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Esophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer in China and is closely associated with malignant biological characteristics and poor survival. Ferroptosis is a newly discovered iron-dependent mode of cell death that plays an important role in the biological behavior of ESCC cells. The clinical significance of ferroptosis-related long noncoding RNAs (FRLs) in ESCC remains unknown and warrants further research. The current study obtained RNA sequencing profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and FRLs were obtained through coexpression analysis. Consensus clustering was employed to divide the subjects into clusters, and immune-associated pathways were identified by functional analysis. The current study observed significant differences in the enrichment scores of immune cells among different clusters. Patients from TCGA-ESCC database were designated as the training cohort. A ten-FRL prediction signature was established using the least absolute shrinkage and selection operator Cox regression model and validated using the GEO cohort and our own independent validation database. Real-time quantitative polymerase chain reaction was used to verify the expression of the ten FRLs, and the ssGSEA analysis was employed to evaluate their function. In addition, the IMvigor database was used to assess the predictive value of the signature in terms of immunotherapeutic responses. Multivariate Cox and stratification analyses revealed that the ten-FRL signature was an independent predictor of the overall survival (OS). Patients with ESCC in the high-risk group displayed worse survival, a characteristic tumor immune microenvironment, and low immunotherapeutic benefits compared to those in the low-risk group. Collectively, the risk model established in this study could serve as a promising predictor of prognosis and immunotherapeutic response in patients with ESCC.

Background Immune dysregulation plays an important role in cancer onset and development. The causal relationships between innate leukocytes prior to cancer and the risk of digestive system cancers remain unknown. This study assesses the causal correlations between white blood cells (WBC) and digestive system cancer risk in East Asians and Europeans. Methods Summary-level data of WBC-related genetic variation were extracted from Biobank Japan (107,964 and 62,076 participants), and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analysis was performed in East Asians and Europeans separately. Results Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in the East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69–0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77–0.97, P = 0.013). An inverse suggestive association was observed between levels of basophil and risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72–0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57–0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70–0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67–0.94, P = 0.007). Conclusions Our MR analyses reveal the genetically causal effect of blood eosinophils on decreased risk of CRC in both Europeans and East Asians, and of basophils on decreased risk of GC in Europeans.

Zhonghua Zou,1 Jinping Li,2 Xiang Ji,2 Tingxing Wang,1 Qingqing Chen,1 Zhengcao Liu,1 Shengjun Ji1 1Department of Radiotherapy & Oncology, the Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China; 2Department of Gastroenterology, Fangzi People’s Hospital, Weifang, People’s Republic of ChinaCorrespondence: Shengjun Ji, Department of Radiotherapy & Oncology, the affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, No. 16 Baita Road, Suzhou, 215001, People’s Republic of China, Email drshengjunji@163.comBackground: The Naples Prognostic Score (NPS) can reflect patient’s nutritional and inflammatory status, which is identified as a prognostic indicator for various malignant tumors. However, its significance in patients with resected locally advanced non-small cell lung cancer (LA-NSCLC) patients who receive neoadjuvant treatment remains unclear so far.Methods: A total of 165 LA-NSCLC patients surgically treated from May 2012 to November 2017 were retrospectively investigated. The LA-NSCLC patients were divided into three groups according to NPS scores. The receiver operating curve (ROC) analysis was performed to reveal the discriminatory ability of NPS and other indicators for predicting the survival. The NPS and clinicopathological variables were further evaluated the prognostic value by univariate and multivariate Cox analysis.Results: The NPS was related to age (P = 0.046), smoking history (P = 0.004), Eastern Cooperative Oncology Group (ECOG) score (P = 0.005), and adjuvant treatment (P = 0.017). Patients with high NPS scores had worse overall survival (OS) (group 1 vs 0, P = 0.006; group 2 vs 0, P < 0.001) and disease-free survival (DFS) (group 1 vs 0, P < 0.001; group 2 vs 0, P < 0.001). The ROC analysis demonstrated that NPS had better predictive ability than other prognostic indicators. Multivariate analysis revealed that NPS was independent prognostic indicator of OS (group 1 vs 0, hazard ratio [HR] =2.591, P = 0.023; group 2 vs 0, HR = 8.744, P = 0.001) and DFS (group 1 vs 0, HR =3.754, P < 0.001; group 2 vs 0, HR = 9.673, P < 0.001).Conclusion: The NPS could be an independent prognostic indicator in patients with resected LA-NSCLC receiving neoadjuvant treatment and more reliable than the other nutritional and inflammatory indicators.Keywords: surgery, locally advanced NSCLC, NPS, prognosis, neoadjuvant treatment

