Assessment of tumor response to chemotherapy in patients with breast cancer using (18)F-FLT: a meta-analysis.

PURPOSE: To determine the diagnostic performance of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography/computed tomography (FLT PET/CT) and FLT PET for evaluating response to chemotherapy in patients with breast cancer. METHODS: Databases such as PubMed (MEDLINE included) and excerpta medica database (EMBASE), were searched for relevant original articles. The included studies were assessed for methodological quality with quality assessment of diagnosis accuracy studies (QUADAS) score tool. Histopathological analysis and/or clinical and/or radiological follow-up for at least 6 months were used as the reference standard. The data were extracted by two reviewers independently to analyze the sensitivity, specificity, summary receiver operating characteristic (SROC) curve, area under the curve (AUC), and heterogeneity. RESULTS: The present study analyzed a total of 4 selected articles. The pool sensitivity was 0.773 [95% confidence interval (CI): 0.594-0.900]. The pooled specificity was 0.685 (95% CI: 0.479-0.849) on basis of FEM. The pooled LR+, LR-, and DOR were 2.874 (1.492-5.538), 0.293 (0.146-0.589), and 14.891 (3.238-68.475), respectively. The AUC was 0.8636 (±0.0655), and the Q* index was 0.7942 (±0.0636). CONCLUSIONS: Our results indicate that (18)F-FLT PET/CT or PET is useful to predict chemotherapy response in breast cancer with reasonable sensitivity, specificity and DOR. However, future larger scale clinical trials will be needed to assess the regimen of (18)F-FLT PET/CT or PET in monitoring the response to chemotherapy in breast cancer patients.

Diagnosis of bone metastases: a meta-analysis comparing ¹8FDG PET, CT, MRI and bone scintigraphy.

OBJECTIVE: To perform a meta-analysis to compare (18)FDG PET, CT, MRI and bone scintigraphy (BS) for the diagnosis of bone metastases. METHODS: Databases including MEDLINE and EMBASE were searched for relevant original articles published from January 1995 to January 2010. Software was used to obtain pooled estimates of sensitivity, specificity and summary receiver operating characteristic curves (SROC). RESULTS: 67 articles consisting of 145 studies fulfilled all inclusion criteria. On per-patient basis, the pooled sensitivity estimates for PET, CT, MRI and BS were 89.7%, 72.9%, 90.6% and 86.0% respectively. PET=MRI>BS>CT. ("="indicated no significant difference, P > 0.05; ">" indicated significantly higher, P < 0.05). The pooled specificity estimates for PET, CT, MRI and BS were 96.8%, 94.8%, 95.4% and 81.4% respectively. PET = CT = MRI>BS. On per-lesion basis, the pooled sensitivity estimates for PET, CT, MRI and BS were 86.9%, 77.1%, 90.4% and 75.1% respectively. PET = MRI>BS>CT. The pooled specificity estimates for PET, CT, MRI and BS were 97.0%, 83.2%, 96.0% and 93.6% respectively. PET>MRI>BS>CT. CONCLUSION: PET and MRI were found to be comparable and both significantly more accurate than CT and BS for the diagnosis of bone metastases.

FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells.

BACKGROUND: Cervical cancer is one of the most common causes of cancer-associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. METHODS: Western blot was applied to determine the expression of FEN1- and apoptosis-related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. RESULTS: Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. CONCLUSION: FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.

Fatal interstitial lung disease associated with AZD9291.

AZD9291 is one of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) induced by AZD9291 is very seldom. We provide a case of NSCLC treated with AZD9291 who developed ILD and died in order to improve the knowledge on AZD9291.

Effect of gemcitabine on the uptake of (18)F-fluorodeoxyglucose and (18)F-fluorothymidine in lung adenocarcinoma A549 cells and the animal tumor model.

