Survival Outcomes In Patients Research Articles

237. THE PROGNOSTIC VALUE OF NODAL SKIP METASTASIS IN PATIENTS WITH ESOPHAGEAL CANCER

Abstract Background Nodal skip metastasis (NSM), a common form of lymphatic spread in esophageal cancer (EC), refers to metastatic involvement of distant lymph nodes (LNs) without prior engagement of adjacent LNs. Previous studies examining the association between NSM and survival outcomes in EC patients have yielded inconsistent and even contradictory results. This systematic review and meta-analysis aim to assess the prognostic value of NSM and summarize NSM definitions used in prior studies. Methods Four databases were employed for this meta-analysis. The relationship between NSM and overall survival (OS) was assessed using pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Sensitivity analysis and funnel plots were utilized to evaluate publication bias. Results This meta-analysis incorporated nine studies, and the pooled results revealed no significant association between NSM and OS (HR = 0.99, 95% CI: 0.75–1.31; P = 0.951). Sub-group analyses based on histological features, method of lymphadenectomy, node staging system, and NSM definitions also failed to identify a significant association between NSM and OS. Conclusions Based on the available evidence, NSM cannot be considered a prognostic factor for EC patients. Future studies examining the prognostic value of NSM should focus on employing three-field lymphadenectomy with an adequate number of harvested LNs. NSM definitions based on lymph node station and anatomical compartment could both serve as feasible classifications for EC.

Longitudinal assessment of quality of life indicators and prognosis in esophageal cancer patients with curative resection.

The relationship between quality of life and survival outcomes in esophageal cancer patients following curative resection is not well established. This study aimed to longitudinally assess quality of life indicators and their association with overall survival (OS) in these patients. A total of 232 patients were included in the study, and their quality of life was prospectively assessed at different time points using the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30) and the disease-specific esophageal module (QLQ-OES18). The scores of QLQ indicators at each time point were summarized, and changes in postoperative assessment were compared with preoperative assessments. The association of deterioration in certain indicators with OS was evaluated at each time point using Cox univariable analysis. Further confirmation of independent variables was carried out using Cox multivariable analysis. The study cohort comprised 62 females (26.7%), and 113 patients (48.7%) aged over 60 years. The median follow-up time was 80 months (range, 8-118 months). At 24 months after discharge, patients reported improvements in role function, fatigue, cognition function, emotional function, social function, insomnia, appetite loss, nausea and vomiting, constipation, financial status, trouble swallowing saliva, and pain related to esophageal cancer. However, physical function, dyspnea, diarrhea, global health status, choking when swallowing, trouble talking, and reflux remained compromised. Multivariable regression analysis revealed deterioration in role function, emotional function, and coughing difficulty at 6 months, and dyspnea, pain, and cognitive function at 24 months post-discharge were identified as independent prognostic factors for OS. Our findings underscore the importance of monitoring quality of life indicators in esophageal cancer patients as they may significantly influence survival outcomes. The identification of specific quality of life indicators as prognostic factors highlights the need for a patient-centered approach in clinical practice to enhance care and potentially improve survival.

Predictive value of prognostic nutritional index as prognostic biomarkers in patients with lymphoma: a systematic review and meta-analysis.

Several research have indicated the significant potential of the Prognostic Nutritional Index (PNI) as a prognostic biomarker in lymphoma patients. However, there is some inconsistency in the findings of a few studies. Hence, to offer a thorough evaluation of the predictive significance of PNI in lymphoma patients, we performed a meta-analysis to examine the prognostic value of PNI for survival outcomes in lymphoma patients. We conducted a comprehensive search for pertinent works published up until December 2023 in databases such as PubMed, EMBASE, Cochrane Library, and Web of Science. We obtained hazard ratio (HR) data related to survival outcomes and computed aggregated HRs with their corresponding 95% confidence intervals (CIs) to evaluate the correlation between PNI and both overall survival (OS) and progression-free survival (PFS) in lymphoma patients. By analyzing data from 1260 patients in 28 studies, we found that PNI levels were associated with prognosis in lymphoma patients. High PNI levels predicted that patients had longer OS (HR: 0.46, 95% CI 0.37-0.58, P < 0.05) and better PFS (HR: 0.56, 95% CI 0.45-0.70, P < 0.05). Subgroup analyses showed that the predictive ability of PNI for patient prognosis may differ depending on the type of lymphoma. In addition, we found that the critical PNI value had greater predictive potential at 40-45 and above 45. Our study suggests a strong association between PNI and prognostic outcomes in lymphoma patients, indicating that PNI holds substantial prognostic value in this population.

