Predictive potential of preoperative Naples prognostic score-based nomogram model for the prognosis in surgical resected thoracic esophageal squamous cell carcinoma patients: A retrospective cohort study.

The present study aimed to establish an effective prognostic nomogram model based on the Naples prognostic score (NPS) for resectable thoracic esophageal squamous cell carcinoma (ESCC). A total of 277 patients with ESCC, who underwent standard curative esophagectomy and designated as study cohort, were retrospectively analyzed. The patients were divided into different groups, including NPS 0, NPS 1, NPS 2, and NPS 3 or 4 groups, for further analysis, and the results were validated in an external cohort of 122 ESCC patients, who underwent surgery at another cancer center. In our multivariate analysis of the study cohort showed that the tumor-node-metastasis (TNM) stage, systemic inflammation score, and NPS were the independent prognostic factors for the overall survival (OS) and progression-free survival (PFS) durations. In addition, the differential grade was also an independent prognostic factor for the OS in the patients with ESCC after surgery (all P < .05). The area under the curve of receiver operator characteristics for the PFS and OS prediction with systemic inflammation score and NPS were 0.735 (95% confidence interval [CI] 0.676-0.795, P < .001) and 0.835 (95% CI 0.786-0.884, P < .001), and 0.734 (95% CI 0.675-0.793, P < .001) and 0.851 (95% CI 0.805-0.896, P < .001), respectively. The above independent predictors for OS or PFS were all selected in the nomogram model. The concordance indices (C-indices) of the nomogram models for predicting OS and PFS were 0.718 (95% CI 0.681-0.755) and 0.669 (95% CI 0.633-0.705), respectively, which were higher than that of the 7th edition of American Joint Committee on Cancer TNM staging system [C-index 0.598 (95% CI 0.558-0.638) for OS and 0.586 (95% CI 0.546-0.626) for PFS]. The calibration curves for predicting the 5-year OS or PFS showed a good agreement between the prediction by nomogram and actual observation. In the external validation cohort, the nomogram discrimination for OS was better than that of the 7th edition of TNM staging systems [C-index: 0.697 (95% CI 0.639-0.755) vs 0.644 (95% CI 0.589-0.699)]. The calibration curves showed good consistency in predicting the 5-year survival between the actual observation and nomogram predictions. The decision curve also showed a higher potential of the clinical application of predicting the 5-years OS of the proposed nomogram model as compared to that of the 7th edition of TNM staging systems. The preoperative NPS-based nomogram model had a certain potential role for predicting the prognosis of ESCC patients.

Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy.

OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

A novel fatty acid metabolism-related signature identifies MUC4 as a novel therapy target for esophageal squamous cell carcinoma.

Fatty acid metabolism has been identified as an emerging hallmark of cancer, which was closely associated with cancer prognosis. Whether fatty acid metabolism-related genes (FMGs) signature play a more crucial role in biological behavior of esophageal squamous cell carcinoma (ESCC) prognosis remains unknown. Thus, we aimed to identify a reliable FMGs signature for assisting treatment decisions and prognosis evaluation of ESCC. In the present study, we conducted consensus clustering analysis on 259 publicly available ESCC samples. The clinical information was downloaded from The Cancer Genome Atlas (TCGA, 80 ESCC samples) and Gene Expression Omnibus (GEO) database (GSE53625, 179 ESCC samples). A consensus clustering arithmetic was used to determine the FMGs molecular subtypes, and survival outcomes and immune features were evaluated among the different subtypes. Kaplan-Meier analysis and the receiver operating characteristic (ROC) was applied to evaluate the reliability of the risk model in training cohort, validation cohort and all cohorts. A nomogram to predict patients' 1-year, 3-year and 5-year survival rate was also studied. Finally, CCK-8 assay, wound healing assay, and transwell assay were implemented to evaluate the inherent mechanisms of FMGs for tumorigenesis in ESCC. Two subtypes were identified by consensus clustering, of which cluster 2 is preferentially associated with poor prognosis, lower immune cell infiltration. A fatty acid (FA) metabolism-related risk model containing eight genes (FZD10, TACSTD2, MUC4, PDLIM1, PRSS12, BAALC, DNAJA2 and ALOX12B) was established. High-risk group patients displayed worse survival, higher stromal, immune and ESTIMATE scores than in the low-risk group. Moreover, a nomogram revealed good predictive ability of clinical outcomes in ESCC patients. The results of qRT-PCR analysis revealed that the MUC4 and BAALC had high expression level, and FZD10, PDLIM1, TACSTD2, ALOX12B had low expression level in ESCC cells. In vitro, silencing MUC4 remarkably inhibited ESCC cell proliferation, invasion and migration. Our study fills the gap of FMGs signature in predicting the prognosis of ESCC patients. These findings revealed that cluster subtypes and risk model of FMGs had effects on survival prediction, and were expected to be the potential promising targets for ESCC.

