Dataset Information

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography.

ABSTRACT: Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

SUBMITTER: Esmail H

PROVIDER: S-EPMC5055809 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose positron emission and computed tomography.

Esmail Hanif H Lai Rachel P RP Lesosky Maia M Wilkinson Katalin A KA Graham Christine M CM Coussens Anna K AK Oni Tolu T Warwick James M JM Said-Hartley Qonita Q Koegelenberg Coenraad F CF Walzl Gerhard G Flynn JoAnne L JL Young Douglas B DB Barry Iii Clifton E CE O'Garra Anne A Wilkinson Robert J RJ

Nature medicine 20160905 10

Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identifica ...[more]

PMID: 27595321

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Project description:PurposeCervical cancer metabolic tumour volume (MTV) derived from [18F]-FDG PET/CT has a role in prognostication and therapy planning. There is no standard method of outlining MTV on [18F]-FDG PET/CT. The aim of this study was to assess the optimal method to outline primary cervical tumours on [18F]-FDG PET/CT using MRI-derived tumour volumes as the reference standard.Methods81 consecutive cervical cancer patients with pre-treatment staging MRI and [18F]-FDG PET/CT imaging were included. MRI volumes were compared with different PET segmentation methods. Method 1 measured MTVs at different SUVmax thresholds ranging from 20 to 60% (MTV20-MTV60) with bladder masking and manual adjustment when required. Method 2 created an isocontour around the tumour prior to different SUVmax thresholds being applied. Method 3 used an automated gradient method. Inter-observer agreement of MTV, following manual adjustment when required, was recorded.ResultsFor method 1, the MTV25 and MTV30 were closest to the MRI volumes for both readers (mean percentage change from MRI volume of 2.9% and 13.4% for MTV25 and - 13.1% and - 2.0% for MTV30 for readers 1 and 2). 70% of lesions required manual adjustment at MTV25 compared with 45% at MTV30. There was excellent inter-observer agreement between MTV30 to MTV60 (ICC ranged from 0.898-0.976 with narrow 95% confidence intervals (CIs)) and moderate agreement at lower thresholds (ICC estimates of 0.534 and 0.617, respectively for the MTV20 and MTV25 with wide 95% CIs). Bladder masking was performed in 86% of cases overall. For method 2, excellent correlation was demonstrated at MTV25 and MTV30 (mean % change from MRI volume of -3.9% and - 8.6% for MTV25 and - 16.9% and 19% for MTV30 for readers 1 and 2, respectively). This method also demonstrated excellent ICC across all thresholds with no manual adjustment. Method 3 demonstrated excellent ICC of 0.96 (95% CI 0.94-0.97) but had a mean percentage difference from the MRI volume of - 19.1 and - 18.2% for readers 1 and 2, respectively. 21% required manual adjustment for both readers.ConclusionMTV30 provides the optimal correlation with MRI volume taking into consideration the excellent inter-reader agreement and less requirement for manual adjustment.

Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Project description:AIM:To evaluate the usefulness of serum squamous-cell carcinoma antigen (SCC-Ag) and 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) for the detection of recurrent squamous-cell carcinoma (SqCC) of the uterine cervix, and its prediction of patient survival. METHODS:FDG-PET/CT was performed for patients with serum SCC-Ag levels elevated to ?1.5 ng/mL (Group 1) and those with suspicious recurrences without any increase in serum SCC-Ag levels (Group 2). The results were analyzed on the basis of histological data, disease progression and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of FDG-PET/CT. The outcome was determined using medical records. RESULTS:In total, 88 consecutive patients with cervical SqCC cancer with suspected recurrence (62 in Group 1 and 26 in Group 2) were enrolled. Recurrences were observed in 55 patients (77.4% (48/62) in Group 1 vs. 26.9% (7/26) in Group 2, p < 0.001). The overall sensitivity, specificity and accuracy of serum SCC-Ag were 87.3%, 57.6% and 76.1%, respectively, and those of FDG-PET/CT were 98.2%, 90.9% and 95.5%, respectively; the corresponding values were 97.9%, 92.9% and 96.8% for Group 1 and 100%, 89.5% and 92.3% for Group 2. Surgical resection was performed for 16 patients. At the end of the study, 40.3% (25/62) of Group 1 patients and 88.5% (23/26) of Group 2 patients were alive (p < 0.001). The survival of patients who underwent surgical resection for recurrent tumors was higher than that of patients who did not undergo resection (62.5% (10/16) vs. 17.9% (7/39), p = 0.001). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from FDG-PET/CT showed significantly different in-patient survival. CONCLUSIONS:Serum SCC-Ag could predict tumor recurrence and the survival of patients with SqCC cervical cancer. As such, the surgical resection of limited recurrent disease, as determined using FDG-PET/CT, might improve the survival of patients with cervical cancer. MTV and TLG may serve as a prognostic biomarker of survival in patients with recurrent cervical cancer.

Dataset Information

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography.

Publications

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose positron emission and computed tomography.

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