Xinwei Guo,1,* Han Zhang,2,* Liben Xu,3,* Shaobing Zhou,1 juying Zhou,4 yangchen Liu,1 Shengjun Ji5 1Department of Radiation Oncology, Affiliated Taixing People’s Hospital of Yangzhou University, Taixing, People’s Republic of China; 2School of Mathematical Science and Application, Nanjing Normal University, Taizhou College, Taizhou, People’s Republic of China; 3Department of Radiotherapy, Jiangsu University Affiliated People’s Hospital, Zhenjiang, People’s Republic of China; 4Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: yangchen LiuDepartment of Radiation Oncology, Affiliated Taixing People’s Hospital of Yangzhou University, Taixing, 225400, People’s Republic of ChinaTel +86 13961001669Email liuyctx@163.comShengjun JiDepartment of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, 215002, People’s Republic of ChinaTel +86 18914087033Email drshengjunji@163.comBackground: The aim of this study was to explore the influence of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically lymph node metastasis (LNM) regions on survival prognosis of esophageal squamous cell carcinoma (ESCC) patients.Methods: A total of 296 patients with ESCC treated by standard curative esophagectomy were retrospectively analyzed. These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically LNM regions. Kaplan–Meier method was used to calculate survival rate and survival comparison was performed by Log rank test. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Nomogram model was established by integrating statistically significant clinicopathological parameters, and the predictive value was further verified by calibration curve, concordance index (C-index) and decision curve.Results: The univariate and multivariate Cox regression analysis all showed that differentiation grade, TNM stage, adjuvant therapy, preoperative tumor volume and the number of post operative pathologically LNM regions were independent prognostic factors for PFS and OS (all P< 0.05). The C-indexes of PFS and OS by nomograms were predicted to be 0.747 (95% CI: 0.717– 0.777) and 0.732 (95% CI: 0.697– 0.767), respectively, which were significantly higher than the 7th AJCC TNM stage, the C-indexes 0.612 (95% CI: 0.574– 0.650) and 0.633 (95% CI: 0.595– 0.671), separately. In addition, the calibration curves of nomogram models were highly consistent with actual observation for the five-year PFS and OS rate, and the decision curve analysis also showed that nomogram models had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery.Conclusion: The nomograms incorporated preoperative tumor volume and the number of postoperative pathologically LNM areas are of great value in predicting survival prognosis of patients with thoracic ESCC.Keywords: esophageal neoplasm/post-operation, tumor volume, the number of lymph node metastasis areas, nomograms, prognosis

Objective: The purpose of this study was to evaluate the efficacy of two radiotherapy techniques for breast cancer patients with post-mastectomy. The intensity-modulated radiotherapy for treating the chest wall and regional nodes contoured as a whole planning target volume was compared with the conventional segmented 3-dimensional conformal radiotherapy undergoing modified radical mastectomy. Materials and methods: Patients who received the two post-mastectomy radiation therapies were retrospectively analyzed. The chest wall and supra/infraclavicular region +/- internal mammary nodes were contoured as a whole planning target volume on the planning computed tomography. We evaluated differences in survival, recurrence, and late side effects between the integrated intensity-modulated radiotherapy group and the conventional segmented group. Results: A total of 223 patients were recruited. The mean follow-up was 104.3 months. Of these patients, 129 received integrated radiotherapy and 94 patients received segmented radiotherapy. The 8-year disease-free survival rates were 86.0% and 73.4% for patients treated with integrated radiotherapy and traditional segmented radiotherapy, respectively (P = 0.022). The 8-year overall survival rates were 91.4% and 86.2% for patients treated with integrated radiotherapy and traditional segmented radiotherapy, respectively (P = 0.530). Multivariate analysis demonstrated that radiotherapy was an independent prognostic factor for disease-free survival. No significant difference was observed in late side-effects between the two groups. Conclusion: Intensity-modulated radiotherapy for treating the chest wall and regional nodes contoured as a whole planning target volume reduces the recurrence rate for post-mastectomy breast cancer patients with tolerable toxicities.

