Ronald Walker

• MD
• Professor at Vanderbilt University

Rationale- Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model which combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods - In this prospectively co...

Rationale: A prospective longitudinal cohort of individuals at high-risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer. Objective: The goal...

Background: Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from...

Purpose: The purpose of the following commentary is to discuss recent controversies in the use of radioactive iodine for differentiated thyroid cancer (DTC). Methods: R. M. Tuttle (Thyroid 2010; 20:257-263), at Memorial Sloan Kettering Cancer Center, has enumerated the well-accepted goals of radioactive iodine therapy (RAIT) in DTC: (1) ablate r...

PET/CT imaging is frequently used for cancer diagnosis and restaging as metabolically active cells, including cancer, utilize glucose for proliferation. F-FDG is the most commonly utilized radiopharmaceutical in PET/CT imaging. Limitations of F-FDG imaging include intense physiologic uptake in benign tissues such as the brain and myocardium. We pre...

This study assessed the inter-user reproducibility of Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel analytical tool that risk stratifies lung adenocarcinomas (ADCs) according to defined computed tomography (CT) structural characteristics. CANARY detects nine distinct voxel signatures in ADCs based on standard CT imaging, thereby...

We examined somatostatin receptor type 2A (SSTR2A) expression in primary and metastatic small intestinal neuroendocrine tumors (SI-NETs). We retrieved 156 liver metastases from 26 patients (10 males, 16 females) who had two or more liver lesions resected. A representative formalin-fixed paraffin-embedded section of tumor tissue from each liver meta...

Purpose ¹⁸F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs). False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to ¹⁸F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR) are expres...

Pathological specimens and tissue microarrays with hematoxylin and eosin (H&E) and SSTR2A immunohistochemical (IHC) staining. Black arrows (when present) indicate tumor cells. Red arrows (when present) indicate IHC staining for SSTR2A in stroma and/or inflammatory cells. (PDF)

Complete dataset of prospective imaging of 30 patients with 31 total lesions with 18F-FDG and 68Ga-DOTATATE PET/CT. (PDF)

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole-body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this present study is to characterize both active and inactive supraclavicu...

Background: We propose a systematic methodology to quantify incidentally identified lung nodules based on observed radiological traits on a point scale. These quantitative traits classification model was used to predict cancer status. Materials and Methods: We used 102 patients’ low dose computed tomography (LDCT) images for this study, 24 semantic...

Purpose: Neuroendocrine tumors (NETs) are uncommon but with increasing incidence and prevalence. Current reports suggest (68)Ga-DOTATATE PET/CT imaging improves diagnosis and staging of NETs compared to (111)In-DTPA-octreotide (octreotide) and conventional imaging. We performed a systematic review of (68)Ga-DOTATATE for safety and efficacy compare...

Rationale: Our purpose was to evaluate safety and efficacy of (68)Ga-DOTATATE PET/CT compared to (111)In-Pentetreotide imaging for diagnosis, staging and re-staging of pulmonary and gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Methods: (68)Ga-DOTATATE PET/CT and (111)In-Pentetreotide scans were performed in 78 of 97 consecutively e...

Beyond estimation of depot volumes, quantitative analysis of adipose tissue properties could improve understanding of how adipose tissue correlates with metabolic risk factors. We investigated whether the fat signal fraction (FSF) derived from quantitative fat-water magnetic resonance imaging (MRI) scans at 3.0 T correlates to CT Hounsfield units (...

Purpose: To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up. Methods: We performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3-13 mm diameter in 71 patients who unde...

This pilot study evaluated the utility of 3'-deoxy-3'[18F]-fluorothymidine ([(18)F]-FLT) positron emission tomography (PET) to predict response to neoadjuvant therapy that included cetuximab in patients with wild-type KRAS rectal cancers. Baseline [(18)F]-FLT PET was collected prior to treatment initiation. Follow-up [(18)F]-FLT was collected after...