A comprehensive meta-analysis of stem cell therapy for liver failure: Assessing treatment efficacy and modality

Introduction and ObjectivesThis meta-analysis aims to evaluate the efficacy of stem cell therapy (SCT) for liver failure. Materials and MethodsThe study adhered to the recommended guidelines of the PRISMA statement. Eligible studies published prior to May 13, 2023, were comprehensively searched in databases including PubMed, Web of Science, and Embase. Quality assessment was conducted using the Cochrane risk-of-bias tool, and the standard mean differences were calculated for the clinical parameters. The hazard ratios were determined by extracting individual patient data from the Kaplan-Meier curve. ResultsA total of 2,937 articles were retrieved, and eight studies were included in the final analysis. Most of the studies focused on HBV-related liver failure and were randomized controlled trials. All studies utilized mesenchymal stem cells (MSCs), with the majority (62.5%) being allogeneic. The analysis revealed that combining stem cell therapy with standard medical treatment or plasma exchange significantly enhanced patient survival and reduced MELD scores. Specifically, allogeneic stem cells showed superior efficacy in improving survival outcomes compared to autologous stem cells. Furthermore, deep vessel injection plus a single injection demonstrated better effectiveness than peripheral vessel injection plus multiple injections in reducing MELD scores. ConclusionsThis comprehensive analysis underscores the potential of MSC therapy in significantly improving survival and clinical outcomes in patients with liver failure, highlighting the superior benefits of allogeneic MSCs and deep vessel plus single injection administration.

Improvement of survival outcomes of cholangiocarcinoma by ultrasonography surveillance: Multicenter retrospective cohorts

BackgroundMost cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients. MethodsThe retrospective clinical data and medical records for this study were accessed in June 30, 2021. 5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using the Kaplan-Meier method. Multivariate analyses were performed for significant factors from univariate analyses. ResultsA total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9 %, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9 % and MST was 15.6 months (p < 0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014). ConclusionUS is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.

203. THE NUMBER OF RESECTED LYMPH NODES FROM THE UPPER MEDIASTINAL AREA PREDICTS LONG-TERM OUTCOMES OF ESOPHAGEAL CANCER AFTER MIE

Abstract Background The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, resected LN counts from which areas affect long-term outcomes remain unclear. Methods: This study comprised 406 patients who underwent minimally invasive esophagectomy (MIE) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. Results: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18 in patients with upper and middle thoracic (Ut/Mt) ESCC, respectively, and 7, 6, 5, and 24 in patients with lower thoracic (Lt) ESCC, respectively. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, lymph node metastasis and the resected LN count from the UM area were independent risk factors for overall survival (hazard ratio = 7.04; 95% confidence interval = 4.47-11.1, hazard ratio = 4.01; 95% confidence interval = 1.96-8.21, hazard ratio = 2.18; 95% confidence interval = 1.24-3.82, respectively). In patients with Lt ESCC, tumor invasion depth, lymph node metastasis and pulmonary complication were independent risk factors for overall survival (hazard ratio = 4.23; 95% confidence interval = 2.14-8.35, hazard ratio = 3.83; 95% confidence interval = 1.75-8.38, hazard ratio = 2.80; 95% confidence interval = 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. Conclusions: The number of resected LNs from the UM area influenced survival outcomes of patients with Ut/Mt ESCC after MIE.

The prognostic analysis and a machine-learning based disease-specific survival state model in pulmonary large-cell neuroendocrine carcinomas.