Congli Jia,1 Zhengquan Li,2 Dong Guo,1 Zhen Zhang,3 Jingming Yu,4 Guangdong Jiang,1 Xiaobo Xing,3 Shengjun Ji,5 Feng Jin3 1Weifang Medical University, Weifang, People’s Republic of China; 2Department of Laboratory Pathology, People’s Liberation Army 80th Group Military Hospital, Weifang, People’s Republic of China; 3Department of Radiotherapy & Oncology, Qingdao Center Hospital, Qingdao, People’s Republic of China; 4Department of Radiotherapy & Oncology, Shandong Hospital, Jinan, People’s Republic of China; 5Department of Radiotherapy & Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, People’s Republic of ChinaCorrespondence: Shengjun JiDepartment of Radiotherapy & Oncology, Nanjing Medical University Affiliated Suzhou Hospital, No. 16 Baita Road, Suzhou 215001, People’s Republic of ChinaEmail drshengjunji@163.comFeng JinDepartment of Radiotherapy & Oncology, Qingdao Center Hospital, No. 127 Siliu Road, Qingdao 266042, People’s Republic of ChinaEmail 1093910079@qq.comBackground: Brain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM.Patients and Methods: MRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis.Results: The average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (P< 0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (P=0.009) and PFS (P=0.006) after stereotactic radiotherapy.Conclusion: The positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy.Keywords: brain metastases, magnetic resonance spectroscopy, stereotactic radiotherapy

Background. The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. Methods. A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. Results. Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV ( HR = 0.442 , 95% CI = 0.236 -0.827, p = 0.011 ), vascular invasion ( HR = 2.182 , 95% CI = 1.243 -3.829, p = 0.007 ), and the high-ΔSII group ( HR = 4.301 , 95% CI = 2.517 -7.350, p < 0.001 ) were independent predictors for OS. Adjuvant therapy ( HR = 0.415 , 95% CI = 0.250 -0.687, p = 0.001 ), vascular invasion ( HR = 3.305 , 95% CI = 1.944 -5.620, p < 0.001 ), and the high-ΔSII group ( HR = 4.924 , 95% CI = 2.992 -8.102, p < 0.001 ) were significant prognostic factors for DFS. Conclusions. The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker.

Background This study aimed to identify potential genes and transcription factors involved in postradiation cognitive dysfunction using bioinformatics analysis. Methods Bioinformatics tools were used to identify differentially expressed mRNAs between postradiation cognitive dysfunctional and control tissue. The GSE115735 dataset containing mRNA expression profiles was downloaded from the Gene Expression Omnibus database. The mRNA expression data corresponded to three hippocampus and three brain lateral ventricles from postradiation cognitive dysfunctional mice and controls. The differentially expressed mRNAs between the two groups were identified, and protein-protein interaction network was constructed. This was followed by functional enrichment and pathway analysis with further prediction of transcription factors that targeted differentially expressed mRNAs. Network analysis was conducted between the differentially expressed mRNAs and these potential transcription factors. Results A total of 134 differentially expressed mRNAs were obtained, including 64 mRNAs in the hippocampus and 84 in the posterior lateral ventricles. Fourteen mRNAs were expressed differentially in both tissues. Furthermore, genes in the network were strongly enriched in neuroactive ligand-receptor interactions, regulation of calcium ion transport, mitotic spindle associated pathway, and TGF-beta signaling pathways. Six transcription factors associated with the regulation of target genes were identified. Conclusions Most of the genes identified were involved in transcriptional regulation, including TFAP4, RUNX1, and CUX2, which may play important roles in the development of postradiation cognitive dysfunction.

Cognitive deficit is one of the most serious complications of cranial radiotherapy of head and neck cancers. However, the underlying mechanism of this cognitive impairment remains unclear. In the present study, the role of tropomyosin receptor kinase A (TrkA) and its ligand neurotrophin nerve growth factor (NGF) were investigated following whole‑brain irradiation (WBI). Young male Sprague‑Dawley rats underwent WBI at a single dose of 10 Gy. WBI was determined to result in notable memory decline and substantial neurogenesis impairment in the hippocampus 3 months post‑irradiation. Compared with the control group, TrkA protein expression was greater in irradiated rats 1 week after WBI, which then decreased significantly by the 3‑month time‑point. However, no difference in NGF expression was observed from 1 day to 3 months post‑WBI. Overexpression of hippocampal TrkA in rats using adeno‑associated virus ameliorated memory decline induced by irradiation. Additionally, upregulating TrkA expression rescued irradiation‑induced hippocampal precursor cell proliferation and promoted neurogenesis. PI3K, Akt and ERK1/2 phosphorylation were also revealed to be significantly inhibited by WBI, which was ameliorated by TrkA overexpression. Findings of the present study indicated that the TrkA‑dependent signaling pathway may serve a critical role in radiotherapy‑induced cognitive deficit and impairments in neurogenesis.