The role of brown adipose tissue (BAT) in human lipid metabolism and whole‐body energy expenditure is not well understood. To study BAT in humans it is necessary to reliably measure the quantitative properties of BAT. The purpose of this study is to assess the volume and activity of BAT prospectively using PET in a cohort of healthy male and female...

Brown adipose tissue (BAT) is a small but significant tissue, which may play an important role in obesity and the pathogenesis of metabolic syndrome. Interest in studying BAT in adult humans is increasing, but in order to quantify BAT volume in a single measurement or to detect changes in BAT over the time course of a longitudinal experiment, BAT n...

We examined Ki-67 heterogeneity within single and between synchronous liver metastases of small intestine neuroendocrine tumors. There were 27 patients (10 men and 17 women) with two or more liver metastases. The Ki-67 index was used to classify the tumors into World Health Organization grade 1, 2, or 3. The association between Ki-67 heterogeneity...

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer (18)F-Fluorodeoxyglucose ((18)F-FDG) into adipose tissue depots, as measured by positron emission tomogra...

This perspective discusses the report by Pinsky and colleagues, which addresses whether non-calcified pulmonary nodules identified on CT screening carry short- and long-term risk for lung cancer. We are facing challenges related to distinguishing a large majority of benign nodules from malignant ones and among those a majority of aggressive from in...

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the 5th most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post thyroidectomy patient has included radioactive iodine (...

Importance Positron emission tomography (PET) combined with fludeoxyglucose F 18 (FDG) is recommended for the noninvasive diagnosis of pulmonary nodules suspicious for lung cancer. In populations with endemic infectious lung disease, FDG-PET may not accurately identify malignant lesions.Objectives To estimate the diagnostic accuracy of FDG-PET fo...

Background: Existing predictive models for lung cancer focus on improving screening or referral for biopsy in general medical populations. A predictive model calibrated for use during preoperative evaluation of suspicious lung lesions is needed to reduce unnecessary operations for a benign disease. A clinical prediction model (Thoracic Research Ev...

PURPOSE Effective implementation of personalized medicine in oncology requires tailoring an individualized therapeutic regimen for a given patient based upon the molecular characteristics of their disease, and deploying effective biomarkers that predict responses early in the course of therapy. In this pilot study, we evaluated [18F]-FLT PET, a non...

The results of the National Lung Screening Trial strongly support early detection and definitive treatment to reduce lung cancer mortality. Once lung cancer is discovered, accurate staging at baseline is imperative to maximize patient benefit and cost-effective use of health care resources. Although computed tomography (CT) remains a powerful tool...

Lung cancer predictive models, such as the Mayo model (Swensen, 1997), that are used for screening and referral to surgery are based on only traditional variables and are outdated. Clinical information such as FEV1, FDG-PET and lesion growth increasingly are used in treatment decisions. This information needs to be incorporated into our clinical pr...

Unlabelled: Measured human dosimetry of the (68)Ga-labeled synthetic somatostatin analog (68)Ga-DOTATATE has not been reported in the peer-reviewed literature. (68)Ga-DOTATATE is an investigational PET/CT imaging agent that binds with high affinity to somatostatin receptor subtype 2, found on many human cancers, most classically neuroendocrine tum...

SESSION TYPE: Lung Cancer Posters IPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PMPURPOSE: The objective of this study is to validate candidate biomarkers for the detection of lung cancer, to develop a high risk cohort and to determine whether a surveillance program will lead to early diagnosis and improved outcomes.METHODS: We pla...

Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[(18)F]-fluorothymidine ([(18)F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study...

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secr...

Pulmonary nodules often require operative resection to obtain a diagnosis. However, 10 to 30% of operations result in a benign diagnosis. Our purpose was to determine whether negative thoracic operations are futile by describing the pathological diagnoses; determining new diagnoses and treatment changes initiated based on operative findings; and as...

