Cox Multivariate Analysis Research Articles

Evaluation of optimal timing and therapeutic efficacy of radium-223 therapy for metastatic castration-resistant prostate cancer: a multicenter collaborative study.

Despite its demonstrated efficacy in prolonging overall survival (OS) and delaying skeletal-related events in the ALSYMPCA trial, the optimal timing of radium-223 initiation remains unclear. This study investigated factors influencing radium-223 treatment outcomes, including completion rates and survival. This retrospective, multi-institutional study included 164 patients with metastatic castration-resistant prostate cancer (CRPC) who received radium-223 therapy. The primary endpoint was OS following radium-223 initiation. Secondary endpoints included factors associated with incomplete radium-223 treatment (< sixcycles) and poor OS. Multivariate Cox regression and multivariate logistic regression analyses were conducted to identify prognostic factors. The median OS times after CRPC diagnosis and radium-223 initiation were 39 and 12.5months, respectively. Kaplan-Meier analysis showed that the OS of patients who completed six cycles of radium-223 treatment was longer than that of those who did not (18 vs. 5months; P<.001). Multivariate Cox analysis identified Eastern Cooperative Oncology Group performance status (ECOG-PS)≥1 (hazard ratio [HR]=1.74, P=.046), PSA>17ng/ml (HR=2.93, P<.001), and radium-223 incompletion (HR=3.23, P<.001) as independent predictors of poor OS. The radium-223 completion rate was 68.3%, and incompletion was significantly associated with prior docetaxel use (odds ratio [OR]=5.97, P=.001), bone pain (OR=2.64, P=.024), and PSA>17ng/ml at the start of radium-223 treatment (OR=3.12, P=.013). Completion of all six cycles of radium-223 treatment were associated with favorable survival outcomes in metastatic CRPC patients. Prior docetaxel use, bone pain, and elevated PSA levels were significant risk factors for radium-223 incompletion. These findings suggest the importance of initiating radium-223 earlier in the treatment course for patients with favorable clinical profiles to maximize the therapeutic benefits.

Prognostic value of changes in vibration-controlled transient elastography parameters for liver, cardiovascular and mortality outcomes in individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: The Rio de Janeiro type 2 diabetes cohort.

The prognostic importance of changes in vibration-controlled transient elastography (VCTE) parameters, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP), in individuals with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. A prospective cohort of 288 patients underwent 2 VCTE exams at least 2 years apart, and the relative percentage changes in LSM and CAP were calculated. Outcomes were the occurrence of any liver-related events (LREs), cardiovascular events (CVEs), and all-cause mortality. Multivariable Cox analyses, adjusted for liver and cardiometabolic factors, assessed associations between VCTE parameters changes, both as continuous and dichotomical variables (LSM increase >15% and CAP reduction >10%), and outcomes. During a median follow-up of 6 years, there were 22 LREs, 28 CVEs, and 37 all-cause deaths. For LREs, baseline LSM was the strongest predictor, but LSM increases added further prognostic value (hazard ratio [HR]: 1.5 [1.0-2.1], 1-SD increment). For CVEs, both LSM increase (HR: 1.7 [1.3-2.3]) and CAP reduction (HR: 1.5 [1.0-2.3], 1-SD decrease) were significant predictors. For all-cause mortality, baseline CAP was a protective predictor. When classified into subgroups based on LSM and CAP changes, the subgroup with both increased LSM and reduced CAP had the highest risks for CVEs (HR:5.3 [1.4-19.6]) and all-cause mortality (HR: 3.4 [1.2-9.6]). The highest risk for LREs was observed in the subgroup with increased LSM without CAP reduction (HR: 3.5 [0.9-12.9]). VCTE parameters changes, LSM increase and CAP reduction, provide prognostic information for adverse liver, cardiovascular, and mortality outcomes in individuals with T2D and MASLD.

Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis

BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) refers to a subset of patients who fail to achieve adequate disease control after the use of two or more biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different mechanisms of action, while maintaining active inflammatory disease. This presents a therapeutic challenge and highlights the need to explore contributing factors such as the potential role of the gut microbiota. Therefore, the aim of this study was to analyze the gut microbiota and inflammation in patients with D2T RA in comparison to patients with easy-to-treat RA (E2T RA).ObjectiveTo analyze the gut microbiota and inflammation in patients with D2T RA.MethodsWe performed an observational study of a prospective cohort between 2007 and 2011 and analyzed the gut microbiota. In 2022, we identified 2 extreme patient phenotypes: (1) D2T RA, which was defined as failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (with different mechanisms of action) plus signs of active disease; and (2) easy-to-treat RA (E2T RA), i.e., stable disease managed with a single treatment. The gut microbiota was analyzed using 16S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2, and its functionality was inferred through PICRUSt. We recorded data on clinical findings, inflammation, and cytokines. A Cox multivariate analysis was performed to identify factors related to D2T RA.ResultsThe study population comprised 39 patients: 13 (33%) with D2T RA and 26 (66%) with E2T RA. The families Lachnospiraceae and Pasteurellaceae, and their genera Coprococcus and Haemophilus were more abundant in E2T RA patients, while the genus Megasphaera was more abundant in D2T RA patients. The Firmicutes/Bacteroidetes ratio decreased in D2T RA patients. The metabolic profile of the gut microbiota was characterized by differences in Degradation/Utilization/Assimilation pathway and the Biosynthesis pathway. The factors associated with D2T RA were inflammatory activity according to DAS28-ESR (HR, 2.649; p = 0.013), prednisone (HR, 3.794; p = 0.008), and the Firmicutes/Bacteroidetes ratio (HR, 0.288; p = 0.033).ConclusionThe composition of the gut microbiota of patients with D2T RA differed from that of E2T RA patients, as did the metabolic pathways.

RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma

BackgroundRecent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA modifications in the tumor microenvironment (TME) are still unknown.MethodsWe assessed the expression properties and genetic alterations of 26 RNA modification writers, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A, and m6A in 502 lung adenocarcinoma (LUAD) samples from the Cancer Genome Atlas (TCGA) datasets. Then, we used differentially expressed gene (DEGs) to develop a signature for predicting patient outcomes, which was dubbed the “writer score” for RNA-modified writers. In addition, we analyzed the association between TME features, molecular subtypes, treatment sensitivity, and immunotherapy efficacy.ResultsWe comprehensively evaluated the changes in multilayer RNA modification writers and identified the role of RNA modification writer expression imbalances in LUAD emergence and progression. Additionally, we constructed a risk-score model based on six LUAD prognosis-associated differentially expressed RNA modification writer genes. Kaplan–Meier (K–M) analyses revealed that the low risk-score signature had high overall patient survival. The predictive significance of the risk-score model was demonstrated using both univariate and multivariate Cox analyses. The risk-score model was positively correlated with the immune- and proliferation-related pathways. In response to anti-cancer treatment, high-risk score is related with high TMB, which has been discovered to correlate with immunotherapy effectiveness.ConclusionThis study showed a strong correlation between the TME variety, level of complexity, and the four types of RNA modification writers. In addition, this scoring system could potentially predict effective immunotherapy and deepens our understanding of TME characteristics.

Quantifying Tumor Budding: Implications for Prognosis in Gastric Adenocarcinoma.

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.

Ternary complex components responsible for rapid LDL internalization as biomarkers for breast cancer associated with proliferation and early recurrence.

