Independent Predictor Of Overall Survival Research Articles

Evaluating the prognostic role of glucose-to-lymphocyte ratio in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors in first line: a study by the Turkish Oncology Group Kidney Cancer Consortium (TKCC).

Identifying prognostic indicators for risk stratification in metastatic renal cell carcinoma (mRCC) is crucial for optimizing treatment strategies and follow-up plans. This study aims to investigate the prognostic role of the glucose-to-lymphocyte ratio (GLR) in patients with mRCC receiving tyrosine kinase inhibitors (TKIs) as first-line therapy. A retrospective cohort study was conducted using data from the Turkish Oncology Group Kidney Cancer Consortium Database. GLR was calculated by dividing the fasting glucose (mmol/L) by the lymphocyte count (×109/L). We categorized patients into two categories based on their median GLR level. The analysis included a total of 598 patients. We found that progression-free survival (PFS) was significantly longer in the GLR-low group, with a median PFS of 15.05 months (95% CI 12.7-17.4) compared to 7.79 months (95% CI 6.6-9.0) in the GLR-high group (p < 0.001). Multivariate analysis identified GLR as an independent risk factor for poor PFS (HR 1.39, 95% CI 1.12-1.72; p = 0.003). Overall survival (OS) was also significantly longer in the GLR-low group, with a median OS of 38.47 months (95% CI, 30.9-46.0) compared to 24.15 months (95% CI 18.0-30.2) in the GLR-high group (p = 0.001). GLR was an independent predictor for OS in multivariate analysis (HR 1.45, 95% CI 1.12-1.86; p = 0.004). The GLR can be a valuable prognostic marker for glucose metabolism and systemic inflammatory status in this patient population. Our research highlights the potential prognostic value of GLR in patients with mRCC receiving TKIs, indicating its potential as a useful tool for clinical decision-making.

Screening for Predictive Factors of Efficacy of Second‐Generation Androgen Receptor Axis‐Targeted Agents in Patients With High‐Risk Metastatic Hormone‐Sensitive Prostate Cancer

ABSTRACTBackgroundDifferences in the effectiveness of second‐generation androgen receptor axis‐targeted agents (ARATs) in high‐risk metastatic hormone‐sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high‐risk mHSPC and compare their long‐term effectiveness.MethodsFour hundred and sixty‐six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients.ResultsUnivariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high‐risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA‐PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high‐risk mHSPC with Gleason pattern 5 treated with ARATs.ConclusionGleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high‐risk mHSPCs.

Development and Validation of a Prognostic Nomogram Incorporating Neutrophil-to-Albumin Ratio for Predicting Overall Survival in Patients with Nasopharyngeal Carcinoma Undergoing Concurrent Chemoradiotherapy

BackgroundRecent research suggests that the emerging neutrophil-albumin ratio (NAR) has a significant correlation with the survival outcomes across a range of tumors, yet its predictive significance for nasopharyngeal carcinoma (NPC) remains insufficiently investigated. This study aimed to evaluate the relationship between the neutrophil-to-albumin ratio (NAR) and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC), as well as to develop a corresponding prognostic model. MethodsThis retrospective analysis included 861 nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy (CCRT), who were randomly divided into a training group (n=605) and a validation group (n=256). To identify factors associated with overall survival (OS) and construct a prognostic nomogram, both univariate and multivariate Cox regression analyses were performed. The nomogram's prognostic accuracy was evaluated and independently validated. ResultsThe NAR score successfully segregated NPC patients into two categories with significantly different OS (HR=0.536; 95% CI: 0.296-0.972, P=0.040). Through multivariate analysis, factors such as age, T stage, N stage, and NAR score were identified as independent predictors of OS, leading to the creation of a prognostic nomogram. This nomogram demonstrated superior predictive capability for OS [C-index=0.702 (95% CI: 0.636-0.768)], surpassing that of the conventional staging system [C-index=0.651(95% CI: 0.549-0.752)]. The findings underwent internal validation within an independent cohort. ConclusionsThe NAR, an emergent biomarker combining nutritional and inflammatory status, offers a practical, low-cost, and non-invasive prognostic measure for NPC patients treated with CCRT. Additionally, the prognostic nomogram derived from NAR surpasses traditional staging systems in predictive accuracy.

The Prognostic Value of CRP/Alb Ratio in Predicting Overall Survival for Hepatocellular Carcinoma Treated with Transcatheter Intra-Arterial Therapy Combined with Molecular-Targeted Agents and PD-1/PD-L1 Inhibitors.

