Kyoungjune Pak

Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis in Head and Neck Cancer: A Systematic Review and Meta-Analysis

We conducted a comprehensive systematic review of the literature on volumetric parameters and a meta-analysis of the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with head and neck cancer (HNC). Methods: A systematic search of MEDLINE and EMBASE was performed using the key words PET, head and neck, and volume. Inclusion criteria were 18F-FDG PET used as an initial imaging tool; studies limited to HNC; patients who had not undergone surgery, chemotherapy, or radiotherapy before PET scans; and studies reporting survival data. Event-free survival and overall survival were considered markers of outcome. The impact of MTV or TLG on survival was measured by the effect size hazard ratio (HR). Data from each study were analyzed using Review Manager. Results: Thirteen studies comprising 1,180 patients were included in this study. The combined HR for adverse events was 3.06 (2.33–4.01, P < 0.00001) with MTV and 3.10 (2.27–4.24, P < 0.00001) with TLG, meaning that tumors with high volumetric parameters were associated with progression or recurrence. Regarding overall survival, the pooled HR was 3.51 (2.62–4.72, P < 0.00001) with MTV and 3.14 (2.24–4.40, P < 0.00001) with TLG. There was no evidence of significant statistical heterogeneity at an I2 of 0%. Conclusion: MTV and TLG are prognostic predictors of outcome in patients with HNC. Despite clinically heterogeneous HNC and the various methods adopted between studies, we can confirm that patients with a high MTV or TLG have a higher risk of adverse events or death.

Prognostic value of volumetric parameters measured by F-18 FDG PET/CT in surgically resected non-small-cell lung cancer.

Objectives The aim of this study was to evaluate the usefulness of the tumor burden as characterized by the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by F-18 fluoro-2-deoxyglucose (F-18 FDG) PET-computed tomography (CT) in predicting recurrence-free survival (RFS) and overall survival (OS) in surgically resected non-small-cell lung cancer (NSCLC) patients. Methods We retrospectively reviewed 91 patients with pathologically documented stages I–IIIA NSCLC. MTV and TLG were obtained according to various thresholds of the standard uptake value (SUV) of primary tumor using preoperative F-18 FDG PET-CT. We used comparison receiver-operating characteristic curve analysis to test the statistical significance of the differences among the multiple volumetric parameters calculated by various SUV cutoff values. RFS and OS were evaluated with the Kaplan–Meier method and Cox regression analysis. Results On comparison receiver-operating characteristic curve analysis, no significant difference was found among the volumetric parameters calculated using various thresholds of SUV. Regardless of the thresholds, patients with smaller MTV and lower TLG showed longer RFS and OS. MTV and TLG measured by F-18 FDG PET-CT were found to have better predictive performance than SUVmax for recurrence and death. According to multivariate analyses, MTV2.5 was revealed as a significant prognostic factor for RFS. Tumor size over 3 cm was selected as a significant prognostic indicator of OS. Conclusion Volume-based parameters of F-18 FDG PET-CT may have a role in providing prognostic information in NSCLC patients who have received surgical treatment.

Clinical Implication of PET/MR Imaging in Preoperative Esophageal Cancer Staging: Comparison with PET/CT, Endoscopic Ultrasonography, and CT

This was a study to compare the diagnostic efficacies of endoscopic ultrasonography (EUS), CT, PET/MR imaging, and PET/CT for the preoperative local and regional staging of esophageal cancer, with postoperative pathologic stage used as the reference standard. Methods: During 1 y, 19 patients with resectable esophageal cancer were enrolled and underwent preoperative EUS, CT, PET/CT, and PET/MR imaging. A chest radiologist and nuclear medicine physician retrospectively reviewed the images and assigned tumor and lymph node stages according to the seventh version of the TNM system and the American Joint Committee on Cancer staging system. Four patients who were treated nonsurgically were excluded from data analysis. The efficacies of EUS, CT, PET/CT, and PET/MR imaging were compared. Results: Primary tumors were correctly staged in 13 (86.7%), 10 (66.7%), and 5 (33.3%) patients at EUS, PET/MR imaging, and CT, respectively (P value ranging from 0.021 to 0.375). The accuracy of determining T1 lesions was 86.7%, 80.0%, and 46.7% for EUS, PET/MR imaging, and CT, respectively. For distinguishing T3 lesions, the accuracy was 93.3% for EUS and 86.7% for both PET/MR imaging and CT. For lymph node staging, the accuracy was 83.3%, 75.0%, 66.7%, and 50.0% for PET/MR imaging, EUS, PET/CT, and CT, respectively. In addition, area-under-the-curve values were 0.800, 0.700, 0.629, and 0.543 for PET/MR imaging, EUS, PET/CT, and CT, respectively. Conclusion: PET/MR imaging demonstrated acceptable accuracy for T staging compared with EUS and, although not statistically significant, even higher accuracy than EUS and PET/CT for prediction of N staging. With adjustments in protocols, PET/MR imaging may provide an important role in preoperative esophageal cancer staging in the future.