BACKGROUND: Gemcitabine is the first-line drug for nonsmall cell lung cancer, and 18F-fluorodeoxyglucose. (18F-FDG) and 18F-fluorothymidine. (18F-FLT) are positron emission tomography. (PET) imaging agents. The aim of this study was to explore the effect of gemcitabine on the uptake of 18F-FDG and 18F-FLT in A549 cells and the animal tumor model. MATERIALS AND METHODS: The inhibitory effects of gemcitabine on cell growth were determined by tetrazolium blue method, and uptake rates of 18F-FDG and 18F-FLT were determined under the same conditions. The adenocarcinoma-bearing nude mice before and after gemcitabine treatments were performed microPET imaging with 18F-FDG and 18F-FLT. Hematoxylin and eosin staining and immunohistochemical analysis of tumor specimens were conducted. RESULTS: After the administration of gemcitabine, positive correlations were observed between inhibition of 18F-FDG or 18F.FLT uptake and cell growth. (r = 0.957 or 0.981, P < 0.01). SUVmax values by 18F-FDG in the tumor, before and after administration of gemcitabine at the dose of 60 mmol/L, revealed an increase by. (35.83 ± 10.58) %. After administration of 120 mmol/L gemcitabine, the SUVmax values decreased by (12.37 ± 7.33) %. The SUVmax values by 18F-FLT at the dose of 60 mmol/L gemcitabine revealed a decrease by (56.47 ± 10.83) %. Pathological staining showed obvious vasodilation and invasion of lymphocytes and plasma cells at the dose of 60 mmol/L, and the expression of glucose transporter protein-1, Ki-67 and proliferating cell nuclear antigen in tumor cells were inhibited. CONCLUSION: 18F-FLT imaging can assess the proliferation of tumor cells and 18F-FDG imaging can reflect the changes of the tumor microenvironment after administration of gemcitabine.

Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG) and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis.

OBJECTIVE: To study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles. METHODS: We searched PubMed (MEDLINE included), EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014), according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2). The correlation coefficient (r) was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r) and the 95% confidence interval (CI) were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses. RESULTS: According to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46), but with a significant heterogeneity (I2 = 80.9%, P<0.01). Subgroup analysis for different tumor types indicated that most subgroups showed a reduced heterogeneity. Malignant melanoma (n = 1) had the minimum correlation coefficient (-0.22) between 18F-FDG uptake and Ki-67 expression, while the thymic epithelial tumors (TETs; n = 2) showed the maximum correlation coefficient of 0.81. The analytical results confirmed that correlation between 18F-FDG uptake and Ki-67 expression was extremely significant in TETs, significant in gastrointestinal stromal tumors (GISTs), moderate in patients with lung, breast, bone and soft tissue, pancreatic, oral, thoracic, and uterine and ovarian cancers, average in brain, esophageal and colorectal cancers, and poor in head and neck, thyroid, gastric and malignant melanoma tumors. Subgroup analysis indicated that positron emission tomography (PET) or PET/CT imaging technology or Ki-67 and standardized uptake value (SUV) measurement technology did not significantly affect the results of r values, and Begg's test showed no significant publication bias. CONCLUSION: In cancer patients, 18F-FDG uptake showed a moderate positive correlation with tumor cell proliferation. Different tumor types exhibited varied degree of correlation, and the correlation was significant in TETs and GSTs. However, our results need further validation by clinical trials with a large sample of different tumor types.

Extracellular volume fraction in coronary chronic total occlusion patients.

(1) To assess extracellular volume fraction (ECV) and regional systolic function in patients presenting with coronary chronic total occlusion (CTO) in areas without significant late gadolinium enhancement (LGE), and (2) to investigate the correlation between angiography collateral flow and ECV in territories supplied by CTO vessels. A total of 50 angiographically documented CTO patients and 15 age- and sex-matched normal controls were recruited to the study. Myocardial ECV, was calculated in infarcted, global non-infarcted and the entire myocardium respectively. Segmental ECV was calculated from myocardial segments within the perfusion territory of a CTO vessel. The global and regional systolic function was evaluated using ejection fraction and percent systolic thickening. ECVs in global myocardium and global non-infarcted myocardium were significantly elevated in comparison with that in controls (29.1 ± 4.2% and 26.6 ± 2.6% vs. 23.3 ± 2.0%, all P < 0.005). Global ECV significantly correlated with LV ejection fraction (r = -0.56, P < 0.001) and ECV inversely correlated with systolic thickening in global non-infarcted myocardium (r = -0.31, P < 0.05). The lower segmental ECV was associated with the presence of well-developed collaterals (P = 0.004), and multivariate binary logistic analysis demonstrated that mean segmental ECV and course of disease were the independent discriminator of collateral flow with overall diagnostic accuracy of 74.4%. In patients with CTO, ECV is found to be increased beyond that observed with LGE, and correlates with LV regional wall motion abnormality, which appears to reflect diffuse myocardial fibrosis. Mean segmental ECV value, combined with course of disease, may serve as good predictors of collateral flow.

Detection of glioma recurrence by ¹¹C-methionine positron emission tomography and dynamic susceptibility contrast-enhanced magnetic resonance imaging: a meta-analysis.

