Differences in [123I]Ioflupane Striatal Binding Between African American and White Patients.

Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore whether differences exist in [123I]ioflupane binding, which reflects dopamine transporter binding, between African American and White individuals. Methods: Medical charts were reviewed for patients who underwent [123I]ioflupane SPECT imaging as part of routine practice in a single academic medical center. All images were visually graded as showing normal or abnormal presynaptic dopaminergic function (normal or abnormal scan status). Quantitative [123I]ioflupane uptake as measured by the specific binding ratios in the right and left striata and their subregions (caudate nucleus and anterior and posterior putamen) and by bilateral putamen-to-caudate ratios were compared between African American and White patients using multiple linear regression adjusted for age, sex, and abnormal scan status. Additional models included an ethnicity-by-abnormal-scan-status interaction term to determine whether abnormal scan status was modulated by ethnicity effect. Results: The percentage of patients with abnormal scan status was comparable between African American and White patients. Compared with White patients (n = 173), African American patients (n = 82) had statistically significantly higher uptake as measured by specific binding ratios in the right and left striata and some of their subregions (right and left caudate nuclei and right posterior putamen). Ethnicity-by-abnormal-scan-status interactions were not statistically supported for any models. Conclusion: We observed differences in [123I]ioflupane binding between African American and White patients independent of presynaptic dopaminergic dysfunction status. Future studies are needed to examine whether and how ethnicity affects dopamine transporter binding activities and its clinical relevance.

Increasing Utilization and Improving Documentation in a Radiology Critical Alert System.

Effective communication of critical imaging findings is an important patient safety issue. Despite an increase in exam volumes, our institution saw a decrease in the number of alerts sent through our critical alert system, indicating that critical findings were not being communicated. The purpose of our interventions was to increase the number of critical alerts, while also improving documentation and improving our provider database. We used a program of education for our radiologists and systematic reinforcement to increase the usage of our critical alert system. We also implemented a new time-stamp macro in our dictation system to improve documentation of emergency alerts, and engaged with other departments to improve the contact information in our provider database. Our interventions led to an increase in the monthly number of critical alerts, most notably for findings that require clinical or imaging follow-up (17 alerts per month). There was also a steady improvement in documentation (96.9% compliance), along with an increase in the number of alerts to providers with current contact information (0.5% per month). Our efforts show that educational and collaborative efforts can result in improved communication of radiologic critical results.

Imaging Advancements in Nuclear Medicine: Pancreatic Neuroendocrine Tumor Localization and Treatment.

BACKGROUND: This case report details a 57-year-old African American man with pancreatic neuroendocrine tumors (NETs). The patient underwent positron emission tomography (PET) imaging using gallium Ga 68 dotatate, which localized the tumors. Selected tumors were treated with 4 doses of 200 mCi of lutetium Lu 177 dotatate during a period of 8 months. At the conclusion of treatment, the patient demonstrated improvement, progressing from bedbound and confused to ambulatory and coherent. In addition, the patient stated he felt no adverse effects. DISCUSSION: Pancreatic NETs are rare tumors affecting 0.001% of the population. These tumors are associated with various symptoms and are classified as functional or nonfunctional. Imaging modalities, such as computed tomography (CT), magnetic resonance (MR) imaging, and gallium Ga 68-labeled PET, are essential in detecting and evaluating pancreatic NETs. For patients with localized NETs, the primary treatment is surgery; however, the radiopharmaceuticals yttrium Y 90 microspheres and lutetium Lu 177 dotatate are used as therapy to treat nonresectable tumors. CONCLUSION: Lutetium Lu 177 dotatate is used in NET cases that are deemed inoperable and for patients who are not responding to treatment. This case study demonstrates the effectiveness of combining imaging with Ga 68-labeled PET and treatment with lutetium Lu 177 dotatate. This treatment is not a cure but has been shown to improve a patient's quality of life.

Changing Role of PET/CT in Cancer Care With a Focus on Radiotherapy.

Positron emission tomography (PET) integrated with computed tomography (CT) has brought revolutionary changes in improving cancer care (CC) for patients. These include improved detection of previously unrecognizable disease, ability to identify oligometastatic status enabling more aggressive treatment strategies when the disease burden is lower, its use in better defining treatment targets in radiotherapy (RT), ability to monitor treatment responses early and thus improve the ability for early interventions of non-responding tumors, and as a prognosticating tool as well as outcome predicting tool. PET/CT has enabled the emergence of new concepts such as radiobiotherapy (RBT), radioimmunotherapy, theranostics, and pharmaco-radiotherapy. This is a rapidly evolving field, and this primer is to help summarize the current status and to give an impetus to developing new ideas, clinical trials, and CC outcome improvements.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

OBJECTIVES: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. METHODS: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. RESULTS: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. CONCLUSIONS: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Pitfalls and Artifacts of 123I-Ioflupane SPECT in Parkinsonian Syndromes: A Quality Improvement Teaching Tool.

