Marker For Overall Survival Research Articles

Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and Meta-Analysis.

Prognostic markers for overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) are well-established but remain unclear following neoadjuvant therapy (NAT). This systematic review and meta-analysis aimed to determine factors associated with OS following NAT in resected PDAC. The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from inception till May 2024. Studies that reported univariable and multivariable hazard ratios (HRs) were included if patients underwent NAT and resection for localized PDAC. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. Among 2,208 unique articles identified by the search, 92 were included in the meta-analysis. Eighty-five of these were of 'good' and 7 of 'poor' quality. The NAT regimen was described in 84 studies, of which 62 included patients treated with FOLFIRINOX (FFX). Margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT were prognostic for OS, while age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN-substages was not significant in the multivariable model. Neoadjuvant FFX was associated with better survival than other regimens. This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT as prognostic factors for OS in patients with resected localized PDAC following NAT.

Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Setting.

Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep learning strategies on histology samples to predict outcome for OSA in the neoadjuvant setting. Our study relies on a training cohort from New York University (New York, NY) and an external cohort from Charles university (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content, and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphological features could serve as a potential marker for OS in the setting of neoadjuvant. Excellent correlation between the trained network and the pathologists was obtained for the quantification of necrosis content (R2=0.899, r=0.949, p < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). Morphology-based supervised approach predicted OS with p-value=0.0028, HR=2.43 [1.10-5.38]. The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS (lg2HR; -2.366; -1.164; -1.175; 95% CI=[-2.996; -0.514]). Viable/partially viable tumor and fat necrosis were associated with worse OS (lg2HR;1.287;0.822;0.828; 95% CI=[0.38-1.974]). Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphological biomarkers specific to the necrotic and tumor regions themselves which can be used as predictors.

Abstract PR017: A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition

Abstract Immune checkpoint inhibitors (ICI) are increasingly used as first line of treatment in a range of cancer types, owing to their efficacy and advantageous toxicological profile. Currently, PD-L1 expression and tumor mutation burden (TMB) are the most common biomarkers to select patients for ICI treatment, yet response to ICI remains highly variable between patients, necessitating more accurate early predictors of treatment response. Circulating cell-free DNA (cfDNA) originates from dying cells throughout the body, each molecule carrying unique epigenetic features of its cell-type of origin. Most studies on cfDNA focus on tumor-derived fragments for diagnostics or minimal residual disease detection. However, variations in the contribution of immune cells and other stromal cell populations could provide important clues to classify a tumor with respect to treatment. To address this, we collected tumor and adjacent normal tissue as well as cfDNA from the blood of 33 patients enrolled in the LUD2015-005 trial in which ICI were administered to patients with non-resectable esophageal adenocarcinoma (EAC) for four weeks, before adding standard-of-care chemotherapy (ICI+CTX). For each patient, we took samples at diagnosis, before ICI+CTX, during and at the end of treatment. Tissue and cfDNA samples were sequenced using TET-Assisted Pyridine-borane Sequencing (TAPS), a method recently developed in Oxford which provides genome-wide high-depth, base- resolution DNA methylation and mutation information from low-input samples. We then selected a representative set of high-purity tumor tissue samples and combined them with whole- genome TAPS data from 9 healthy blood cell types and 5 gastrointestinal tissues to generate a GI-specific atlas of cell-type specific methylation. This atlas allows us to accurately quantify the contribution of tumor and 14 healthy cell types to the cfDNA collected from each patient at each timepoint. Strikingly, the presence of T-cell derived cfDNA at time of diagnosis (tDNA) is a strong positive predictive marker of overall survival (p=0.0024). In contrast, the fraction of tumor-resident T-cells, estimated by either bulk tissue TAPS or RNA sequencing, correlated only weakly with treatment response in this cohort, indicating that T-cell activity is more accurately captured by tDNA. Furthermore, we find that patients with a combination of high TMB and high tDNA have an 80% 2-year survival probability, as opposed to below 25% for others, suggesting that tDNA is derived from T-cells actively engaging tumor cells with high neoantigen load. In summary, we demonstrate that T-cell turnover, as reflected in differential methylation in a set of marker regions spanning only 24kb, is a promising biomarker of treatment response, especially when combined with neoantigen load: in the presented cohort, all but one long-term survivors (alive at last follow up &amp;gt; 3 years after diagnosis) were tDNA positive with high TMB. This demonstrates the power of cfDNA composition analysis for risk stratification in ICI treatment. Citation Format: Phil Xie, Zohar Etzioni, Chun-Xiao Song, Richard P Owen, Mark R Middleton, Xin Lu, Benjamin Schuster-Boeckler. A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR017.

