Quantitative PET Imaging and Clinical Parameters as Predictive Factors for Patients With Cervical Carcinoma: Implications of a Prediction Model Generated Using Multi-Objective Support Vector Machine Learning.

PURPOSE: Quantitative features from pre-treatment positron emission tomography (PET) have been used to predict treatment outcomes for patients with cervical carcinoma. The purpose of this study is to use quantitative PET imaging features and clinical parameters to construct a multi-objective machine learning predictive model. MATERIALS/METHODS: Seventy-five patients with stage IB2-IVA disease treated at our institution from 2009-2012 were analyzed. Models predicting locoregional and distant failure were generated using clinical parameters (age, race, stage, histology, tumor size, nodal status) and imaging features (12 textural, 9 intensity, 8 geometric features, 2 additional imaging features) from pre-treatment PET. Model features were selected based on a multi-objective evolutionary algorithm to maximize specificity given a fixed moderately high sensitivity using support vector machine learning methods. Model 1 used clinical parameters only (C), Model 2 used imaging features only (I), and Model 3 used clinical and imaging features (C+I). Sensitivity, specificity, area under a receiver-operating characteristic curve (AUC), and p-values were compared to assess ability to predict locoregional and distant failure. RESULTS: C+I had the highest performance for both locoregional failure (AUC 0.84, p < 0.01; specificity: 0.86; sensitivity: 0.79) and distant failure (AUC 0.75, p < 0.01; specificity: 0.75; sensitivity: 0.75). CONCLUSIONS: Based on a moderately high fixed sensitivity and optimized for specificity, the model using both clinical parameters and imaging features (C+I) had the best performance in predicting both locoregional failure and distant failure.

Does Tumor FDG-PET Avidity Represent Enhanced Glycolytic Metabolism in Non-Small Cell Lung Cancer?

BACKGROUND: In non-small cell lung cancer (NSCLC), 18fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One variable of FDG-PET, the maximum standard uptake value (SUVm), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. This study used stable glucose isotope tracing to determine whether the SUVm predicts glycolytic metabolism or other glucose fates in tumors. METHODS: In this prospective Institutional Review Board-approved clinical trial, 52 untreated potentially resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During the surgical procedure, the patients were infused with 13C-labeled glucose. Blood, tumor, and normal lung samples were analyzed by mass spectrometry to determine 13C enrichment in glycolytic intermediates. These values were compared with clinical variables, including SUVm, maximum tumor diameter, stage, grade, and MIB-1/Ki67 proliferation index. RESULTS: For each patient, 13C enrichment in each metabolite was compared between tumor and adjacent lung. Although all tumors metabolized glucose, SUVm did not correlate with glycolytic intermediate labeling. Rather, SUVm correlated with markers indicating the use of other respiratory substrates, including lactate, and with the proliferation index. CONCLUSIONS: SUVm does not correlate with glycolytic metabolism in human NSCLC but does correlate with the proliferation index, suggesting that SUVm predicts glucose use by pathways other than glycolysis. These pathways may offer alternative therapeutic targets, including biosynthetic pathways required for cell proliferation. The research techniques in this study offer the opportunity to understand the relationships between SUVm, tumor metabolism, and therapeutic vulnerabilities in human NSCLCs.

Role of FDG PET/CT in the Eighth Edition of TNM Staging of Non-Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality in the United States, and accurate staging plays a vital role in determining prognosis and treatment. The recently revised eighth edition of the TNM staging system for lung cancer defines new T and M descriptors and updates stage groupings on the basis of substantial differences in survival. There are new T descriptors that are based on the findings at histopathologic examination, and T descriptors are reassigned on the basis of tumor size and extent. No changes were made to the N descriptors in the eighth edition of the TNM staging of lung cancer, because the four N categories that are based on the location of the diseased nodes can be used to consistently predict prognosis. The eighth edition includes a new M1b descriptor for patients with a single extrathoracic metastatic lesion in a single organ (M1b), because they have better survival and different treatment options, compared with those with multiple extrathoracic lesions (M1c). Examination with fluorine 18 fluorodeoxyglucose (FDG) PET/CT is the standard of care and is an integral part of the clinical staging of patients with lung cancer. To provide the treating physicians with accurate staging information, radiologists and nuclear medicine physicians should be aware of the updated classification system and should be cognizant of the site-specific strengths and limitations of FDG PET/CT. In this article, the eighth edition of the TNM staging system is reviewed, as well as the role of FDG PET/CT in the staging of non-small cell lung carcinoma. ©RSNA, 2018.

Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy.

PURPOSE: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). METHODS AND MATERIALS: A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. RESULTS: Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P = .04). CONCLUSIONS: DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.

Lactate Metabolism in Human Lung Tumors.

Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.

Usefulness of nuclear whole-body bone scanning for diagnosis of leprosy.

Leprosy, or Hansen's disease, is rare in the United States. Given its rarity, as well as the pathognomonic dermatologic findings, there are few cases in which nuclear medicine imaging plays a role in the diagnostic workup. We present a 39-year-old man who presented with chronic abdominal pain, skin ulcers, and hypercalcemia who underwent computed tomography of the chest and a whole-body bone scan to evaluate for possible underlying neoplasm due to his profound hypercalcemia. Although the diagnosis of leprosy had been established by lower-extremity skin biopsy upon admission, workup for other potential concurrent etiologies of hypercalcemia was performed before initiating therapy. We present the computed tomography scans, nuclear medicine images, and corresponding skin findings of this case.

PET/Computed Tomography Scanning and Precision Medicine: Esophageal Cancer.

Esophageal cancer commonly has a poor prognosis, which requires an accurate diagnosis and early treatment to improve outcome. Other modalities for staging, such as endoscopic ultrasound imaging and computed tomography (CT) scans, have a role in diagnosis and staging. However, PET with fluorine-18 fluoro-2-deoxy-d-glucose/CT (FDG PET/CT) scanning allows for improved detection of distant metastatic disease and can help to prevent unnecessary interventions that would increase morbidity. FDG PET/CT scanning is valuable in the neoadjuvant chemotherapy assessment and predicting survival outcomes subsequent to surgery. FDG PET/CT scanning detects recurrent disease and metastases in follow-up.

Ectopic Thyroid Tissue in the Mediastinum Characterized by Histology and Functional Imaging with I-123 SPECT/CT.

Ectopic thyroid tissue is a rare entity and when discovered it is typically along the pathway of embryologic migration of the thyroid. We present a case of incidental finding of ectopic thyroid tissue within mediastinum in a 61-year-old female patient with a history of total thyroidectomy for thyroiditis and nodules. The patient presented to emergency room with cough and right chest pain and underwent a chest computed tomographic angiogram (CTA) to exclude pulmonary embolism as part of chest pain workup. One right paratracheal mediastinal soft tissue nodule was visualized on the images of CTA. This right paratracheal soft tissue mass was found to be ectopic benign thyroid tissue by histological analysis of the biopsied tissue samples. The function of this ectopic thyroid tissue was characterized by I-123 radioiodine uptake and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. This case illustrates that ectopic thyroid tissue should be included for differential diagnosis of a hyperdense soft tissue mass located within mediastinum. I-123 SPECT/CT is useful for guiding tissue biopsy of ectopic thyroid tissue distant from orthotopic thyroid gland and functional and anatomic characterization of mediastinal ectopic thyroid tissue for surgical resection when it is medically necessary.

Intrathoracic Accessory Lobe of Liver Masquerading as a Paraesophageal Mass.

Heterotopic liver tissue is a relatively rare finding, which has historically been discovered incidentally during surgery or at autopsy. However, we present a 28-year-old woman who presented to the emergency department with shortness of breath and stabbing chest pain. An emergent CT angiogram of the chest was performed, which incidentally revealed a mediastinal paraesophageal mass. Subsequent endoscopic ultrasound showed a hypoechoic area that appeared to connect to the liver. A liver/spleen scan with SPECT/CT with Tc sulfur colloid demonstrated that the mass was paraesophageal heterotopic liver tissue with a connection to the orthotropic liver by a small stalk.

The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer.

OBJECTIVE: The purpose of this article is to summarize the evidence regarding the role of FDG PET/CT in treatment response assessment and surveillance of lung cancer and to provide suggested best practices. CONCLUSION: FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.

Immune-mediated Disease in Ipilimumab Immunotherapy of Melanoma with FDG PET-CT.