PURPOSE: This study aimed to compare the diagnostic value of ¹¹C-methionine (¹¹C-MET) PET and dynamic susceptibility contrast-enhanced (DSCE) MRI in detecting glioma recurrence by meta-analysis. MATERIALS AND METHODS: Databases such as PubMed (MEDLINE included), EMBASE, Science Direct, Springerlink, EBSCO, and Cochrane Database of Systematic Review were searched for relevant original articles on the detection of recurrent glioma using DSCE MRI or ¹¹C-MET PET with or without computed tomography. No restriction was imposed over the types and grades of glioma. The included studies were assessed for methodological quality. Results from histopathological analysis and/or close clinical and/or radiological follow-up for at least 3 months were used as the reference standard. The data were extracted by two reviewers independently to analyze the sensitivity, specificity, summary receiver-operating characteristic curve, area under the curve, and heterogeneity. RESULTS: The present study analyzed a total of 17 selected articles including different types and grades of glioma and showed that ¹¹C-MET PET and DSCE MRI had comparable sensitivity (0.870 and 0.884, respectively), specificity (0.813 and 0.853, respectively), positive likelihood ratio (4.355 and 5.806, respectively), negative likelihood ratio (0.192 and 0.134, respectively), and diagnostic odds ratio (21.857 and 41.918, respectively) without statistically significant differences, except for the fact that DSCE MRI displayed higher area under the curve and Q* index compared with ¹¹C-MET PET (P<0.05). CONCLUSION: Both ¹¹C-MET PET and DSCE MRI are accurate tools for detecting glioma recurrence. Although DSCE MRI seems to be superior to ¹¹C-MET PET, the latter can also be used to assess glioma recurrence when the former is not available.

Early evaluation for treatment efficacy of 5-fluorouracil and hyperthermia on HCT-116 colon cancer cells by fluorine-18-fluorodeoxyglucose uptake.

BACKGROUND: Fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography imaging can be used to assess the treatment efficacy of chemotherapy and prognosis. The aim of this study was to determine the uptake rate of (18)F-FDG in colon cancer HCT-116 cells, and to evaluate the treatment efficacy of chemotherapy, hyperthermia and thermo-chemotherapy through the uptake inhibition rate of (18)F-FDG. METHODS: The uptake rate of (18)F-FDG in HCT-116 cells was determined at various experimental conditions. The inhibition rate of cell growth, uptake rate of (18)F-FDG and uptake inhibition rate of (18)F-FDG in HCT-116 cells treated with 5-fluorouracil (5-FU) at various concentrations were determined. In HCT-116 cells subjected to chemotherapy (5-FU, 100 µg/ml), hyperthermia (43°C, 40 minutes) and thermo-chemotherapy for 24 hours, the inhibition rate of cell growth and uptake inhibition rate of (18)F-FDG were determined; early apoptosis, the morphology and ultrastructure of HCT-116 cells were examined; and the contents of glucose and lactate dehydrogenase (LDH) in the cell culture medium of HCT-116 cells were determined. One-way analysis of variance (ANOVA) and correlation analyses were conducted by using SPSS 16.0 software. RESULTS: The uptake rate of (18)F-FDG in HCT-116 cells was (44.25 ± 2.19)%. Under the condition of adding 5-FU at various concentrations for 24 hours, the uptake rate of (18)F-FDG was negatively correlated with 5-FU dosage (r = -0.879, P < 0.01); the inhibition rate of cell growth revealed a positive correlation with the uptake inhibition rate of (18)F-FDG (r = 0.831, P < 0.01). In HCT-116 cells subjected to hyperthermia, chemotherapy, and thermo-chemotherapy for 24 hours, the uptake inhibition rates of (18)F-FDG were (12.94 ± 2.80)%, (28.25 ± 4.59)%, and (21.60 ± 3.68)%, respectively. The early apoptotic rates of HCT-116 cells were (9.80 ± 0.16)%, (19.80 ± 2.40)%, and (15.70 ± 1.80)%, respectively. Moreover, the contents of glucose and LDH in cell culture medium of HCT-116 cells after treatments were higher than those before treatment. CONCLUSION: The uptake inhibition rate of (18)F-FDG can be used for early evaluation of hyperthermia and 5-FU treatment efficacy on cancer cells although hyperthermia (43°C, 40 minutes) does not reveal the synergistic effect on 5-FU at the low dosage.