CTNI-13. 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL

Abstract INTRODUCTION Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between tumor progression (TP) and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques. METHODS Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity score analysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation. RESULTS Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting. CONCLUSION This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.

Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma

Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.

Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (GAS5, HAND2-AS1, KCNK15-AS1, MAGI2-AS3, MEG3, SEMA3B-AS1, SNHG6, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues (p < 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs < -0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes (HAND2-AS1), peritoneum (KCNK15-AS1, MEG3, and SEMA3B-AS1), and greater omentum (MEG3, SEMA3B-AS1, and ZNF667-AS1). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent (p < 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial-mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA (p < 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1, SSTR5-AS1, and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC.

Use of albumin and CRP related immuno-nutritional markers for prediction of locoregional response to treatment in unresectable hepatocellular carcinoma

Objective:We analysed the relationship between albumin and CRP related inflammation markers (Controlling nutritional status(Conut)score, lymphocyte albumin factor(LA), albumin-bilirubin score (ALBI), highly sensitive modified Glasgow prognostic score (Hs-mGPS), Glasgow prognostic score(GPS)) and locoregional treatment response in HCC. Materials and methods:Among 180 HCC patients, 63 patients who underwent locoregional therapy were included in this study. Albumin and CRP related immuno-nutrition scores were calculated by recording routine laboratory tests between the fourth and eighth week after treatment. The predictive and prognostic value of these markers for overall survival(OS) and disease free survival after treatment(DFS) were analysed. Results:The mean age was 63 years (min-max:26-87) and 59 (93.7%) of the patients were male. The mean follow up period was 25 months and 53 patients were deceased (84.1%). mOS: 18.56 months (min-max: 13.13-23.99); mDFS: 7 months (min-max: 3.63-10.37) after locoregional treatment. Cut-off values of prognostic markers were determined by Roc analysis. Statistically significant correlation was found between age(p=0.019), Conut(p=0.001), GPS(p=0.028), Hs-mGPS(p=0.012), LA(p=0.017) and ALBI(p=0.002) and mOS. The relationship between Conut(p=0.002), GPS(p

CT-Defined Coronary Artery Calcification as a Prognostic Marker for Overall Survival in Lung Cancer: A Systematic Review and Meta-analysis

Rationale and ObjectivesCoronary artery calcification (CAC) can be quantified by computed tomography (CT). It is an important predictive and prognostic imaging marker for cardiovascular disease. The prognostic role for CAC in oncological patients is provided in preliminary studies, especially in lung cancer patients. The aim of the present study was to establish the effect of CAC score on overall survival (OS) in lung cancer patients based on the published literature Materials and MethodsLiterature databases were screened for papers analyzing the association between CAC and overall survival in lung cancer patients up to June 2024. The primary endpoint of the present systematic review was the OS. Overall, 7 studies were suitable for the analysis and were included. ResultsThe included studies comprised 2292 patients. The pooled hazard ratio for the association between CAC score and OS was HR=1.42 (95% CI=(1.19; 1.69), p<0.0001) in the univariable analysis and HR=1.56 (95% CI=(1.25; 1.94), p<0.0001) in the multivariable analysis. The pooled odds ratio for the association between CAC score and major cardiovascular events was OR=1.97 (95% CI=(1.24; 3.13)], p=0.004. ConclusionCT-defined CAC has a meaningful impact on overall survival and prediction of major cardiovascular events in lung cancer patients undergoing curative treatment. The sole presence of CAC on staging CT should be reported as an important prognostic marker in these patients.