Predictive Value of F-18 FDG PET/CT for Malignant Pleural Effusion in Non-Small Cell Lung Cancer Patients

Background: The purpose of this study was to evaluate the accuracy of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) imaging in the detection of malignant pleural effusion and pleural metastasis in patients with non-small cell lung cancer (NSCLC). Materials and Methods: We analyzed F-18 FDG PET/CT images of 33 lung cancer patients with pleural effusion. We used 2 categorical parameters to differentiate malignant from benign pleural effusion: i) quantitative parameters using maximum standardized uptake value (SUVmax of effusion and pleura, and the following ratios: lesion to aorta (L/Ao), to cerebellum (L/Cbl), to liver (L/Liv), to nonlesion (L/NL), and to primary lung cancer (L/Prim)) and ii) various parameters determined by PET and CT scans (uptake at the pleural region, Hounsfield unit, size, and morphology of any solid abnormality). Results: Malignant pleural effusions showed significantly higher L/Prim values than benign pleural effusions. The presence of pleural abnormality on CT and pleural region uptake on PET images were found to be significantly more frequent in cases of malignant pleural disease. These parameters could differentiate malignant and benign pleural effusion according to receiver operating characteristic (ROC) analyses. There were no statistical differences between L/Prim, pleural abnormality on CT, and pleural region uptake on PET images. Abnormal pleural region uptake on PET images was the most accurate parameter identifying malignant pleural effusion by logistic regression analysis. Conclusions: Our results suggest that F-18 FDG PET/CT can be used as a reliable and noninvasive method for the differentiation of malignant and benign pleural disease in patients with NSCLC.

The clinical implication and prediction of diffuse splenic FDG uptake during cancer surveillance.

Objective: The purpose of this study was to investigate correlations between diffuse splenic FDG uptake and hematological and inflammatory parameters to clarify the significance of splenic FDG uptake on PET/CT images. Methods: We retrospectively analyzed the consecutive records of F-18 FDG PET/CT scans and selected 31 patients with diffuse splenic FDG uptake as patient group. A total of 25 patients who underwent F-18 FDG PET/CT scans for simple health checkup were enrolled as control group. ROIs were placed on the liver and spleen to measure maximal standardized uptake value (SUVmax). The spleen SUVmax was divided by the liver SUVmax to calculate the spleen/liver ratio. The correlations between the S/L ratio and various hematological parameters were evaluated. Results: The S/L ratio was positively correlated with serum C-reactive protein level, white blood cell count, and neutrophil count and negatively correlated with hemoglobin, hematocrit, and red blood cell count. Under multiple regression analysis, the Hb level and the C-reactive protein level were the significant predictors for diffuse splenic FDG uptake. Conclusion: In conclusion, our study suggests that concurrent inflammation or anemia at the time of PET/CT study could be one of various causes of diffuse splenic FDG uptake.

Impact of cytokines on diffuse splenic 18F-fluorodeoxyglucose uptake during positron emission tomography/computed tomography.

