Independent Factor For Survival Research Articles

The role of upfront neck dissection in definitive radiotherapy for locally advanced hypopharyngeal squamous cell carcinoma: A single-center retrospective analysis.

Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma. This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate. This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control. This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy

BackgroundThe liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy.MethodsBetween July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan–Meier survival curves were utilized to access the predictive performance of LFIS.ResultsA total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child–Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature.ConclusionThe LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

Development and comprehensive validation of a predictive prognosis model for very early HCC recurrence within one year after curative resection: a multicenter cohort study.

The high incidence of early recurrence after liver resection for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Consecutive patients who underwent liver resection for HCC with curative intent at multi-centers in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. 7401 patients were enrolled and divided randomly into 3 cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT and prothrombin time) were identified as independent risk factors for recurrence-free survival on uni- and multi-variate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1 year: 0.722)) and was validated comprehensively by the internal, external and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence free survival rates (low-risk: 80.4%-85.4%; intermediate-risk: 59.7%-64.8%; high-risk: 32.6%-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after liver resection with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.

Retrospective study of BRAF inhibitor-based therapy in patients with BRAF mutated advanced solid tumors (RBAST study).

e23265 Background: BRAF mutations are frequently found in melanoma, non-small cell lung cancer (NSCLC), thyroid cancer, to a lesser degree in other tumor types. These mutations constantly activate the kinase domain and result in MAPK pathway hyperactivation. Successful inhibition of this pathway with BRAF/MEK inhibitors (BRAFi/MEKi) results in a clinically meaningful benefit for some patients. The RBAST study, to assess the efficacy and survival outcomes of BRAF inhibitor-based therapy were investigated in patients with solid tumors harboring BRAF mutations. Methods: Data was collected on a total of 697 cases of solid tumor throughout China between Sep 2018 and Dec 2023. Next Generation Sequencing (NGS) is based on the sequencing of tissue samples. Among the samples, the primary endpoints of this study were objective response rate (ORR), disease control rate (DCR), progress-free survival (PFS) and overall survival (OS). The impact of co-mutations with other genes and BRAF variant allele frequency on treatment efficacy was also assessed in this study. Results: BRAF mutations were detected in 36 cases and 15 patients received BRAFi based therapy were identified. For patients who received BRAFi therapy, the best ORR was 26.7% with 4 patients recorded partial response (PR). There were 2 patients with progressive disease giving a DCR of 86.7%. Responses were observed in 4 types of tumors. PR was observed in patients with colorectal cancer (CRC) and melanoma. Median PFS (mPFS) and median OS (mOS) of these patients were 6.0 months (95% CI: 2.3-7.0) and 17.1 months (95% CI: 4.4-NA), respectively. The co-occurring mutation rates of TP53, PTEN, FAT2 and NF1 were 40% (6/15), 20% (3/15), 20% (3/15) and 13.3% (2/15), respectively. No significant difference (p>0.05) in PFS and OS was observed in any co-occurrence of mutations. BRAF mutation variant allele frequency is not an independent prognostic factor for survival with patients received BRAF inhibitor treatment (p>0.05). Conclusions: To the best of our knowledge, this is the first retrospective study exploring BRAFi treatment effectiveness to BRAF mutated solid tumors for Chinese patients. Treatment with BRAF inhibitors is effective for BRAF mutated advanced solid tumors with DCR of 86.7%, mPFS of 6.0 months and mOS of 17.1 months. Co-mutations with other genes and BRAF variant allele frequency did not impact survival outcomes.

ARHGAP4 as a Prognostic Biomarker for Colon Liver Metastases After Surgical Resection.