This study aimed to evaluate the prognostic value of C-reactive protein to albumin (CRP/Alb) ratio in hepatocellular carcinoma (HCC) treated with transcatheter intra-arterial therapy combined with molecular targeted agents (MTAs) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. Medical records of 271 consecutive patients with HCC receiving this combination therapy in China between 2019 and 2023 were retrospectively analyzed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses. The discriminatory capability of inflammation-based prognostic scores-including the CRP/Alb ratio, C-reactive protein and alpha-fetoprotein in immunotherapy (CRAFITY) score, modified Glasgow prognostic score (mGPS), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-was assessed using the area under the curve (AUC). A total of 133 patients met the inclusion criteria. The optimal cutoff value for the binary classification of CRP/Alb ratio in predicting OS, as determined using X-tile software, was 0.02. Multivariate analysis identified the CRP/Alb ratio (hazard ratio [HR] = 2.61, p < 0.001), tumor size (HR = 2.45, p = 0.018), and extrahepatic metastases (HR = 1.93, p = 0.015) as independent predictors of OS. For PFS, significant factors included Eastern Cooperative Oncology Group Performance Status (HR = 1.55, p = 0.033) and macrovascular invasion (HR = 1.48, p = 0.046). Patients with higher CRP/Alb ratios were more likely to experience fever and fatigue. The CRP/Alb ratio demonstrated significantly higher AUCs than PLR and SII at 24 months (all p < 0.05) and showed comparable AUCs to CRAFITY score and mGPS at 12, 24, and 36 months. The CRP/Alb ratio is a valuable prognostic marker for predicting OS and treatment-related adverse events in HCC patients receiving transcatheter intra-arterial therapy combined with MTAs and PD-1/PD-L1 inhibitors. This ratio can be used as a simple and reliable biomarker for assessing prognosis and guiding patient selection in clinical practice.

RASGEF1C as a novel prognostic biomarker for LUAD.

Lung adenocarcinoma (LUAD) is a common histologic lung cancer with high morbidity and mortality, and most patients have distant metastases at diagnosis. RasGEF Domain Family Member 1C (RASGEF1C) could regulated Alzheimer's disease. However, its function in various cancers, including LUAD, is poorly understood. In the present study, we discovered that high expression of RASGEF1C in LUAD was associated with poorer prognosis, unfavorable histological features, and poorer pathological staging. In addition, RASGEF1C expression was an independent predictor of overall survival, disease specific survival, and progress free interval in patients with LUAD. High expression of RASGEF1C was linked to signaling pathways that are involved in the immune response and cell proliferation, according to KEGG enrichment analysis. Additionally, we verified that RASGEF1C was highly expressed in LUAD cell lines and that RASGEF1C knockdown dramatically decreased the capacity of LUAD cell lines to invade, migrate, and proliferate. Our research provides mechanistic insights into the function of RASGEF1C in the progression of LUAD and suggests that RASGEF1C is a prospective target for future therapy.

Therapeutic patterns and outcomes in older patients (aged≥65 years) with stage III-IVB inoperable oral cavity squamous cell carcinoma (OCSCC): an investigational study from the SEER database

ABSTRACT Background The aim of this retrospective study is to explore therapeutic patterns and survival outcomes for a cohort of older patients with stage III-IVB inoperable oral squamous cell carcinoma (OCSCC) patients receiving radiation therapy (RT) with or without chemotherapy (CT). Methods This study conducted a retrospective review of 316 patients ≥ 65 aged years with stage III-IVB OCSCC from the Surveillance, Epidemiology, and End Results (SEER) registry (2010–2015). It compared RT alone (n = 109) with RT+CT (n = 207), utilizing Kaplan-Meier and Log-rank tests. Results The estimated overall survival (OS) and cancer-specific survival (CSS) rates at 3 years were 20.6% and 25.9%, respectively. Both univariate and multivariate analyses identified that age and treatment option as independent prognosticators of OS and CSS. Further subgroup analyses showed that the combination of RT and CT significantly improved OS for all OCSCC patients, except those with hard palate tumors. Moreover, this combined treatment approach was linked to enhanced CSS in patients with gingival and tongue squamous cell carcinoma. Conclusion RT+CT significantly enhanced survival in elderly OCSCC patients, particularly those with gingival and tongue cancers, but not in those with hard palate tumors.