Lung cancer is a deadly disease that is difficult to diagnose and even more difficult to treat effectively. Many pathways are known to affect tumor growth, and targeting these pathways provides the cornerstone by which cancer is treated. Somatostatin receptors (SSTR) are a family of G protein coupled receptors that signal to alter hormonal secretio...

A variety of benign and malignant tumors occur in the liver. The most common benign hepatic tumors are cysts followed by cavernous hemangiomas. Focal nodular hyperplasia and adenomas more often affect women on oral contraceptives, whereas fatty infiltration and regenerating nodules more commonly occur in patients with cirrhosis. Abscesses and angio...

The significance of medical imaging in multiple myeloma was established in 1975 with the classic description of the Durie–Salmon staging system which incorporated the presence and number of focal osteolytic lesions in the staging scheme. A third of a century later, this staging system remains in use, though augmented by advances in medical imaging....

Malignant cerebral tumors represent a small percentage (approximately 2%) of all malignancies, but have severe prognosis due to high morbidity and mortality. According to the American Cancer Society, in 2007 there were 23,300 new benign cerebral tumors and 20,500 new malignant cerebral tumors diagnosed in the United States, with an estimated number...

Colorectal cancer (CRC) is the third most common cause of malignancy in both men and women. The incidence rate has decreased over the last two decades partially due to an increase in screening. The American Cancer Society estimates that there are approximately 149,000 new cases of CRC per year and approximately 50,000 patients per year die from thi...

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untre...

8532 Background: PET and MRI can reveal intramedullary focal lesions (FL) before osteolysis is detected on metastatic bone survey (MBS). Diagnostic merits, biological/molecular correlates, and outcome implications of the imaging techniques were prospectively and serially evaluated in 269 of 303 newly-diagnosed patients receiving TT3. Methods: Exami...

Infection imaging became widespread in 1971 with the release of 67Ga citrate. Multiphase skeletal scintigraphy and radiolabeled white blood cells (WBCs) have since become the most widespread clinically used agents for the imaging of infection. A wide variety of other radiolabeled probes are under investigation, based on antibodies, cytokines, assor...

Fluorodeoxyglucose (FDG) whole body positron emission tomography (PET) scan may show clinically occult second lesions. Such lesions in the thyroid are increasingly common. There are several recent reports of a high probability of malignancy in these lesions ranging from 14% to 63%. This is a retrospective review of 15,711 PET scans at a multi-disci...

Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs). Both baseline MBS and MRI were available in 611 of 668 myeloma patients who were treated uniformly with a tandem autologous transplantation-based protocol a...

Dickkopf-1 (DKK1), a soluble inhibitor of Wnt signaling secreted by multiple myeloma (MM) cells contributes to osteolytic bone disease by inhibiting the differentiation of osteoblasts. In this study, we tested the effect of anti-DKK1 therapy on bone metabolism and tumor growth in a SCID-rab system. SCID-rab mice were engrafted with primary MM cells...

To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on 2 separate protocols. Using log-rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, most up-regula...

Background: The Durie-Salmon (DS) staging system represented the first clinically useful classification of MM. While distinguishing patients with differing event-free (EFS) and overall survival (OS), considerable outcome heterogeneity persisted. Patients and Methods: As part of a high-dose melphalan-based tandem transplant trial, Total Therapy 2 (T...

Background: The Durie-Salmon staging system utilizes both laboratory features and information on MBS-FL. We hypothesized that, by detecting FL in the bone marrow prior to MBS-recognizable bone destruction, MRI would provide a biologically and clinically more relevant feature of FL-type MM (Tian et al, NEJM 2003). Patients and Methods: As part of a...

In MM and related plasma cell dyscrasias, FDG-PET or PET/CT imaging are useful and reliable techniques for assistance in the diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease, and for monitoring response to treatment. They are equally effective in secretory or nonsecretory d...

To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by...