Fibrinogen to pre-albumin ratio is an independent prognostic index for patients with pancreatic ductal adenocarcinoma after radical resection

BackgroundThis study aims to elucidate the significance of the preoperative fibrinogen to pre-albumin ratio (FPR) in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC), a correlation not extensively explored previously.MethodsA cohort of 563 patients diagnosed with PDAC and subjected to radical surgical resection was examined. We meticulously documented a range of inflammatory markers, clinical-pathological features, and oncological outcomes. The prognostic value of preoperative FPR was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression modeling. Furthermore, the predictive accuracy of FPR was evaluated through time-dependent receiver operating characteristic (ROC) curves and decision curve analyses (DCA).ResultsThe determined optimal threshold for FPR was 14.77, which facilitated the stratification of patients into groups with low and high FPR levels. Notably, patients in the high FPR cohort exhibited significantly reduced recurrence-free survival (RFS) and overall survival (OS) rates compared to their low FPR counterparts. Multivariate Cox regression analysis underscored FPR as an independent prognostic indicator for both RFS and OS. In comparison to the neutrophil-to-lymphocyte ratio (NLR), FPR demonstrated superior prognostic accuracy and clinical utility.ConclusionThe preoperative fibrinogen to pre-albumin ratio serves as an independent prognostic marker for RFS and OS among PDAC patients undergoing radical resection. Our findings suggest that FPR could be a valuable addition to the current prognostic models, potentially guiding therapeutic decision-making and patient management strategies in PDAC.

Real-World Analysis of the Correlation between Overall Survival and Progression-Free Survival in Advanced Pancreatic Cancer: Results of NAPOLEON-1 and 2 Studies

Plain Language SummaryThis study aimed to investigate whether progression-free survival (PFS) can predict overall survival (OS) in patients with pancreatic cancer undergoing chemotherapy. Specifically, the study compared the effectiveness of first-line and second-line chemotherapy, regarding their effect on OS and PFS. An integrated analysis was conducted using real-world data from the NAPOLEON and NAPOLEON-2 studies in Japan. The correlation between OS and PFS was assessed using MM estimation. The study only included patients with confirmed OS at the end of follow-up. Among 479 patients studied, a strong correlation was depicted between PFS and OS in both first- and second-line chemotherapies, with R-squared values of 0.74 and 0.76 for first- and second-line treatments, respectively. The findings suggest that PFS can serve as a substitute marker of OS in both first- and second-line therapies for pancreatic cancer. This means that longer PFS is associated with longer OS. These results can help physicians better predict treatment outcomes and make more informed decisions when selecting therapies for patients with pancreatic cancer.

AML typical mutations (CEBPA, FLT3, NPM1) identify a high-risk chronic myelomonocytic leukemia independent of CPSS molecular

AbstractMutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2, and NPM1, are rarely found in chronic myelomonocytic leukemia (CMML), and their prognostic significance in CMML has not been clearly identified. In 127 patients with CMML, we have retrospectively analyzed next-generation sequencing and polymerase chain reaction data from bone marrow samples collected at the time of CMML diagnosis. Seven patients harbored CEBPA mutations, 8 FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations, and 11 NPM1 mutations. Patients with CMML harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN) more frequently had the myeloproliferative subtype, a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CMML Prognostic Scoring System molecular classification, mutCFN patients with CMML had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN patients with CMML closely resembled that of patients with AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible. Furthermore, certain targeted therapies approved for use in AML should be considered.

Overexpression of TPD52L2 in HNSCC: prognostic significance and correlation with immune infiltrates.