Pulmonary large-cell neuroendocrine carcinoma (PLCNEC) is a rare and highly malignant lung cancer. Due to the paucity of data from clinical studies, its clinical characteristics and treatment remain controversial. The present study explored factors influencing the prognosis and survival outcomes of patients with PLCNEC and developed a dependable prognostic model using machine learning. The clinical data of PLCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. A total of 2,897 PLCNEC patients were enrolled and univariate and multivariate Cox regression analyses were performed to explore independent prognostic factors for disease-specific survival (DSS). Ten machine learning algorithms were utilized to predict the 2-year survival. The clinicopathological data collected from The First Affiliated Hospital of Sun Yat-sen University between 2010 and 2022 were used to test the trained machine. Sex [hazard ratio (HR) 1.168, 95% confidence interval (CI): 1.063-1.284], age (HR 1.262, 95% CI: 1.144-1.391), surgery (HR 0.481, 95% CI: 0.413-0.559), chemotherapy (HR 0.450, 95% CI: 0.404-0.501), bone metastasis (HR 1.284, 95% CI: 1.124-1.466), brain metastasis (HR 1.167, 95% CI: 1.023-1.331), liver metastasis (HR 1.223, 95% CI: 1.069-1.399), American Joint Committee on Cancer-Node (AJCC-N), and tumor stage were independent prognostic factors. The gradient boosting decision tree (GBDT) performed better than other models, with an F1-score of 0.791 and an area under the curve of 0.831. Male, age ≥65 years, distant metastasis to the bone, liver, and brain are associated with a worse prognosis in PLCNEC patients, while surgery and chemotherapy are associated with improved prognosis. GBDT showed promising performance in predicting 2-year survival, which can serve as a valuable reference for clinical diagnosis and treatment of PLCNEC.

Risk factors and prognostic modeling in bridging extracorporeal membrane oxygenation patients before lung transplantation.

The increased use of preoperative extracorporeal membrane oxygenation (ECMO) as a life support system before lung transplantation demands a better understanding of the associated prognostic factors. This study aims to discern the critical factors influencing the survival outcomes of ECMO patients and design a prognostic model tailored to this patient group. We retrospectively gathered and analyzed baseline and clinical data of patients who underwent preoperative bridging ECMO before lung transplantation from the United Network for Organ Sharing (UNOS) database. Univariate and multivariate Cox regression analyses were conducted and a prognostic model was generated to identify the independent factors influencing survival outcomes in these patients. The predictive model was cross-validated using the k-fold method where k=5. Our study included 1,202 patients. Both single and multiple analyses showed that age over 51 years, high body mass index (BMI), a history of dialysis before transplantation, donor hypertension, prolonged cold ischemia time, and high serum total bilirubin are adverse prognostic factors for the survival of ECMO-bridged lung transplant patients. Using the multivariate analysis, we created a prognosis model and a nomogram to predict 1-year post-transplant survival, with a receiver operating characteristic (ROC) curve area of 0.760 in internal validation. The 1-year survival rate calibration curve supported the nomogram's accuracy. This study involved the development of a survival prognosis model for patients undergoing lung transplantation with preoperative ECMO bridging, which was validated through extensive data analysis. The prognosis model exhibited high accuracy and predictive capability, effectively predicting the survival outcomes of patients both pre- and post-surgery.

Redefining YAP1 in small cell lung cancer: shifting from a dominant subtype marker to a favorable prognostic indicator.

Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry. One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case. The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03). Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD.

Relationship between preoperative glucose level and all-cause mortality in patients with osteoporotic vertebral compression fracture who underwent percutaneous vertebroplasty

To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002–1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.

Analyzing the role of TM4SF1 expression in pancreatic adenocarcinoma: understanding prognostic implications and therapeutic opportunities.

Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of TM4SF1 and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities. Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with TM4SF1 emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising BPIFB4, PLEKHN1, CPTP, DVL1, and DDR1 was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels. Lower TM4SF1 expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated TM4SF1 levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation. This study advances understanding of the molecular landscape of PAAD, emphasizing TM4SF1 as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting TM4SF1 and other identified genes in PAAD management.