The ternary complex of PGRMC1-σ2R/TMEM97-LDLR has recently been discovered and plays a role in cholesterol transport. This study investigated whether individual components of that complex are prognostic breast cancer biomarkers and defined expression in established molecular subtypes. 4,463 invasive breast cancers were analyzed as a function of molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival. A gene expression signature-based assay was utilized to estimate cellular proliferation. Cox proportional hazards regression estimated relapse-free survival and multivariate Cox analysis adjusted for the association of proliferation with early relapse. PGRMC1-σ2R/TMEM97-LDLR expression was stratified by immunohistochemical and molecular subtype, tumor grade and size. TMEM97 exhibited the strongest correlation with proliferation, highest in ER+ disease (r=0.712, p=6.5-200). TMEM97 and PGRMC1 were associated with risk of early recurrence, dependent upon their association with proliferation. The risk of early recurrence was highest with TMEM97 and only seen in ER+/HER2- disease (HR 1.5 [1.35,1.67], p=5.4-14) and ER+ malignancies (HR1.49 [1.31;1.68], p=3.1-10). There was no increased risk of recurrence with TMEN97 expression in ER-/HER2- (HR 1.05 [0.88; 1.25], p=0.63) or ER- disease (HR1.02 [0.89; 1.17], p=0.75). Components of a ternary complex associated with rapid internalization of LDL are biomarkers associated with cellular proliferation and early recurrence, which should help guide studies exploring them in the context of additional markers of aggressive disease. Elucidating the role of PGRMC1, TMEM97, and LDLR in breast cancer will facilitate a mechanistic understanding of how proliferation interplays with cholesterol metabolism in malignant transformation or propagation.

The most important prognostic factors for predicting major adverse cardiovascular, cerebrovascular, and renal events during 5-year follow-up of patients with chronic kidney disease with or without haemodialysis.

Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. The purpose of this study is to evaluate the prognostic predictors over 5 years in patients with CKD including haemodialysis. In this multicenter, prospective cohort study performed with the Gunma-CKD SPECT Study protocol, 311 patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml/1.73 m2], including 50 patients on haemodialysis, undergoing stress Tc-99m-tetrofosmin SPECT for suspected ischaemic heart disease were followed for 5 years. MACCRE was evaluated, and summed stress score, summed rest score, summed difference score (SDS), left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV) and ejection fraction (LVEF) were evaluated by electrocardiogram-gated SPECT. Of the 311 patients, 268 were followed for 5 years, and of those patients, 126 experienced MACCRE: cardiac death, n = 15; sudden death, n = 5, nonfatal myocardial infarction, n = 5; hospitalization for heart failure, n = 16; cerebrovascular accident, n = 9; revascularization, n = 49; renal events (haemodialysis initiation/kidney transplantation), n = 20 and other cardiovascular events, n = 7. In univariate Cox analysis, eGFR (P < 0.0001), haemoglobin (P = 0.001), SDS (P = 0.0001), LVEDV (P = 0.002), LVESV (P = 0.0003) and LVEF (P < 0.0001) were associated with MACCRE, and in multivariate Cox analysis, eGFR (P = 0.014) and SDS (P = 0.002) were strongly associated with MACCRE. In Kaplan-Meier analysis, the event-free survival rate for MACCRE was better in patients with SDS below 3 than in those with SDS of 3 or higher (P < 0.0001, log-rank test) and in patients with eGFR of 18 or higher than in those with eGFR below 18 (P < 0.0001, log-rank test). In patients with CKD, SDS and eGFR are reliable prognostic markers for the occurrence of MACCRE over 5 years.

SUGT1 is a prognostic biomarker and is associated with immune infiltrates in ovarian cancer

BackgroundOvarian cancer (OC) is a prevalent gynecological malignancy with a relatively dismal prognosis. The SGT1 homolog (SUGT1) protein, which interacts with heat shock protein 90 and is essential for the G1/S and G2/M transitions, was formerly thought to be a cancer promoter, but its precise role in OC remains unknown.MethodsWe conducted a comprehensive bioinformatics analysis of SUGT1 expression in patients with OC compared with their normal controls, including the data from the cancer genome atlas (TCGA), genotype–tissue expression (GTEx) databases, gene ontology (GO) analysis, Kyoto Encylopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA). In addition, Kaplan–Meier (KM) analysis, univariate and multivariate Cox analyses were applied to investigate the prognostic role of SUGT1 in ovarian cancer. Furthermore, we validated the expression of SUGT1 in OC and normal tissues through immunohistochemistry.ResultsSUGT1 was significantly overexpressed in OC than in normal tissues. In addition, the GO, KEGG and GSEA analysis revealed that SUGT1 was associated with the functions related to immunoglobulin complex, antigen binding, immunoglobulin receptor binding, among others. Besides, ssGSEA demonstrated a positive correlation between SUGT1 expression and the abundance of T central memory cells, natural killer cells, and T gamma delta cells, although it showed a negative association with activated dendritic cells, cytotoxic cells, T cells, and T helper 1 cells. Subsequently, KM survival analysis revealed that high SUGT1 expression indicated a shorter overall survival, disease specific survival and progression free interval in OC patients. Univariate and multivariate Cox regression revealed that SUGT1 could serve as an independent risk factor for prognosis of patients with OC.ConclusionsAll these results of this study show that SUGT1 is an important molecular component in immune infiltration in OC and may have a new significant prognostic role in OC.

