patients with PSA <0.5 ng/mL. MATERIALS AND METHODS: We identified a retrospective cohort who underwent piflufolastat F-18 PSMA PET/CT across an eleven-hospital system from 7/2021-2/2023. PSMA positivity was determined by radiology reports. Univariable and multivariable logistic regression identified factors associated with suspicious PSMA activity. RESULTS: Median PSA was 0.37 ng/mL (IQR 0.15, 1.29 ng/mL), with 49% of patients overall having at least one suspicious PSMA-avid lesion. Rates of scan positivity among patients with PSA <0.2 and 0.2-0.5 ng/mL were 34% and 38%, respectively. Among all patients, 25% (104/415) had pelvic disease (prostate bed or N1), and 24% (100/415) had M1 disease. Among patients with PSA <0.5 ng/mL, prior post-operative radiation was associated with suspicious PSMA activity. In the overall cohort, age, PSA at PSMA PET/CT, and RP Gleason Grade (GG) were associated with PSMA positivity. PSADT, EAU risk, and CAPRA-S were all associated with suspicious PSMA activity. CONCLUSIONS: Over one-third of patients with PSAs <0.2 ng/mL had imaging findings concerning for recurrence. Prior post-operative radiation was associated with higher rates of PSMA positivity among patients with PSA <0.5 ng/mL, and half of patients with evidence of PSMA avid distant metastatic disease underwent metastasis directed therapy. PET-PSMA imaging at low PSAs can be considered to inform salvage therapies.

Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system.

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.

A Practical Guide to the Pearls and Pitfalls of PSMA PET Imaging.

Prostate-specific membrane antigen (PSMA)-targeted PET agents have revolutionized the care of patients with prostate cancer, supplanting traditional methods of imaging prostate cancer, and improving the selection and delivery of therapies. This has led to a rapid expansion in both the number of PSMA PET scans performed and the imaging specialists required to interpret those scans. To aid those imagers and clinicians who are new to the interpretation of PSMA PET, this review provides an overview of the interpretation of PSMA PET/CT imaging and pearls for overcoming commonly encountered pitfalls. We discuss the physiologic distribution of the clinically available PSMA-targeted radiotracers, the commonly encountered patterns of prostate cancer spread, as well as the benign and malignant mimics of prostate cancer. Additionally, we review the standardized PSMA PET reporting systems and the role of PSMA in selecting appropriate patients for PSMA-targeted therapies.

The utility of [18F]Fluciclovine PET/CT in Evaluating Nonmetastatic Castrate-Resistant Prostate Cancer Patients (nmCRPCp): diagnostic performance and impact on management.

OBJECTIVE: To evaluate the role of [18F]Fluciclovine PET/CT scan in restaging nmCRPCp and its impact on management. METHODS AND MATERIALS: This retrospective study included all patients with nonmetastatic castrate-resistant prostate cancer, who underwent [18F]Fluciclovine PET/CT scans for restaging who had concern for disease progression. Two radiologists independently reviewed the PET/CT studies, assigned an overall impression, and reported the site and number of radiotracer activities in consensus and impact on management was recorded. Available tissue diagnosis and/or six-month clinical and imaging follow-up were used as reference standards. RESULTS: Thirty-five patients were included in this study. At least one lesion was detected in 73% (26/35) of the scans. Management changed in 71% (25/35) of patients, (22 positives and three negative scans). 26.9% (7/26) of patients were found to have an oligometastatic disease. Based on the reference standards, the diagnostic performance of [18F]Fluciclovine PET/CT in detecting recurrence in nmCRCP has 86%, sensitivity, 83% specificity, 96.1% PPV, and 55.5% NPV. There was no relationship between the Gleason score and a positive PET/CT scan in our patient population. CONCLUSION: Detecting the source of recurrence is challenging in nmCRCP patients when conventional imaging fails. Given the high PPV, sensitivity, and specificity, [18F]Fluciclovine PET/CT can be used instead of conventional imaging as a first-line choice due to its superiority over bone scan and added value of detecting soft tissue metastasis regardless of the initial Gleason score. ADVANCES IN KNOWLEDGE: The study highlights the added value of [18F]Fluciclovine PET/CT in detecting soft tissue metastasis regardless of the initial Gleason score, which is not possible with conventional imaging such as bone scans.The study highlights the potential role of [18F]Fluciclovine PET/CT guiding management change for nonmetastatic castrate-resistant prostate cancer patients, particularly those with oligometastatic disease.

Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma: A Multi-institutional Phase 2 Investigator-Initiated Nonrandomized Clinical Trial.

Importance: To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant. Objective: To evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma. Design, Setting, and Participants: A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT. Interventions: Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment. Main Outcomes and Measures: The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety. Results: Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting. Conclusions and Relevance: Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant. Trial Registration: ClinicalTrials.gov Identifier: NCT03077828.

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma.

In a multicenter, phase 2, investigator-initiated trial of sequential pembrolizumab and AVD (doxorubicin, vinblastine, and dacarbazine), nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma (cHL) achieved positron emission tomography (PET)-defined, complete or near-complete metabolic responses (CMRs), following pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD, with 100% of patients alive and without relapse at initial publication. We now report long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received 3 cycles of single-agent pembrolizumab, followed by AVD chemotherapy for 4 to 6 cycles depending on the stage and bulk. PET/computed tomography scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and programmed cell death protein 1 (PD-1) pathway markers. At a median follow-up of 33.1 months (range, 26.0-43.0), progression-free survival and OS remained 100%. All patients had genomic alterations in 9p24.1 and were positive for programmed death ligand 1 (PD-L1) by immunohistochemistry. There was no relationship between depth of response to single-agent pembrolizumab and 9p24.1 alterations or PD-1 pathway H-scores. After additional follow-up, sequential pembrolizumab and AVD remained highly effective. The high response rates observed at all PD-L1 levels suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase 2 trial (registered at www.clinicaltrials.gov as #NCT03226249) is ongoing to confirm our findings.

A Framework for Harmonization of Radiomics Data for Multicenter Studies and Clinical Trials.

PURPOSE: Variability in computed tomography images intrinsic to individual scanners limits the application of radiomics in clinical and research settings. The development of reproducible and generalizable radiomics-based models to assess lesions requires harmonization of data. The purpose of this study was to develop, test, and analyze the efficacy of a radiomics data harmonization model. MATERIALS AND METHODS: Radiomic features from biopsy-proven untreated hepatic metastasis (N = 380) acquired from 167 unique patients with pancreatic, colon, and breast cancers were analyzed. Radiomic features from volume-match 551 samples of normal liver tissue and 188 hepatic cysts were included as references. A novel linear mixed effect model was used to identify effects associated with lesion size, tissue type, and scanner model. Six separate machine learning models were then used to test the effectiveness of radiomic feature harmonization using multivariate analysis. RESULTS: Proposed model identifies and removes scanner-associated effects while preserving cancer-specific functional dependence of radiomic features on the tumor size. Data harmonization improves the performance of classification models by reducing the scanner-associated variability. For example, the multiclass logistic regression model, LogitBoost, demonstrated the improvement in sensitivity in the range from 15% to 40% for each type of liver metastasis, whereas the overall model accuracy and the kappa coefficient increased by 5% and 8% accordingly. CONCLUSION: The model removed scanner-associated effects while preserving cancer-specific functional dependence of radiomic features.

Multimodality imaging findings of infection-induced tumors.

Several infections can predispose to certain malignancies in different body parts. These infections include viral, bacterial, and fungal pathogens. Imaging plays a vital role in the diagnosis, staging, and management of these neoplastic conditions. Furthermore, it can help in differentiating infection-related non-neoplastic processes that can mimic malignancies. Both radiologists and clinicians should be familiar with these conditions. This review discusses the epidemiology, pathogenesis, and imaging features of infection-related tumors.

Combined modality PET/MR for the detection of severe large vessel vasculitis.

BACKGROUND: Large vessel vasculitis (LVV) can be characterized based on symptom severity, and this characterization helps clinicians decide upon treatment approach. Our aim was to compare the imaging findings of combined modality positron emission tomography/magnetic resonance (PET/MR) and inflammatory markers between severe and non-severe LVV. A retrospective query was performed to identify all patients with LVV who underwent PET/MR at our institution between January 2015 and January 2021. RESULTS: Eleven patients (nine females; age 62.2 ± 16.4 years) underwent 15 PET/MR scans. Positivity was defined by findings indicative of active LVV on each modality: PET positive if vessel metabolic activity > liver metabolic activity; MR positive if wall thickening or contrast enhancement. When positive PET or positive MR findings were considered a positive scan, LVV patients with severe disease (n = 9 scans) showed a higher number of positive scans (n = 9) compared to the number of positive scans in non-severe patients (n = 3) (p < 0.05). The sensitivity and specificity for the detection of severe LVV were 1.00 and 0.50, respectively. When only the presence of both positive PET and positive MR findings were considered a positive scan, inflammatory marker levels were not significantly different between severe and non-severe LVV groups (severe: erythrocyte sedimentation rate (ESR) = 9.8 ± 10.6 mm/h; C-reactive protein (CRP) = 0.6 ± 0.4 mg/dL) (non-severe: ESR = 14.3 ± 22.4 mm/h; CRP = 0.5 ± 0.6 mg/dL). Blood- and liver-normalized maximum standardized uptake values were not significantly different between severe and non-severe patients (1.4 ± 0.3 vs 1.5 ± 0.4; 1.1 ± 0.4 vs 1.0 ± 0.3, respectively). CONCLUSIONS: Because of the differences observed, PET/MR appears to be better suited to facilitate the characterization of LVV as severe or non-severe compared to inflammatory marker measurements and quantitative measurements of metabolic activity. Qualitative assessment of PET and MR positivity by 18F-fluorodeoxyglucose PET/MR may be able to supplement clinical symptoms-based LVV classification decisions and may be helpful when clinical symptoms overlap with other disease processes.

Primary splenic lymphoma on top of intrahepatic splenosis: A unique case report.

Solid organ splenosis is a challenging diagnosis with many atypical imaging features that can overlap with neoplastic masses of the affected organ. We present a sporadic case of intrahepatic splenosis in a 68-year-old woman with transformation into a low-grade B cell lymphoma. Initial cross-sectional imaging suggested focal nodular hyperplasia (FNH) ruled out on contrast-enhanced Magnetic Resonance Imaging (MRI) using a hepatobiliary-specific contrast agent. A Tc-99m sulfur colloid scan was negative. The final diagnosis was confirmed by a needle-guided biopsy revealing intrahepatic splenosis with transformation into a low-grade B cell lymphoma.

Ibrutinib Plus R-ICE Induces Remission in Blastoid Variant Mantle Cell Lymphoma with CNS Relapse.

Mantle cell lymphoma (MCL) is an aggressive, difficult to treat subtype of lymphoma, resulting in relapses and poor outcomes. Novel agents such as Bruton tyrosine kinase (BTK) inhibitors have been studied in the treatment of relapsed/refractory (R/R) MCL. BTK inhibitor ibrutinib, in particular, has demonstrated improvement in survival outcomes of R/R MCL. Despite these advancements, many cases of MCL, including the more aggressive blastoid and pleomorphic variants, will undergo disease progression leading to poor survival outcomes. Blastoid variant MCL is associated with an increased risk of central nervous system (CNS) involvement, causing high mortality rates. In this case report, we discuss a patient with a diagnosis of blastoid MCL with CNS relapse who achieved a complete response (CR) after receiving standard rituximab plus ifosfamide-carboplatin-etoposide (R-ICE) salvage chemotherapy with the addition of ibrutinib. The patient subsequently underwent autologous stem cell transplantation (autoSCT) and maintained CR with ibrutinib maintenance.