Background Pancreatic cancer (PC) is aggressive and with poor clinical prognosis. However, mechanisms underlying the aggressiveness of PC remain unclear. Increasing evidence indicates that cholesterol, a major source of bio-energy, is required for the progression of human cancers including PC. Therefore, this study aimed to investigate the anti-tumor effect of atorvastatin, a widely used lipid-lowering agent that blocks the production of cholesterol, on human PC. Methods We firstly assessed the impacts of atorvastatin on the proliferation, apoptosis, cell cycle distribution, migration and invasion of human PC cells PANC-1 and SW1990. Furthermore, we studied the effects of atorvastatin on neurotrophin receptor signaling, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and their downstream receptors tropomyosin receptor kinase (Trk) Trk A, Trk B and Trk C in human PC cells. Results Atorvastatin significantly inhibited the proliferation, migration and invasion, and induced G1-phase cell cycle arrest and apoptosis in both PANC-1 and SW1990 cells. Meanwhile, atorvastatin treatment remarkably suppressed the expression of NGF, BDNF, and NT-3 as well as that of their downstream receptors Trk A and Trk C. Conclusions These results provide evidence that atorvastatin inhibits the proliferation, migration and invasion ability of human PC cells, and atorvastatin may exert the anti-tumor effect in PC via the inhibition of neurotrophin signaling pathway.

Objective: To evaluate the prognostic value of conversion of high-risk human papillomavirus (HR-HPV) status after treatment for cervical cancer. Methods: A total of 112 cervical cancer patients with HR-HPV positivity without distant metastasis treated with surgery or radical concurrent radiochemotherapy were enrolled. HR-HPV status was analyzed before and after treatment and at the time point of recurrence or metastasis. Log-rank tests and Cox proportional hazard models were used to evaluate the association between conversion of HR-HPV status after treatment and survival. Results: Eighty-four (75%) patients had negative conversion HR-HPV (ncHR-HPV) after treatment and twenty-eight (25%) were persistent positive HR-HPV (ppHR-HPV). The negative conversion rate was 75.8% in patients who received surgical treatment and 71.4% in patients who received radical concurrent radiochemotherapy. There was no significant difference between the two groups (χ2=0.000, P=1.000). There was no significant correlation between HR-HPV conversion after treatment with age (χ2=0.616, P=0.252), FIGO stage (χ2=0.051, P=0.823) and pathological type (χ2=0.000, P=1.000). Univariate analysis showed that treatment regimen and ncHR-HPV was closely related to progression-free survival (PFS) and overall survival (OS) of cervical cancer patients. Multivariate COX regression model showed that treatment regimen (HR=3.57, 95% CI: 1.57-8.11, P=0.002) and ncHR-HPV (HR=5.14, 95% CI: 2.32-11.46, P

Zhaokang Bao,1,&ast; Jiale Cheng,1,&ast; Jiahao Zhu,2,&ast; Shengjun Ji,3 Ke Gu,2 Yutian Zhao,2 Shiyou Yu,1 You Meng1 1Department of Oncology Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Radiotherapy and Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Radiotherapy and Oncology, The affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Meng, Department of Oncology Surgery, The affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, 16 West Baita Road, Suzhou, Jiangsu, People’s Republic of China, Email drmengyou@163.comObjective: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC).Materials and Methods: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan–Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER.Results: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages.Conclusion: Our results indicate that the ten hub genes may be involved in BC’s carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.Keywords: breast neoplasms, immunohistochemistry, polymerase chain reaction, biomarker

Aim: To compare treatment outcomes of total neoadjuvant therapy (TNT) and the standard treatment for locally advanced rectal cancer (LARC). Materials & methods: Patients with LARC (cT2-4 and/or cN1-2) who were treated with preoperative chemoradiotherapy plus induction and consolidation chemotherapy followed by surgery or the standard treatment were recruited. Pathologic complete response (pCR) rate, overall survival, disease-free survival and the sphincter preservation rate as well as safety were evaluated. Results: 49 cases were treated with TNT and 71 cases received the standard treatment. Multivariate analysis demonstrated that TNT and tumor size were independent risk factors for pCR. Grade 3 chemoradiotherapy toxicity and postoperative complications were similar between the two groups. Conclusion: TNT improved the pCR rate for patients with LARC, with tolerable toxicities.