To select and stratify patients for optimal treatment plans is challenging. Identification of cancer-related biomarkers that serve as predictors for prognosis and treatment response is essential to better predict treatment outcome and find future targets for therapy. Previous data has suggested ARHGAP4 as a relevant biomarker in colorectal cancer (CRC). The purpose of this study was to assess how ARHGAP4 expression affected patients undergoing surgery for colon liver metastasis (CLM) in terms of overall survival (OS). A total of 251 patients undergoing resection of CLM from 2006 to 2017 were included. Corresponding resected tumor specimens were examined for ARHGAP4 expression levels by immunohistochemistry (IHC). The correlation between ARHGAP4 expression and postoperative survival was analyzed. High expression levels of ARHGAP4 were seen in 60% of patients. High expression levels of ARHGAP4 were correlated with adverse prognosis after hepatectomy due to CLM. Survival data generated using Cox proportional hazard model showed a statistically significant difference between high and low ARHGAP4 expression groups by univariate (HR=1.5, 95% CI=1.1-2.2) and multivariate (HR=1.5, 95% CI=1.0-2.1) analysis. In multivariate Cox regression, high ARHGAP4 expression, preoperative CEA levels and presence of vascular invasion by pathological examinations were independent predictive factors of overall survival. ARHGAP4 is a novel prognostic biomarker after resection of CLM.

Prognostic value analysis and survival model construction of different treatment methods for advanced intestinal type gastric adenocarcinoma

BackgroundIntestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). MethodsWe extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. ResultsAge, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. ConclusionThe nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.

Risk factors and clinical significance of lower perigastric lymph node metastases in Siewert type II and III esophagogastric junction adenocarcinoma: a retrospective cohort study.

No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0cm), TG with LPLN dissection is prioritized for clinical recommendation.

Clinicopathological features, prognostic factors, and prognostic survival prediction in patients with extrahepatic bile duct cancer liver metastasis.

Extrahepatic bile duct cancer (EBDC) is a compound malignant tumor mainly consisting of extrahepatic cholangiocarcinoma and gallbladder carcinoma. Most EBDC patients are diagnosed at an advanced stage characterized by distant metastases, and the liver is one of the common sites of metastasis. Hence, the purpose of this study is to investigate the clinicopathological features, identify prognostic risk factors, and assess the long-term prognosis of extrahepatic bile duct cancer liver metastasis (EBDCLM). We identified 1922 eligible EBDCLM patients from the SEER database.Cox regression models were used to predict independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS),and Kaplan-Meier survival curves were drawn. A nomogram was constructed based on the results of multivariate Cox analysis, and the predictive effect of the nomogram was evaluated. Age, surgery, chemotherapy, brain metastasis, and lung metastasis were common independent prognostic factors for OS and CSS, and radiotherapy and bone metastasis were independent prognostic factors for CSS. The Kaplan-Meier survival curves showed a significant increase in survival for patients aged less than or equal to 70 years, undergoing surgery and chemotherapy, and without lung metastases. The results showed that the nomogram constructed by us had good predictability and ha d strong clinical application value. Our study identified age, surgery, chemotherapy, brain metastasis, and lung metastasis as independent prognostic factors for EBDCLM patients. The nomogram can accurately predict the survival probability, which is helpful for clinicians to assess the prognosis of patients with advanced EBDC and provide personalized clinical decisions.

In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma.

Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma.

Clinical implications and molecular features of extracellular matrix networks in soft tissue sarcomas.

The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterised. We aimed to investigate the tumour ECM and adhesion signalling networks present in STS and their clinical implications. Proteomic and clinical data from 321 patients across 11 histological subtypes were analysed to define ECM and integrin adhesion networks. Subgroup analysis was performed in leiomyosarcomas (LMS), dedifferentiated liposarcomas (DDLPS) and undifferentiated pleiomorphic sarcomas (UPS). This analysis defined subtype-specific ECM profiles including enrichment of basement membrane proteins in LMS and ECM proteases in UPS. Across the cohort, we identified three distinct co-regulated ECM networks which are associated with tumour malignancy grade and histological subtype. Comparative analysis of LMS cell line and patient proteomic data identified the LCP1 cytoskeletal protein as a prognostic factor in LMS. Characterisation of ECM network events in DDLPS revealed three subtypes with distinct oncogenic signalling pathways and survival outcomes. Evaluation of the DDLPS subtype with the poorest prognosis nominates ECM remodelling proteins as candidate anti-stromal therapeutic targets. Finally, we define a proteoglycan signature which is an independent prognostic factor for overall survival in DDLPS and UPS. STS comprise heterogeneous ECM signalling networks and matrix-specific features have utility for risk stratification and therapy selection which could in future guide precision medicine in these rare cancers.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection

IntroductionDysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. MethodsNinety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. ResultsThe median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38–4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28–5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28–0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01–3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19–2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26–3.41), etiology factor (HR = 0.49; 95 % CI: 0.29–0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14–3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. ConclusionsLow serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.

Identification of the CD8+ T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data.

The infiltration of CD8+ T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8+ T-cell differential genes were from the TISCH database. We determined 896 CD8+ T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8+ T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8+ T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

Temporal dynamics of RAS mutations in circulating tumor DNA in metastatic colorectal cancer: clinical significance of mutation loss during treatment

PurposeIn metastatic colorectal cancer (mCRC), RAS mutation loss may occur during the standard-of-care regimen. In this study, we aimed to investigate the temporal dynamics of the RAS gene and its clinical significance.MethodsThis was a retrospective, single-center study that included 82 patients with tissue RAS-mutant (RAS-MT) mCRC who underwent circulating tumor DNA (ctDNA) RAS monitoring between January, 2013–April, 2023. Patients were analyzed for the rate of change over time to acquired RAS mutation loss (aRAS-ML) and clinicopathological factors. The prognostic relevance of mutation loss was assessed.ResultsaRAS-ML was detected in 33 (40.2%) patients, 32 of whom had a mutation loss in the first ctDNA RAS assay. Patients with a RAS mutation detected in the first assay had a median time of 8 months until the second ctDNA RAS assay, with 4.5% cases newly converted to aRAS-ML; no new conversions were detected at the third assay. The aRAS-ML group exhibited more single-organ metastases in the target organ during ctDNA measurement (aRAS-ML: 84.8% vs. RAS-MT: 59.2%, p = 0.02). Of the 33 patients with aRAS-ML, seven (21.2%) received anti-epidermal growth factor receptor (EGFR) therapy, with a median progression-free survival of 8 months. Multivariate analysis revealed that persistent ctDNA RAS mutation was an independent prognostic factor for overall survival (hazard ratio: 2.7, 95% confidence interval: 1.1–6.3, p = 0.02).ConclusionThe rate of ctDNA mutation loss in patients with RAS-MT mCRC decreases over time. Therefore, using a ctDNA RAS assay early in treatment will assist in challenging the use of EGFR regimens.

Important Predictive Factors for the Prognosis of Patients With Peritoneal Metastasis of Gastric Cancer.

This study investigated predictive factors for patients with peritoneal metastases of gastric cancer (PMGC) who underwent conversion cytoreductive surgery (C-CRS) and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) after responding to induction chemotherapy (laparoscopic HIPEC [LHIPEC]) followed by concomitant systemic and intraperitoneal chemotherapy (bidirectional intraperitoneal and systemic chemotherapy [BIC]). Diagnostic laparoscopy was performed for 62 patients with PMGC between January 2017 and December 2022. The patients underwent LHIPEC and BIC induction chemotherapy using intraperitoneal docetaxel (30mg/m2) and cisplatin (30mg/m2), and intravenous chemotherapy for three cycles. The predictive parameters for progression-free and overall survival were analyzed using Kaplan-Meier and Cox regression analyses. The optimal cutoff values for Ki-67 parameters were assessed using receiver operating characteristic curve analysis. The study retrospectively examined 36 (58 %) of 62 patients who responded to induction therapy and underwent C-CRS or HIPEC. A Ki-67 index lower than 10 (p = 0.000), lymph node involvement (LNI) less than 2 (p = 0.039), and an omental lesion size score lower than 0.5 cm (p = 0.002) were predictive of recurrence-free and overall survival in addition to completeness of cytoreduction and the peritoneal cancer index. Cox regression analysis showed that the independent factors associated with recurrence-free survival were decreased Ki-67 expression (≥10 % vs <10 %) (hazard ratio [HR] 4.7; 95 % confidence interval [CI] 1.6-5.210; p = 0.020) and LNI higher than 2 (HR 1.92; 95% CIS 0.923-4.0; p = 0.023). Lymph node involvement and decreased Ki-67 expression are independent predictive factors of recurrence-free survival for patients with PMGC after induction chemotherapy.