SQSTM1/p62 predicts prognosis and upregulates the transcription of CCND1 to promote proliferation in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare, highly invasive non-Hodgkin's lymphoma. The main pathogenesis of MCL is associated with the formation of the IgH/CCND1 fusion gene and nuclear overexpression of cyclin D1, which accelerates the cell cycle, leading to tumorigenesis. The prognosis with current standard chemotherapy is still unsatisfactory. SQSTM1/p62 is a multifunctional adaptor that plays an important role in various tumors. Here, we found that the expression of p62 in MCL tissues was higher than that in hyperplastic lymphadenitis patients. Patients with low p62 expression in MCL cells had better overall survival and progression-free survival rates than those with high expression (p = 0.024 and p = 0.025, respectively). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of p62 increased to 2.742 (95% confidence interval (CI) of 1.268-5.852, p = 0.01), which was higher than those with low levels. Silencing p62 impaired Jeko-1 and Granta519 cell proliferation while downregulating CCND1 mRNA and protein expression, thereby inducing G0/G1 cell cycle arrest. However, silencing p62 does not affect the fusion of IgH and CCND1. Luciferase reporter gene analysis and chromatin immunoprecipitation analysis demonstrated that p62 may regulate CCND1 gene expression through Nrf2. These results provide evidence that p62 can predict poor prognosis in MCL. The precise targeting of p62 therapy reduces the promoting effect of Nrf2 on CCND1, thereby preventing cell cycle progression and effectively inhibiting tumor proliferation. Therefore, p62 may provide a potential target for MCL.

Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study.

The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS. There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9-177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4-NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00-6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27-5.41; p = 0.009). Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy.

Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.

Ovarian Cancer (OC) was known for its high mortality rate among gynecological malignancies, often resulting in a poor prognosis. This study sought to identify prognostic necroptosis-related long non-coding RNAs (lncRNAs) (NRlncRNAs) with prognostic potential and to construct a reliable risk prediction model for OC patients. The transcriptome and clinic data were sourced from TCGA and GTEx databases. Initially, NRlncRNAs were discovered by assessing gene correlations and evaluating differences in gene expression. Subsequently, Cox regression and LASSO methods were employed to develop the NRlncRNAs risk model, which was further validated through survival analysis, ROC curves, Cox regression, and nomograms across both the test and entire datasets. Multivariate Cox analysis revealed that the risk score based on 14 NRlncRNAs can independently predict the prognosis of OC. The low-risk group demonstrated significantly higher immune cell infiltration scores and lower tumor immune dysfunction, exclusion, and TIDE scores, as well as an increased number of neoantigens and higher TMB. Notably, the low-risk group also exhibited an elevated HRD score. The model's predictive accuracy was further substantiated through ROC analysis, showing superior performance compared to many existing models.Finally, the expression levels of 14 NRlncRNAs were confirmed using the qRT-PCR in two OC cell lines. These findings suggested that the NRlncRNAs risk model could serve as a more precise indicator for forecasting immune response and outcomes of targeted treatments in OC.

Predicting Time to First Rejection Episode in Lung Transplant Patients Using a Comprehensive Multi-Indicator Model.