BackgroundPrimary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC.MethodsData of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts.Results323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS.ConclusionSCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC.

Dong Guo,1 Jiafeng Liu,2 Yanping Li,3 Chao Li,3 Quan Liu,3 Shengjun Ji,4 Shuchai Zhu1 1Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Radiotherapy, Rizhao Center Hospital, Rizhao, People’s Republic of China; 3Sunshine Union Hospital, Weifang, People’s Republic of China; 4Department of Radiotherapy & Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of ChinaCorrespondence: Shengjun Ji; Shuchai Zhu Email drshengjunji@163.com; 3562069484@qq.comBackground: Naples prognosis score (NPS) is a new prognostic score according to host inflammatory and nutritional state, and it could be useful for predicting tumor prognosis based on albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. This study aimed to evaluate the clinical significance of Naples prognostic score (NPS) in stage III non-small cell lung cancer patients (NSCLC).Patients and Methods: In this study, 206 patients diagnosed with locally advanced NCCLC receiving chemoradiotherapy were retrospectively reviewed from January 2013 to January 2017. The included patients were divided into 3 groups according to NPS (group 0, group 1, and group 2), and the associations of the NPS with clinical characteristics and outcomes were evaluated among the groups. Survival curves for the NPS were analyzed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to evaluate the prognostic value of overall survival (OS) and progression-free survival (PFS).Results: The median follow-up time of this study was 37.0 (range, 13– 59) months. The median OS was 27 months in group 0, 23 months in group 1, and 21 months in group 2, and median PFS was 15, 12 and 13 in group 0, group 1 and group 2, respectively. Age was significantly different among the 3 groups. The NPS was superior to other host inflammatory and nutritional indexes for prognostic risk stratification. In the multivariate analysis, NPS was identified as an independent prognostic indicator for OS and PFS (all P< 0.05).Conclusion: The NPS system is considered to be a useful predictor of outcomes in patients with stage III NSCLC.Keywords: Naples prognostic score, stage III NSCLC, predictive values

Background: The aim of this study was to evaluate the significance of combination of the magnetic resonance spectroscopy (MRS) parameters and systemic immune-inflammation (SII) in patients with brain metastases (BM) from non-small-cell lung cancer (NSCLC) treated with stereotactic radiotherapy. Methods: 118 NSCLC patients with BM who treated with stereotactic radiotherapy were retrospectively enrolled into this study. All patients underwent MRS and blood samples test for SII analysis before the initiation of stereotactic radiotherapy. The correlation between the parameters of MRS and SII level were assessed using the spearman correlation coefficient. The cut-off values for the parameters of MRS, SII and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis to quantify these predictive value. The prognostic factors of overall survival (OS) and progression-free survival (PFS) curves were assessed using Kaplan-Meier and Cox proportional hazards models.Results: The median follow-up time was 25 months (range, 12-49months). The optimal cutoff point for the cho/cr and SII were 1.50 and 480, respectively. The cho/cr was negatively correlated with SII (rs = 0.164, P = 0.075), but there was a trend. C-SII score was established by combining cho/cr and SII. Patients with both an elevated cho/cr (> 1.50) and an elevated SII (> 480) were given a C-SII score of 2, and patients with one or neither were given a C-SII score of 1 or 0, respectively. Kaplan–Meier analysis showed that the C-SII score of 2 was significantly linked with poor OS and PFS (P < 0.001, P < 0.001). In the Cox proportional hazards model, the C-SII score independently predicted OS [hazard ratio (HR), 1.749; 95% CI, 1.176-2.601; P = 0.006] and PFS (HR, 2.472; 95% CI, 1.624-3.763; P < 0.001). Conclusion: C-SII score was more accurate for predicting the clinical outcomes of NSCLC patients with BM who undergo stereotactic radiotherapy. The C-SII score, which was superior to either score alone, which could be used to identify for BM from NSCLC patients with poor outcomes.

A series of novel 7-arylaminopyrazolo[1,5-a]pyrimidine derivatives containing the hydrazone moiety has been synthesized by a five-step procedure including cyclization, chlorination, animation, hydrazinolysis, and condensation. Structures of the products have been characterized by IR, 1H NMR and MS spectra, and single-crystal X-ray diffraction. The bioassay results indicate most of the compounds as potentially antiproliferation agents against A549 and HT-29 cell lines. Among those, compounds 6e and 6f exhibit remarkable inhibitory activity against HT-29 cell lines, that are comparable with that of the positive control sorafenib. Preliminary structure-activity relationship is considered.