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short- and long-term survivors of IDH-wildtype GB (STS and LTS, respectively) by data-independent acquisition mass spectrometry (DIA-MS)-based proteomics, with the aim of identifying such markers. DIA-MS identified 5422 and 826 normalized proteins in tumor and serum samples, respectively, with only three tumor proteins and 26 serum proteins displaying significant differential expression between the STS and LTS groups. These dysregulated proteins were principally associated with the detoxification of reactive oxygen species (ROS). In particular, GB patients in the STS group had high serum levels of malate dehydrogenase 1 (MDH1) and ribonuclease inhibitor 1 (RNH1) and low tumor levels of fatty acid-binding protein 7 (FABP7), which may have enabled them to maintain low ROS levels, counteracting the effects of the first-line treatment with radiotherapy plus concomitant and adjuvant temozolomide. A blood score built on the levels of MDH1 and RNH1 expression was found to be an independent prognostic factor for survival based on the serum proteome data for a cohort of 96 IDH-wildtype GB patients. This study highlights the utility of circulating MDH1 and RNH1 biomarkers for determining the prognosis of patients with IDH-wildtype GB. Furthermore, the pathways driven by these biomarkers, and the tumor FABP7 pathway, may constitute promising therapeutic targets for blocking ROS detoxification to overcome resistance to chemoradiotherapy in potential GB STS.

Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma.

Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.

Enhancing clinical decision-making: A novel nomogram for stratifying cancer-specific survival in middle-aged individuals with follicular thyroid carcinoma utilizing SEER data

BackgroundThyroid cancer (TC) is the most common malignant tumor in the endocrine system, is also one of the head and neck tumor. Follicular Thyroid Carcinoma (FTC) plays an important role in the pathological classification of thyroid cancer. This study aimed to develop an innovative predictive tool, a nomogram, for predicting cancer specific survival (CSS) in middle-aged FTC patients. MethodsWe collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. The data from patients between 2004 and 2015 were used as the training set, and the data from patients between 2016 and 2018 were used as the validation set. To identify independent risk factors affecting patient survival, univariate and multivariate Cox regression analyses were performed. Based on this, we developed a nomogram model aimed at predicting CSS in middle-aged patients with FTC. The consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the accuracy and confidence of the model. ResultsA total of 2470 patients were enrolled in this study, in which patients from 2004 to 2015 were randomly assigned to the training cohort (N = 1437) and validation cohort (N = 598), and patients from 2016 to 2018 were assigned to the external validation cohort (N = 435) in terms of time. Univariate and multivariate Cox regression analysis showed that marriage, histological grade and TNM stage were independent risk factors for survival. The C-index for the training cohort was 0.866 (95 % CI: 0.805–0.927), for the validation cohort it was 0.944 (95 % CI: 0.903–0.985), and for the external validation cohort, it reached 0.999 (95 % CI: 0.997–1.001). Calibration curves and AUC suggest that the model has good accuracy. ConclusionsWe developed an innovative nomogram to predict CSS in middle-aged patients with FTC. Our model after a rigorous internal validation and external validation process, based on the time proved that the high level of accuracy and reliability. This tool helps healthcare professionals and patients make informed clinical decisions.