The aim of the current article is to describe how to improve the quality of imaging with 123I-ioflupane SPECT and to serve as a teaching tool on this topic. The radiopharmaceutical 123I-ioflupane is used to visualize the nigrostriatal pathway. Parkinson disease and parkinsonian syndromes are movement disorders that exhibit nigrostriatal degeneration, with a decreased dopamine transporter level in the pathway and thus a decreased 123I-ioflupane distribution. Other nonparkinsonian movement disorders, such as essential tremor, will have intact dopaminergic neurons and exhibit a normal distribution of the radiopharmaceutical throughout the striata. Parkinsonian disorders are usually diagnosed clinically. However, 123I-ioflupane SPECT can be a valuable tool when the clinical features are not sufficiently clear. 123I-ioflupane SPECT image interpretation is not always straightforward. Many pitfalls, including biologic factors, technical factors, medications, and factors such as age, race, ethnicity, and body habitus, can make the interpretation challenging. The technologist and nuclear radiologist must identify the expected imaging findings to avoid the most common mistakes related to artifacts. This article reviews the usual pitfalls and artifacts of 123I-ioflupane SPECT that can compromise an accurate diagnosis and lead to misinterpretation of image findings.

Lack of Racial Survival Differences in Metastatic Prostate Cancer in National Cancer Data Base (NCDB): A Different Finding Compared to Non-metastatic Disease.

Background: Inconsistent findings have been reported in the literature regarding racial differences in survival outcomes between African American and white patients with metastatic prostate cancer (mPCa). The current study utilized a national database to determine whether racial differences exist among the target population to address this inconsistency. Methods: This study retrospectively reviewed prostate cancer (PCa) patient data (N = 1,319,225) from the National Cancer Database (NCDB). The data were divided into three groupings based on the metastatic status: (1) no metastasis (N = 318,291), (2) bone metastasis (N = 29,639), and (3) metastases to locations other than bone, such as brain, liver, or lung (N = 952). Survival probabilities of African American and white PCa patients with bone metastasis were examined through parametric proportional hazards Weibull models and Bayesian survival analysis. These results were compared to patients with no metastasis or other types of metastases. Results: No statistically supported racial disparities were observed for African American and white men with bone metastasis (p = 0.885). Similarly, there were no racial disparities in survival for those men suffering from other metastases (liver, lung, or brain). However, racial disparities in survival were observed among the two racial groups with non-metastatic PCa (p < 0.001) or when metastasis status was not taken into account (p < 0.001). The Bayesian analysis corroborates the finding. Conclusion: This research supports our previous findings and shows that there are no racial differences in survival outcomes between African American and white patients with mPCa. In contrast, racial disparities in the survival outcome continue to exist among non-metastatic PCa patients. Further research is warranted to explain this difference.

Single-Institution Experience of Synovial Sarcoma.

OBJECTIVES: The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution. METHODS: A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed. RESULTS: Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages. CONCLUSIONS: Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.

Rare Orbital Metastasis Originating From a Neuroendocrine Tumor.

BACKGROUND: This case study details a rare orbital metastasis originating from the gastrointestinal tract. A patient presented with proptosis of the right eye precipitated by a slow-growing orbital tumor. A biopsy confirmed a low-grade neuroendocrine tumor. Imaging studies were completed, with magnetic resonance (MR) imaging of the orbits providing the most detailed images of the mass. Fusion software images were created from the MR images and indium In 111 pentetreotide (octreoscan) studies, which confirmed the presence of the neuroendocrine carcinoid tumor. DISCUSSION: Orbital metastases are a rare condition associated with various symptoms, most commonly proptosis and diplopia. Imaging modalities, such as MR, computed tomography, and nuclear medicine technology, are instrumental in detecting and assessing these masses. Fusion imaging software can provide additional opportunities for facilities without hybrid scanners. The treatment of choice for orbital metastases is octreotide therapy; however, radiation therapy, partial or complete surgical removal of the tumor, and chemotherapy also are used. CONCLUSION: Traditional imaging techniques and fusion imaging techniques are essential for diagnosing and treating orbital metastases.

