Quantifying Tumor Vascular Heterogeneity with Dynamic Contrast-Enhanced Magnetic Resonance Imaging: A Review

Tumor microvasculature possesses a high degree of heterogeneity in its structure and function. These features have been demonstrated to be important for disease diagnosis, response assessment, and treatment planning. The exploratory efforts of quantifying tumor vascular heterogeneity with DCE-MRI have led to promising results in a number of studies. However, the methodological implementation in those studies has been highly variable, leading to multiple challenges in data quality and comparability. This paper reviews several heterogeneity quantification methods, with an emphasis on their applications on DCE-MRI pharmacokinetic parametric maps. Important methodological and technological issues in experimental design, data acquisition, and analysis are also discussed, with the current opportunities and efforts for standardization highlighted

Feasibility of Na18F PET/CT and MRI for Noninvasive In Vivo Quantification of Knee Pathophysiological Bone Metabolism in a Canine Model of Post-traumatic Osteoarthritis.

PURPOSE To assess and quantify by molecular imaging knee osseous metabolic changes serially in an in vivo canine model of posttraumatic osteoarthritis (PTOA) of the knee utilizing sodium fluoride (Na18F) positron emission tomography (PET)/computed tomography (CT) coregistered with magnetic resonance imaging (MRI). MATERIALS AND METHODS Sodium fluoride PET imaging of 5 canines was performed prior to anterior cruciate ligament transection (ACLT) and 2 times post-ACLT (3 and 12 weeks). The PET/CT was coregistered with MRI, enabling serial anatomically guided visual and quantitative three-dimensional (3D) region of interest (ROI) assessment by maximum standardized uptake value. RESULTS Prior to ACLT, every 3D ROI assessed in both knees showed no Na18F uptake above background. The uptake of Na18F in the bone of the ACLT knees increased exponentially, presenting significantly higher uptake at 12 weeks in every region compared to the ACLT knees at baseline. Furthermore, the uninjured contralateral limb and the ipsilateral distal bones and joints presented Na18F uptake at 3 and 12 weeks post-ACLT. CONCLUSION This study demonstrated that Na18F PET/CT coregistered with MRI is a feasible molecular imaging biomarker to assess knee osseous metabolic changes serially in an in vivo canine model of knee PTOA. Moreover, it brings a novel musculoskeletal preclinical imaging methodology that can provide unique insights into PTOA pathophysiology

Theranostic Imaging of Yttrium-90

This paper overviews Yttrium-90 ( 90 Y) as a theranostic and nuclear medicine imaging of 90 Y radioactivity with bremsstrahlung imaging and positron emission tomography. In addition, detection and optical imaging of 90 Y radioactivity using Cerenkov luminescence will also be reviewed. Methods and approaches for qualitative and quantitative 90 Y imaging will be briefly discussed. Although challenges remain for 90 Y imaging, continued clinical demand for predictive imaging response assessment and target/nontarget dosimetry will drive research and technical innovation to provide greater clinical utility of 90 Y as a theranostic agent. Yttrium-90 and Its Role in Targeted Radiotherapy In general, theranostics are agents that possess diagnostic and therapeutic attributes for personalized patient treatment for various diseases 90 Y has a physical half-life of 64.1 h [4] which makes it amenable for a variety of targeted radiotherapy applications including 90 Y-labeled colloid 90 Y can be administered via direct injection into a space or cavity (e.g., radiosynovectomy), intravenously for peptide receptor radionuclide therapy (PRRT) and radioimmunotherapy (RIT), and intra-arterially for radioembolization (RE) therapy. Other therapeutic − emitting radioisotopes (e.g., 131 I for thyroid cance

Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to combine intraoperative gamma probe (GP) detection with preoperative fluorine 18-fluoro-2-deoxy-glucose positron emission tomography (¹⁸F FDG-PET) imaging in order to improve detection of tumor recurrence in colorectal cancer (CRC) patients.</p> <p>Methods</p> <p>Twenty-one patients (12 females, 9 males) with a mean age of 54 years (range 31–78) were enrolled. Patients were suspected to have recurrent CRC by elevated CEA (n = 11), suspicious CT findings (n = 1), and clinically suspicious findings (n = 9). Preoperative FDG-PET scan and intraoperative GP study were performed in all patients. Mean time interval between preoperative FDG-PET scan and surgery was 16 days (range 1–41 days) in 19 patients. For intraoperative GP studies, 19 patients were injected with a dose of 10–15 mCi ¹⁸F FDG at approximately 30 minutes before the planned surgery time. In two patients, the intraoperative GP study was performed immediately after preoperative FDG-PET scan.</p> <p>Results</p> <p>Preoperative FDG-PET and intraoperative GP detected 48 and 45 lesions, respectively. A total of 50 presumed site of recurrent disease from 20 patients were resected. Thirty-seven of 50 presumed sites of recurrent disease were histological-proven tumor positive and 13 of 50 presumed sites of recurrent disease were histological-proven tumor negative. When correlated with final histopathology, the number of true positive lesions and false positive lesions by preoperative FDG-PET and intraoperative GP were 31/9 and 35/8, respectively. Both preoperative FDG-PET and intraoperative GP were true positive in 29 lesions. Intraoperative GP detected additional small lesions in the omentum and pelvis which were not seen on preoperative FDG-PET scan. FDG-PET scan demonstrated additional liver metastases which were not detected by intraoperative GP. Preoperative FDG-PET detected distant metastasis in the lung in one patient. The estimated radiation dose received by a surgeon during a single 18F FDG GP surgery was below the occupational limit.</p> <p>Conclusion</p> <p>The combined use of preoperative FDG-PET and intraoperative GP is potentially helpful to the surgeon as a roadmap for accurately locating and determining the extent of tumor recurrence in patients with CRC. While intraoperative GP appears to be more sensitive in detecting the extent of abdominal and pelvic recurrence, preoperative FDG-PET appears to be more sensitive in detecting liver metastases. FDG-PET is also a valuable method in detecting distant metastases.</p

Alliance Foundation Trial 09: A randomized, multicenter, phase 2 trial evaluating two sequences of pembrolizumab and standard platinum-based chemotherapy in patients with metastatic NSCLC

INTRODUCTION: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy. METHODS: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a pick a winner design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy for four cycles). Patients in both arms without disease progression after the initial eight cycles continued pembrolizumab until disease progression, unacceptable toxicity, or a maximum of 2 years. RESULTS: From March 2016 to July 2018, a total of 90 eligible patients were randomized (43 patients to arm A and 47 patients to arm B). The objective response rate at 24 weeks in arms A and B was 39.5 % (95 % confidence interval [CI]: 24.9%-54.1 %) and 40.4 % (95 % CI: 26.4%-54.5 %), respectively ( CONCLUSIONS: Additional evaluation of either sequence in a phase 3 trial is not warranted

Implementation of the Combined--Nonlinear Condensation Transformation

We discuss several applications of the recently proposed combined nonlinear-condensation transformation (CNCT) for the evaluation of slowly convergent, nonalternating series. These include certain statistical distributions which are of importance in linguistics, statistical-mechanics theory, and biophysics (statistical analysis of DNA sequences). We also discuss applications of the transformation in experimental mathematics, and we briefly expand on further applications in theoretical physics. Finally, we discuss a related Mathematica program for the computation of Lerch's transcendent.Comment: 23 pages, 1 table, 1 figure (Comput. Phys. Commun., in press

Is local review of positron emission tomography scans sufficient in diffuse large B-cell lymphoma clinical trials? A CALGB 50303 analysis

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS). METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. RESULTS: Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (\u3c66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. CONCLUSIONS: These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338