Prognostic Value of Systemic Inflammatory Markers in Elderly Patients with Tumor-associated Venous Thromboembolism.

Elderly tumor patients are more prone to venous thrombotic events than nontumor patients. To investigate the relationship between systemic inflammatory markers and overall survival (OS) in elderly patients with tumorassociated venous thromboembolism (TAVTE). And to evaluate the prognostic value of combined lymphocyte platelettolymphocyte ratio (PLR) with neoplasm metastasis in elderly patients. A prospective study was conducted. A total of 172 elderly patients with TAVTE admitted to the hospital from January 2017 to December 2019 were included in the study, which were followed up for 2 years. Clinical and laboratory data were collected. All-cause mortality within after discharge were followed up. The optimal cutoff values of neutrophiltolymphocyte ratio (NLR), PLR, systemic immuneinflammation index (SII), and monocyte to highdensity lipoprotein ratio (MHR) for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve (AUC). Kaplan-meier curves were used to analyze the survival time. Univariate and multivariate COX logistic regression analyses were used to analyze the independent predictors of OS in elderly patients with TAVTE. The cut-off values for NLR, PLR, SII, and MHR were 3.375, 274.63, 399.73 and 0.58, respectively. And the area under the curve (AUC) was 0.639(95%CI: 0.556-0.721), 0.628(95%CI:0.544-0.712), 0.595(95%CI:0.510-0.680) and 0.596(95%CI: 0.510-0.683). Survival analysis showed that OS was longer in the NLR≤3.375 group (181.07 weeks, 95% CI: 150.11 ~ 212.03) than in the NLR >3.375 group (108.95 weeks, 95%CI: 90.38 ~ 127.51) (P = 0.005). The OS of PLR≤274.63 group (160.40 weeks, 95%CI: 138.41 ~ 182.38) was longer than that of PLR >274.63 group (43.85 weeks, 95%CI: 34.08 ~ 53.63) (P < 0.001). The OS of SII≤399.73 group (176.62 weeks, 95%CI:147.26 ~ 205.97) was longer than that of SII>399.73 group (126.55 weeks,95%CI: 105.04 ~ 148.05) (P = 0.012). The OS was longer in the MHR≤0.58 group (156.24 weeks, 95% CI: 127.05-185.43) than in the MHR>0.58 group (108.11 weeks, 95%CI:86.85-129.38) (P = 0.011). Univariate and multivariate Cox analysis showed that tumor metastasis and PLR>274.63 were independent predictors of the lower OS in elderly patients with TAVTE (P < 0.001). According to the tumor metastasis and the cut-off value of PLR, a combined scoring system MPS (Metastasis and PLR System) was designed. The OS of the 0, 1 and 2 score groups was 184.08 weeks (95%CI:158.11-210.05), 82.60 weeks (95%CI:61.57-103.64), and 23.83 weeks (95%CI: 9.575-38.09) (P < 0.001), respectively. Our findings suggest that the systemic inflammatory markers (NLR, PLR, SII, MHR) may have predictive value for all-cause mortality in elderly patients with TAVTE. PLR combined with tumor metastasis may be an effective index to predict the prognosis of elderly patients with TAVTE.

Clinical and molecular prognostic nomograms for patients with papillary renal cell carcinoma

ObjectiveTo summarize the clinicopathological characteristics and prognostic factors of papillary renal cell carcinoma (pRCC) and to construct clinical and molecular prognostic nomograms using existing databases.MethodsClinical prognostic models were developed using the Surveillance, Epidemiology, and End Results (SEER) database, while molecular prognostic models were constructed using The Cancer Genome Atlas (TCGA) database. Cox regression and LASSO regression were employed to identify clinicopathological features and molecular markers related to prognosis. The accuracy of the prognostic models was assessed using ROC curves, C-index, decision curve analysis (DCA) curves, and calibration plots.ResultsIn the 2004–2015 SEER cohort, Cox regression analysis revealed that age, grade, AJCC stage, N stage, M stage, and surgery were independent predictors of overall survival (OS) and cancer-specific survival (CSS) in pRCC patients. ROC curves, C-index, and DCA curves indicated that the prognostic nomogram based on clinical independent predictors had better predictive ability than TNM staging and SEER staging. Additionally, in the TCGA cohort, M stage, clinical stage, and the molecular markers IDO1 and PLK1 were identified as independent risk factors. The prognostic nomogram based on molecular independent risk factors effectively predicted the 3-year and 5-year OS and CSS for pRCC patients.ConclusionsThe clinical and molecular nomograms constructed in this study provide robust predictive tools for individualized prognosis in pRCC patients, offering better accuracy than traditional staging systems.