[123I]Ioflupane imaging in Caucasians and non-Caucasians: Are there any differences?

PURPOSE OF THE REPORT: To compare diagnostic performance of [123I]ioflupane SPECT imaging in different racial groups. In previous registration trials of [123I]ioflupane, 99% of the subjects enrolled were Caucasians. MATERIALS AND METHODS: A multicenter retrospective case-control study was conducted to evaluate whether the diagnostic performance of [123I]ioflupane SPECT imaging is different in non-Caucasians than in Caucasians matched by age, sex, and final clinical diagnosis. Subjects who had received an initial diagnosis of suspected Parkinson's disease (PD) or essential tremor (ET) and then underwent [123I]ioflupane SPECT imaging to assist with the subject's final clinical diagnosis were enrolled. Each subject's image was rated as normal or abnormal by 3 blinded expert readers. The majority interpretation was then compared with the final clinical diagnosis. Diagnostic performance of [123I]ioflupane SPECT imaging (as measured by positive percent agreement (equivalent to sensitivity), negative percent agreement (equivalent to specificity), overall percent agreement (OPA), and measures of inter-rater agreement) were compared between the Caucasian and non-Caucasian groups. RESULTS: In total, 102 non-Caucasians (58 with PD and 44 with ET as a final clinical diagnosis) and 102 Caucasians (58 with PD, 43 with ET, and 1 with "other") were included in the intent-to-diagnose (ITD) population. There was no significant difference between Caucasians and non-Caucasians in the diagnostic performance of [123I]ioflupane SPECT imaging as measured by sensitivity, specificity, OPA, and measures of inter-rater agreement. CONCLUSION: In this study, the diagnostic performance of [123I]ioflupane SPECT imaging was comparable between Caucasians and non-Caucasians.

Somatostatin receptor expression in non-classical locations - clinical relevance?

In-111 pentetreotide (Octreoscan) is a radiolabeled somatostatin analog with high binding affinity to somatostatin receptors (SSTR) used in somatostatin receptor scintigraphy (SRS). Pentetreotide labelled with In-111 is widely used due to its high affinity to SSTR 2 and 5. SSTR are expressed on neuroendocrine cells as well as several non-neural and non-endocrine cells with varying levels of density. We retrospectively reviewed articles and publications related to octreoscan accumulation in sites that classically do not have high concentrations of SSTR as well as in organs and tissues from diseases which are not usually diagnosed by octreoscan. The significance of a positive uptake as assessed by octreoscan in non-somatostatin receptor related diseases is not fully understood yet. Localization of octreotide in non-oncological disease states such as inflammation is due to presence of SSTR in activated immunological cells, over-expression by activated cells in the respective tissue and SSTR expression by blood vessels. In granulomatous diseases, over-expression of SSTR2 preferential binding sites were detected in epitheloid and giant cells. The purpose of the current study is to identify octreoscan localization in non-somatostatin receptor related disease sites to better understand the mechanism of this nonspecific accumulation which may help expand the clinical utilization of functional imaging utilizing somatostatin receptor scintigraphy in diagnosis and perhaps therapy.

Integrative Analysis of MicroRNA-Mediated Gene Signatures and Pathways Modulating White Blood Cell Count in Childhood Acute Lymphoblastic Leukemia.

MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. We discovered a signature of miRNAs differentially expressed in ALL and a signature of mRNA target genes distinguishing patients with high WBC from patients with low WBC. In addition, we identified molecular networks and biological pathways, among them PI3/AKT, JAK/STAT, IL-17, TGF-ß, apoptosis, IL-15, STAT3, IGF-1, FGF, mTOR, VEGF, NF-kB, and P53 signaling pathways, enriched for or targeted by miRNAs. The discovered miRNAs and their target genes and pathways represent potential clinically actionable biomarkers and therapeutic targets.

Enriching gene expression profiles will help personalize prostate cancer management for African-Americans: A perspective.

