Browsing by Author "Wong, Terence Z"

Filter results by typing the first few letters
Now showing 1 - 10 of 10
  • Thumbnail Image
    ItemOpen Access
    18F-FDG-PET/CT Imaging for Gastrointestinal Malignancies.
    (Radiologic clinics of North America, 2021-09) Howard, Brandon A; Wong, Terence Z
    Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.
  • Thumbnail Image
    ItemOpen Access
    Cortical β-amyloid levels and neurocognitive performance after cardiac surgery.
    (BMJ Open, 2013-09-20) Klinger, Rebecca Y; James, Olga G; Wong, Terence Z; Newman, Mark F; Doraiswamy, P Murali; Mathew, Joseph P
    INTRODUCTION: Neurological and neurocognitive dysfunction occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Perioperative cognitive deficits have been shown to persist after discharge and up to several years after surgery. More importantly, perioperative cognitive decline is predictive of long-term cognitive dysfunction, reduced quality of life and increased mortality. The proposed mechanisms to explain the cognitive decline associated with cardiac surgery include the neurotoxic accumulation of β-amyloid. This study will be the first to provide molecular imaging to assess the relationship between neocortical β-amyloid deposition and postoperative cognitive dysfunction. METHODS AND ANALYSIS: 40 patients providing informed consent for participation in this Institutional Review Board-approved study and undergoing cardiac (coronary artery bypass graft (CABG), valve or CABG+valve) surgery with cardiopulmonary bypass will be enrolled based on defined inclusion and exclusion criteria. At 6 weeks after surgery, participants will undergo (18)F-florbetapir positron emission tomography imaging to assess neocortical β-amyloid burden along with a standard neurocognitive battery and blood testing for apolipoprotein E ε-4 genotype. RESULTS: The results will be compared to those of 40 elderly controls and 40 elderly patients with mild cognitive impairment who have previously completed (18)F-florbetapir imaging. ETHICS AND DISSEMINATION: This study has been approved by the Duke University Institutional Review Board. The results will provide novel mechanistic insights into postoperative cognitive dysfunction that will inform future studies into potential treatments or preventative therapies of long-term cognitive decline after cardiac surgery.
  • Thumbnail Image
    ItemOpen Access
    Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.
    (International journal of radiation oncology, biology, physics, 2020-11) Mowery, Yvonne M; Vergalasova, Irina; Rushing, Christel N; Choudhury, Kingshuk Roy; Niedzwiecki, Donna; Wu, Qiuwen; Yoo, David S; Das, Shiva; Wong, Terence Z; Brizel, David M

    Purpose

    Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes.

    Methods and materials

    Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs).

    Results

    From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively.

    Conclusions

    PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.
  • Thumbnail Image
    ItemOpen Access
    Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series.
    (Clinical nuclear medicine, 2021-07) James, Olga G; Linares, Alexandra R; Hellegers, Caroline; Doraiswamy, P Murali; Wong, Terence Z