Association of preoperative muscle-adipose index measured by computed tomography with survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Conventional nutritional metrics are closely associated with the prognosis of patients with radically resected esophageal squamous cell carcinoma (ESCC). Nevertheless, the prognostic implications of muscle and adipose tissue composite indexes in ESCC remain unknown. METHODS: We retrospectively analyzed clinicopathological data of 304 patients who underwent resected ESCC. To obtain measurements of the muscle and adipose indexes, preoperative computed tomography (CT) images were used to quantify skeletal-muscle adipose tissue. The diagnostic threshold for muscle-adipose imbalance was determined using X-tile software and used to analyze the association between the muscle-adipose index (MAI) and survival. Instantaneous risk of recurrence was assessed using a hazard function. We constructed a nomogram based on the MAI and other clinical characteristics and established a novel predictive model with independent prognostic factors. The prognostic capabilities of these nomograms were evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision-curve analysis (DCA). RESULTS: The overall survival (OS) and disease-free survival (DFS) rates in the muscle-adipose-balanced group were significantly better than those in the muscle-adipose-imbalanced group. Multivariate analyses revealed that the MAI, prognostic nutritional index (PNI), tumor stage, and tumor differentiation were independent prognostic factors for OS and DFS in patients with resected ESCC (P < 0.05). The nuclear density curve indicated a lower risk of recurrence for patients in the muscle-adipose-balanced group than that for their imbalanced counterparts. Conversely, the nuclear density curve for PNI was confounded. Postoperative radiotherapy- (RT) benefit analysis demonstrated that patients with ESCC in the muscle-adipose-balanced group could benefit from adjuvant RT. CONCLUSION: This study confirmed that preoperative MAI could serve as a useful independent prognostic factor in patients with resected ESCC. A nomogram based on the MAI and other clinical characteristics could provide individualized survival prediction for patients receiving radical resection. Timely and appropriate nutritional supplements may improve treatment efficacy.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF/TrkB Pathway.

Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), ß-tubulin and dendritic spines were decreased. In the irradiated neurons, the ß-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.

Assessment of Naples prognostic score in predicting survival for small cell lung cancer patients treated with chemoradiotherapy.

BACKGROUNDS: The Naples prognosis score (NPS) is a novel prognostic biomarker-based immune and nutritional status and that can be used to evaluate prognosis. Our study aimed to investigate the prognostic role of NPS in SCLC patients. METHODS: Patients treated with chemoradiotherapy were retrospectively analyzed between June 2012 and August 2017. We divided patients into three groups depending on the NPS: group 0, n = 31; group 1, n = 100; and group 2, n = 48, and associations between clinical characteristics and NPS group were analyzed. The univariable and multivariable Cox analyses were used to evaluate the prognostic value of clinicopathological characteristics and laboratory indicators for overall survival (OS) and progression-free survival (PFS). RESULTS: Data from 179 patients were analyzed. Treatment modality (p < 0.001) and serum CEA (p = 0.03) were significantly different among the NPS groups. The age, sex, smoking status, KPS, Karnofsky performance score (KPS), disease extent, and number of metastatic sites were not correlated with NPS (all p > 0.05). KPS, disease extent, prophylactic cranial irradiation, treatment response and NPS Group were associated with OS. In addition, KPS, disease extent, prophylactic cranial irradiation, treatment response and NPS Group were associated with PFS. Multivariate analysis results showed that NPS was identified as an independent prognostic factor for OS (Group 1: hazard ratio [HR] = 2.704, 95% confidence interval [CI] = 1.403-5.210; p = 0.003; Group 2: HR = 5.154, 95% CI = 2.614-10.166; p < 0.001) and PFS (Group 1: HR = 2.018, 95% CI = 1.014-4.014; p = 0.045; Group 2: HR = 3.339, 95% CI = 1.650-6.756; p = 0.001). CONCLUSIONS: NPS is related to clinical outcomes in patients with SCLC.

Despite the high clinical curative effect to radiation therapy and chemotherapy in SCLC, most patients subsequently experience tumor recurrence or metastasis.Whether NPS has prognostic values in SCLC has not been investigated to date.NPS is related to clinical outcomes in patients with SCLC.NPS as an innovative scoring system, can improves prediction of survival in SCLC patients.