To explore the clinical efficacy and safety of bevacizumab combined with temozolomide dose-dense regimen in the treatment of recurrent glioma.The clinical data of 102 patients with recurrent glioma after surgery, radiotherapy or chemotherapy treated in our hospital from March 2016 to December 2018 were retrospectively analyzed. There were 51 patients undergoing bevacizumab combined with temozolomide treatment (Bevacizumab group), and the remaining 51 patients received temozolomide treatment alone (Control group). The clinical data of all patients were collected, the short-term efficacy, adverse reactions after treatment and quality of life score were compared between the two groups, and the levels of serum immune factors were recorded. The patients were followed up, and the overall survival (OS) rate and progression-free survival (PFS) rate were recorded.All patients underwent bevacizumab treatment for 2-12 cycles, with an average of 6.3 cycles. The objective response rate (ORR) was 47.1% (24/51) and 23.5% (12/51), and the clinical benefit rate (CBR) was 82.4% (42/51) and 60.8% (31/51), respectively, in the Bevacizumab group and Control group. Both ORR and CBR in the Bevacizumab group were superior to those in the Control group. After treatment, the scores of the SF-36 scale significantly rose in the two groups. After treatment, the levels of serum vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin-2 (IL-2) and IL-6 obviously declined in the two groups compared with those before treatment, while they were obviously lower in the Bevacizumab group than those in the Control group. The median OS was 9.2 months and 8.7 months, and the median PFS was 4.1 months and 3.3 months, respectively, in the Bevacizumab group and the Control group. Log-rank test revealed that the OS had no statistically significant difference between the two groups, but the PFS in the Bevacizumab group was remarkably better than that in the Control group.Bevacizumab combined with temozolomide can significantly improve the clinical efficacy, increase the quality of life of patients, and delay the progression of recurrent glioma, with tolerable adverse reactions.

Background: Although the systemic immune-inflammation index (SII) has been used to predict recurrence and survival in non-small-cell lung cancer (NSCLC) patients, the prognostic significance of change in SII (ΔSII) is unclear for stage III NSCLC patients treated with concurrent chemoradiotherapy (CCRT). In the present study we aimed to explore the association between ΔSII and the clinical outcomes of 142 patients with stage III NSCLC treated with CCRT. Methods: A total of 142 patients were included in this retrospective study. The SII values were calculated based on laboratory data regarding platelet, neutrophil and lymphocyte counts, and ΔSII was calculated using data acquired before and approximately 2 weeks after CCRT. The receiver operating characteristic curve was used to determine the optimal cut-off value for the peripheral blood inflammation index. Kaplan–Meier analysis and Cox proportional regression were used to analyze the prognostic value of ΔSII for overall survival (OS) and progression-free survival (PFS). Results: The area under the receiver operating characteristic curve for ΔSII (0.708) was larger than those for pre-CCRT SII (0.578) and post-CCRT SII (0.610). The optimal cut-off point for ΔSII was defined as 43. OS and PFS were better in patients with low ΔSII and in multivariate analysis, the ΔSII was an independent predictor of OS and PFS (p = 0.006 and p = 0.017, respectively). Conclusions: ΔSII is related to progression and death in patients with stage III NSCLC. The ΔSII can provide a detailed prognostic prediction for stage III NSCLC.

Cisplatin-based chemoradiation is the standard of care for patients with locally advanced cervical cancer. Nevertheless, an increasing number of radio-resistant tumors still recur. Three hundred cervical cancer patients with FIGO stages IB2–IVA and no para-aortic lymphadenopathy (> 10 mm) will be enrolled. All patients will be randomly divided into four arms to receive either (1) intensity modulated radiation therapy (IMRT), (2) RapidArc, (3) positron emission tomography/computed tomography (PET/CT) with F-18 fluorodeoxyglucose (FDG), or (4) Comet assay-guided IMRT, PET/CT, and Comet assay-guided RapidArc. All patients will receive definitive radiotherapy consisting of external beam whole pelvic radiation therapy and high-dose rate intracavitary brachytherapy. Cisplatin 30 mg/m2 weekly will be administered concurrently for five courses. Two to four cycles of TP (Taxol 135 mg/m2, D1, and DDP 75 mg/m2, D1–3) sequential chemotherapy will be performed according to MRI or PET/CT after cisplatin-based chemoradiation. The primary outcome measure is progression-free survival, and the second outcome measures are overall survival and time to progression. RapidArc has an obvious advantage in improving the degree of target coverage, improving organs at risk, sparing healthy tissue, and significantly reducing the treatment time. FDG-PET/CT can increase the agreement between biopsies and delineated tumor volume and has the potential to positively impact the course of treatment. The Comet assay is attractive as a potential clinical test of tumor radiosensitivity. During radiotherapy, accurately defining disease areas is critical to avoid the unnecessary irradiation of normal tissue. Based on FDG-PET/CT and Comet assay, higher doses can be safely delivered to accurate tumor volumes, while the doses to the bladder and rectum are relatively low. ClinicalTrials.gov Protocol Registration and Results System Receipt Release Date: May 21, 2017 – Retrospectively registered. NCT03163979 .

