Dataset Information

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

ABSTRACT:

Background

In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET.

Patients and methods

We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes.

Results

A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ?7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039).

Conclusion

Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC.

SUBMITTER: Cho KM

PROVIDER: S-EPMC4524751 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

Cho Kyoung-Min KM Oh Do-Youn DY Kim Tae-Yong TY Lee Kyung Hun KH Han Sae-Won SW Im Seock-Ah SA Kim Tae-You TY Bang Yung-Jue YJ

The oncologist 20150622 8

<h4>Background</h4>In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET.<h4>Patients and methods</h4>We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to p ...[more]

PMID: 26099746

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Project description:Background and objectiveNumerous previous studies have assessed the prognostic role of 18F-fluorodeoxyglucose positron-emission tomography (18F FDG PET) in patients with biliary tract cancer (BTC), but those results were inconsistent. The present study aims to determine the predictive value of 18F FDG PET in BTC patients via a meta-analysis.MethodsThe underlying studies related to 18F FDG PET and BTC patients` outcomes were searched and identified in the online databases. The interested parameters include total lesion glycolysis (TLG), metabolic tumor volume (MTV), primary tumor and metastatic lymph node (LN) maximum standardized uptake value (SUVmax), as well as change of SUVmax (ΔSUVmax) during treatment. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were considered as the primary endpoints. Hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were defined as the effective measure and calculated by a pooled analysis. Publication bias was assessed by funnel plot, Bagg's and Egger's tests.ResultsTotally, 23 studies involving 1478 patients were included in the present meta-analysis. After a pooled analysis, it revealed that a high SUVmax was significantly associated with a poor OS (HR:2.07, 95%CI: 1.74-2.46, P = 0.000) and DFS (HR: 2.28, 95%CI: 1.53-3.41, P = 0.000). In addition, an increased TLG level contributed to a shorter OS (HR:1.91, 95%CI: 1.26-2.90, P = 0.002) and DFS (HR: 4.34, 95%CI: 1.42-13.27, P = 0.01). Moreover, we confirmed that an elevated MTV was significantly associated with increased mortality (HR:2.04, 95%CI:1.26-3.31, P = 0.004) and disease relapse (HR: 3.88, 95%CI:1.25-12.09, P = 0.019) risks. Besides, the present study uncovered that increased ΔSUVmax could predict poor OS (HR:1.26, 95%CI:1.06-1.50, P = 0.008) instead of PFS (HR: 1.96, 95%CI: 0.82-4.72, P = 0.280). Lastly, we found that LN SUVmax did not link to OS (HR: 1.49, 95%CI: 0.83-2.68, P = 0.178). No obvious publication bias was detected in the present study.Conclusion18F FDG PET parameters, including SUVmax, TLG, MTV, and ΔSUVmax, could be applied as convenient and reliable factors for predicting BTC patients` outcomes.

Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

Project description:COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.

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

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

Background

Patients and methods

Results

Conclusion

Publications

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

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