Evidence has been presented that the tumor protein D52 (TPD52) family plays a critical role in tumor development and progression. As a member of the TPD52 family, the changes in TPD52L2 gene status are instrumental in kinds of cancer development. However, its effects on patient prognosis and immune infiltration in Head and Neck Squamous Carcinoma (HNSCC) are still poorly understood. The Tumor Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and c-BioPortal database was used to explore the expression pattern, prognostic value, and variation of gene status in HNSCC. The LinkedOmics database was used to obtain the co-expression genes of TPD52L2 and identify the diagnostic value of TPD52L2 in HNSCC. The correlations between TPD52L2 expression and six main types of immune cell infiltrations and immune signatures were explored using Tumor Immune Estimation Resource (TIMER). The correlation between TPD52L2 expression and immune checkpoint genes (ICGs) was analyzed by TCGA database. Immunohistochemistry (IHC) was performed to validate the expression of three ICGs (PDL1, PDL2, EGFR) and TPD52L2 using 5 paired HNSCC and normal head and neck tissues. Polymerase Chain Reaction (PCR) and Western Blot (WB) of HNSCC and normal head and neck cell lines were performed to verify the high level of TPD52L2 mRNA and protein expression. protein expression of TPD52L2 in pan-cancer was also validated using UALCAN. TPD52L2 was overexpressed in tumor tissues, and it predicted worse survival status in HNSCC. ROC analysis suggested that TPD52L2 had a diagnostic value. Multivariate Cox analysis identified TPD52L2 as an independent negative prognostic marker of overall survival. Functional network analysis suggested that TPD52L2 was associated with immune-related signaling pathways, cell migration pathways, and cancer-related pathways. High expression of TPD52L2 was associated with a more mutant frequency of TP53. Notably, we found that the expression of TPD52L2 was closely negatively correlated with the infiltration levels of 15 types of immune cells and positively correlated with several immune markers. PCR, WB experiments, and UALCAN database verified the high level of TPD52L2 mRNA and protein expression. TPD52L2 is upregulated in HNSCC, which is an independent factor for adverse prognosis prediction. It probably plays a role in the negative regulation of immune cell infiltration. TPD52L2 might be a promising prognostic biomarker and therapeutic target in HNSCC.

Prognostic factors and surgical management in pediatric primary lung cancer: a retrospective cohort study using SEER data.

Primary lung cancer (LC) is extremely rare in pediatric patients, making diagnosis and management particularly challenging. Currently, there are no established guidelines for treating LC in this age group, and both prognosis and treatment experiences are scarcely studied. This study aims to evaluate prognostic factors and assess the survival benefits of surgical intervention in pediatric LC patients. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 1988 to 2019, encompassing 337 children aged 0-19 years diagnosed with primary LC. Clinical characteristics, prognostic factors, and surgical approaches were elucidated. Prognostic markers for overall survival (OS) were evaluated through univariate and multivariate Cox proportional hazards regression models. Survival analysis between groups utilized Kaplan-Meier survival curves. The children indicated a median age of 15 years and the female-to-male ratio was close to 1:1. The most common pathological type was carcinoid tumor (31.45%). Most of the tumors were <5 cm in diameter (63.79%) or confined in situ (46.77%). The 5-year OS rate for the entire cohort was 77.9%, with pathologic classification, SEER stage, surgery, and tumor size identified as independent prognostic factors. Pulmonary/pleuropulmonary blastoma [hazards ratio (HR): 6.41; 95% confidence interval (CI): 1.69-24.35; P=0.006] or adenocarcinoma (HR: 8.82; 95% CI: 2.20-35.25; P=0.002), no surgery (HR: 2.05; 95% CI: 1.13-3.72; P=0.02), and tumor size ≥5 cm (HR: 2.87; 95% CI: 1.20-6.89; P=0.02) were associated with a worse prognosis in pediatric LC patients. In localized of SEER stage (HR: 0.15; 95% CI: 0.04-0.56; P=0.005) was associated with a better prognosis in pediatric LC patients. Common pathological types including carcinoid, pulmonary/pleuropulmonary blastoma, and mucoepidermoid carcinoma demonstrated the most favorable prognosis (P<0.001). Surgery did not significantly benefit patients with American Joint Committee on Cancer (AJCC) stage IV (HR: 0.83; 95% CI: 0.42-1.62; P=0.58) or distant-stage disease (HR: 0.59; 95% CI: 0.33-1.06; P=0.06). Conversely, children with regional lymph node metastasis (HR: 0.23; 95% CI: 0.06-0.88; P=0.02) or AJCC stage III-IV (HR: 0.40; 95% CI: 0.19-0.87; P=0.02) showed improved survival following lymph node dissection. Tumor size also influenced surgical decision-making, with smaller tumors (<5 cm) favoring surgical resection, including lobectomy (P<0.001) or local tumor resection (P=0.03), while larger tumors exhibited advantages with less specificity regarding surgical approach (P=0.15). This study identified pathologic classification, SEER stage, surgery, and tumor size as independent prognostic factors for pediatric LC. For children with advanced-stage LC, surgical intervention may not extend survival time. This study underscores the importance of tailoring therapeutic strategies based on histology, disease stage, and tumor size. These findings offer valuable insights into managing pediatric LC, enabling more informed clinical decisions and potentially enhancing patient outcomes.