    Abstract

    Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.
  • Thumbnail Image
    ItemOpen Access
    Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.
    (Oncoimmunology, 2023-01) Oldan, Jorge D; Giglio, Benjamin C; Smith, Eric; Zhao, Weiling; Bouchard, Deeanna M; Ivanovic, Marija; Lee, Yueh Z; Collichio, Frances A; Meyers, Michael O; Wallack, Diana E; Abernethy-Leinwand, Amber; Long, Patricia K; Trembath, Dimitri G; Googe, Paul B; Kowalski, Madeline H; Ivanova, Anastasia; Ezzell, Jennifer A; Nikolaishvili-Feinberg, Nana; Thomas, Nancy E; Wong, Terence Z; Ollila, David W; Li, Zibo; Moschos, Stergios J
    Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment 'high' vs. 'low' C11-AMT SUVmax of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.
  • Thumbnail Image
    ItemOpen Access
    Initial In Vivo Quantification of Tc-99m Sestamibi Uptake as a Function of Tissue Type in Healthy Breasts Using Dedicated Breast SPECT-CT.
    (J Oncol, 2012) Mann, Steve D; Perez, Kristy L; McCracken, Emily KE; Shah, Jainil P; Wong, Terence Z; Tornai, Martin P
    A pilot study is underway to quantify in vivo the uptake and distribution of Tc-99m Sestamibi in subjects without previous history of breast cancer using a dedicated SPECT-CT breast imaging system. Subjects undergoing diagnostic parathyroid imaging studies were consented and imaged as part of this IRB-approved breast imaging study. For each of the seven subjects, one randomly selected breast was imaged prone-pendant using the dedicated, compact breast SPECT-CT system underneath the shielded patient support. Iteratively reconstructed and attenuation and/or scatter corrected images were coregistered; CT images were segmented into glandular and fatty tissue by three different methods; the average concentration of Sestamibi was determined from the SPECT data using the CT-based segmentation and previously established quantification techniques. Very minor differences between the segmentation methods were observed, and the results indicate an average image-based in vivo Sestamibi concentration of 0.10 ± 0.16 μCi/mL with no preferential uptake by glandular or fatty tissues.
  • Thumbnail Image
    ItemOpen Access
    Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC).
    (Clinical genitourinary cancer, 2020-10) Eulitt, Patrick J; Altun, Ersan; Sheikh, Arif; Wong, Terence Z; Woods, Michael E; Rose, Tracy L; Wallen, Eric M; Pruthi, Raj S; Smith, Angela B; Nielsen, Matthew E; Whang, Young E; Kim, William Y; Godley, Paul A; Basch, Ethan M; David, Grace U; Ramirez, Juanita; Deal, Allison M; Rathmell, W Kimryn; Chen, Ronald C; Bjurlin, Marc A; Lin, Weili; Lee, Joseph K; Milowsky, Matthew I

    Introduction

    Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC.

    Patients and methods

    Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT).

    Results

    Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology.

    Conclusions

    This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.
  • Thumbnail Image
    ItemOpen Access
    Pitfalls of post-treatment PET after de-intensified chemoradiotherapy for HPV-associated oropharynx cancer: Secondary analysis of a phase 2 trial.
    (Oral oncology, 2018-03) Wang, Kyle; Wong, Terence Z; Amdur, Robert J; Mendenhall, William M; Sheets, Nathan C; Green, Rebecca; Thorp, Brian D; Patel, Samip N; Hackman, Trevor G; Zanation, Adam M; Weissler, Mark C; Chera, Bhishamjit S
    OBJECTIVES:We evaluated patterns of nodal response and positive predictive value (PPV) of 3 month post-treatment PET in patients with HPV-associated oropharyngeal cancer treated on a multi-institutional de-intensification trial. MATERIALS AND METHODS:Eligibility criteria included: (1) T0-3, N0-2c, M0, (2) HPV+/p16+ oropharyngeal squamous cell carcinoma, and (3) ≤10 pack-years smoking or ≤30 pack-years and abstinent ≥5 years. Patients received 60 Gy radiation alone (T0-2, N0-1) or with concurrent weekly cisplatin 30 mg/m2 and surveillance PET three months post-radiation. Nodal responses were categorized as complete (CR), equivocal (ER), or incomplete (IR) using both local and central radiographic review. A "true positive" was ER/IR with clinical/radiographic progression or positive pathology. RESULTS:79 node-positive pts (84% N2) were analyzed. Distribution of nodal CR, ER, and IR was 44 (56%), 27 (34%), and 8 (10%), respectively. 29 (37%) had ER/IR in pre-treatment node-positive neck levels, whereas 14 (18%) had ER/IR in pre-treatment node-negative levels. Of patients with ER/IR, 5 were observed clinically, 19 received repeat imaging, and 11 received either biopsy (1) or neck dissection (10). The PPV was 9% for ER/IR and 13% for IR, with 3 patients found to have persistent disease on neck dissection. There was no difference in nodal relapse rate in patients with nodal CR vs. nodal ER/IR. CONCLUSION:Post-treatment PET may not accurately predict the presence of persistent disease in patients with favorable-risk oropharynx cancer. These results support close surveillance rather than surgical evaluation in most favorable-risk patients.
  • Thumbnail Image
    ItemOpen Access
    Predictors of survival in 211 patients with stage IV pulmonary and gastroenteropancreatic mIBG positive neuroendocrine tumors treated with I-131 mIBG.
    (Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2018-05-18) Kane, Ari; Thorpe, Matthew P; Morse, Michael A; Howard, Brandon A; Oldan, Jorge D; Zhu, Jason; Wong, Terence Z; Petry, Neil A; Reiman, Robert; Borges-Neto, Salvador
    Purpose: This retrospective analysis identifies predictors of survival in a cohort of patients with mIBG positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with I-131 mIBG therapy, in order to inform treatment selection and post-treatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from n = 211 P/GEP-NET patients treated with mIBG between 1991-2014. For patients with computed tomography (CT) follow up (n = 125), imaging response was assessed by Response Evaluation Criteria on Solid Tumors (RECIST) 1.1 where images were available (n = 76) or by chart review of the radiology report where images could not be reviewed (n = 49). Kaplan Meier analysis and Cox multivariate regression estimated survival and progression free survival benefits predicted by initial imaging, biochemical and symptomatic response. Results: All patients had stage IV disease at time of treatment. Median survival was 29 months from time of treatment. 71% of patients demonstrated symptomatic response with median duration of symptomatic relief of 12 months. Symptomatic response at first follow-up predicted a survival benefit of 30 months (p<0.001). Biochemical response at first clinical follow up was seen in 34% of patients with stability of labs in 48%; response/stability vs. progression extended survival 40 months (p<0.03). Imaging response (20% of patients) or stability (60%) at initial 3 month follow up imaging extended survival 32 months (p<0.001). Additionally, multiple mIBG treatments was associated with 24 months additional survival (p<0.05). Conclusion: Therapeutic I-131-mIBG for metastatic pulmonary or gastroenteropancreatic neuroendocrine tumors appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up each help prognosticate expected survival following mIBG therapy. Multiple rounds of mIBG are associated with prolonged survival; it is unclear whether this represents cause or effect.
  • Thumbnail Image
    ItemOpen Access
    Tumor protein p53 mutation in archived tumor samples from a 12-year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long-term survival with DeltaRex-G: A case report and literature review.
    (Molecular and clinical oncology, 2021-09) Morse, Michael A; Chawla, Sant P; Wong, Terence Z; Bruckner, Howard W; Hall, Frederick L; Gordon, Erlinda M
    DeltaRex-G is a replication-incompetent amphotropic murine leukemia virus-based retroviral vector that displays a collagen-matrix-targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal 'dominant negative', i.e. a truncated construct of the executive cyclin G1 (CCNG1) oncogene. DeltaRex-G inhibits the CCNG1 function of promoting cell competence and survival through the commanding CCNG1/cyclin-dependent kinase (CDK)/Myc/mouse double minute 2 homolog (Mdm2)/p53 axis. In 2009, DeltaRex-G was granted Fast Track designation from the US Food and Drug Administration for the treatment of pancreatic cancer. In 2019, the results of a phase 1/2 study that used DeltaRex-G as monotherapy for stage 4 chemotherapy-resistant pancreatic ductal adenocarcinoma (PDAC) were published. A unique participant of the aforementioned phase 1/2 study is now an 84-year-old Caucasian woman with chemoresistant PDAC who was treated with DeltaRex-G, 3x1011 colony forming units (cfu)/dose, 3 times/week for 4 weeks with a 2-week rest period, for 1.5 years. During the treatment period, the patient's tumors in the liver, lymph node and peritoneum exhibited progressive decreases in size, which were accompanied by a reduction and normalization of serum carbohydrate antigen 19-9 levels, and the patient achieved complete remission after 8 months of DeltaRex-G therapy with minimal side effects (grade 2 fatigue). Henceforth, the patient has been in remission for 12 years with no evidence of disease, no late therapy-related adverse events, and no further cancer therapy following DeltaRex-G treatment. The present study reports a mutation of tumor protein p53 (TP53) (G199V) found retrospectively in the patient's archived tumor samples. TP53 is a well-characterized tumor suppressor gene, and a critical regulatory component of the executive CCNG1/CDK/Myc/Mdm2/p53 axis, which regulates proliferative cell competence, DNA fidelity and survival. Studies are underway to determine whether TP53 mutations in pancreatic cancer can help identify a subset of patients with advanced metastatic cancer with an otherwise poor prognosis who would respond favorably to DeltaRex-G, which would broaden the treatment options for patients with otherwise lethal PDAC.