Xin-Wei Guo,1,* Yang-Chen Liu,2,* Fei Gao,2,* Sheng-Jun Ji,3 Ju-Ying Zhou,1 Lei Ji,1 Shao-Bing Zhou2 1Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Taixing People’s Hospital of Yangzhou University, Taixing, People’s Republic of China; 3Department of Radiotherapy and Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study was to investigate the prognostic values of Nutritional Risk Screening 2002 (NRS-2002) and hematologic inflammation markers in patients with esophageal squamous cell carcinoma (ESCC) receiving curative esophagectomy. Materials and methods: A total of 277 patients with ESCC treated with standard curative esophagectomy were retrospectively analyzed. These patients were grouped for further analysis according to the systemic inflammation score (SIS), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (CNP) score and NRS-2002 score. The Kaplan–Meier method and log-rank test were adopted to calculate and compare the progression-free survival (PFS) and overall survival (OS) rates with these parameters. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were applied to verify the accuracy of SIS, CNP and NRS-2002 for survival prediction. Results: In univariate analysis, the following factors were significantly associated with poor PFS and OS: sex, T stage, N stage, TNM stage, SIS, CNP and NRS-2002 (all P

Irradiation to developing brains results in progressive cognitive dysfunction. Changes in the morphology of mature neurons are thought to be related to impairments of cognitive function. However, little is known about the effects of radiation on neurite outgrowth of immature neurons. Therefore, we sought to evaluate the structural alterations of immature neurons following X-ray irradiation and determine potential strategies to reverse it. Our data revealed damage to the neurite outgrowths of cultured neurons after 2 Gy and 8 Gy irradiation at 1 d and 3 d, respectively. De-phosphorylation of nuclear factor of activated T-cells c4/3 (NFATc4/3) was inhibited post-irradiation. Extraneous brain-derived neurotrophic factor (BDNF) ameliorated impairment of neurite growth and activated the NFATc4/3 signaling pathway. These data indicate that BDNF confers neuroprotective effects against irradiation by modulating the NFATc4/3 pathway.

Impairment of neurogenesis in the hippocampus following whole-brain irradiation is the most important mechanism of radiation-induced cognitive dysfunction. However, the underlying mechanism remains obscure, meaning an ideal therapeutic target has not been identified. Evidence indicates that DNA methylation in neurons regulates synaptic plasticity and neuronal network activity. In the present study, the expression of DNA methyltransferases (DNMTs) in the hippocampus was analyzed to investigate their potential function in radiation-induced neurogenesis impairment. Sprague-Dawley rats were used throughout the present study, apportioned to the following groups: Control, radiation only, zebularine (a DNMT inhibitor) only, and radiation and zebularine together. Immunofluorescence staining revealed that radiation inhibited cellular proliferation and dendritic growth within new neurons of the hippocampus. In addition, western blot analysis demonstrated lower expression levels of DNMT1 and DNMT3A protein following radiation treatment compared with that in the non-irradiated control. Furthermore, compared with the radiation-only group, the radiation and zebularine group had significantly lower cell proliferative abilities, dendritic growth, and DNMT1 and DNMT3A protein levels. The results of the present study indicated that DNMT1 and DNMT3A may be involved in the pathogenesis of whole-brain radiation-induced neurogenesis impairment.