Prognostic value of inflammatory and nutritional indexes among patients with unresectable advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy-a retrospective study.

Recent studies have revealed that inflammatory factors and nutritional status of patients with advanced gastric cancer (AGC) are related to the efficacy of drug therapy and patient prognosis. This study seeks to evaluate the correlation between inflammatory markers, nutritional status, and clinical outcomes of immune checkpoint inhibitor (ICI)-based therapies among inoperable AGC patients. This retrospective study included 88 AGC patients who received ICIs combined with chemotherapy. Inflammatory and nutritional indicators from patients before and after two cycles of treatment were collected. Finally, the correlations between these indicators and the clinical response and survival of AGC patients with ICI treatment were examined. The results revealed that an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0, neutrophil count to lymphocyte count ratio (NLR) < 2.84, platelet count to lymphocyte count ratio (PLR) < 82.23, lymphocyte count to monocyte count ratio ≥ 2.35, the hemoglobin, albumin, lymphocyte and platelet score (HALP) ≥ 31.17, prognostic nutritional index (PNI) ≥ 46.53, albumin ≥ 41.65, the decreased HALP group and the decreased PNI group were significantly correlated with improved objective response rate. Additionally, an ECOG PS score of 0, NLR < 2.84 and the decreased HALP group was associated with a superior disease control rate. Meanwhile, an ECOG PS score of 0 (progression-free survival (PFS): P = 0.003; overall survival (OS): P = 0.001) and decreased PLR following treatment (PFS: P = 0.011; OS: P = 0.008) were significant independent predictors of PFS and OS. Lastly, a systemic immune inflammation index ≥ 814.8 was also a positive independent predictor of OS among AGC patients. Our study supports the potential of inflammatory and nutritional factors to serve as predictors of the efficacy and prognosis in patients undergoing ICI-based therapies for AGC. However, further investigations are necessary to validate these findings.

Predictive and Prognostic Values of Glycoprotein 96, Androgen Receptors, and Extranodal Extension in Sentinel Lymph Node-Positive Breast Cancer: An Immunohistochemical Retrospective Study.

Objectives: In this paper, we investigate the association of glycoprotein 96 (GP96) and androgen receptor (AR) expression with clinicopathological factors, additional axillary lymph node burden, and their potential role in predicting 5-year overall survival (OS) and disease-free survival (DFS) in breast cancer (BC) patients with sentinel lymph node (SLN) involvement. We also explore the prognostic value of the presence of extranodal extension (ENE) in SLN. Methods: We retrospectively enrolled 107 female patients with cT1-T2 invasive BC and positive SLN biopsy. GP96 and AR expression were immunohistochemically evaluated on tissue microarrays constructed from two 2 mm diameter cores of formalin-fixed paraffin-embedded tumor tissues from each patient. ENE in SLN was measured in the highest (HD-ENE) and widest diameter (WD-ENE). Relative GP96 gene expression was determined using real-time quantitative PCR. Results: The analysis revealed ENE in SLN as the strongest predictive factor for non-SLN metastases. Patients with WD-ENE > HD-ENE had a higher risk of non-SLN metastases and worse DFS compared to those with WD-ENE ≤ HD-ENE. High GP96 expression was associated with a greater relative risk for locoregional recurrence but showed no significant impact on OS or DFS. Histological grade 3, extensive intraductal component (EIC), higher lymph node ratio (LNR), and negative AR were associated with worse DFS, while age, histological grade 3, EIC, and higher LNR were independent predictors of OS. GP96 mRNA levels were elevated in BC tissue compared to normal breast tissue. Conclusions: ENE in SLN is the strongest predictor of non-SLN involvement and could also have prognostic significance. While GP96 expression does not influence survival outcomes, AR expression could be used as a valuable biomarker in the follow-up of BC patients.

Development and validation of web-based risk score predicting prognostic nomograms for elderly patients with primary colorectal lymphoma: A population-based study.