Bioinformatics analysis of SH2D4A in glioblastoma multiforme to evaluate immune features and predict prognosis.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer in adults. This study aimed to obtain data on immune cell infiltration based on public datasets and to examine the prognostic significance of SH2 domain containing 4A (SH2D4A) for GBM. SH2D4A expression in GBM was analyzed using a Tumor Immunity Estimation Resource (TIMER) 2.0 dataset, and a gene expression profile interaction analysis (GEPIA), and the results were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The Chinese Glioma Genome Atlas (CGGA) dataset was used to assess the effect of SH2D4A on GBM patient survival. The SH2D4A co-expression network of the LinkedOmics dataset and GeneMANIA dataset was also investigated. Least absolute shrinkage and selection operator (LASSO) regression models and a nomogram were constructed to assess the prognosis of GBM patients. A Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset to find functional differences. The relationship between SH2D4A expression and tumor-infiltrating immune cells was analyzed using xCELL, the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, and the TIMER dataset. We discovered that SH2D4A expression was upregulated in GBM patients, and elevated SH2D4A expression was also substantially correlated with tumor grade. The survival curve analysis and multivariate Cox regression analysis showed that high SH2D4A expression was a significant independent predictor of poor overall survival (OS) in GBM patients. The immunoassay results suggested that altered SH2D4A expression may affect the immune infiltration of GBM tissues and thus the survival outcomes of GBM patients. In addition to being a possible prognostic marker and therapeutic target for GBM, SH2D4A may also accelerate the progression of GBM.

Trilaciclib use in extensive-stage small cell lung cancer (ES-SCLC): are clinical benefits seen in the real-world setting?

BackgroundTrilaciclib, in comparison to placebo plus carboplatin, etoposide, ± atezolizumab (PEA), has shown significant reductions in incidence of severe neutropenia (SN) among patients with extensive-stage small cell lung cancer (ES-SCLC). Despite these findings, real-world utility remains limited.MethodsA single-center quasi-experimental study compared trilaciclib + PEA (PEAT) versus PEA in ES-SCLC patients. The study period ranged from April 1, 2021 to July 31, 2022, for the PEAT recipients and February 1, 2020, to February 28, 2021, for PEA recipients. The primary endpoint evaluated was incidence of SN after cycle 1 and during the treatment period. Secondary endpoints included measures related to myelopreservation and patient outcomes.ResultsAmong 34 PEAT and 44 PEA patients, baseline characteristics were similar, except for a higher median age (69 vs 64 years) and more males (64.7% vs 38.6%) in the PEAT cohort. The PEAT cohort exhibited a lower SN rate (3%) versus the PEA cohort (18%), with statistical significance demonstrated on multivariate analysis (p = 0.015). Additionally, the PEAT cohort also demonstrated significant reductions in red blood cell transfusion requirements (3% vs 23%; p = 0.02), grade 3–4 anemia (6% vs 25%; p = 0.03), and grade 3–4 thrombocytopenia (0% vs 11%, p = 0.045).ConclusionTrilaciclib, in combination with PEA, demonstrated an improvement in the safety profile without compromising survival outcomes in ES-SCLC patients. These findings underscore the potential benefits of incorporating trilaciclib in real-world clinical settings for enhanced patient care.

The role of cholesterol-modified prognostic nutritional index in nutritional status assessment and predicting survival after liver resection for hepatocellular carcinoma.

Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.

The benefit of adjuvant chemotherapy in pathological T1-3N0M0 rectal mucinous adenocarcinoma: no improvement survival outcomes based on long-term survival analysis of large population data.

