Dataset Information

Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma.

ABSTRACT: Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. This study aims to investigate the utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-dihydroxyphenylalanine (FDOPA) in determining the prognosis of NB. During 2007-2014, forty-two NB patients (male:female, 28:14; median age, 2.0 years) undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maximum standardized uptake value (SUV(max)) of FDG or FDOPA by the primary tumor. Patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUV(max) (all P < 0.02). Receiver operating characteristics analysis identified FDG SUV(max) ? 3.31 and FDOPA SUV(max) < 4.12 as an ultra-high-risk feature (PET-UHR) that distinguished the most unfavorable genomic types, i.e. segmental chromosomal alterations and/or MYCN amplification, at a sensitivity of 81.3% (54.4%-96.0%) and a specificity of 93.3% (68.1%-99.8%). Considering with age, stage, MYCN status, and anatomical image-defined risk factor, PET-UHR was an independent predictor of inferior event-free survival (multivariate hazard ratio, 4.9 [1.9-30.1]; P = 0.012). Meanwhile, the ratio between FDG and FDOPA SUV(max) (G:D) correlated positively with HK2 (Spearman's ? = 0.86, P < 0.0001) and negatively with DDC (? = -0.58, P = 0.02) gene expression levels, which might suggest higher glycolytic activity and less catecholaminergic differentiation in NB tumors taking up higher FDG and lower FDOPA. In conclusion, the intensity of FDG and FDOPA uptake on diagnostic PET scans may predict the tumor behavior and complement the current risk stratification systems of NB.

SUBMITTER: Liu YL

PROVIDER: S-EPMC4951328 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma.

Liu Yen-Lin YL Lu Meng-Yao MY Chang Hsiu-Hao HH Lu Ching-Chu CC Lin Dong-Tsamn DT Jou Shiann-Tarng ST Yang Yung-Li YL Lee Ya-Ling YL Huang Shiu-Feng SF Jeng Yung-Ming YM Lee Hsinyu H Miser James S JS Lin Kai-Hsin KH Liao Yung-Feng YF Hsu Wen-Ming WM Tzen Kai-Yuan KY

Oncotarget 20160401 14

Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. This study aims to investigate the utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-dihydroxyphenylalanine (FDOPA) in determining the prognosis of NB. During 2007-2014, forty-two NB patients (male:female, 28:14; median age, 2.0 years) undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maxi ...[more]

PMID: 26959748

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Project description:ObjectiveWe aimed to evaluate the diagnostic value and prognostic relevance of FDG positron emission tomography/computed tomography (PET-CT) in extrahepatic cholangiocarcinoma patients.Materials and methodsThis study included 234 extrahepatic cholangiocarcinoma patients who underwent FDG PET-CT between June 2008 and February 2016. The diagnostic performance of FDG PEG-CT was compared to that of contrast-enhanced multidetector row CT (MDCT) and MRI. Independent prognosticators for poor survival were also assessed.ResultsThe sensitivity of FDG PET-CT for detecting primary tumor and regional lymph node metastases was lower than that of MDCT or MRI (p < 0.001), whereas the specificity and positive predictive value for detecting regional lymph nodes metastases was significantly better in FDG PET-CT compared to MDCT and MRI (all p < 0.001). There was no significant difference in the diagnostic yield of distant metastases detection among three diagnostic imaging techniques. In a multivariate analysis, maximum standardized uptake values (SUVmax) of the primary tumor (adjusted hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.13-2.69) and of the metastatic lesions ≥ 5 (adjusted HR, 8.10; 95% CI, 1.96-33.5) were independent contributors to poor overall survival in extrahepatic cholangiocarcinoma patients. In a subgroup analysis of 187 patients with periductal infiltrating type of cholangiocarcinoma, an SUVmax of the primary tumor ≥ 5 was associated with an increased risk of regional lymph node (adjusted odds ratio [OR], 1.60; 95% CI, 0.55-4.63) and distant metastases (adjusted OR, 100.57; 95% CI, 3.94-2567.43) at diagnosis as well as with poor overall survival (adjusted HR, 1.81; 95% CI, 1.04-3.15).ConclusionFDG PET-CT showed lower sensitivity for detecting primary tumor and regional lymph node involvement than MDCT and MRI. However, the SUVmax of primary tumors and metastatic lesions derived from FDG PET-CT could have significant implications for predicting prognoses in extrahepatic cholangiocarcinoma patients.

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.

Dataset Information

Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma.

Publications

Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma.

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