Faculty Bibliography

INTRODUCTION/BACKGROUND:The successful management of infected pelvic pressure ulcer patients (PPUP) depends on the distinction between infections limited to soft tissue (STI) and those with underlying osteomyelitis (OM), which can be difficult to determine clinically. Dual-isotope (DI) comprehensive imaging has excellent accuracy in localizing diabetic foot infection and differentiating OM from STI with SPECT/CT utilization. In this study, we assess the accuracy and confidence of the different DI SPECT/CT imaging steps in PPUP with confirmed diagnoses. PATIENTS AND METHODS/METHODS:Pelvic flow and blood pool imaging were followed by labeled white blood cell reinjection and Tc-99m hydroxymethylene-diphosphonate bone (bone scan) and In-111-leukocytes (white blood cell scan) DI planar and SPECT/CT (step 1) acquisitions. Tc-99m sulfur colloid (bone marrow scan)/WBCS SPECT/CT (step 2) images were obtained on the following day. DI step 1 planar, step 1 SPECT/CT, step 2 SPECT/CT, and combined step 1/step 2 SPECT/CT were reviewed separately for diagnosis and diagnosis confidence. The final diagnosis was confirmed by culture/pathology in 21 patients and clinical/imaging follow-up in 12 patients. RESULTS:There were 19 OM patients, three STI patients, and 11 patients with no infection. The final diagnosis agreement to DI combined step 1/step 2 SPECT/CT was higher than DI step 2 or step 1 SPECT/CT alone, or DI step 1 planar, as assessed by λ and error reduction %, respectively. Combined DI step 1/step 2 SPECT/CT was more sensitive than DI step 2 SPECT/CT and more specific than DI step 1 SPECT/CT, and showed higher diagnostic confidence than both imaging techniques. CONCLUSION/CONCLUSIONS:DI SPECT/CT is highly useful in evaluating PPUP with suspected infection. DI step 1 is more sensitive, whereas step 2 is more specific. Both step 1 and step 2 DI SPECT/CT images are needed to accurately and confidently assess for infection and distinguish OM from STI, which are crucial for optimal management.

In Part 1, we reviewed the role of interim positron emission tomography (PET)/CT scans in Hodgkin lymphoma. In advanced Hodgkin lymphoma, interim PET is a useful prognostic tool that can be used to implement risk-adapted therapy with potential benefits for both patients who have negative interim scans and those whose scans are positive. Interim PET/CT has not shown as encouraging results in diffuse large B-cell lymphoma (DLBCL), with the exception of germinal center B-cell DLBCL. Thus, quantitative methods of interpreting interim PET scans have been pursued in an effort to improve their predictive value. Early results using the change in maximal standardized uptake value between baseline and interim PET (ΔSUVmax) to quantitatively interpret interim PET scans in DLBCL patients showed promise, but later results were contradictory. Thus, there is not firm evidence of a prognostic value for interim PET interpreted using either visual or ΔSUVmax-based analysis in patients with DLBCL. Nor are there data to support altering treatment in DLBCL on the basis of an interim PET scan. More sophisticated methods of quantitative interpretation of interim PET, using metabolic tumor volume and tumor lesion glycolysis measurements, have been investigated in both Hodgkin lymphoma and DLBCL. Although to date studies of these approaches have been small and heterogeneous, they do provide some support for the potential of a PET-derived volumetric approach to discriminate between risk groups better than ΔSUVmax; this remains to be proven in well-designed large-scale studies.

Interim positron emission tomography (PET)/CT has shown encouraging results when used as a prognostic tool early in the course of treatment of advanced Hodgkin lymphoma, allowing for a reduction in treatment for patients with favorable characteristics, while suggesting a benefit from changing therapy for those with a positive scan. For patients with limited disease, a negative scan allows for a decrease in treatment; however, the benefits for those patients whose scans are positive are less certain. Here we critically analyze the role of PET/CT in the early assessment of Hodgkin lymphoma. In Part 2, we will review the role of interim PET/CT in diffuse large B-cell lymphoma (DLBCL), and also explore the question of whether new approaches to quantitative assessment improve the prognostic value of interim PET scans in both Hodgkin lymphoma and DLBCL.

Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for reporting and latest developments. Particular attention is given to response-adapted therapy, which is emerging as a cornerstone of clinical management.

Lymphoid malignancies are a heterogeneous group of tumors that have distinctive clinical and biological behaviors. The increasing prevalence of disease reflects both treatment advances and the fact that some of these tumors are indolent. The ability to determine treatment needs at diagnosis remains problematic for some of the tumors, such as in follicular lymphomas. Major clinical advances will likely depend on precision oncology that will enable identification of specific disease entities, prognostic determination at diagnosis, and identification of precise therapeutic targets and essential pathways. However, refinement in diagnostic evaluation is an evolving science. The ability to determine prognosis at diagnosis is variable, and for many of the lymphoid malignancies prognosis can only be made after initial treatment. Clinical trials that aim to evaluate specific features of these diseases are required in order to advance clinical practice that meaningfully addresses this important public health challenge. Herein, we describe the process and general recommendation from the National Cancer Institute (NCI) clinical trials planning meeting in November 2014 to address clinical trial design and biomarker proposals in the context of NCI-supported lymphoma clinical trials in the National Clinical Trials Network.

PURPOSE/OBJECTIVE:Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN/METHODS:F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS:[AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS:F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

PURPOSE/OBJECTIVE:Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study. METHODS:The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach. RESULTS:Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder. CONCLUSIONS:MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.

The effectiveness of cancer therapy, both in individual patients and across populations, requires a systematic and reproducible method for evaluating response to treatment. Early efforts to meet this need resulted in the creation of numerous guidelines for quantifying posttherapy changes in disease extent, both anatomically and metabolically. Over the past few years, criteria for disease response classification have been developed for specific cancer histologies. To date, the spectrum of disease broadly referred to as lymphoma is perhaps the most common for which disease response classification is used. This review article provides an overview of the existing response assessment criteria for lymphoma and highlights their respective methodologies and validities. Concerns over the technical complexity and arbitrary thresholds of many of these criteria, which have impeded the long-standing endeavor of standardizing response assessment, are also discussed.