Preoperative prediction of mediastinal lymph node metastasis in non-small cell lung cancer based on 18F-FDG PET/CT radiomics.

AIM: To establish and verify a 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics nomogram to predict mediastinal lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) patients preoperatively. MATERIALS AND METHODS: This retrospective study enrolled 155 NSCLC patients (primary cohort, n=93; validation cohort, n=62). For each patient, 2,704 radiomic features were extracted from the primary lung cancer regions. Four procedures including the Mann-Whitney U-test, Spearman's correlation analysis, minimum redundancy-maximum relevance (mRMR), and least absolute shrinkage and selection operator (LASSO) binary logistic regression were utilised for determining essential features and establishing a radiomics signature. After that, a nomogram was established. The nomogram's potential was assessed based on its discrimination, calibration, and clinical usefulness. The radiomics signature and nomogram predictive performances were evaluated with respect to the area under the receiver operating characteristic curve (AUC), specificity, accuracy, and sensitivity. RESULTS: The radiomics signature composed of eight selected features had good discriminatory performance of LNM versus non-LNM groups an AUC of 0.851 and 0.826 in primary and validation cohorts, respectively. The nomogram also indicated good discrimination with an AUC of 0.869 and 0.847 in the primary and validation cohorts, respectively. Furthermore, good calibration was demonstrated utilising the nomogram. CONCLUSIONS: An 18F-FDG PET/CT-based radiomics nomogram that integrates the radiomics signature and age was promoted to predict mediastinal LNM within NSCLC patients, which could potentially facilitate individualised therapy for mediastinal LNM before treatment. The nomogram was beneficial in clinical practice, as illustrated by decision curve analysis.

Optimal radiotherapy after breast-conserving surgery for early breast cancer: A network meta-analysis of 23,418 patients.

PURPOSE: In order to explore whether partial breast irradiation can replace hypofractionated whole breast irradiation and whether the former two are superior to conventional fractionated whole breast irradiation, we conducted a network meta-analysis based on the data from the latest randomized controlled trials to evaluate the efficacy of these radiotherapy modalities. MATERIAL AND METHODS: Data from eligible studies were analyzed to determine the published events for ipsilateral breast tumor recurrence, distant metastasis, total deaths, and non-breast cancer-related deaths. In the case of low or high heterogeneity, the fixed-effect or random-effect model was used for statistical analysis respectively. NMA was performed by using the node-splitting model for two-category data among three radiotherapies based on a Bayesian method. RESULTS: A total of 23,418 patients were included in 16 studies. For ipsilateral breast tumor recurrence, both pairwise (OR=1.9; CI95%: 1.2 -2.8; p<0.05) and indirect (OR=1.7; CI95%: 1.2 -2.4; p<0.05) comparison of three radiotherapies by network meta-analysis showed that conventional fractionated whole breast irradiation was significantly better than partial breast irradiation. Indirect comparison of three radiotherapies by network meta-analysis showed that hypofractionated whole breast irradiation was significantly better than partial breast irradiation (OR=1.6; CI95%: 1.0 -2.5; p<0.05). Network and paired meta-analyses found no significant differences in other endpoints among the three radiotherapies. CONCLUSION: Overall, this network meta-analysis showed that partial breast irradiation was related to the increase of ipsilateral breast tumor recurrence compared with hypofractionated or conventional fractionated whole breast irradiation in patients with early-stage breast cancer.

Exon 19 deletion was associated with better survival outcomes in advanced lung adenocarcinoma with mutant EGFR treated with EGFR-TKIs as second-line therapy after first-line chemotherapy: a retrospective analysis of 128 patients