ObjectivesConcurrent inflammation or anemia at the time of PET/computed tomography (CT) could be one of several causes of diffuse splenic 18F-fluorodeoxyglucose (18F-FDG) uptake. In this study, we focused on cytokines to investigate interactions during this phenomenon and clarify the significance of splenic 18F-FDG uptake in PET/CT. MethodsWe selected 40 patients (17 women and 23 men) with cholangiocarcinoma, pancreatic cancer, or gallbladder cancer who had undergone PET/CT. These patients were subdivided into two groups (group A: patients showing splenic 18F-FDG uptake exceeding hepatic uptake; group B: patients showing hepatic 18F-FDG uptake exceeding splenic uptake). Blood sampling was performed for each patient on the same day as PET/CT, and 22 types of cytokines and hematologic indices were analyzed. ResultsGroup A showed higher levels of interleukin (IL)-1&bgr; (P=0.0478), IL-1RA (P=0.0044), IL-4 (P=0.0118), IL-6 (P=0.0375), IL-7 (P=0.0478), and IL-13 (P=0.0081) compared with group B. However, interferon-inducible protein-10 (IP-10; P=0.1714), IL-9 (P=0.8022), IL-8 (P=0.1631), IL-5 (P=0.5273), IL-3 (P=0.3097), IL-23 (P=0.1194), IL-2 (P=0.1099), IL-1&agr; (P=0.4439), IL-17&agr; (P=0.8811), IL-16 (P=0.3201), IL-15 (P=0.0580), interferon-&ggr; (IFN-&ggr;; P=0.5308), growth-regulated oncogene (GRO; P=0.2847), granulocyte macrophage-colony-stimulating factor (GM-CSF; P=0.0913), granulocyte-colony-stimulating factor (G-CSF; P=0.5244), and soluble CD40 ligand (sCD40L; P=0.1714) levels in group A were not statistically significantly different compared with those in the control group. In addition, the white blood cell counts and C-reactive protein levels in group A showed higher values compared with group B. IL-13 among the cytokines and C-reactive protein among the hematologic indices were significant predictors of splenic 18F-FDG uptake exceeding hepatic 18F-FDG uptake. ConclusionThis study showed that splenic 18F-FDG uptake is related to IL-1&bgr;, IL-1receptor antagonist, IL-4, IL-6, IL-7, and IL-13. These cytokines may reflect the activation of humoral immunity of the spleen.

Prognostic value of microRNAs in osteosarcoma: a meta-analysis

BACKGROUND Osteosarcoma is the most common primary bone malignancy. We meta-analyzed the prognostic value of altered miRNAs in patients with osteosarcoma. METHODS Sources from MEDLINE (from inception to August 2016) and EMBASE (from inception to August 2016) were searched. Studies of osteosarcoma with results of miRNA and studies that reported survival data were included and two authors performed the data extraction independently. Any discrepancies were resolved by a consensus. The outcome was overall survival and event-free survival assessed using hazard ratios (HRs). RESULTS After reviewing the full text of 65 articles, 25 studies including 2,278 patients were eligible in this study. The pooled HR for deaths was 1.40 (95% confidence interval [CI] 1.01-1.94, p=0.04) with random-effects model (χ2=113.08, p<0.00001, I2=79%) for patients of osteosarcoma with lower expression of miRNA. However, the pooled HR for events was not significant (HR 0.97, 0.63-1.48, p=0.87, χ2=72.65, p<0.00001, I2=79%). In pathway analysis of miRNAs, miRNA449a, 199-5p, 542-5p have common target genes. CONCLUSIONS Expression level of miRNA in patients of osteosarcoma is important as a prognostic factor.

Diffuse increased splenic F-18 fluorodeoxyglucose uptake may be an indirect sign of acute pyogenic cause rather than tuberculous in patients with infectious spondylitis.

ObjectiveThe aim of this study was to investigate whether diffuse increased splenic fluorodeoxyglucose (FDG) uptake may be an indirect sign of an acute pyogenic cause of infectious spondylitis (IS). MethodsA retrospective review identified consecutive records of patients with IS who underwent F-18 FDG positron emission tomography−computed tomography scans between January 2007 and July 2008 and recruited 23 patients (57.8±15.6 years, range: 20–81 years, eight men, 15 women) and their hematological laboratory data. The regions of interest were used to measure the maximum standardized uptake value (SUVmax) for the bone marrow (BM), liver, and spleen in each patient. We calculated the spleen/liver ratio (S/L ratio) by dividing the spleen SUVmax by liver SUVmax and the spleen/BM ratio (S/B ratio) by dividing spleen SUVmax by BM SUVmax as a parameter to assess the splenic FDG uptake. ResultsThe acute pyogenic cause of the IS group showed statistically significantly higher values of spleen SUVmax (median, 1.71 vs. 1.16, P=0.0108), S/L ratio (median, 1.08 vs. 0.88, P=0.0454), and S/B ratio (median, 1.30 vs. 0.94, P=0.0055) than the chronic tuberculous cause of the IS. The optimal cut-off values for the quantitative indices were spleen SUVmax>1.49, S/B ratio>0.957, and S/L ratio>0.889. ConclusionOn the basis of the results presented, this study demonstrated that some quantitative indices from F-18 FDG positron emission tomography/computed tomography images could be indirect signs of an acute pyogenic cause of the IS. Among the various quantitative indices, spleen SUVmax, S/B ratio, and S/L ratio were potent indicators for an acute pyogenic cause of the IS.