Rejection hinders long-term survival in lung transplantation, and no widely accepted biomarkers exist to predict rejection risk. This study aimed to develop and validate a prognostic model using laboratory data to predict the time to first rejection episode in lung transplant recipients. Data from 160 lung transplant recipients were retrospectively collected. Univariate Cox analysis assessed the impact of patient characteristics on time to first rejection episode. Kaplan-Meier survival analysis, LASSO regression, and multivariate Cox analysis were used to select prognostic indicators and develop a riskScore model. Model performance was evaluated using Kaplan-Meier analysis, time-dependent ROC curves, and multivariate Cox regression. Patient characteristics were not significantly associated with the time to the first rejection episode. Six laboratory indicators-Activated Partial Thromboplastin Time, IL-10, estimated intrapulmonary shunt, 50% Hemolytic Complement, IgA, and Complement Component 3-were identified as significant predictors and integrated into the riskScore. The riskScore demonstrated good predictive performance. It outperformed individual indicators, was an independent risk factor for rejection, and was validated in the validation dataset. The riskScore model effectively predicts time to first rejection episode in lung transplant recipients.

Growth Differentiation Factor-15 IsAssociated With Congestion-Related Anorexia and Weight Loss in AdvancedHeartFailure.

Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with HeartFailure Questionnaire, and right heart catheterization. The median GDF-15 level was 1,503ng/L (Q1-Q3: 955-2,332ng/L) (reference range:<1,200ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95%CI: 1.47-3.66]; P< 0.001). In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.

Identification of a Risk Signature and Immune Cell Infiltration Based on Extracellular Matrix-Related lncRNAs in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths globally, with late diagnoses often resulting in poor prognoses. The extracellular matrix (ECM) plays a crucial role in cancer cell processes. Using big data from RNA-seq of LUAD, we aimed to screen ECM-related lncRNAs (long noncoding RNAs) to determine their prognostic significance. Our study analyzed the LUAD cohort from The Cancer Genome Atlas (TCGA). Univariate Cox analysis identified prognostic lncRNAs, and least absolute shrinkage and selection operator (LASSO) regression analysis, followed by multivariate Cox analysis, was used to construct a prognostic model. Kaplan-Meier and ROC curves evaluated the model's prognostic performance. A nomogram was created to predict 3-year survival. Enrichment analysis identified biological processes and pathways involved in the signature. Correlations with the tumor microenvironment (TME) and tumor mutation burden (TMB) were analyzed, and potential drug sensitivities for LUAD were predicted. We initially identified 218 ECM-associated genes and 427 ECM-associated lncRNAs within the TCGA LUAD cohort. Subsequent univariate Cox regression analysis selected 26 lncRNAs with significant prognostic value, and an overall survival (OS)-based LASSO Cox regression model further narrowed this to 14 lncRNAs. Multiple Cox regression analyses then distilled these down to 8 critical lncRNAs forming our prognostic risk signature. Nomograms accurately predicted survival. Finally, several potential therapeutic drugs, including afatinib and crizotinib, were identified. Big data analysis established a prognostic signature that predicts survival and immunization in LUAD patients, providing new insights into survival and treatment options.

Development and Validation of a Prognostic Molecular Phenotype and Clinical Characterization in Grade III Diffuse Gliomas Treatment with Radio-Chemotherapy.

The relationship between molecular phenotype and prognosis in high-grade gliomas (WHO III and IV, HGG) treated with radiotherapy and chemotherapy is not fully understood and needs further exploration. The HGG patients following surgery and treatment with radiotherapy and chemotherapy. Univariate and multivariate Cox analyses were used to assess the independent prognostic factors. The nomogram model was established, and its accuracy was determined via the calibration plots. A total of 215 and 88 patients had grade III glioma and grade IV glioma, respectively. Grade III oligodendroglioma (OG-G3) patients had the longest mPFS and mOS than other grade III pathology, while grade III astrocytoma (AA-G3) patients were close to IDH-1 wildtype glioblastoma (GBM) and had a poor prognosis. The IDH-1 mutant group had a better mPFS and mOS than the IDH-1 wildtype group in all grade III patients, OG-G3 and AA-G3 patients. Furthermore, 1p/19q co-deletion group had a longer mPFS and mOS than 1p/19q non-deletion group in all grade III patients. IDH-1 mutation and 1p/19q co-deletion patients had the best prognosis than other molecular types. Also, the MGMT methylation and IDH-1 mutation or 1p/19q co-deletion group had a longer mPFS and mOS than the MGMT unmethylation and IDH-1 wildtype or 1p/19q non-codeletion of grade III patients. In addition, the low Ki-67 expression group had a better prognosis than high Ki-67 expression group in grade III patients. Univariate and multivariate COX showed that 1p/19q co-deletion and MGMT methylation were the independent prognostic factors for mPFS and mOS. The calibration curve showed that the established nomogram could well predict the survival based on these covariates. The AA-G3 with IDH-1 wildtype, MGMT unmethylation or 1p/19q non-codeletion patients was resistant to radiotherapy and chemotherapy, has a poor prognosis and needs a more active treatment.