Primary colorectal lymphoma (PCL) is an infrequently occurring form of cancer, with the elderly population exhibiting an increasing prevalence of the disease. Furthermore, advanced age is associated with a poorer prognosis. Accurate prognostication is essential for the treatment of individuals diagnosed with PCL. However, no reliable predictive survival model exists for elderly patients with PCL. Therefore, this study aimed to develop an individualized survival prediction model for elderly patients with PCL and stratify its risk to aid in the treatment and monitoring of patients. Patients aged 60 or older with PCL from 1975 to 2013 in the Surveillance, Epidemiology, and End Results database were selected and randomly divided into a training cohort (n = 1305) and a validation cohort (n = 588). The patients from 2014-2015 (n = 207) were used for external validation. The research team utilized both Cox regression and the least absolute shrinkage and selection operator (LASSO) regression to analyze potential predictors, in order to identify the most suitable model for constructing an OS-nomogram and an associated network version. The risk stratification is constructed on the basis of this model. The performance of the model was evaluated based on the consistency index (C-index), calibration curve, and decision curve analysis (DCA) to determine its resolving power and calibration capability. Age, gender, marital status, Ann Arbor staging, primary site, surgery, histological type, and chemotherapy were independent predictors of Overall Survival (OS) and were therefore included in our nomogram. The Area Under the Curve (AUC) of the 1, 3, and 5-year OS in the training, validation, and external validation sets ranged from 0.732 to 0.829. The Receiver Operating Characteristic (ROC) curves showed that the nomogram model outperformed the Ann Arbor stage system when predicting elderly patients with PCL prognosis at 1, 3, and 5 years in the training set, validation dataset, and external validation cohort. The Concordance Index (C-index) also demonstrated that the nomogram had excellent predictive accuracy and robustness. The calibration curves demonstrated a strong agreement between observed and predicted values. In the external validation cohort, the C-index (0.769, 95%CI: 0.712-0.826) and calibration curves of 1000 bootstrap samples also indicated a high level of concordance between observed and predicted values. The nomogram-related DCA curves exhibited superior clinical utility when compared to Ann Arbor stage. Furthermore, an online prediction tool for overall survival has been developed: https://medkuiwang.shinyapps.io/DynNomapp/. This was the first study to construct and validate predictive survival nomograms for elderly patients with PCL, which is better than the Ann Arbor stage. It will help clinicians manage elderly patients with PCL more accurately.

Development and validation of a nomogram for incorporating 18F-FDG PET/CT spleen uptake for predicting prognosis in elderly esophageal cancer patients treated with radiotherapy.

There is currently no widely accepted prognostic model specifically for elderly patients with esophageal squamous cell carcinoma (ESCC) undergoing radiotherapy. This study aimed to develop a nomogram incorporating metabolic imaging parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to predict overall survival (OS) in this patient population. The clinical need for such a prediction model is significant given the challenges of treatment planning in elderly patients with ESCC undergoing radiotherapy. A retrospective analysis was conducted on 118 elderly patients with ESCC treated with radiotherapy. The patients were evaluated using 18F-FDG PET/CT imaging prior to treatment, and the spleen:liver ratio (SLR) and length of visual tumor (Lv) were identified as potential prognostic indicators. These variables, along with clinical tumor, node, metastasis (cTNM) staging, were used to develop a nomogram model. Key baseline clinical factors, PET variables, inclusion criteria, and follow-up procedures were documented. The model's predictive accuracy was assessed using time-dependent receiver operating characteristic (ROC) curves, the concordance index (C-index), and decision curve analysis (DCA). The patient cohort was stratified into three risk groups based on the total scores derived from the nomogram. SLR and Lv were found to be independent predictors of OS in elderly patients with ESCC. The nomogram developed by incorporating these factors, along with cTNM staging, showed superior predictive power compared to the traditional TNM staging system. ROC curve analysis demonstrated greater accuracy in predicting 1-, 2-, and 3-year OS rates, with area under the curve (AUC) values of 0.771, 0.763, and 0.815, respectively. DCA confirmed that the nomogram provided a greater clinical benefit. Patients were stratified into low-risk, intermediate-risk, and high-risk groups, with corresponding 3-year OS rates of 60.3%, 25.0%, and 3.6%, respectively. The developed nomogram incorporating SLR, Lv, and cTNM staging offers a reliable tool for the risk stratification of elderly patients with ESCC undergoing radiotherapy. This model may serve as a reference for personalized treatment planning, potentially improving clinical outcomes in this patient population.

Long non-coding RNA H19 as a prognostic biomarker for oral squamous cell carcinoma.