Prostate cancer (PCa) remains the most common form of cancer affecting men in the Western Hemisphere. Mortality rate is 130% higher among African-American men (AAM) than Caucasian-American men. As this trend is not new nor changing, there is an urgent need to identify markers with the ability to specifically distinguish aggressive PCa in the context of race. Gene expression patterns have been used as a tool to identify prognostic biomarkers for PCa to help reduce this disparity. Gene expression profiles reveal molecular mechanisms useful in understanding the biologic basis of tumorigenesis. Thus far, gene expression profiling analyses focused on race between AAM and Caucasian-American men (CAM) demonstrated distinct tumor microenvironments in the tumor-adjacent stroma and pathways associated with inflammation, lipid metabolism, and regulation of epithelial-to-mesenchymal transition. Additionally, we and others have established that hypoxia, another component of the tumor microenvironment, can been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcome in PCa. Gene expression panels, including distinct components related to the biology of PCa in AAM, may increase prognostic accuracy for this ethnic group. Furthermore, reference gene expression patterns, especially in the context of the emerging molecular taxonomy of PCa, would be buttressed by including more AAM in their development to consider the aspects of expression profiles differentially associated with race.

Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia.

Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL.

Multimodality Imaging in Pediatric Osteosarcoma in the Era of Image Gently and Image Wisely Campaign With a Close Look at the CT Scan Radiation Dose.

The increasing use of serial multimodality imaging in the management of pediatric osteosarcoma raises concern of over exposure to ionizing radiation in children, especially from repeated computed tomographic (CT) scans. This study reviews the utilization of multimodality imaging in patients with osteosarcoma at our institution and analyzes any potential radiation-related complications. Twenty-eight patients were identified. Three patients developed late complications-acute myeloid leukemia, myelodysplastic syndrome, and early menopause. Using the patient's age and body part imaged, CT dose length product and effective dose was estimated with the use of a conversion factor for 19 patients. The effective doses were higher in the 3 patients with late complications than the other patients in the cohort (P=0.018). These results suggest an increased risk for adverse effects with higher CT exposures and effective doses. On the basis of our data and published data, methods to decrease the doses of radiation from medical imaging need to be explored. The number of CT scans may be limited. Implementing the Image Gently concept to decrease radiation exposure can be beneficial in modification of CT acquisition parameters.

Pediatric osteosarcoma: a single institution's experience.

OBJECTIVES: The aim of the study was to evaluate outcomes with an examination of individual predictors influencing survival at a single institution. METHODS: This was a retrospective review of the 28 pediatric osteosarcoma patients diagnosed and studied from 2000 through 2012. Twenty-eight patient charts and imaging studies were reviewed for age, race, sex, location, extent of disease at presentation, imaging results, histology, treatment options, and overall survival. RESULTS: Of the 28 patients who were identified, the median age at diagnosis was 14 years. The majority of the patients were male African Americans with the tumor located in the lower long bones and most had conventional osteosarcoma histology. Four patients had metastasis at diagnosis. Of the 28 patients, 16 patients underwent limb salvage surgery, 6 underwent amputation, 4 had biopsy only, 1 had hip disarticulation, and 1 moved out of state and had no information available. All 28 patients received chemotherapy. Four patients received additional radiation therapy. On follow-up, 15 patients were still alive at last clinical contact and 13 died. Of the deceased, the median survival time was 2.3 years. The patient who lived the longest survived 8.3 years. Metastasis at diagnosis was associated with poorer outcome (P = 0.002). The 5-year overall survival rate was 40% (95% confidence interval 18-62) for our entire population of patients. CONCLUSIONS: Survival in our patient cohort tended to be at the lower end of the spectrum reported by other contemporary treatment centers of excellence or Surveillance, Epidemiology, and End Results databases probably because of the large number of African American patients with associated poor socioeconomic status. Future studies should be conducted to explore biological and nonbiological factors that may affect the prognosis in this disease.

Graves orbitopathy: update on diagnosis and therapy.

Graves orbitopathy (GO) is an autoimmune disorder representing the most frequent extrathyroidal manifestation of Graves disease. It is rare, with an age-adjusted incidence of approximately 16.0 cases per 100,000 population per year in women and 2.9 cases per 100,000 population per year in men. GO is an inflammatory process characterized by edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease activity at initial presentation. A Hertel exophthalmometer measurement of >2 mm above normal for race usually categorizes a patient as having moderate-to-severe GO. Encouraging smoking cessation and achieving euthyroidism in the individual patient are important. Simple treatment measures such as lubricants for lid retraction, nocturnal ointments for incomplete eye closure, prisms in diplopia, or botulinum toxin injections for upper-lid retraction can be effective in mild cases of GO. Glucocorticoids, orbital radiotherapy, and decompression/rehabilitative surgery are generally indicated for moderate-to-severe GO and for sight-threatening optic neuropathy. Future therapies, including rituximab aimed at treating the molecular and immunological basis of GO, are under investigation and hold promise for the future.