The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis

Background and objectiveNeoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease. MethodsPatients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted. ResultsIncluded were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12–7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43–12.3], P = 0.009) were predictive of disease relapse. ConclusionsPatients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.

Mutant Pattern of p53 as a Feasible Predictor of Distant Metastasis Following Curative Gastrectomy for Advanced-stage Gastric Cancer.

Objective: The TP53 mutation is a poor prognostic factor for malignant tumors in a number of organs. The present study primarily aimed to clarify the impact of the mutant pattern of p53 on the prognosis and recurrence of gastric cancer. Methods: For this purpose, 519 patients who underwent radical gastrectomy for cancer were enrolled in the present study. Immunohistochemistry (IHC) was used to examine p53 expression in tissues and a three-stage classification system was used to divide the patient tissues into three groups according to the expression of p53: Heterogeneous (wild-type), absent and overexpression (mutant). Results: After 5 years of follow-up, recurrence and metastasis occurred in 38.7% of patients with stomach cancer, with a p53 mutant pattern in 48.4% of these patients. Patients with a p53 mutant pattern had lower recurrence-free and overall survival rates at 5 years compared with those who were p53 wild-type (P<0.001). It was found that the p53 pattern differed significantly (P<0.001) between the wild-type and mutant patterns, including the pN0 and pN+ gastric cancer subgroups (P<0.001 and P=0.014, respectively). The p53 mutant pattern was also significant in the determination of the recurrence-free survival of patients with progressive stomach cancer (P<0.0001). The 5-year overall survival rates were 71.7 and 36.2%, and the recurrence-free survival rates were 71.2 and 35.2% in the pN0 and pN+ groups, respectively (P<0.001). The mutant pattern of p53 was a significant prognostic factor for both distant metastasis [relative risk (RR)=2.881, P<0.001] and overall survival (RR=2.809, P<0.001) in the univariate Cox regression analysis. In the multivariate analysis, distant metastasis (RR=2.767, P<0.001) remained significant in the mutant pattern of p53 staining. After propensity score matching, 189 patients with a p53 wild-type and 189 patients with a p53 mutant pattern were extracted for analysis. The 5-year overall survival rate in patients with the p53 mutant pattern (n = 189) was worse than that in the patients with p53 wild-type (n = 189) and with significant differences (log-rank P<0.01). The study was statistically significant after Cox univariate and multivariate regression analysis, which revealed that the mutant pattern of p53 is an independent prognostic factor impacting distant metastases following curative gastrectomy for advanced-stage gastric cancer (p = 0.48).

Identification and Clinical Validation of High HSP60 Expression Predicts Poor Prognosis in Patients with Ovarian Cancer.

This study aimed to investigate the clinical significance of heat shock protein 60 (HSP60) expression in ovarian cancer and evaluate its correlation with patient survival outcomes. A total of 260 ovarian cancer patients diagnosed between 2017 and 2019 were enrolled. Immunohistochemistry was performed to assess HSP60 expression in tumor tissues. Patients were categorized into high- or low-HSP60 expression groups based on immunohistochemical staining intensity. The correlation between HSP60 expression status and the clinicopathological features of ovarian cancer patients was analyzed. Kaplan-Meier survival curves and Cox regression models were utilized to evaluate overall survival and disease-free survival. HSP60 expression was significantly higher in ovarian cancer tissues compared to normal ovarian tissues. High HSP60 expression was associated with larger tumor size, advanced FIGO stage, and increased lymph node metastasis. Patients with high HSP60 expression exhibited significantly shorter overall survival and disease-free survival than those with low expression. Multivariate Cox analysis identified HSP60 as an independent prognostic factor for both overall survival and disease-free survival. High HSP60 expression is associated with poor prognosis and aggressive tumor characteristics in ovarian cancer. HSP60 may serve as a valuable biomarker for prognosis and a potential therapeutic target. Further randomized clinical trials are warranted to explore its role in ovarian cancer progression and treatment strategies.