H19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC. The present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival. A longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan-Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC. H19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox's proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence. The findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.

Delayed surgery during the Covid-19 pandemic did not affect long-term outcomes of pancreatic adenocarcinoma

BackgroundDuring the Covid-19 pandemic cancer surgery was severely affected due to relocation of healthcare resources and the resulting restructuring of cancer pathways. Although this potentially affected rapidly progressing malignancies like pancreatic cancer the most, little is known about long-term outcomes following pancreatectomy. Materials and methodsSurvival data from two pancreatic surgery centres in the UK was analysed with patients being compared across pre-pandemic (C19-) and intra-pandemic (C19+) groups. Demographic, pathological and surgical pathway parameters were evaluated with multivariate analysis and propensity score matching. ResultsOut of 123 patients, 60 had surgery during the pandemic. The main strategy to reduce disruptions to pancreatic surgery was relocation of services to private sector facilities without emergency medicine departments. Although time to surgery was delayed by almost 20 days during the pandemic, there were no significant differences in overall survival at 22 months vs. 24 months or disease free survival at 15 months vs. 16 months for the C19+ and C19- groups, respectively. Adjuvant chemotherapy, Charlson comorbidity score, tumour stage and resection margin status were found to be independent predictors for overall survival whereas only adjuvant chemotherapy and Charlson comorbidity score were predictive of disease free survival. ConclusionThis article provides a template for the effective restructuring of pancreatectomy pathways during a pandemic with associated lockdowns and provides the first evidence that the quality of outcomes can be maintained in this difficult environment. It is hoped that these results will provide a framework for addressing surgical oncology challenges in future pandemics.

Low Expression of Mitochondrial Ribosomal Protein S5 is Associated With Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma.

Mitochondrial ribosomal protein S5 (MRPS5) is abnormally expressed in various tumor tissues and may be a key molecule for the regulation of tumors. Our aim is to investigate the relationship between the expression of MRPS5 in clear cell renal cell carcinoma (ccRCC) and the prognosis of patients. MRPS5 expression in fresh tumoral tissues and peritumoral tissues of patients with ccRCC was examined by quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemical staining, respectively. MRPS5 expression level in paraffin-embedded tumoral tissue samples with ccRCC was evaluated by immunohistochemical scoring criteria. The relationship between the expression of MRPS5 and the clinicopathological parameters and prognosis of patients with ccRCC was analyzed statistically. The expression of MRPS5 mRNA and protein in fresh tumoral tissues was lower than that in peritumoral tissues. Among 160 paraffin-embedded tumoral tissue samples, 99 cases (61.9%) showed high expression and 61 cases (38.1%) showed low expression of MRPS5. The expression level of MRPS5 was significantly correlated with T classification, TNM stage, and Fuhrman grade. Kaplan-Meier method and log-rank test indicated that patients with low MRPS5 expression had significantly poorer overall survival and recurrence-free survival than high MRPS5 expression. Multivariate analysis revealed that MRPS5 expression was an independent predictor of overall survival and recurrence-free survival, respectively. MRPS5 low expression was a risk factor for the prognosis of patients. The expression level of MRPS5 is significantly correlated with the postoperative survival status, which has the potential to be used as a novel prognostic biomarker for patients with ccRCC.

Medium-term survival of patients with mechanical and biological aortic prosthesis at the 6th decade of life.

The best aortic prosthesis type in 60-70 year old patients is not established. Our aim was to evaluate the survival in a National cohort of patients between 60-70 years old who required surgical aortic valve replacement for aortic stenosis (SAVR) with either a mechanical (MP) or bioprosthesis (BP) valve. This is a retrospective study using national data from the Ministry of Health. We included all patients between 60 to 70 years old who underwent SAVR for aortic stenosis in Uruguay from 2011 to 2021. The primary outcome was overall survival according to type of prosthesis used stratified by effect modifiers. The independent effects of gender and use of statins were evaluated. We included 1196 patients (66±3.0 years old; 39.1% female). Mortality was higher for BP (296, 29.9%%) than MP (36, 17.1%; p<0.001). Median follow-up time was 4.5 years (Interquartile range [IQR] 3.4-6.5). The unadjusted incidence rate ratio was higher for BP (Incidence rate ratio [IRR] = 1.43;95%CI: 0.99, 2.14, p = 0.045). The effect of BP on mortality rate was greater in males (IRR = 1.82;95%CI:1.14,2.92. p interaction = 0.08) and patients who were not taking statins (IRR = 1.97;95%CI:1.14,3.41. p interaction = 0.06). The use of BP was an independent predictor of overall survival in male patients (Hazard ratio [HR] = 1.32;95%CI: 1.68, 1.04. p = 0.021) and in patients who were not taking statins (HR = 2.07;95%CI: 1.17, 3.67. p = 0.013). The use of BP was associated with worse survival in male patients and patients not taking statins. Gender and statins use should contribute to type of prosthesis decision in the 60-69 age group.