RATIONALE AND OBJECTIVES: The purposes of this study were to provide a case-based overview of various immune-mediated side effects detected by 18F-Fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) in the patients receiving ipilimumab immunotherapy for treatment of malignant melanoma, and discuss the importance of recognizing immune-mediated side effects in the use of F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on metastatic melanoma. MATERIALS AND METHODS: This is a retrospective case series study of the patients diagnosed with melanoma who were subjected to immunomodulating therapy with ipilimumab. F-18 FDG PET-CT findings were reviewed, and the patients with immune-mediated side effects were selected for further analysis, in conjunction with review of clinical progress notes, the results of laboratory tests, and findings of other imaging tests. RESULTS: Four patients with immune-mediated side effects were identified among the patients being treated with ipilimumab and subjected to F-18 FDG PET-CT for monitoring therapeutic effects. These immune mediated side effects include new findings of abnormal increased FDG uptake associated with immune-mediated pancreatitis and hypophysitis, as well as immune-mediated thyroiditis and colitis reported previously. CONCLUSIONS: Various immune-mediated side effects were detected by F-18 FDG PET-CT in the patients subjected to immunomodulating therapy with ipilimumab. It is essential for the interpreting provider to recognize and differentiate abnormal FDG uptake associated with immune-mediated side effects from hypermetabolic malignant lesions when using F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on melanoma lesions.

Asymmetric radiotracer activity of enlarged cerebral spinal fluid space on radionuclide cisternography with SPET/CT.

OBJECTIVE: Cerebrospinal fluid (CSF) leak is a well-known complication of skull or sinus surgery. Radionuclide cisternography has high sensitivity for detection of CSF leak, commonly performed in conjunction with radioactivity assay of nasal pledgets. Our objective was to highlight the usefulness of single photon emission tomography/computed tomography (SPET/CT) in radionuclide cisternography by presenting a case of a 41 years old man with right sided rhinorrhea following craniotomies and sinus surgery, who was subjected to radioactivity assay of nasal pledgets and radionuclide cisternography for suspected CSF leak. Although no CSF leak was detected by radioactivity assay of pledgets placed in the nasal cavity, asymmetric radiotracer activity was noted on cisternographic images in the left temporal region, which was found to correspond to an enlarged CSF space in the left middle cranial fossa, not CSF leak, on SPET/CT images. CONCLUSION: SPET/CT was useful in the differentiation of asymmetric CSF radiotracer activity caused by a normal variant or post surgical changes of anatomic structures from abnormal radiotracer activity secondary to CSF leakage on radionuclide cisternography.

Serendipitous discovery of peritoneal mesothelioma.

We present the case of a 64-year-old patient with a history of Birt-Hogg-Dube syndrome, polycystic kidney disease treated with renal transplantation in May 2013, and multiple types of skin cancers, including malignant melanoma. He presented for lymphoscintigraphy for sentinel lymph node identification of the melanoma. Subsequent biopsy of the right axillary sentinel lymph node yielded a diagnosis of epithelial type malignant mesothelioma without a known primary tumor. Follow-up positron emission tomography with 2-deoxy-2-(fluorine-18)fluoro-D-glucose integrated with computed tomography (F-18 FDG PET/CT) demonstrated several suspicious hypermetabolic abdominal masses that were later confirmed to be epithelial-type mesothelioma via percutaneous biopsy.

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

Detection of Widespread Metastasis in a Case of Aggressive Carcinoma Showing Thymuslike Differentiation (CASTLE Disease) Using 18F-FDG PET/CT.

A 30-year-old man had a diagnosis of aggressive carcinoma showing thymuslike differentiation (CASTLE disease) and underwent thyroidectomy for tumor resection and bilateral cervical lymph node dissection. Multiple hypermetabolic nodal metastases were detected in the neck and upper mediastinum with fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT). The patient received radiation therapy and chemotherapy for treatment of metastases. Follow-up (18)F-FDG PET/CT demonstrated resolution of several hypermetabolic lesions previously seen in the neck, but innumerable new hypermetabolic metastatic lesions were visualized. The patient died of this aggressive CASTLE disease despite treatment with surgery, radiation, and systemic chemotherapy.

Thorax: normal and benign pathologic patterns in FDG-PET/CT imaging.

This article describes the normal patterns of thoracic (18)F-fluorodeoxyglucose (FDG) biodistribution, and expands on the role of FDG-PET/computed tomography (CT) for the evaluation of patients suffering from a spectrum of benign pathologic conditions that affect the chest. The discussion addresses the applications of FDG-PET/CT imaging in a wide variety of chest-related disorders. Familiarity with the normal thoracic biodistribution of FDG, coupled with knowledge of the potential nonmalignant causes of increased FDG uptake in the chest, is essential to minimize the incidence of incorrect interpretation of FDG-PET images in daily clinical practice.