Exploring SSR1 as a novel diagnostic and prognostic biomarker in hepatocellular carcinoma, and its relationship with immune infiltration.

Although signal sequence receptor subunit 1 (SSR1) has undergone thorough examination in different cancer types, its importance in hepatocellular carcinoma (HCC) remains largely uncharted and warrants further investigation. The aim of this study is to explore the role of SSR1 in HCC progression and to decipher its underlying molecular mechanisms. We employed the ONCOMINE, Tumor IMmune Estimation Resource (TIMER), and The Cancer Genome Atlas databases to assess SSR1 expression levels within tumor tissues. Logistic and Cox regression analyses, Kaplan-Meier survival plots, nomograms, and forest plots were employed to establish correlation between SSR1 and prognosis. Receiver operating characteristic (ROC) curves demonstrated diagnostic utility of SSR1. Additionally, Gene Ontology (GO) and gene set enrichment analysis (GSEA) analyses were conducted to uncover relevant molecular pathways. TIMER was instrumental in elucidating the connection between SSR1 and immune cell infiltration. Actions of SSR1 in HCC proliferation and migration were investigated through quantitative real-time polymerase chain reaction, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine cell proliferation assays, and Transwell migration and wound healing experiments. Elevated SSR1 levels were found to be correlated with clinical parameters such as age and pathologic stage, thereby predicting a reduced overall survival (OS) rate in HCC patients. Multivariate survival analysis underscored SSR1 as an independent prognostic marker for OS. A nomogram underscored SSR1's effectiveness as a predictive tool for HCC outcomes, while ROC analysis indicated its high diagnostic accuracy. GO and GSEA analyses suggested that elevated SSR1 expression may be associated with epithelial-mesenchymal transition (EMT) pathway. SSR1 exhibited a negative correlation with cytotoxic cells and a positive correlation with Th2 cells. Our in vitro experiments provided evidence that heightened SSR1 levels may impact HCC proliferation and migration through EMT pathway. SSR1 surfaces as a new diagnostic and potentially prognostic biomarker, showing an association with immune cell infiltration and cell proliferation in HCC.

Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP’s therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Radiomics analysis of cerebral blood flow suggests a possible link between perfusion homogeneity and poor glioblastoma multiforme prognosis