Osteolytic bone disease is the most debilitating manifestation of myeloma. However, myeloma-induced effects on the bone-active cells in the bone marrow are more than just a manifestation of disease--the myeloma derives essential support from the changed balance between bone-forming and -resorbing cells. This observation has lead to the notion that...

Multiple myeloma (MM) growth in the bone marrow is associated with increased osteoclast activity and a reduced number of osteoblasts. Experimental studies suggest that bone disease drives the progression of MM. Whereas those studies focused on the critical role of myeloma-induced osteoclastogenesis in disease progression, little is known about the...

Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM). The medical records of 248 patie...

LEARNING OBJECTIVES 1. To review appearances of FDG uptake at sites of infections in patients with hematological cancers. 2. Make the viewer aware that clinically silent infections can be detected among pts undergoing FDG-PET for cancer staging. ABSTRACT FDG-PET is known to be useful for the evaluation of malignancy and data also suggests a role f...

Introduction: To further evaluate the utility of surface-enhanced laser desorption and ionization-time of flight mass spectroscopy (SELDI-TOF MS) proteomics in the diagnosis, prognosis, monitoring response to therapy, and follow up of patient with myeloma, we examined the ability of protein chips with 4 different surface chemistries to detect bioma...

18F-labeled Fluorodeoxyglucose Positron Emission Tomography - computed tomography (PET-CT) imaging results from newly diagnosed patients with multiple myeloma (MM) were correlated with serum free light chain (FLC) results from Total Therapy 3 (TT3). Patients had baseline PET-CT scans and serum kappa and lamda FLC analysis at diagnosis and at 2, 14...

Remarkable observations in haplo-identical, T-cell-depleted allogeneic transplantation (Tx) for AML have focused attention on the anti-tumor effects mediated by KIR-lig mismatched NK cells. In this study we evaluated whether haplo-identical KIR-lig-mismatched NK cells transfused after immunosuppression and tumor reduction with high dose chemotherap...

Introduction: Magnetic Resonance Imaging (MRI) and 18F-labeled fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT) imaging are both useful for diagnosis, staging, and restaging of multiple myeloma (MM), yet they are based on different physical principles and do not give equivalent results. It is widely known that FD...

Diagnosing bone infection in the context of post-surgical inflammation is problematic since many of the early signs of infection are similar to normal post-surgical changes. We used a rabbit osteomyelitis model to evaluate the use of 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG-PET) as a means of detecting post-operative inf...

To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transpl...

Heparanase is an enzyme that cleaves heparan sulfate and through this activity promotes tumor growth, angiogenesis, invasion, and metastasis in several tumor types. In human breast cancer patients, heparanase expression is associated with sentinel lymph node metastases. However, the precise role of heparanase in the malignant progression of breast...

Background: FDG-PET is useful for detecting cancer (ca) sites and preliminary data suggest a role in bone and joint infection, mostly in non-immunosuppressed hosts. Purpose: To determine the role of FDG-PET in the management of infection in patients (pts) with hematological ca. Patients and Methods: Between 10/01/2001 and 5/31/2004, FDG-PET scans p...

This study updates our previous molecular classification of myeloma (MM) using gene expression profiling (GEP) of plasma cells from 351 newly diagnosed MM cases and a microarray containing ~33,000 genes. After normalization of expression values, 2,800 genes exhibited a high degree of variation (SD >0.6) across a training set of 177 cases. Unsupervi...

Fluorodeoxyglucose Positron Emission Tomography (PET) scanning can rapidly detect and quantify changes in tumor metabolism. We present early results from the first 47 patients enrolled in Total Therapy III for multiple myeloma using PET scanning and correlating with serum M protein. Since we have previously demonstrated that diffuse uptake patterns...

Macrofocal lesions (FL) in the medullary space are a hallmark of mm readily detected by MRI scans, both at diagnosis and at relapse. In this study we evaluated, among 25 patients enrolled in TT II, with FL at relapse and a preceding clinical CR (by M protein and marrow examinations) the relationship to presence and location of FL at diagnosis. On r...