Role of hepatic metastatic lesion size on inter-reader reproducibility of CT-based radiomics features.

OBJECTIVES: To evaluate the effect of hepatic metastatic lesion size on inter-reader reproducibility of CT-based 2D radiomics imaging features. METHODS: Computerized tomography (CT) scans of 59 liver metastases from 34 patients with colorectal cancer were evaluated. Image segmentation was performed manually by three readers blinded to each other's results. For each radiomics feature, we created two datasets by sorting measurements according to size, i.e., (i) from the smallest to the largest lesion and (ii) from the largest to the smallest lesion. The Lin concordance correlation coefficient (CCC) was employed to analyze the reproducibility of radiomics features. In particular, the CCC was computed as a function of a number of elements in the dataset, by gradually adding lesions from each sorted dataset. To evaluate the effect of lesion size, we analyzed the difference between these two functions thus assessing the contribution of small and large lesions into the reproducibility of radiomics features. RESULTS: Inter-reader reproducibility of CT-based 2D radiomics features assessed using Lin's CCC demonstrates tumor-size dependence. For example, the Lin CCC for GLCM contrast equals 0.88 (95% C.I. 0.84 to 0.92, p < 0.003) and could change by an additional + / - 0.06 depending on the presence of large or small lesions. CONCLUSIONS: Groups of "large" and "small" lesions show different inter-reader reproducibility. The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution and can vary widely. This finding could partially explain variability in reproducibility of radiomics features in the literature. KEY POINTS: • Groups of "large" and "small" lesions show different inter-reader reproducibility. • The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution.

Abdominal and pelvic splenosis: atypical findings, pitfalls, and mimics.

Splenosis is an acquired form of ectopic splenic tissue that typically arises after trauma or splenectomy. It is often an incidental image finding in an otherwise asymptomatic patient, but the spectrum of symptoms varies based on the site of implantation. Radiologists should be familiar with the imaging features of splenosis to avoid mistaking it for malignancy. Splenosis has identical imaging features to that of the native spleen on US, CT, MRI, and nuclear medicine examinations. Therefore, when the radiologic findings support the diagnosis of splenosis, the patient can be spared invasive procedures for tissue sampling.

Advancements in Positron Emission Tomography/Magnetic Resonance Imaging and Applications to Diagnostic Challenges in Neuroradiology.

Since the clinical adoption of magnetic resonance (MR) in medical imaging, MR has proven to be a workhorse in diagnostic neuroradiology, with the ability to provide superb anatomic detail as well as additional functional and physiologic data, depending on the techniques utilized. Positron emission tomography/computed tomography has also shown irreplaceable diagnostic value in certain disease processes of the central nervous system by providing molecular and metabolic information through the development of numerous disease-specific PET tracers, many of which can be utilized as a diagnostic technique in and of themselves or can provide a valuable adjunct to information derived from MR. Despite these advances, many challenges still remain in neuroradiology, particularly in malignancy, neurodegenerative disease, epilepsy, and cerebrovascular disease. Through improvements in attenuation correction, motion correction, and PET detectors, combining the 2 modalities of PET and MR through simultaneous imaging has proven feasible and allows for improved spatial and temporal resolution without compromising either of the 2 individual modalities. The complementary information offered by both technologies has provided increased diagnostic accuracy in both research and many clinical applications in neuroradiology.

Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis.