KIF20A activated by transcription factor GATA2 promotes cell growth in hepatitis B virus-related hepatocellular carcinoma.

Elevated evidence suggests that KIF20A plays an important role in hepatocellular carcinoma (HCC) progression. Nevertheless, the underlying mechanism by which KIF20A promotes HCC cell growth are not well understood. Using TCGA-LIHC RNAseq and GEO datasets, we assessed the KIF20A expression and patient survival in HCC and hepatitis B virus (HBV)-related HCC. Mutant and CNV analysis were performed to evaluate the genetic alteration of KIF20A in HCC. PPI network and GSEA enrichment was utilized for analyzing the KIF20A-related genes and involved pathways in HCC. To further explore regulatory mechanism in HBV-related HCC, PROMO prediction and luciferase reporter system was utilized for verifying HBx/GATA2/KIF20A binding sites. CCK-8 and flow cytometry were carried out to determine the regulation of GATA2-KIF20A on HBV-related HCC cell proliferation and apoptosis. KIF20A was significantly upregulated in pan-cancer (including HCC). KIF20A mRNA level was a significant independent predictor of overall survival in HBV-related HCC patients. Genetic alterations analysis revealed the copy number gain and amplification triggered KIF20A upregulation in HCC. In addition, the genes associated with KIF20A expression in HCC was enriched in PLK1 pathway and cell cycle in HCC. HBx might indirectly binds to KIF20A promoter via regulating GATA2. Additionally, transcription factor GATA2 directly binds to the promoter region of KIF20A. Overexpression of GATA2 promotes HepG2.2.15 cell growth and inhibits cell apoptosis via modulating KIF20A. Our findings demonstrated that HBx contributed to cell proliferation by interacting with GATA2 and KIF20A in HBV-related HCC.

Real-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.

Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity. We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens. The median follow-up duration was 48 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. The cohort consisted of 590 male and 481 female patients with a median age of 63.8 years (range, 19.3-93.6). Most were stage III-IV at diagnosis (60.9%) and of non-germinal center B-cell like (non-GCB) subtype by Han's criteria (56.5%). The vast majority received R-CHOP(-like) regimens (n = 997, 93.1%), including rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-R) (n = 95), achieving a 5-year progression-free survival (PFS) and overall survival (OS) of 64.5% and 74.7% respectively. Male sex (p = 0.0294), age > 60 years (p < 0.0001), poor ECOG scores (2-4) (p < 0.0001), advanced stage (III-IV) (p < 0.0001), presence of B-symptoms (p = 0.0305), and raised LDH (p = 0.0161) were independent predictors of OS, 4 of which are risk factors in the International Prognostic Index (IPI). In the intermediate to high-risk subgroup (IPI scores 2-5; n = 752), the 5-year PFS and OS were only 59.0% and 69.8% respectively. EBV status, MYC and/or BCL2/BCL6 rearrangements, were not significantly associated with survival outcomes. EPOCH-R was used more frequently than R-CHOP in patients with MYC rearrangements (n = 82, p < 0.0001), including those with MYC/BCL2 double-hit genetics (n = 31, p < 0.0001). Notably, neither regimen significantly affected survival outcomes, both in MYC-rearranged (PFS: HR 0.60, p = 0.1704; OS: HR 0.49, p = 0.0852), and in MYC/BCL2 double-hit DLBCL (PFS: HR 1.30, p = 0.6433; OS: HR 1.02, p = 0.9803). Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

Textbook oncological outcome of locally advanced gastric cancer patients with preoperative sarcopenia: a multicenter clinical study.

The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI < 36.4 cm2/m2 in males and < 28.4 cm2/m2 in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P = 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5-2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequateLND (< 6 LN) (C index: 0.87). An online calculator was developed ( https://catalano-giovanni.shinyapps.io/LoddsGBC/ ). A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.