Multiple myeloma results in both diffuse infiltration and/or focal lesions (FL) of the marrow. MRI detects FL long before X-ray. We routinely perform MRI of skull, entire spine, pelvis, sternum and shoulders. MRI-defined number of FL (#FL) is an adverse prognostic variable for both EFS and OS for patients treated according to Total Therapy 2, 2nd i...

Purpose: To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. Patients And Methods: We reviewed the medical records of 561 myeloma patients (553 evaluable) enrolled in a treatment protocol consisting of dexamethasone-containing ind...

We have performed 2,000+ Fluorodeoxyglucose PET (PET) scans for multiple myeloma (MM) staging and restaging at our facility since October 2001. While the usefulness of the PET scan for MM is reported by us and others elsewhere, we have reviewed our list of “incidental” but important findings, some of which are unique or occur more commonly with MM...

The aim of this study was to evaluate the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the diagnosis of infection of implantable vascular catheters. We evaluated six patients with haematological cancer and infection of their implantable vascular catheter and who underwent FDG PET imaging around the time of the...

Multiple myeloma (MM) plasma cells (PCs) express receptor for hyaluronan-mediated motility (RHAMM), a hyaluronan-binding, cytoskeleton and centrosome protein. The most abundant RHAMM isoforms in MM are full-length RHAMM (RHAMMFL) and the splice variant RHAMM-exon4. We separately examined the significance of RHAMM expression, and isoform balance, in...

Medical imaging is migrating from anatomic imaging to functional imaging and fused anatomic/functional imaging. The technology is being adapted for biomedical research using both clinical and small animal scanners. The ability to externally image real-time physiologic processes in both normal and deranged conditions, including various models to ima...

To determine the role of the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan in the diagnosis and management of deep septic thrombophlebitis (STP). We conducted a prospective observational evaluation of FDG-PET in patients with cancer and suspected STP. Retrospective evaluation of patients with cancer and deep venous thro...

Multiple myeloma (MM) is a malignant clonal neoplasm of plasma cells of B-lymphocyte origin that commonly results in overproduction of large amounts of monoclonal immunoglobulins. Important advances in the therapeutic management of this disease in the past decade have resulted in higher rates of durable complete remission, prolonged event-free surv...

Myeloma cells may secrete factors that affect the function of osteoblasts, osteoclasts, or both. We subjected purified plasma cells from the bone marrow of patients with newly diagnosed multiple myeloma and control subjects to oligonucleotide microarray profiling and biochemical and immunohistochemical analyses to identify molecular determinants of...

PET systems, which are based on many years of work in theoretical and practical physics, provide a window into both normal and disease state biochemical processes not possible by other external imaging techniques. FDG is a workhorse of PET chemistry, helping to visualize the accumulation of glucose in cancer cells. A complex series of steps is invo...

PET is one of the most exciting advancements in medicine in many years. Its ability to image physiology rather than anatomy, combined with the wide range of organic "probes" or molecules that can be utilized, offer remarkable possibilities for medical imaging in the coming years.

In multiple myeloma and related plasma cell dyscrasias, either FDG PET or PET-CT imaging is useful and reliable technique for diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease and monitoring response to treatment, though PET-CT is superior for precise localization of regions...

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PURPOSE/AIM After reviewing this educational exhibit the participants will become familiar with the imaging characteristics, pathophysiology , spectrum of presentation castleman’s disease and the role of FDG PET and FDG PET-CT in the diagnosis and staging of castleman’s disease. CONTENT ORGANIZATION Benjamin Castleman first described Castleman’s d...

PURPOSE/AIM 1. Briefly Discuss Radiofrequency ablation. 2. Demonstrate utility of PET/CT imaging in the planning and assessment of treatment response of a Radiofrequency procedure. 3. Demonstrate the pre and post ablation appearance on PET/CT with and without recurrent or residual disease over a 2 year period following repeated RFA procedures. CON...