OBJECTIVE: To identify clinical factors, including esophageal dilation on chest high-resolution computed tomography (HRCT), that are associated with pulmonary function decline in patients with systemic sclerosis (SSc). METHODS: Patients fulfilled 2013 SSc criteria and had ≥ 1 HRCT and ≥ 2 pulmonary function tests (PFTs). According to published methods, widest esophageal diameter (WED) and radiographic interstitial lung disease (ILD) were assessed, and WED was dichotomized as dilated (≥ 19 mm) vs not dilated (< 19 mm). Clinically meaningful PFT decline was defined as % predicted change in forced vital capacity (FVC) ≥ 5 and/or diffusion capacity for carbon monoxide (DLCO) ≥ 15. Linear mixed effects models were used to model PFT change over time. RESULTS: One hundred thirty-eight patients with SSc met the study criteria: 100 (72%) had radiographic ILD; 49 (35%) demonstrated FVC decline (median follow-up 2.9 yrs). Patients with antitopoisomerase I (Scl-70) autoantibodies had 5-year FVC% predicted decline (-6.33, 95% CI -9.87 to -2.79), whereas patients without Scl-70 demonstrated 5-year FVC stability (+1.78, 95% CI -0.59 to 4.15). Esophageal diameter did not distinguish between those with vs without FVC decline. Patients with esophageal dilation had statistically significant 5-year DLCO% predicted decline (-5.58, 95% CI -10.00 to -1.15), but this decline was unlikely clinically significant. Similar results were observed in the subanalysis of patients with radiographic ILD. CONCLUSION: In patients with SSc, Scl-70 positivity is a risk factor for FVC% predicted decline at 5 years. Esophageal dilation on HRCT was associated with a minimal, nonclinically significant decline in DLCO and no change in FVC during the 5-year follow-up. These results have prognostic implications for SSc-ILD patients with esophageal dilation.

DeepCOVID-XR: An Artificial Intelligence Algorithm to Detect COVID-19 on Chest Radiographs Trained and Tested on a Large U.S. Clinical Data Set.

Background There are characteristic findings of coronavirus disease 2019 (COVID-19) on chest images. An artificial intelligence (AI) algorithm to detect COVID-19 on chest radiographs might be useful for triage or infection control within a hospital setting, but prior reports have been limited by small data sets, poor data quality, or both. Purpose To present DeepCOVID-XR, a deep learning AI algorithm to detect COVID-19 on chest radiographs, that was trained and tested on a large clinical data set. Materials and Methods DeepCOVID-XR is an ensemble of convolutional neural networks developed to detect COVID-19 on frontal chest radiographs, with reverse-transcription polymerase chain reaction test results as the reference standard. The algorithm was trained and validated on 14 788 images (4253 positive for COVID-19) from sites across the Northwestern Memorial Health Care System from February 2020 to April 2020 and was then tested on 2214 images (1192 positive for COVID-19) from a single hold-out institution. Performance of the algorithm was compared with interpretations from five experienced thoracic radiologists on 300 random test images using the McNemar test for sensitivity and specificity and the DeLong test for the area under the receiver operating characteristic curve (AUC). Results A total of 5853 patients (mean age, 58 years ± 19 [standard deviation]; 3101 women) were evaluated across data sets. For the entire test set, accuracy of DeepCOVID-XR was 83%, with an AUC of 0.90. For 300 random test images (134 positive for COVID-19), accuracy of DeepCOVID-XR was 82%, compared with that of individual radiologists (range, 76%-81%) and the consensus of all five radiologists (81%). DeepCOVID-XR had a significantly higher sensitivity (71%) than one radiologist (60%, P < .001) and significantly higher specificity (92%) than two radiologists (75%, P < .001; 84%, P = .009). AUC of DeepCOVID-XR was 0.88 compared with the consensus AUC of 0.85 (P = .13 for comparison). With consensus interpretation as the reference standard, the AUC of DeepCOVID-XR was 0.95 (95% CI: 0.92, 0.98). Conclusion DeepCOVID-XR, an artificial intelligence algorithm, detected coronavirus disease 2019 on chest radiographs with a performance similar to that of experienced thoracic radiologists in consensus. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by van Ginneken in this issue.

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation.

Pulmonary mucormycosis (PM) is an uncommon fungal infection most often seen in immunocompromised patients. The fungus grows on decaying food, soil, and animal excrement. Patients usually become infected by inhalation of spores. The most common risk factors include diabetes mellitus, hematologic malignancy, and solid organ or stem cell transplant. PM can have a nonspecific appearance at imaging. For example, early imaging may show peribronchial ground-glass opacity. Later, the disease progresses to consolidation, nodules, or masses. Because patients are usually immunocompromised, the differential diagnosis often includes invasive pulmonary aspergillosis (IPA). Various radiologic findings suggestive of PM have been identified to help differentiate it from IPA. For example, the reverse halo sign is more closely associated with PM than with IPA. The reverse halo sign is an area of ground-glass opacity surrounded by a rim of consolidation. In addition, the presence of pleural effusions and more than 10 nodules is more suggestive of PM than it is of IPA. PM can progress rapidly in neutropenic patients. Identification of the hyphae in tissue by using endobronchial or percutaneous sampling can allow differentiation from IPA and help confirm the diagnosis of mucormycosis. Because of the high mortality rate associated with PM, early identification of the disease is critical for an improved likelihood of survival. A multimodality treatment approach with antifungal agents and surgical débridement has been shown to improve outcomes. The authors review the risk factors for PM, describe its imaging appearance and disease process, and describe the treatment of the disease. ©RSNA, 2020.

Utility of minimally invasive thoracoscopy for assessment of residual mediastinal lymphoma.

BACKGROUND: Patients with primary mediastinal lymphomas frequently present with a residual mass after completion of first-line therapy. Although a positron emission tomography scan is usually recommended, it fails to distinguish between persistent lymphoma and inflammation. Although percutaneous biopsy may have a high diagnostic yield for the initial diagnosis of mediastinal lymphomas, this biopsy has poor accuracy for detecting persistent disease in a residual mass given the heterogeneity of these residual masses. Because persistent disease has important therapeutic implications, we evaluated the role of operative biopsy in detecting lymphoma in the residual mass. METHODS: Between 2009 and 2015, consecutive patients (n = 77) undergoing tissue biopsy for initial diagnosis as well as for a positron emission tomography-positive residual mass were included. Tissue biopsy for a residual mass was repeated until frozen section was diagnostic or at least the mass on the ipsilateral hemi-mediastinum was resected. RESULTS: Of the initial 77 patients, 34 underwent operative restaging for a residual mass after chemotherapy, while 43 had a complete response. In these 34 patients, operative biopsy revealed the presence of lymphoma in 53%, predominantly Hodgkin's disease and diffuse large B-cell lymphoma. There was no significant difference in tumor volume (51% versus 39%) and a decrease in the positron emission tomography-standardized uptake valuemax (68% vs 60%) in patients with or those without persistent lymphoma. There were no surgical complications and the duration of stay for all patients undergoing thoracoscopy was <24 hours. Residual lymphoma was treated with second-line therapy guided by the pathologic analysis. CONCLUSION: A large proportion of patients with residual positron emission tomography-avidity after first-line chemotherapy of mediastinal lymphomas have residual disease that can be detected safely using minimally invasive thoracoscopy.

Extraosseous Findings on Bone Scintigraphy Using Fusion SPECT/CT and Correlative Imaging.

OBJECTIVE: Extraosseous radioactivity outside of the expected biodistribution is often encountered on (99m)Tc-methylene diphosphate (MDP) bone scintigraphy, and proper interpretation requires an understanding of the mechanisms underlying this uptake and knowledge of the possible causes, depending on the site or structure involved. CONCLUSION: We present examples of extraosseous radiotracer uptake seen on (99m)Tc-MDP bone scans in which either SPECT with integrated CT or correlative imaging improved the study's interpretation.