Role of endogenous and exogenous antioxidants in risk of six cancers: evidence from the Mendelian randomization study.

Background: Although oxidative stress is known to contribute to cancer, and endogenous and exogenous antioxidants are thought to prevent tumorigenesis by suppressing oxidative stress-induced DNA damage, antioxidants have also been reported to show negative effects on tumor formation, necessitating characterization of the causal associations between antioxidants and cancer risk. Methods: In this study, Mendelian randomization (MR) analysis, primarily inverse-variance weighted MR, was used to assess the causal effect of six endogenous and five exogenous diet-derived antioxidants on the risk of six cancers. MR-Egger intercept test and Cochran's Q statistic were utilized to assess pleiotropy and heterogeneity, respectively. Results: For endogenous antioxidants, a bidirectional two-sample MR analysis was conducted. Our findings suggested that serum albumin has a negative causal association with the risk of prostate cancer [odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.68-0.91, p = 0.001]. The risks of the six cancers showed no significant associations with endogenous antioxidants in the converse MR analysis. For exogenous antioxidants, the unidirectional two-sample MR analysis exhibited a nominal relationship between the serum retinol level and non-small-cell lung cancer risk (OR = 0.29, 95% CI: 0.11-0.76, p = 0.011). Conclusions: Thus, our study revealed the protective effects of genetic susceptibility to high circulating albumin levels on prostate cancer, providing potential targeted interventions for prostate cancer prevention.

Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?

Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients.

Naples Prognostic Score as an Independent Predictor of Survival Outcomes for Resected Locally Advanced Non-Small Cell Lung Cancer Patients After Neoadjuvant Treatment.

Background: 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.

Correlation between Ferroptosis-Related Gene Signature and Immune Landscape, Prognosis in Breast Cancer.

Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related death in women worldwide. Ferroptosis, an iron-dependent newly discovered mode of cell death, can be induced by lenaltinib and plays an important role in the biological behaviors of BC. Therefore, the prognostic value of ferroptosis-related genes (FRGs) in BC warrants further investigation. FRG expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). Immune-related pathways were found in the functional analysis. Significant differences in enrichment scores for immune cells were observed. Some patients from TCGA-BRCA were included as the training cohort. A six-gene prediction signature was constructed with the least absolute shrinkage and selection operator Cox regression. This model was validated in the rest of the TCGA-BRCA and GEO cohort. The expressions of the six FRGs were verified with real-time quantitative polymerase chain reaction and immunohistochemistry in the Human Protein Atlas. Relapse or metastasis was more likely in the high-risk group. Risk score was an independent predictor of disease-free survival. Collectively, the ferroptosis-related risk model established in this study may serve as an effective tool to predict the prognosis in BC.

Ferroptosis-Related lncRNA Signature Correlates with the Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity of Esophageal Squamous Cell Carcinoma.

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.

A Novel Score Combining Magnetic Resonance Spectroscopy Parameters and Systemic Immune-Inflammation Index Improves Prognosis Prediction in Non-Small Cell Lung Cancer Patients With Brain Metastases After Stereotactic Radiotherapy.

Objective: The aim of this study was to evaluate the prognostic significance of the combination of the magnetic resonance spectroscopy (MRS) parameters and systemic immune-inflammation index (SII) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC) treated with stereotactic radiotherapy. Methods: A total of 118 NSCLC patients with BM who were treated with stereotactic radiotherapy were retrospectively enrolled in 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 was assessed using Spearman's correlation coefficient. The cutoff 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 values. The prognostic factors of overall survival (OS) and progression-free survival (PFS) curves were assessed using the Kaplan-Meier and Cox proportional hazards models. Results: The median follow-up time was 25 months (range, 12-49 months). The optimal cutoff point for the choline/creatine (Cho/Cr) ratio and SII were 1.50 and 480, respectively. The Cho/Cr ratio was negatively correlated with SII (rs = 0.164, p = 0.075), but there was a trend. The C-SII score was established by combining the Cho/Cr ratio and SII. Patients with both an elevated Cho/Cr ratio (>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. The Kaplan-Meier analysis showed that a C-SII score of 2 was significantly linked with poor OS and PFS (p < 0.001 and p < 0.001, respectively). 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: The C-SII score was more accurate for predicting the clinical outcomes of NSCLC patients with BM who underwent stereotactic radiotherapy. The C-SII score, which was superior to either score alone, could be used to identify BM in NSCLC patients with poor outcomes.

Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival.

Objective: 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.

Epidemiology, Treatment and Prognosis Analysis of Small Cell Breast Carcinoma: A Population-Based Study.

Background: Primary 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. Methods: Data 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. Results: 323 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. Conclusion: SCBC 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.

Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer.

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.

Plain language summary Outcomes of two treatment schemes were compared for locally advanced rectal cancer (LARC), including the new preoperative treatment strategy and conventional standard preoperative chemoradiotherapy. The new preoperative treatment strategy includes the addition of four cycles of preoperative chemotherapy to the standard treatment. A total of 49 cases were treated with the new preoperative treatment strategy and 71 cases received the standard treatment. Patients treated with the new preoperative treatment demonstrated higher rates of tumor regression and organ preservation. Additionally, chemoradiotherapy-related toxicity and postoperative complications were similar between the two treatment schemes. However, neither treatment strategy prolonged the survival of patients with LARC. This new preoperative treatment strategy should be recommended first for LARC.

Evaluation of Predictive Values of Naples Prognostic Score in Patients with Unresectable Stage III Non-Small Cell Lung Cancer.

BACKGROUND: 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.

The Value of the Systemic Immune-Inflammation Index in Predicting Survival Outcomes in Patients with Brain Metastases of Non-Small-Cell Lung Cancer Treated with Stereotactic Radiotherapy.

BACKGROUND: As a parameter integrating platelet (P), neutrophil (N), and lymphocyte (L) levels, the systemic immune-inflammation index (SII) has been used as a prognostic marker for patient survival in various types of solid malignant tumors. However, there is no in-depth study in non-small-cell lung cancer (NSCLC) patients with brain metastases after stereotactic radiotherapy. Therefore, we performed a retrospective analysis to determine the clinical and prognostic value of the SII in NSCLC patients with brain metastases who underwent stereotactic radiotherapy. MATERIALS AND METHODS: We enrolled 124 NSCLC patients with brain metastases treated with stereotactic radiotherapy in our hospital between May 2015 and June 2018. We obtained all baseline blood samples within one week prior to stereotactic radiotherapy. The SII was calculated by the following formula: neutrophil counts × platelet counts/lymphocyte counts. The optimal cutoff value of the SII for predicting prognosis was assessed by receiver operating characteristic (ROC) curves with the maximum log-rank values. The discriminative ability of predicting prognosis was calculated and compared using the Kaplan-Meier method and log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the prognostic impact of the blood index on overall survival (OS) and progression-free survival (PFS). Only those parameters that proved to be associated with statistically significant differences in clinical outcomes were compared in multivariate analysis using a multiple Cox proportional hazard regression model to identify independent prognostic factors. RESULTS: Of the total enrolled patients, 53.2% and 46.8% have high SII and low SII, respectively. In this study, Kaplan-Meier curve analysis revealed that the median PFS was 9 months (range: 2-22 months) and the median OS was 18 months (range: 4-37 months). Applying an optimal cutoff of 480 (SII), the median PFS was better in the low SII group patients (11.5 vs. 9 months), and the median OS was significantly longer in the low SII group patients (20 vs. 18 months). A SII > 480 was significantly associated with worse OS (HR: 2.196; 95% CI 1.259-3.832; P = 0.006) and PFS (HR: 2.471; 95% CI 1.488-4.104; P < 0.001) according to univariate analysis. In multivariate analysis, only age (HR: 2.159; 95% CI 1.205-3.869; P = 0.010), KPS (HR: 1.887; 95% CI 1.114-3.198; P = 0.018), and SII (HR: 1.938; 95% CI 1.046-3.589; P = 0.035) were independently correlated with OS, and SII (HR: 2.224; 95% CI 1.298-3.810; P = 0.004) was an independent prognostic predictor of PFS, whereas we found that other inflammation-based indices lost their independent value. CONCLUSIONS: The SII, which is an integrated blood parameter based on platelet, neutrophil, and lymphocyte counts, may be an independent prognostic indicator and may be useful for the identification of NSCLC patients with brain metastases after stereotactic radiotherapy at high risk for recurrence.

Value of Nomogram Incorporated Preoperative Tumor Volume and the Number of Postoperative Pathologically Lymph Node Metastasis Regions on Predicting the Prognosis of Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: 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.

Efficacy of bevacizumab combined with temozolomide dose-dense regimen on recurrent glioma.

PURPOSE: To explore the clinical efficacy and safety of bevacizumab combined with temozolomide dose-dense regimen in the treatment of recurrent glioma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.