Maintaining first-line therapy plus radiotherapy may prolong progression-free survival and delay second-line therapy for oligoprogressive hepatocellular carcinoma.

Optimal treatment strategies for patients with hepatocellular carcinoma (HCC) with oligoprogression after first-line systemic therapy (FLST) remain undefined. We aimed to determine if maintaining [i.e., continuing] FLST plus radiotherapy for oligoprogressive lesions (m-FLST + RT) would result in progression-free survival (PFS) equal to or greater than that of second-line systemic therapy (s-SLST), either alone or with radiotherapy (s-SLST + RT). From October 2018 to February 2024, 154 patients from seven medical centers who developed oligoprogression after FLST were enrolled and assigned to one of three groups based on post-oligoprogression treatment strategy: m-FLST + RT, s-SLST + RT, or s-SLST-only. The primary outcome was PFS, and early patterns of recurrence were noted. At a median follow-up time of 8.4 months, median PFS time was longer in the m-FLST + RT group (8.6 months) compared with the s-SLS-only group (3.1 months) (hazard ratio [HR] =3.163, 95% CI 2.133-4.690, p<0.001) and the s-SLST + RT group (5.8 months) (HR=2.183, 95% CI 1.110-4.293, p=0.006). Multivariate Cox analysis demonstrated that albumin-bilirubin (ALBI) grade and post-oligoprogression treatment strategy were independent prognostic factors for PFS. Stratified analysis by ALBI grade showed that m-FLST + RT resulted in significantly longer median PFS in both ALBI-1 and ALBI-2 patients compared with s-SLST-only (p<0.001). Regarding subsequent patterns of relapse, the m-FLST + RT group had a lower rate of re-enlargement of recently oligoprogressive lesions (27.6%) than the s-SLST + RT (31.8%) and s-SLST-only (50.0%) groups. It also had the lowest rate of re-enlargement of previously identified metastases that did not progress during FLST (13.8%) compared with s-SLRT + RT (27.3%) and s-SLST-only (24.4%). Our study suggests a potential clinical benefit of m-FLST + RT without the need for s-SLST and provides insights to optimize treatment strategies for oligoprogressive HCC.

Impact of Treatment Strategies on Survival and Within Multivariate Predictive Model for Renal Cell Carcinoma Based on the SEER Database: A Retrospective Cohort Study

Background This project aims to shed light on how various treatment approaches affect RCC patients’ chances of survival and create a prediction model for them. Methods Data from the Surveillance, Epidemiology, and End Results database were used in this investigation. OS and RCSS after radiation, chemotherapy, and surgery were investigated using the Kaplan-Meier approach. Fourteen factors, including gender, age, race, and others, were subjected to univariate and multivariate COX analyses. Predicting RCSS at three, five, or ten years is the main goal. Predicting OS at three, five, or ten years is the secondary endpoint. Cox analyses, both univariate and multivariate, were used to identify prognostic factors. Furthermore, a nomogram was developed to precisely forecast patient survival rates at 3-, 5-, and 10-year intervals. DCA, calibration curves, and ROC were used to assess the nomogram’s efficacy. Results Kaplan-Meier analysis revealed that PN was associated with better survival compared to RN for tumors ≤10 cm. Cox analysis identified 10 independent prognostic factors. These variables included gender, age, race, histological type, histological grade, AJCC stage, N stage, T stage, M stage, and surgical type. Based on these variables, a nomogram for OS and RCSS prediction was created. Conclusion PN is advised over RN for RCC patients whose tumors are less than 10 cm in diameter since it offers more advantages. The combined nomogram model, which is based on clinicopathological characteristics, therapy data, and demographic variables, may be used to predict the survival of RCC patients and perform prognostic and survival analysis with accuracy.