SLC2A2 (GLUT2) as a novel prognostic factor for hepatocellular carcinoma

High rates of glucose transport via solute carrier (SLC2A, GLUT) family members are required to satisfy the high metabolic demands of cancer cells, and because of this characteristic of cancer cells 2-18fluoro-deoxy-D-glucose (18FDG)-PET has become a powerful diagnostic tool. However, its sensitivity for hepatocellular carcinoma (HCC) is lower than for other malignancies, which suggests SLC2A family members are differentially expressed in HCC. In the present study, the expression patterns of SLC2A family members in tumor tissues and their associations with HCC progression were analyzed using data obtained from The Cancer Genome Atlas (TCGA). It was found that the expression of SLC2A2 (GLUT2) was higher in HCC than those of other members of the SLC2A family. The associations of the expression levels of SLC2A family members and previously known prognostic factors with clinical stages were examined using the T-test or the Mann-Whitney U test, and interestingly, SLC2A2 expression was found to be associated with an advanced clinical stage (p = 0.0015). Furthermore, Kaplan-Meier analysis using the log-rank or the Gehan-Breslow-Wilcoxon test showed SLC2A2 expression was positively associated with overall survival (p < 0.001, Gehan-Breslow-Wilcoxon test and p = 0.0145 by multivariate Cox regression). The prognostic significance of SLC2A2 was similar in both early and late stages. However, it was more significant in HCC patients without alcohol consumption history and hepatitis C infection. Taken together, SLC2A2 was associated with clinical stages and independently associated with overall survival in patients with HCC. We suggest that SLC2A2 be considered a new prognostic factor for HCC.

Determination of regional lymph node status using (18)F-FDG PET/CT parameters in oesophageal cancer patients: comparison of SUV, volumetric parameters and intratumoral heterogeneity.

OBJECTIVE We aimed to investigate whether the standardized uptake values, volumetric parameters and intratumoral heterogeneity of fluorine-18-fludeoxyglucose ((18)F-FDG) uptake could predict regional lymph node (rLN) metastasis in oesophageal cancer. METHODS 51 patients with surgically resected oesophageal cancer were included in the present study. The (18)F-FDG positron emission tomography (PET)/CT findings and rLN metastasis were compared with the histopathological results. The intratumoral metabolic heterogeneity was represented by the heterogeneity factor (HF), which was determined for each patient. Univariate and multivariate analyses were used to analyse the associations between the rLN metastasis and clinical findings, standardized uptake values, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and HF. RESULTS The rLN(+) group showed statistically significant higher values of MTV (median, 13.59 vs 6.6; p = 0.0085), TLG (median, 119.18 vs 35.96; p = 0.0072) and HF (median, 3.07 vs 2.384; p = 0.0002) than the rLN(-) group. Univariate analysis showed that maximum standardized uptake value, mean standardized uptake value, MTV, TLG and HF were significantly associated with pathologic rLN involvement. However, in multivariate analysis, the HF was a potent associated factor for the prediction of pathologic rLN metastasis in oesophageal cancer. CONCLUSION In conclusion, (18)F-FDG PET/CT parameters such as maximum standardized uptake value, mean standardized uptake value, MTV, TLG and HF were useful for the prediction of pathologic rLN status in patients with oesophageal cancer. However, HF might be the most powerful predictor of rLN metastasis of patients with oesophageal cancer. ADVANCES IN KNOWLEDGE Assessment of intratumoral heterogeneity of (18)F-FDG PET/CT may be a useful adjunct for rLN staging of oesophageal cancer.