Objective. To determine whether the specific genotype of exon 19 deletion has a better survival outcome than that of exon 21 substitution in advanced lung adenocarcinoma with EGFR mutant patients that were treated with EGFR-TKIs as second-line therapy after first-line chemotherapy. Methods. Between April 1, 2010 and December 31, 2012, the detailed clinical information of 128 patients was screened from the hospital information database of the First Affiliated Hospital and the Third Affiliated Hospital of Kunming Medical University by inclusion/exclusion criteria. Then, a telephone follow-up and a review of all patients’ image data were done to obtain the survival information of all patients. After that, all patients’ data were processed by IBM® SPSS® version 19.0. Results. There were correlations between EGFR mutation status, gross tumor type and PFS or OS according to the Kaplan–Meier survival analyses and log-rank tests. The exon 19 deletions had significantly better survival outcomes in comparison to exon 21 substitutions (median PFS: 8.1 vs. 6.8 months, P = 0.002; median OS: 17.6 vs. 12.5 months, P = 0.000). Stratification analyses of PFS and OS revealed that exon 19 deletions had a survival superior to exon 21 substitutions. Conclusion. Compared with L858R mutation, the genotype of exon 19 deletion had a better survival outcome in terms of PFS and OS in patients with advanced lung adenocarcinoma treated with EGFR-TKIs as second-line therapy after first-line chemotherapy (AU)

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Knockdown of PTTG1 inhibits the growth and invasion of lung adenocarcinoma cells through regulation of TGFB1/SMAD3 signaling.

Increased expression of pituitary tumor-transforming gene 1 (PTTG1) is expressed in many tumors and regulates tumor growth and progression. However, the precise function of PTTG1 in the tumorigenesis of lung adenocarcinoma (LAC) is not defined yet. Here, we examined the expression of PTTG1 in human LAC tissues by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was carried out to investigate the effects of lentiviral vector-mediated PTTG1 shRNA (shPTTG1) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays. As a consequence, we found that the expression of PTTG1 protein was markedly upregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (54.0% vs. 28.0%, P = 0.008), and was positively associated with the lymphatic invasion of the tumor (P = 0.01). Moreover, knockdown of PTTG1 expression inhibited tumor proliferation and invasion of LAC cells, companied by the decreased expression of CyclinD1 and MMP-2 and increased expression of p-TGFß1 and p-SMAD3. Collectively, our findings indicate that high expression of PTTG1 is correlated with the tumor metastasis of LAC patients, and knockdown of PTTG1 suppresses the growth and invasion of LAC cells through upregulation of the TGFß1/SMAD3 signaling, suggesting that PTTG1 may be a potential target for developing an effective immunotherapeutic strategy for LAC.

Short-term effects of IGF-I and estradiol on LH secretion from female rat gonadotrophs.

OBJECTIVE: Growth factors and ovarian steroids modulate LH-secretion from pituitary gonadotrophs. Our previous studies demonstrated that long-term IGF-I treatment enhanced LH-secretion from female rat pituitary cells and estradiol facilitated this effect. The effects of estradiol on LH secretion are time-dependent. Short-term treatment inhibited, long-term treatment enhanced GnRH-induced LH-secretion in serum-containing medium. Here we tested the short-term actions of IGF-I and its interaction with estradiol and whether IGF-I is a prerequisite for the negative effect of short-term estradiol treatment in female rat pituitary cells. DESIGN: Pituitary cells were incubated with a series of increasing concentrations of estradiol (1 pM, 10 pM, 50 pM, 100 pM, 500 pM, 1 nM, 10 nM and 100 nM) for 4 h, IGF-I (10 pM, 100 pM, 1 nM and 10 nM) for 4 h and 14 h and their combinations for 4h in serum-free medium, and then stimulated with 1 nM GnRH during the last 3h of incubation. To clarify the role of IGF-I, cells were incubated simultaneously with estradiol, IGF-I and antibody against IGF-I. LH was measured by radioimmunoassay. RESULTS: Short-term IGF-I treatment did not modify basal or GnRH-induced LH-secretion. Short-term treatment with estradiol did not affect basal or GnRH-induced LH-secretion in serum-free medium. The addition of 100 pM IGF-I to serum-free medium established the negative effect of estradiol short-term treatment on GnRH-induced LH-secretion. The addition of IGF-I antibody fully abolished the negative effect of estradiol. CONCLUSIONS: In conclusion, effects of IGF-I on LH-secretion in female rat pituitary cells require long-term treatment. The negative effect of estradiol short-term treatment on GnRH-induced LH-secretion is dependent on serum-containing medium or the addition of 100 pM IGF-I to serum-free medium.