Currently, the benefits of the administration of adjuvant chemotherapy (AT) in pathological low-risk rectal mucinous adenocarcinoma (RM) with T1-3N0M0 are unclear. The objective of this study is to retrospectively investigate the clinical significance of AT in terms of survival outcomes for patients with pathological T1-3N0M0 RM using data from a large population. The patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) Program. The Chi-squared test was used to analyze categorical variables. The survival curves were compared using the log-rank test and the Kaplan-Meier method. A multivariate proportional hazards regression (Cox) model was applied to identify the independent prognostic factors of survival outcomes. Propensity score matching (PSM) was utilized to eliminate the differences between groups and estimate AT's effect. The median follow-up duration for the rectal cancer (RC) cohort was 116 months. Multivariate analyses revealed that RM was a significant adverse prognostic factor, correlating with poorer overall survival (OS) and cancer-specific survival (CSS) for RC [hazard ratio (HR): 1.226, 95% confidence interval (CI): 1.094-1.375, P<0.001; HR: 1.446, 95% CI: 1.242-1.683, P<0.001]. Among patients with RM, the rates of 5-year OS and CSS were 68.6% and 79.3% in the AT (-) group, respectively. Additionally, the AT (+) group exhibited similar rates of 65.6% for 5-year OS and 74% for CSS (P=0.80, P=0.26). Subtype analysis according to preoperative therapy status showed that AT also did not significantly affect survival outcomes (P=0.65, P=0.34; P=0.90, P=0.76). Our study found that RM is a poor prognostic factor in pathological T1-3N0M0 RC. However, AT does not appear necessary to improve survival outcomes of pathological T1-3N0M0 RM.

A transformer-based deep learning model for early prediction of lymph node metastasis in locally advanced gastric cancer after neoadjuvant chemotherapy using pretreatment CT images

Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC). A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan-Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers. The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752-0.849), 0.748 (95% CI, 0.660-0.830), 0.788 (95% CI, 0.735-0.835), and 0.766 (95% CI, 0.717-0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P<0.001; Center 2:HR, 1.776, P=0.013]. The transformer-based DLN provides early and effective prediction of LNM and survival outcomes in LAGC patients receiving NAC, with promise to guide individualized therapy. Future prospective multicenter studies are warranted to further validate our model. National Natural Science Foundation of China (NO. 82373432, 82171923, 82202142), Project Funded by China Postdoctoral Science Foundation (NO. 2022M720857), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (NO. U22A20345), National Science Fund for Distinguished Young Scholars of China (NO. 81925023), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (NO. 2022B1212010011), High-level Hospital Construction Project (NO. DFJHBF202105), Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (NO. 2024B1515020091).

Prognostic significance of a 3-gene ferroptosis-related signature in lung cancer via LASSO analysis and cellular functions of UBE2Z

Ferroptosis is a newly identified form of non-apoptotic programmed cell death resulting from iron-dependent lipid peroxidation. It is controlled by integrated oxidation and antioxidant systems. Ferroptosis exerts a crucial effect on the carcinogenesis of several cancers, including pulmonary cancer. Herein, a ferroptosis-associated gene signature for lung cancer prognosis and diagnosis was identified using integrative bioinformatics analyses. From the FerrDB database, 256 ferroptotic regulators and markers were identified. Of these, 25 exhibited differential expression between lung cancer and non-cancerous samples, as evidenced by the GSE19804 and GSE7670 datasets from the GEO database. Utilizing LASSO Cox regression analysis on TCGA-LUAD data, a potent 3-gene risk signature comprising CAV1, RRM2, and EGFR was established. This signature adeptly differentiates various survival outcomes in lung cancer patients, including overall survival and disease-specific intervals. Based on the 3-gene risk signature, lung cancer patients were categorized into high-risk and low-risk groups. Comparative analysis revealed 69 differentially expressed genes between these groups, with UBE2Z significantly associated with overall survival in TCGA-LUAD. UBE2Z was found to be upregulated in LUAD tissues and cells compared to normal controls. Functionally, the knockdown of UBE2Z curtailed aggressive behaviors in LUAD cells, including viability, migration, and invasion. Moreover, this knockdown led to a decrease in the mesenchymal marker vimentin while elevating the epithelial marker E-cadherin within LUAD cell lines. In conclusion, the ferroptosis-associated 3-gene risk signature effectively differentiates prognosis and clinical features in patients with lung cancer. UBE2Z was identified through this model, and it is upregulated in LUAD samples. Its knockdown inhibits aggressive cellular behaviors, suggesting UBE2Z's potential as a therapeutic target for lung cancer treatment.

Disease-specific survival outcomes for patients after locoregional treatment for ductal carcinoma in situ: observational cohort study.

Breast-conserving surgery alone, breast-conserving surgery with adjuvant radiation treatment, and mastectomy are guideline-concordant treatments for ductal carcinoma in situ. The aim of this study was to compare survival outcomes between these treatment options. A stratified random sample of patients diagnosed with pure ductal carcinoma in situ between 2008 and 2014 was selected from 1330 sites in the USA. Data on diagnosis, treatment, and follow-up were abstracted by local cancer registrars. Population-averaged marginal estimates of disease-specific survival and overall survival for breast-conserving surgery alone, breast-conserving surgery with radiation treatment, and mastectomy were obtained by combining sampling and overlap weights. A total of 18 442 women were included, with a median follow-up of 67.8 (interquartile range 46.1-93.5) months. A total of 35 women died from breast cancer, at a median age of 62 (interquartile range 50-74) years. Population-averaged 8-year rates of disease-specific survival were 99.6% or higher for all treatment groups, with no significant differences between groups (breast-conserving surgery alone versus breast-conserving surgery with radiation treatment, HR 1.19 (95% c.i. 0.29 to 4.85); and mastectomy versus breast-conserving surgery with radiation treatment, HR 1.74 (95% c.i. 0.53 to 5.72). There was no difference in overall survival between the patients who underwent a mastectomy and the patients who underwent breast-conserving surgery with radiation treatment (HR 1.09 (95% c.i. 0.83 to 1.43)). Patients who underwent breast-conserving surgery alone had lower overall survival compared with the patients who underwent breast-conserving surgery with radiation treatment (HR 1.29 (95% c.i. 1.00 to 1.67)). This survival difference vanished for all but one subgroup, namely patients less than 65 years (HR 1.86 (95% c.i. 1.15 to 3.00)). There was no statistically significant difference in disease-specific survival between women operated with breast-conserving surgery alone, breast-conserving surgery with radiation treatment, or mastectomy for ductal carcinoma in situ. Given the low absolute risk of disease-specific mortality, these results provide confidence in offering individualized locoregional treatment without fear of compromising survival.

Effects of BRCA variation on prognosis in patients with nonmetastatic breast cancer.

To compare the clinicopathological characteristics of nonmetastatic breast cancer patients with and without BRCA variations and to investigate the impact of BRCA variations on prognosis. This retrospective single-center study involved an analysis of 938 patients with localized or locally advanced breast cancer who underwent BRCA variation testing. The patients were divided into three groups: 757 were without BRCA variation, 64 were with BRCA1 variation, and 117 were with BRCA2 variation. In patients with BRCA1 variation, the Ki67, grade, and frequency of triple-negative breast cancer were significantly higher than in patients without BRCA variation and with BRCA2 variation. The 5-year disease-free survival in patients with BRCA1 variation was significantly worse than the other two groups (without BRCA, BRCA1, and BRCA2; 87.7%, 69.9%, and 95.3%, respectively, p=0.049). Multivariate analysis detected no significant difference between groups. The pathological complete response rates with neoadjuvant therapy were significantly better in patients with BRCA variations than those without BRCA variations (49.2%vs. 29.6%, p=0.024). Patients with BRCA1 variation had more aggressive tumor characteristics, such as higher Ki67 and higher grade. Also, triple-negative breast cancer was more common. The presence of BRCA1 variation may worsen survival outcomes. Neoadjuvant treatment responses of patients with BRCA variations were significantly better, and neoadjuvant treatment may contribute to survival outcomes in nonmetastatic patients with BRCA variations.

Circ_0008315 promotes tumorigenesis and cisplatin resistance and acts as a nanotherapeutic target in gastric cancer

IntroductionCisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies.MethodsHigh-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC.ResultsWe revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance.ConclusionCirc_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.Graphical