// Xin Ding 1, 2, 3, * , Hao-Hao Wu 1, 2, 3, * , Sheng-Jun Ji 1, 4 , Shang Cai 1, 2, 3 , Pei-Wen Dai 1, 2, 3 , Mei-Ling Xu 1, 2, 3 , Jun-Jun Zhang 1, 2, 3 , Qi-Xian Zhang 1, 2, 3 , Ye Tian 1, 2, 3 and Quan-Hong Ma 5 1 Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China 2 Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China 3 Suzhou Key Laboratory for Radiation Oncology, Suzhou, China 4 Department of Radiotherapy and Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China 5 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, China * Co-first author Correspondence to: Ye Tian, email: dryetian@126.com Keywords: hippocampus, cognitive dysfunction, neurogenesis, dendritic spine, p75 NTR Received: October 24, 2016 Accepted: February 22, 2017 Published: March 23, 2017 ABSTRACT Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75 NTR ) is involved in a diverse arrays of cellular responses, including neurite outgrowth, neurogenesis, and negative regulation of spine density, which are associated with various neurological disorders. In this study, male Sprague-Dawley (SD) rats received 10 Gy cranial irradiation. Then, we evaluated the expression of p75 NTR in the hippocampus after cranial irradiation and explored its potential role in radiation-induced synaptic dysfunction and memory deficits. We found that the expression of p75 NTR was significantly increased in the irradiated rat hippocampus. Knockdown of p75 NTR by intrahippocampal infusion of AAV8-shp75 ameliorated dendritic spine abnormalities, and restored synapse-related protein levels, thus preventing memory deficits, likely through normalization the phosphor-AKT activity. Moreover, viral-mediated overexpression of p75 NTR in the normal hippocampus reproduced learning and memory deficits. Overall, this study demonstrates that p75 NTR is an important mediator of irradiation-induced cognitive deficits by regulating dendritic development and synapse structure.

Han Zhang,1,* Xin-Wei Guo,2,* Xiao-Xiang Yin,2,* Yang-Chen Liu,2 Sheng-Jun Ji3 1School of Mathematics, Nanjing Normal University, Taizhou College, Taizhou 225300, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Taixing People’s Hospital of Yangzhou University, Taixing 225400, People’s Republic of China; 3Department of Radiotherapy and Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng-Jun JiDepartment of Radiotherapy and Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, People’s Republic of ChinaTel +86 18914087033Email happy168123@aliyun.comObjective: To investigate the therapeutic effect and survival outcome using nomogram by incorporating significant inflammatory markers in patients with thoracic esophageal squamous cell carcinoma (ESCC) who received chemoradiotherapy (CRT) or single radiotherapy (RT).Method: A total of 266 patients diagnosed with thoracic ESCC receiving standard curative RT only or concurrent CRT were retrospectively analysed. The patients were grouped for statistical analysis depending on the median values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein/albumin (CRP/Alb) ratio. The therapeutic effect was analysed by univariate and multivariate logistic analyses. The survival prognosis was estimated by univariate and multivariate Cox analyses. At last, the nomogram was developed by incorporating the significant inflammatory markers and clinicopathological parameters, and the predictive value was verified by calibration curve, concordance index (C-index) and decision curve.Results: The treatment responses were highly associated with clinical stage, tumor location, NLR, PLR and CRP/Alb ratio (all P

Purpose: Positive results have appeared among nonmetastatic breast cancer patients with the use of cognitive behavioral therapy (CBT). However, earlier stage patient results have been mixed. This novelty of this study was the focus on stage I and II breast cancer patients. The objective of the current study was to conduct a meta-analysis of psychosocial functions in early-stage breast cancer survivors to determine its efficacy. Methods: A search of Cochrane Library, EMBASE, MEDLINE, PsycInfo, and PubMed yielded 3237 abstracts, which were independently evaluated by research pairs. Meta-analysis was conducted on 8 studies that included a total of 1053 patients. Psychosocial functions were categorized according to 3 domains: (1) anxiety, (2) depression, and (3) quality of life. Results: Improvement in anxiety was observed in patients treated with CBT relative to controls without CBT ( P = .04). Depression and quality of life improvement was not observed in the CBT group within or after 4 months of treatment ( P > .05). Conclusions: The results indicated that observed improvements in anxiety in patients with early-stage breast cancer were moderate. The effectiveness of CBT for the improvement of patient outcomes could not be determined, given the methodological and clinical shortcomings of the included trials.

Supplemental material, Appendices for The Efficacy of Cognitive Behavioral Therapy to Treat Depression and Anxiety and Improve Quality of Life Among Early-Stage Breast Cancer Patients by Haoyao Sun, Hualei Huang, Shengjun Ji, Xiaochen Chen, Yongqing Xu, Fenglan Zhu and Jinchang Wu in Integrative Cancer Therapies