Prognostic value of neutrophil-to-lymphocyte ratio change in patients with locally advanced non-small cell lung cancer treated with thoracic radiotherapy

In prior investigations, a correlation was established between patient outcomes in locally advanced non-small cell lung cancer (LA-NSCLC) following thoracic irradiation and parameters, such as pre/post-treatment neutrophil-to-lymphocyte ratio (NLR) and NLR change (ΔNLR). However, these parameters could potentially be influenced by radiation-related variables, such as gross tumor volume (GTV). The primary aim of this study was to elucidate the factors impacting post-treatment NLR and ΔNLR and to further assess their prognostic relevance. In this retrospective study, a cohort of 188 LA-NSCLC patients who underwent thoracic radiation between 2012 and 2017 was assessed. The calculation of pre/post-treatment NLR involved the use of absolute neutrophil and lymphocyte counts. ΔNLR was defined as the difference between post- and pre-treatment NLR values. To assess the relationships between various variables and overall survival (OS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS), the Kaplan–Meier technique and Cox proportional hazards regression were employed. Additionally, Spearman’s rank correlation analysis was carried out to investigate correlations between the variables. The analysis revealed that both post-treatment NLR (r = 0.315, P < 0.001) and ΔNLR (r = 0.156, P = 0.032) were associated with GTV. However, OS, LPFS, and DMFS were not independently correlated with pre/post-treatment NLR. ΔNLR, on the other hand, exhibited independent associations with OS and DMFS (HR = 1.054, P = 0.020, and P = 0.046, respectively). Elevated ΔNLR values were linked to poorer OS (P = 0.023) and DMFS (P = 0.018) in the Kaplan–Meier analysis. Furthermore, when stratifying by GTV, a higher ΔNLR remained to be associated with worse OS and DMFS (P = 0.047 and P = 0.035, respectively) in the GTV ≤ 67.41 cm3 group, and in the GTV > 67.41 cm3 group (P = 0.028 and P = 0.042, respectively), highlighting ΔNLR as the sole independent predictive factor for survival and metastasis, irrespective of GTV.

#2454 Meeting guideline goals at hemodialysis patients impact their survival?

Abstract Background and Aims The Institute of Medicine (IOM) defines clinical practice guidelines as "statements that include recommendations, intended to optimize patient care, that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options". First publication of Clinical Guidelines by the National Kidney Foundation (NKF), addressing good clinical practice in hemodialysis, was published in 1998. The aim of the present study was to investigate the influence of adherence to current guidelines of Mineral and Bone Disorders, Anemia and Adequacy of Dialysis, on their survival in patients undergoing hemodialysis. Method This is a single center retrospective study of 113 chronic hemodialysis patients (79 males and 34 females), with median age 70 years (56, 78), median duration on hemodialysis 52 months (21, 95). Based on whether or not they met the KDIGO guidelines’ targets for anemia, bone disease, dialysis adequacy, and the targets of all three guidelines during the last three years, patients were divided in two groups: group A with the patients who met the goals of the guidelines and group B with the patients who did not meet the goals. Clinical and biochemical parameters were compared among the groups of patients as well as hemodialysis adequacy (Kt/V). The survival analysis of the patients was calculated by Kaplan-Meier, while the possible effect of any parameter on survival was also evaluated with Cox-Regression. Results There was significant difference between the two groups in age, phosphorous (P), PTH, Kt/V, URR and Alb. There was no significant difference between the two groups in sex, duration of HD, Hemoglobin (Hg), Calcium (Ca++), Hypertension and Diabetes (Table). In Cox analyses, patient survival was associated with delivered dialysis dose (single pool Kt/V, p=0.044). There was no significant difference between the two groups when we compare the adherence to guidelines for MBD (p=0.507) and anemia (p=0.394). There was no statistical difference when we compare the achievement of targets of all three guidelines (p=0.796). We identified as an independent risk factor for patient survival the serum albumin (p&amp;lt;0.001). Patient survival was better with higher dialysis dose and adequate serum albumin level. Conclusion Clinical guidelines are useful tools for good clinical practice for hemodialysis patients. Adherence to clinical guidelines regarding dialysis adequacy is an independent risk factor for better survival of patients undergoing hemodialysis.