Objectives. This study investigates the association between cerebral blood flow (CBF) and overall survival (OS) in glioblastoma multiforme (GBM) patients receiving chemoradiation. Identifying CBF biomarkers could help predict patient response to this treatment, facilitating the development of personalized therapeutic strategies. Materials and Methods. This retrospective study analyzed CBF data from dynamic susceptibility contrast (DSC) MRI in 30 newly diagnosed GBM patients (WHO grade IV). Radiomics features were extracted from CBF maps, tested for robustness, and correlated with OS. Kaplan-Meier analysis was used to assess the predictive value of radiomic features significantly associated with OS, aiming to stratify patients into groups with distinct post-treatment survival outcomes. Results. While mean relative CBF and CBV failed to serve as independent prognostic markers for OS, the prognostic potential of radiomic features extracted from CBF maps was explored. Ten out of forty-three radiomic features with highest intraclass correlation coefficients (ICC > 0.9), were selected for characterization. While Correlation and Zone Size Variance (ZSV) features showed significant OS correlations, indicating prognostic potential, Kaplan-Meier analysis did not significantly stratify patients based on these features. Visual analysis of the graphs revealed a predominant association between the identified radiomic features and OS under two years. Focusing on this subgroup, Correlation, ZSV, and Gray-Level Nonuniformity (GLN) emerged as significant, suggesting that a lack of heterogeneity in perfusion patterns may be indicative of a poorer outcome. Kaplan-Meier analysis effectively stratified this cohort based on the features mentioned above. Receiver operating characteristic (ROC) analysis further validated their prognostic value, with ZSV demonstrating the highest sensitivity and specificity (0.75 and 0.85, respectively). Conclusion. Our findings underscored radiomics features sensitive to CBF heterogeneity as pivotal predictors for patient stratification. Our results suggest that these markers may have the potential to identify patients who are unlikely to benefit from standard chemoradiation therapy.

The Importance of Preoperative NLR, PLR, and MPV Values in Predicting the Risk of Complications in Colorectal Peritoneal Carcinomatosis.

Colorectal cancer peritoneal carcinomatosis (CRC PC) necessitates preoperative assessment of inflammatory markers to predict postoperative outcomes and guide treatment. This study aims to evaluate the prognostic value of preoperative Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) in predicting complications for CRC PC patients undergoing surgery. Calculating NLR, PLR, and MPV from patient data: NLR = absolute neutrophil count/total lymphocyte count, PLR = total lymphocyte count/total platelet count × 100, and MPV = platelet crit (PCT)/total platelet count. The study included 196 CRC PC patients and found significant relationships between these markers and overall survival (OS). Patients with an NLR of 3.77 had a median OS of 22.1 months, compared to 58.3 months for those with lower NLR (HR 2.7, 95% CI 1.1-5.3, p < 0.001). For CRC PC patients undergoing CRS+HIPEC, preoperative assessment of NLR, PLR, and MPV can serve as independent prognostic markers for OS. Incorporating these markers into preoperative evaluations may improve patient selection and outcome prediction.

Performance of nutritional and inflammatory markers in patients with pancreatic cancer.

Systemic inflammation and nutrition play pivotal roles in cancer progression and can increase the risk of delayed recovery after surgical procedures. To assess the significance of inflammatory and nutritional indicators for the prognosis and postoperative recovery of patients with pancreatic cancer (PC). Patients who were diagnosed with PC and underwent surgical resection at our hospital between January 1, 2019, and July 31, 2023, were enrolled in this retrospective observational cohort study. All the data were collected from the electronic medical record system. Seven biomarkers - the albumin-to-globulin ratio, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), nutritional risk index (NRI), and geriatric NRI were assessed. A total of 446 patients with PC met the inclusion criteria and were subsequently enrolled. Patients with early postoperative discharge tended to have higher PNI values and lower SII, NLR, and PLR values (all P < 0.05). Through multivariable logistic regression analysis, the SII value emerged as an independent risk factor influencing early recovery after surgery. Additionally, both univariable and multivariable Cox regression analyses revealed that the PNI value was the strongest prognostic marker for overall survival (OS; P = 0.028) and recurrence-free survival (RFS; P < 0.001). The optimal cutoff PNI value was established at 47.30 using X-tile software. Patients in the PNI-high group had longer OS (P < 0.001) and RFS (P = 0.0028) times than those in the PNI-low group. Preoperative systemic inflammatory-nutritional biomarkers may be capable of predicting short-term recovery after surgery as well as long-term patient outcomes.

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Prediction of PSA Response after Dexamethasone Switch during Abiraterone Acetate + Prednisolone Treatment of Metastatic Castration-Resistant Prostate Cancer Patients.

The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85-0.96). After a median follow-up of 27.9 (26.3-84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1-6.5) and 11.1 (8.5-12.9) months and the median overall survival (OS) was 23.2 (15.6-25.8) and 33.5 (26.1-38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated.