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Introduction: The delays in cancer therapies have the potential to impact disease progression by allowing the unchecked growth and spread of cancer cells. However, the understanding of the association between treatment waiting time and survival outcomes in patients with esophageal cancer (EC) is limited. This study aims to assess the impact of waiting time on survival outcomes among EC patients in Hebei province, which is recognized as one of the high-risk areas for EC in China. Methods: A total of 9,977 non-metastatic EC patients who underwent surgical treatment were identified between 2000 and 2020. The survival outcomes of overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier methodology. Univariate and multivariate Cox regression analysis was employed to evaluate the impact of treatment delays on OS and CSS. Results: The average delay time for initiating EC surgical treatment after diagnosis was 1.31 months (95%CI=1.29–1.34). Patients with a long delay (≥ 3 months) in treatment, comprising 9977 EC patients, exhibited significantly lower rates of 3-, 5-, and 10-year OS and CSS compared to those without any delay in treatment initiation. A long delay in EC treatment independently associated with an elevated risk of all-cause and cancer-cause mortality among various patient subgroups, including males, older individuals, single individuals, low-income patients, residents of nonmetropolitan counties, as well as those diagnosed with poorly differentiated and stage IV EC. Discussion: The long delay of treatment initiation impacts the outcomes of OS and CSS in EC patients. Optimizing treatment timing may enhance life expectancy for individuals diagnosed with EC. [ABSTRACT FROM AUTHOR]

Background: Difficulty in achieving complete resection leads to a poor prognosis for retroperitoneal soft tissue sarcoma, hence emphasizing the significance of adjuvant treatment. The benefit of preoperative radiotherapy for retroperitoneal liposarcoma was initially demonstrated by the STRASS trial. However, the impact of intraoperative radiotherapy (IORT) on retroperitoneal liposarcoma remains unexplored. Method: Patients with retroperitoneal liposarcoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database, treated between 2000 and 2019. Subsequently, a 1:1 propensity score-matched (PSM) analysis was conducted based on variables identified from a multivariate analysis. T-tests were used to assess differences in normally distributed continuous variables, while the rank-sum test was applied to variables that did not follow a normal distribution. The chi-squared test was utilized to evaluate differences in categorical variables. Ultimately, survival analysis was performed using SPSS to evaluate patient prognosis. Result: A total of 2129 patients with retroperitoneal liposarcoma were included in our study. Age, sex, histology, grading, chemotherapy, and tumor size as independent prognostic risk factors for these patients through multivariate Cox regression analysis. Subsequently, 66 patients were included in the survival analysis through PSM, with 33 patients receiving IORT. Finally, the survival analysis revealed that there was no difference in overall survival among patients with retroperitoneal liposarcoma, regardless of whether they received IORT or not (p= 0.711). Conclusion: As an exploratory study, our findings suggest that patients may not derive benefit from intraoperative radiotherapy. These observations are intended to lay the groundwork for future prospective clinical studies. [ABSTRACT FROM AUTHOR]

Background: Older patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment. Case presentation: We report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months. Conclusion: The case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress plays a significant role in aging and cancer, yet there is currently a lack of research utilizing machine learning models to examine the relationship between oxidative stress and prognosis in elderly non-small cell lung cancer (NSCLC) patients. Methods: This study included elderly NSCLC patients who underwent radical lung cancer resection from January 2012 to April 2018, exploring the relationship between Oxidative Stress Score (OSS) and prognosis. Machine learning techniques, including Decision Trees (DT), Random Forest (RF), and Support Vector Machine (SVM), were employed to develop predictive models for 5-year overall survival (OS). Results: The datasets consisted of 1647 patients in the training set, 705 in the internal validation set, and 516 in the external validation set. An OSS was formulated from six systemic oxidative stress biomarkers, such as albumin, total bilirubin, and blood urea nitrogen, among others. Boruta variable importance analysis identified low OSS as a key indicator of poor prognosis. The OSS was subsequently integrated into the DT, RF, and SVM models for training. These models, optimized through hyperparameter tuning on the training set, were then evaluated on the internal and external validation sets. The RF model demonstrated the highest predictive performance, with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.794 in the internal validation set, compared to AUCs of 0.711 and 0.760 for the DT and SVM models, respectively. Similarly, in the external validation set, the RF model achieved an AUC of 0.784, outperforming the DT and SVM models, which had AUCs of 0.699 and 0.730, respectively. Calibration plots confirmed the RF model's superior calibration, followed by the SVM model, with the DT model performing the poorest. Conclusion: The OSS-based clinical prediction model, constructed using machine learning methodologies, effectively predicts the prognosis of elderly NSCLC patients post-radical surgery. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) for survival outcomes in bladder cancer patients treated with radical cystectomy. Methods: Studies assessing NLR's prognostic significance for bladder cancer after radical cystectomy were identified from PubMed, Embase, Web of Science, and Cochrane databases until April 2024. Survival outcomes analyzed included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS). Results: The meta-analysis comprised 15 cohort studies with 8,448 patients. Multivariate analysis showed significantly shorter OS, CSS, DFS, and RFS in the high NLR group compared to the low NLR group. However, no significant difference in PFS was observed between the groups. Conclusions: NLR serves as an independent prognostic indicator for bladder cancer patients undergoing radical cystectomy, with elevated NLR associated with poorer survival. Further large-scale, prospective studies are warranted to validate the relationship between NLR and prognosis in bladder cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024549573. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial fusion and fission are critical for the morphology and function of cells. DNM1L encodes dynamin-related protein 1 (DRP1), a key protein mediating mitochondrial fission, which is upregulated in a variety of cancers and is strongly associated with tumorigenesis. We aim to investigate the relationship between DNM1L and the prognosis of gastric cancer, as well as to explore the function and mechanism of DNM1L in gastric cancer (GC). Materials and methods: In this study, we analyzed the expression differences of DNM1L in gastric cancer tissues and paracancerous tissues using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. This was followed by validation through tissue microarrays. We then utilized the cohort information from these microarrays to explore the relationship between DNM1L expression and gastric cancer prognosis. Furthermore, we conducted enrichment analysis to investigate the function and mechanisms of DNM1L in gastric cancer, and lastly, we performed immune cell infiltration analysis using the CIBERSORT algorithm. Results: We discovered that the expression of DNM1L is elevated in GC tissues. TCGA data showed that the overexpression of DNM1L was positively correlated with the T-stage of GC but not with lymph node metastasis, which was also corroborated by our immunohistochemistry experiments. Based on the Kaplan–Meier curves, the high DNM1L expression was remarkably correlated with poor overall survival in patients with GC. In addition, results of COX regression analysis indicated that high DNM1L expression was an independent prognostic factor in patients with GC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) showed that DNM1L was closely associated with multiple signaling pathways and immune responses. CIBERSORT analysis indicated that increased DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment. Conclusion: The results of this study indicate that DNM1L is upregulated in gastric cancer (GC) and positively correlates with the T-stage and poor prognosis of GC patients, and it plays an important role in tumor immune infiltration. [ABSTRACT FROM AUTHOR]

Background: A combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib. Methods: This retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups. Results: After PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively. Conclusions: PD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC. Method: A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured. Results: The non-survival group had increased levels of white blood cells, neutrophils (both p <0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05]. Conclusion: This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools. [ABSTRACT FROM AUTHOR]

Background: In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients. Methods: The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models. Results: In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group. Conclusion: The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is associated with a high risk of endometrial cancer (EC). However, its impact on EC progression remains unclear. This meta-analysis examined the association between MetS and survival outcomes in EC patients. Methods: A comprehensive search of PubMed, EMBASE, and Web of Science databases up to May 22, 2024, was conducted. Two independent reviewers performed study selection, data extraction, and quality assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Nine studies comprising 13,579 endometrial cancer (EC) patients were included. Among these, 2,896 patients (21.3%) had MetS at the time of enrollment. The follow-up durations ranged from 3.4 to 14.2 years. The results showed that EC patients with MetS at baseline demonstrated significantly poorer overall survival (HR = 1.57, 95% CI = 1.19-2.07, p = 0.002; I² = 25%) and progression-free survival (HR = 1.33, 95% CI = 1.08-1.63, p = 0.007; I² = 16%). A similar association was observed for cancer-specific survival (HR = 1.26, 95% CI = 1.10-1.44, p = 0.001; I² = 0%). Subgroup analyses based on study characteristics showed consistent results across studies conducted in countries with different follow-up durations. Conclusion: This meta-analysis suggests that MetS is associated with poor survival outcomes in EC patients. Further prospective studies are required to validate our findings. Systematic review registration: PROSPERO, identifier CRD42024561654. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed. Results: The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P < 0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05). Conclusion: Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients. [ABSTRACT FROM AUTHOR]

Objectives: The role of matrix metalloproteinases (MMPs) in Skin Cutaneous Melanoma (SKCM) development and progression is unclear so far. This comprehensive study delved into the intricate role of MMPs in SKCM development and progression. Methods: RT-qPCR, bisulfite sequencing, and WES analyzed MMP gene expression, promoter methylation, and mutations in SKCM cell lines. TCGA datasets validated findings. DrugBank and molecular docking identified potential regulatory drugs, and cell line experiments confirmed the role of key MMP genes in tumorigenesis. Results: Our findings unveiled significant up-regulation of MMP9, MMP12, MMP14, and MMP16, coupled with hypomethylation of their promoters in SKCM cell lines, implicating their involvement in disease progression. Mutational analysis highlighted a low frequency of mutations in these genes, indicating less involvement of mutations in the expression regulatory mechanisms. Prognostic assessments showcased a significant correlation between elevated expression of these genes and poor overall survival (OS) in SKCM patients. Additionally, functional experiments involving gene silencing revealed a potential impact on cellular proliferation, further emphasizing the significance of MMP9, MMP12, MMP14, and MMP16 in SKCM pathobiology. Conclusion: This study identifies Estradiol and Calcitriol as potential drugs for modulating MMP expression in SKCM, highlighting MMP9, MMP12, MMP14, and MMP16 as key diagnostic and prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: The large-scale proteomic platform known as the SomaScan® assay is capable of simultaneously measuring thousands of proteins in patient specimens through next-generation aptamer-based multiplexed technology. While previous studies have utilized patient peripheral blood to suggest serum biomarkers of prognostic or diagnostic value in osteosarcoma (OSA), the most common primary pediatric bone cancer, they have ultimately been limited in the robustness of their analyses. We propose utilizing this aptamer-based technology to describe the systemic proteomic milieu in patients diagnosed with this disease. Methods: To determine novel biomarkers associated with overall survival in OSA, we deployed the SomaLogic SomaScan® 7k assay to investigate the plasma proteomic profile of naive primary, recurrent, and metastatic OSA patients. Following identification of differentially expressed proteins (DEPs) between 2-year deceased and survivor cohorts, publicly available databases including Survival Genie, TIGER, and KM Plotter Immunotherapy, among others, were utilized to investigate the significance of our proteomic findings. Results: Apo-transcobalamin-II (APO-TCN2) was identified as the most DEP between 2-year deceased and survivor cohorts (Log2 fold change = 6.8, P-value = 0.0017). Survival analysis using the Survival Genie web-based platform indicated that increased intratumoral TCN2 expression was associated with better overall survival in both OSA (TARGET-OS) and sarcoma (TCGA-SARC) datasets. Cell-cell communication analysis using the TIGER database suggested that TCN2+ Myeloid cells likely interact with marginal zone and immunoglobinproducing B lymphocytes expressing the TCN2 receptor (CD320) to promote their proliferation and survival in both non-small cell lung cancer and melanoma tumors. Analysis of publicly available OSA scRNA-sequencing datasets identified similar populations in naive primary tumors. Furthermore, circulating APO-TCN2 levels in OSA were then associated with a plasma proteomic profile likely necessary for robust B lymphocyte proliferation, infiltration, and formation of intratumoral tertiary lymphoid structures for improved anti-tumor immunity. Conclusions: Overall, APO-TCN2, a circulatory protein previously described in various lymphoproliferative disorders, was associated with 2-year survival status in patients diagnosed with OSA. The relevance of this protein and apparent immunological function (anti-tumor B lymphocyte responses) was suggested using publicly available solid tumor RNA-sequencing datasets. Further studies characterizing the biological function of APO-TCN2 and its relevance in these diseases is warranted. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) constitutes a significant peril to global women's health. Contemporary research progressively suggests that mitochondrial dysfunction plays a pivotal role in both the inception and advancement of BC. However, investigations delving into the correlation between mitochondrialrelated genes (MRGs) and the prognosis and metastasis of BC are still infrequent. Methods: Utilizing data from the TCGA database, we employed the "limma" R package for differential expression analysis. Subsequently, both univariate and multivariate Cox regression analyses were executed, alongside LASSO Cox regression analysis, to pinpoint prognostic MRGs and to further develop the prognostic model. External validation (GSE88770 merged GSE425680) and internal validation were further conducted. Our investigation delved into a broad spectrum of analyses that included functional enrichment, metabolic and immune characteristics, immunotherapy response prediction, intratumor heterogeneity (ITH), mutation, tumor mutational burden (TMB), microsatellite instability (MSI), cellular stemness, single-cell, and drug sensitivity analysis. We validated the protein and mRNA expressions of prognostic MRGs in tissues and cell lines through immunohistochemistry and qRT-PCR. Moreover, leveraging the GSE102484 dataset, we conducted differential gene expression analysis to identify MRGs related to metastasis, subsequently developing metastasis models via 10 distinct machine-learning algorithms and then selecting the bestperforming model. The division between training and validation cohorts was set at 70% and 30%, respectively. Results: A prognostic model was constructed by 9 prognostic MRGs, which were DCTPP1, FEZ1, KMO, NME3, CCR7, ISOC2, STAR, COMTD1, and ESR2. Patients within the high-risk group experienced more adverse outcomes than their counterparts in the low-risk group. The ROC curves and constructed nomogram showed that the model exhibited an excellent ability to predict overall survival (OS) for patients and the risk score was identified as an independent prognostic factor. The functional enrichment analysis showed a strong correlation between metabolic progression and MRGs. Additional research revealed that the discrepancies in outcomes between the two risk categories may be attributed to a variety of metabolic and immune characteristics, as well as differences in intratumor heterogeneity (ITH), tumor mutational burden (TMB), and cancer stemness indices. ITH, TIDE, and IPS analyses suggested that patients possessing a low-risk score may exhibit enhanced responsiveness to immunotherapy. Additionally, distant metastasis models were established by PDK4, NRF1, DCAF8, CHPT1, MARS2 and NAMPT. Among these, the XGBoost model showed the best predicting ability. Conclusion: In conclusion, MRGs significantly influence the prognosis and metastasis of BC. The development of dual clinical prediction models offers crucial insights for tailored and precise therapeutic strategies, and paves the way for exploring new avenues in understanding the pathogenesis of BC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is highly aggressive, with delayed diagnosis, poor prognosis, and a lack of comprehensive and accurate prognostic models to assist clinicians. This study aimed to construct an HCC prognosisrelated gene signature (HPRGS) and explore its clinical application value. Methods: TCGA-LIHC cohort was used for training, and the LIRI-JP cohort and HCC cDNA microarray were used for validation. Machine learning algorithms constructed a prognostic gene label for HCC. Kaplan-Meier (K-M), ROC curve, multiple analyses, algorithms, and online databases were used to analyze differences between high- and low-risk populations. A nomogram was constructed to facilitate clinical application. Results: We identified 119 differential genes based on transcriptome sequencing data from five independent HCC cohorts, and 53 of these genes were associated with overall survival (OS). Using 101 machine learning algorithms, the 10 most prognostic genes were selected. We constructed an HCC HPRGS with four genes (SOCS2, LCAT, ECT2, and TMEM106C). Good predictive performance of the HPRGS was confirmed by ROC, C-index, and K-M curves. Mutation analysis showed significant differences between the low- and high-risk patients. The low-risk group had a higher response to transcatheter arterial chemoembolization (TACE) and immunotherapy. Treatment response of highand low-risk groups to small-molecule drugs was predicted. Linifanib was a potential drug for high-risk populations. Multivariate analysis confirmed that HPRGS were independent prognostic factors in TCGA-LIHC. A nomogram provided a clinical practice reference. Conclusion: We constructed an HPRGS for HCC, which can accurately predict OS and guide the treatment decisions for patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T. Methods: In this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes. Results: Among the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS. Conclusion: Patients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy. [ABSTRACT FROM AUTHOR]

Background: Recent research has found a new way of cell death: disulfidptosis. Under glucose starvation, abnormal accumulation of disulfide molecules such as Cystine in Solute Carrier Family 7 Member 11 (SLC7A11) overexpression cells induced disulfide stress to trigger cell death. The research on disulfidptosis is still in its early stages, and its role in the occurrence and development of colorectal malignancies is still unclear. Method: In this study, we employed bioinformatics methods to analyze the expression and mutation characteristics of disulfidptosis-related genes (DRGs) in colorectal cancer. Consensus clustering analysis was used to identify molecular subtypes of Colorectal Adenocarcinoma (COAD) associated with disulfidptosis. The biological behaviors between subtypes were analyzed to explore the impact of disulfidptosis on the tumor microenvironment. Constructing and validating a prognostic risk model for COAD using diverse data. The influence of key genes on prognosis was evaluated through SHapley Additive exPlanations (SHAP) analysis, and the predictive capability of the model was assessed using Overall Survival analysis, Area Under Curve and risk curves. The immunological status of different patients and the prediction of drug treatment response were determined through immune cell infiltration, TMB, MSI status, and drug sensitivity analysis. Single-cell analysis was employed to explore the expression of genes at the cellular level, and finally validated the expression of key genes in clinical samples. Result: By integrating the public data from two platforms, we identified 2 colorectal cancer subtypes related to DRGs. Ultimately, we established a prognosis risk model for COAD using 7 genes (FABA4+GIPC2+EGR3+HOXC6+CCL11+CXCL10+ITLN1). SHAP analysis can further explained the positive or negative impact of gene expression on prognosis. By dividing patients into high-risk and low-risk groups, we found that patients in the high-risk group had poorer prognosis, higher TMB, and a higher proportion of MSI-H and MSI-L statuses. We also predicted that drugs such as 5-Fluorouracil, Oxaliplatin, Gefitinib, and Sorafenib would bemore effective in low-risk patients, while drugs like Luminesib and Staurosporine would be more effective in high-risk patients. Single-cell analysis revealed that these 7 genes not only differ at the level of immune cells but also in epithelial cells, fibroblasts, and myofibroblasts, among other cell types. Finally, the expression of these key genes was verified in clinical samples, with consistent results. Conclusions: Our research findings provide evidence for the role of disulfidptosis in COAD and offer new insights for personalized and precise treatment of COAD. [ABSTRACT FROM AUTHOR]

Access to solid organ transplantation in patients with intellectual disability is associated with health inequities due to concerns about treatment adherence, survival rates, and post-transplant quality of life. This systematic literature review aims to compare outcomes after organ transplantation in patients with intellectual disability compared to patients without intellectual disability. Embase, Medline Ovid, PsycINFO, Web of Science, Cochrane Central Register of Trials, and Google Scholar databases were systematically searched for studies concerning pediatric or adult solid organ transplantation in recipients with a diagnosis of intellectual disability prior to transplantation. Primary outcomes were patient and graft survival rates. Secondary outcomes were acute rejection rate, adherence rates, and quality of life. Nine studies were included, describing kidney (n = 6), heart (n = 4) and liver (n = 1) transplantation. Reported graft survival rates were non-inferior or better compared to patients without intellectual disability, while patient survival was reportedly slightly lower in two studies reporting on kidney transplantation. Although current evidence has a potential selection bias based on including patients with a sufficient support network, intellectual disability alone should not be regarded a relative or absolute contra-indication for solid organ transplantation. [ABSTRACT FROM AUTHOR]

Over the past decade, the prevalence of inflammatory bowel disease (IBD) has significantly increased, making early detection crucial for improving patient survival rates. Medical research suggests that changes in the human gut microbiome are closely linked to IBD onset, playing a critical role in its prediction. However, the current gut microbiome data often exhibit missing values and high dimensionality, posing challenges to the accuracy of predictive algorithms. To address these issues, we proposed the comprehensive data optimization and risk prediction framework (CDORPF), an ensemble learning framework designed to predict IBD risk based on the human gut microbiome, aiding early diagnosis. The framework comprised two main components: data optimization and risk prediction. The data optimization module first employed triple optimization imputation (TOI) to impute missing data while preserving the biological characteristics of the microbiome. It then utilized importance-weighted variational autoencoder (IWVAE) to reduce redundant information from the high-dimensional microbiome data. This process resulted in a complete, low-dimensional representation of the data, laying the foundation for improved algorithm efficiency and accuracy. In the risk prediction module, the optimized data was classified using a random forest (RF) model, and hyperparameters were globally optimized using improved aquila optimizer (IAO), which incorporated multiple strategies. Experimental results on IBD-related gut microbiome datasets showed that the proposed framework achieved classification accuracy, recall, and F1 scores exceeding 0.9, outperforming comparison models and serving as a valuable tool for predicting IBD onset risk. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs) have demonstrated potential as prognostic biomarkers across various cancer types. However, their prognostic implications in non-small cell lung cancer (NSCLC) remain ambiguous. Methods: An exhaustive electronic search was executed across the Pubmed, EMBASE, Web of Science, and Cochrane Library databases to locate relevant studies published up until December 19, 2023. Studies were eligible if they assessed the association between TILs and overall survival (OS) and disease-free survival (DFS) in NSCLC patients. The OS and DFS were subsequently extracted for analysis. The prognostic significance of TILs was evaluated by calculating the Pooled Hazard Ratios (HRs) and their corresponding 95% Confidence Intervals (CIs). Results: The meta-analysis incorporated 60 studies, which collectively included 15829 NSCLC patients. The collective analysis indicated that NSCLC patients exhibiting TILs infiltration demonstrated a significantly improved OS(HR: 0.67; 95%CI: 0.55-0.81). Subgroup analyses, based on TIL subtypes (CD8+, CD3+ and CD4+), consistently revealed a favorable prognostic impact on OS. However, it was observed that FOXP3+ was correlated with a poor OS (HR: 1.35; 95% CI: 0.87-2.11). Conclusion: This comprehensive systematic review and meta-analysis substantiate the prognostic significance of TILs in patients diagnosed with NSCLC. Notably, elevated TILs infiltration correlates with a favorable prognosis, particularly among CD8+, CD3+ and CD4+ subtypes. [ABSTRACT FROM AUTHOR]

Background: Hypoxic conditions in glioma are linked to tumor aggressiveness, poor prognosis, and treatment resistance. Long non-coding RNAs (lncRNAs) play key roles in the hypoxic and immune microenvironment of cancers, but their link to hypoxia-induced immunosuppression in high-grade glioma (HGG) is not well-studied. Methods: Gene expression profiles from TCGA and CGGA, along with clinical and genomic data, were analyzed. Bioinformatics methods including Consensus Clustering, Pearson correlation, and Cox regression analyses were used. Cell proliferation was assessed using cell counting kit-8 and colony formation assays. Glioma-macrophage interactions were evaluated using a co-culture model. Results: Hypoxia subtype clustering showed hypoxic stress correlates with worse HGG prognosis. Eight hypoxia-related lncRNAs (AP000695.4, OSMR-AS1, AC078883.3, RP11-545E17.3, LINC01057, LINC01503, TP73-AS1, and LINC00672) with prognostic value were identified, forming a risk signature that separated patients into distinct prognostic groups. Multivariate Cox regression confirmed the signature as an independent prognostic factor. High-risk patients had greater hypoxia, leading to an immunosuppressive environment and immunotherapy resistance via tumor-associated macrophages (TAMs). TP73-AS1 significantly influenced hypoxia-induced TAM infiltration and M2 polarization. Conclusions: We profiled hypoxic stress in HGG and developed an 8-lncRNA hypoxia-related signature predicting patient survival and immunotherapy response, emphasizing its role in hypoxia-induced immunosuppression. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the characteristics of newly diagnosed marginal zone lymphoma (MZL) patients, evaluate the efficacy of different treatment regimens, and explore prognostic factors in the era of immunotherapy. Methods: We reviewed the clinical data of newly diagnosed MZL patients treated at the Department of Hematology, The First Hospital of Jilin University, from October 2013 to October 2023. Survival differences between groups were analyzed using the log-rank test, and prognostic factors were identified. Results: A total of 265 newly diagnosed MZL patients were included, with a median age of 59 years (range 22-90). The most common pathological type was mucosaassociated lymphoid tissue (MALT) lymphoma, accounting for 66.0% of cases. Among the 147 MZL patients included in the efficacy analysis, the median followup was 43.4 months. Both the median progression-free survival (PFS) and overall survival (OS) were not reached. The 5-year PFS and OS rates were 76.0% and 86.6%, respectively. Patients who achieved complete response (CR) after induction therapy had significantly better PFS (P=0.0045), OS (P<0.001), and time to next treatment (TTNT) (P=0.0045) compared to those who did not achieve CR. A subgroup analysis was conducted on 51 MZL patients with high tumor burden who received ≥4 cycles of treatment. It was found that the CR rate (CRR) in patients receiving obinutuzumab (G) ± chemotherapy was significantly higher than in those receiving rituximab (R) ± chemotherapy (93.8% vs. 48.6%, P=0.002). Multivariate analysis revealed that disease progression or death within 24 months of initial treatment (POD24) was an independent risk factor affecting OS (P<0.001). Patients who experienced POD24 had a median survival of only 19.7 months, with a 3-year OS rate of just 37.6%, whereas those without POD24 had a 3-year OS rate of 97.3%. Conclusion: MZL is predominantly seen in middle-aged and elderly patients and is a specific indolent B-cell lymphoma, with MALT lymphoma being the most common subtype. Achieving CR after induction therapy significantly prolongs survival in MZL patients. Compared to R ± chemotherapy, G ± chemotherapy achieves a higher CRR in high tumor burden MZL patients. In the era of immunotherapy, POD24 is an independent prognostic factor for MZL. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether tumor-associated lymphatic vessel density (LVD) could be a biomarker for the prognosis of patients with esophageal cancer after radical resection. Methods: A systematic literature search was performed through PubMed, EMBASE, Wanfang Data, and Cochrane Library from the inception of databases until March 19, 2024. The selected studies investigated overall survival (OS) and/or recurrence-free survival (RFS) of patients with esophageal cancer with different levels of LVD after radical resection. The OS and RFS data were pooled as hazard ratios (HR) and 95% confidential interval (CI). Furthermore, the standardized mean differences (SMDs) and 95% CI were aggregated to evaluate the correlation between LVD and clinicopathological features. Results: A total of 10 retrospective studies of 1,201 patients were finally included for the meta-analysis. Patients with esophageal cancer with a high level of LVD exhibited worse OS (HR 1.65, 95% CI 1.18 to 2.31) and RFS (HR 1.57, 95% CI 1.09 to 2.26) than those with a low level of LVD. Subgroup analysis of different pathological subtypes revealed that patients with esophageal adenocarcinoma with a high level of LVD had significantly worse RFS (HR 2.84, 95% CI 1.61 to 5.02) than those with a low level of LVD; while patients with esophageal squamous cell carcinoma with a high level of LVD had similar OS (HR 1.52, 95% CI 0.93 to 2.47) and RFS (HR 1.03, 95% CI 0.72 to 1.48) to those with a low level of LVD. Furthermore, tumors with lymph node metastasis had significantly higher levels of LVD than those without lymph node metastasis (SMD = 1.11, 95% CI 0.54 to 1.67). Tumors at the stages III-IV had significantly higher levels of LVD than those at the stages I-II (SMD = 1.62, 95% CI 0.90 to 2.34). Conclusion: A high level of LVD in tumor was associated with worse survival of patients with esophageal cancer after radical resection, especially in patients with esophageal adenocarcinoma. Tumor-associated LVD is a new parameter that should be measured in postoperative pathology for predicting the prognosis of patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Objective: Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. Methods: From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. Results: The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. Conclusions: OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit. [ABSTRACT FROM AUTHOR]

Background: Bladder urothelial carcinoma (BLCA) is one of the most prevalent tumors globally, with its incidence rising notably in developed countries, significantly affecting human health. CSE1L encodes a protein that is involved in various cellular processes and plays a critical role in cancer initiation and progression. However, its role in BLCA remains underexplored. Methods: CSE1L expression in BLCA was analyzed using TCGA data and validated by qRT-PCR and Western blot in clinical samples. Survival analysis and Cox regression models were used to evaluate its prognostic value. Functional enrichment and protein interaction analyses were performed, and immune cell infiltration was assessed using CIBERSORT. Drug sensitivity was analyzed using GDSC data. In vitro assays evaluated the effects of CSE1L knockdown on cell proliferation, migration, and invasion. Results: CSE1L was found to be significantly overexpressed in BLCA tissues compared to normal tissues. High CSE1L expression was associated with poor overall survival and unfavorable clinicopathological features. Functional enrichment analysis revealed that DEGs related to CSE1L were involved in cell cycle regulation and immune-related pathways. Immune infiltration analysis indicated a significant correlation between CSE1L expression and various immune cell types, particularly T cells and macrophages. Drug sensitivity analysis identified several chemotherapeutic agents, including MG-132, Palbociclib, and Nutlin-3a, which were more effective in the low-CSE1L expression group, while the high-CSE1L expression group showed sensitivity to drugs like S-Trityl-L-cysteine, Bleomycin, and Cisplatin. In vitro knockdown of CSE1L in BLCA cell lines inhibited cell proliferation, migration, and invasion. Conclusions: The overexpression of CSE1L is associated with the progression and poor prognosis of bladder cancer, suggesting it could be a promising target for bladder cancer in the future. [ABSTRACT FROM AUTHOR]

Tumor microenvironment (TME) immune cells and gastric mucosal microbiome constitute two vital elements of tumor tissue. Increasing evidence has elucidated their clinicopathological significance in predicting outcomes and therapeutic efficacy. However, comprehensive characterization of immune cell-associated microbiome signatures in the TME is still in the early stages of development. Here, we characterized the gastric mucosa microbiome and its associations with immune-activated related transcripts (IATs) in 170 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and quantitative reverse transcription-PCR. Microbial diversity and richness were significantly higher in GC tumor tissues than in non-tumor tissues. Differences in microbial composition between the groups were evident, with Firmicutes, Proteobacteria, Bacteroidota, Campilobacterota, Actinobacteria, Fusobacteriota, Verrucomicrobiota, Acidobacteriota, and Cyanobacteria being the dominant phyla in the gastric mucosal microbiota. Microbial interaction network analysis revealed distinctive centralities of oral bacteria (such as Fusobacterium, Porphyromonas, Prevotella, etc.) in both tumor and normal mucosae networks, suggesting their significant influence on GC microbial ecology. Furthermore, we analyzed the expression of IATs (CXCL9, CXCL10, GZMA, GZMB, PRF1, CD8A, IFNG, TBX2, and TNF) and characterized IAT-relevant gastric microbiome signatures in GC patients. Our results showed that the expression of CXCL9, CXCL10, GZMA, GZMB, PRF1 and IFNG was significantly higher in tumor tissues than in adjacent normal tissues in GC patients. Notably, high expression of IATs in tumor tissues was associated with improved survival in GC patients and could serve as a powerful predictor for disease-free survival. Additionally, analysis of IAT levels and mucosal microbiota diversity revealed a correlation between higher IAT expression and increased microbiota richness and evenness in the IATs high group, suggesting potential interactions between mucosal microbiota and tumor immunopathology. Spearman correlation analysis showed positive associations between IAT expression and specific mucosal bacterial species. Notably, Akkermansia muciniphila demonstrated potential involvement in modulating GZMB expression in the GC mucosal microenvironment. These findings underscore the importance of mucosal microbiota alterations in GC and suggest potential therapeutic targets focusing on modulating the tumor microbiota for improved clinical outcomes. The detailed characterization of these elements has profound implications for both treatment and survival prediction in GC. We observed that microbial diversity and richness were significantly higher in GC tumor tissues compared to non-tumor tissues. These differences highlight the unique microbial landscape of GC tumors and suggest that the microbiome could influence tumor development and progression. Importantly, our study demonstrated that high expression levels of IATs in GC tumor tissues were associated with improved patient survival. This suggests that IATs not only reflect immune activation but also serve as valuable biomarkers for predicting disease-free survival. The potential of IATs as predictive markers underscores their utility in guiding therapeutic strategies and personalizing treatment approaches. Moreover, the correlation between higher IAT expression and increased microbiota richness and evenness suggests that a diverse and balanced microbiome may enhance immune responses and contribute to better clinical outcomes. These findings highlight the critical need to consider mucosal microbiota alterations in GC management. Targeting the tumor microbiota could emerge as a promising therapeutic strategy, potentially leading to more effective treatments and improved patient outcomes. Understanding and modulating the microbiome’s role in GC opens new avenues for innovative therapeutic interventions and personalized medicine. [ABSTRACT FROM AUTHOR]

Background: More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. Methods: We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. Results: A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75~0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5~0.94), P = 0.01; =2-cm subgroup: HR = 0.79, 95%CI (0.65~0.96),P=0.02] andthemarginstatus [R0subgroup:HR=0.83, 95%CI (0.77~0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61~0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72~0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66~0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43~1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66~1.42), P = 0.87]. Conclusions: Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with the incidence and prognosis of various malignancies, most notably endometrial cancer (EC). This study investigated the connection between diabetes and EC, with a specific focus on elucidating the biological implications of the diabetes mellitus (DM)-related gene WFS1. Methods: Using the CTD, GeneCards, and GSEA databases, we identified WFS1 as a diabetes-related gene and then conducted an extensive investigation focusing on WFS1 in the context of EC. First, we identified WFS1 as the target gene and obtained EC data from the TCGA database. Then, comprehensive analyses and verification experiments, including differential expression analysis, prognostic modeling, functional enrichment analysis, gene mutation profiling, assessment of immune cell infiltration, immunophenoscore (IPS), tumor stemness index scoring, drug sensitivity analysis, single-cell transcriptomic analysis, glycolytic pathway analysis, and clinical verification, were performed to comprehensively evaluate the clinical value of WFS1 in EC. Results: The EC group had significantly lower WFS1 expression, with an AUC of 0.857 for the ROC diagnostic curve. Overall survival analysis revealed that WFS1 was an independent risk factor for EC; low WFS1 expression was correlated with a poor prognosis. Stemness index analysis revealed that decreased WFS1 expression was associated with increased tumor grade and enhanced tumor stemness, suggesting increased malignancy of EC. In addition, WFS1 expression was correlated with tumor microenvironment features such as immune cell infiltration. WFS1 was also associated with tumor drug resistance. Conclusion: EC patients with low WFS1 expression have a worse prognosis. WFS1 can be used as diagnostic and prognostic marker for EC. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical prognostic factors and treatments for angioimmunoblastic T-cell lymphoma (AITL) and develop a novel prognostic model specifically for AITL. Method: We retrospectively analyzed 231 patients with AITL from the First Affiliated Hospital of Zhengzhou University. Patients were enrolled between January 2014 and July 2023. The primary end points were overall survival (OS) and progression-free survival (PFS). Result: The patients' median age was 63 years, with 88.3% at an advanced stage (III/IV). The majority of patients (47.6%) received anthracycline-containing regimens, and there was no significant difference in survival compared with those treated with epigenetic-targeting and gemcitabine- containing regimens. The median PFS and OS were 6 and 17 months, respectively. In multivariate analysis, age >60 years, Eastern Cooperative Oncology Group performance status ≥2, elevated LDH, and splenomegaly were associated with inferior OS. Based on these four factors, a novel prognostic model (AITL model) was constructed that stratified patients into low, intermediate, and highrisk groups, with 2-year OS estimates of 63.6%, 42.1%, and 18.6%, respectively. Conclusion: Currently, there is no consensus on the optimal initial therapy for AITL, and the efficacy of anthracycline-containing regimens remains suboptimal. The novel model developed herein demonstrates predictive significance for both OS and PFS, and exhibits better stratification and discrimination capabilities. [ABSTRACT FROM AUTHOR]

Object: Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery. Methods: We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.0%). The surgical strategy utilized "anatomy-guided resection," targeting specific anatomical compartments infiltrated by the tumor (e.g., temporal pole, anterior temporo-mesial region = uncus and hippocampal head, posterior temporo-mesial, insula) rather than treating the tumor as a single mass. Results: The most frequent histologies were ganglioglioma CNS WHO grade 1 (55 patients, 35.0%) and IDH1 wildtype glioblastoma (36 patients, 22.9%). Tumor infiltration was most commonly found in the anterior temporo-mesial compartment (145 patients, 92.4%). An anterior temporal lobectomy was part of the surgical strategy in 131 cases (83.4%). Seventy-six patients (48.4%) with drug-resistant epilepsy underwent a formal presurgical epilepsy work-up, including depth electrode placement in three cases. Complete resections were achieved in 117 patients (74.5%), with supramarginal resections performed in 89 cases (56.7%). Four patients experienced non-temporary neurological complications (CTCAE grade 3-5). At 6months, 127 of 147 assessable patients (86.4%) were free from seizures or auras (ILAE class 1), excluding early postoperative seizures (<30days). At 24months, 122 of 144 assessable cases (84.7%) remained seizure-free (ILAE class 1). Kaplan-Meier estimates for 5-year overall survival were 98.5% for non-recurrent glioneuronal tumors. The 2-year overall survival estimates were 96.0% for 24 primary diffuse CNS WHO grade 2 and 3 gliomas and 55.2% for 30 patients undergoing first surgeries for glioblastomas/astrocytomas CNS WHO grade 4. Conclusion: Combining both epilepsy and tumor surgery concepts in the surgical treatment of intrinsic brain tumors involving the mesial temporal lobe, often extending into the insula, led to more extensive resections, improved seizure outcomes, and potentially even better patient survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical outcomes and prognostic factors in non-metastatic oral cavity squamous cell carcinoma (OCSCC) patients who underwent surgery with or without adjuvant therapy. Methods: From 2007 and 2018, 116 patients were analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were disease-free survival (DFS), local failure (LF), regional failure (RF), and distant metastases (DM). Kaplan-Meier method and log-rank test assessed survival outcomes, while Cox proportional hazard tests analyzed prognostic factors. Results: Median patient age was 53 years, most were smokers (93.5%) and males (62.9%). Predominant subsite was the oral tongue (58.6%). Treatment included surgery alone (16.4%), adjuvant radiotherapy (46.6%), or adjuvant concurrent chemoradiotherapy (CCRT) (37%). The median follow-up time was 45.9 months. There were significant differences between groups in terms of gender (P=0.028) and RT dose (P=0.01). The 3-year OS, DFS, LF, RF and DM for the entire cohort were 60.9%, 55.1%, 20.11%, 8.43%, and 17.13%, respectively. Surgery alone yielded higher 3-year OS (81.4%) than adjuvant RT (70%) or adjuvant CCRT (41.4%), (p=0.012). Adjuvant CCRT correlated with higher LF compared to adjuvant RT and surgery alone groups (p=0.029). Lymphovascular invasion (LVI) impacted OS (HR=2.034, p=0.0498) and DM (HR=3.380, p=0.0132), while higher tumor grade increased DM likelihood (HR=8.477, p=0.0379). Conclusions: This study reports OCSCC patient outcomes in Jordan across different treatment modalities. Adjuvant CCRT correlated with higher LF rates, and LVI impacted OS and DM, aligning with existing OCSCC treatment literature. [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels. Methods: 1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage. Results: The overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage. Conclusion: Nomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage. [ABSTRACT FROM AUTHOR]

Osteosarcoma stands as the most prevalent bone tumor, characterized by a heightened tendency for local recurrence and distant metastasis, resulting in a bleak prognosis. Presently, there exists a shortage of novel markers to effectively determine the prognosis of osteosarcoma patients. Recent research indicates that hematological markers partially mirror an individual's microenvironment, offering potential insights into predicting patient prognosis. However, prior studies predominantly focused on the prognostic significance of singular hematological indices, failing to comprehensively represent the tumor microenvironment of patients. In our investigation, we meticulously gathered data on 22 hematological and electrolyte markers, utilizing LASSO Cox regression analysis to devise an Electrolyte Prognostic Scoring System (EPSS). The EPSS encompasses various indicators, including immunity, inflammation, coagulation, and electrolyte levels. Our findings indicate that the EPSS stands as an independent prognostic factor for overall survival among osteosarcoma patients. It serves as a valuable addition to clinical characteristics, adept at discerning high-risk patients from those deemed clinically low-risk. Furthermore, EPSS-based nomograms demonstrate commendable predictive capabilities. [ABSTRACT FROM AUTHOR]

Background: Limited real-world evidence is available for patients with diffuse large B-cell lymphoma (DLBCL) who received an autologous stem cell transplantation (ASCT) in Germany. Objectives: This study aims to describe the real-world survival outcomes of patients with DLBCL who received ASCT in Germany after diagnosis. Design: This study is a retrospective database analysis covering the period between 2010 and 2019. Methods: Unadjusted overall survival (OS) was plotted using the Kaplan-Meier estimator for the overall population and stratified by relapse status. A Cox regression was run to identify factors that influence OS. Results: A total of 112 patients received an ASCT, with the average time from first-line treatment to ASCT being 11.7 months. The median OS estimated by Kaplan-Meier was 83.4 months for the entire cohort. The only variable that significantly reduced the OS was the presence of subsequent treatment after ASCT in a time-dependent model Conclusion: OS after ASCT for DLBCL patients in Germany is higher than previously reported and may still be considered a valid option for carefully selected patients with relapsed/refractory DLBCL.. [ABSTRACT FROM AUTHOR]

Background: The third-line treatment for refractory colorectal cancer (CRC) has limited efficacy. This study aimed to evaluate the safety and efficacy of SHR-8068 (an anti-CTLA-4 antibody), combined with adebrelimab (an anti-PD-L1 antibody), and bevacizumab in refractory non-microsatellite instability-high (MSI-H) or proficient mismatch repair (pMMR) CRC. Method: This study is a prospective, open-label, single-center phase Ib/II clinical trial. Patients with pathologically confirmed pMMR/non-MSI-H metastatic colorectal adenocarcinoma who have failed =2 lines prior standard systemic treatments will be enrolled (n=36). The Ib phase will evaluate two dosing regimens of SHR-8068 in combination therapy (n=9 each dosage): SHR-8068 (1 mg per kilogram, every six weeks, intravenously) or SHR-8068 (4 mg per kilogram, every twelve weeks, intravenously) combined with adebrelimab (1200 mg, every three weeks, intravenously) and bevacizumab (7.5 mg per kilogram, every three weeks, intravenously). The efficacy and adverse events (AEs) of these regimens will be assessed to determine the recommended phase II dose (RP2D) of SHR-8068. Those of RP2D group from the phase Ib will be included in the phase II. The study will go to include 18 additional patients according to the onesample log-rank test design in the phase II. The primary endpoint of the Ib phase is safety, with secondary endpoints including the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and quality of life (QOL). The primary endpoint for phase II was PFS, with secondary endpoints including ORR, OS, DCR, safety, and QOL. Identifying biomarkers to predict the efficacy of this regimen is the exploratory study endpoint. Discussion: This proof-of-concept study would provide safety and efficacy signals of this novel combination treatment for the MSS CRCs in the late-line setting. And it may offer new insights on the clinical application of dual immunotherapy combined with anti-angiogenic therapy in the MSS CRC. [ABSTRACT FROM AUTHOR]

Background: Barrier-to-autointegration factor 1 (BANF1) is an abundant and ubiquitously expressed postnatal mammalian protein that is overexpressed in numerous human cancers and can promote cancer cell proliferation. However, the role of BANF1 in prognosis remains unclear in head and neck squamous cell carcinoma (HNSCC). Methods: BANF1 expression data were obtained from the GEO and TCGA databases. We used Cox regression and Kaplan-Meier curves to assess the prognostic potential of BANF1. The role of BANF1-related genes was investigated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. In addition, we explored the link between BANF1, drug sensitivity, and the tumor immune microenvironment. Finally, functional in vitro and in vivo assays were used to explore the effects of BANF1 on tumor growth and metastasis of HNSCC. Results: BANF1 was markedly overexpressed in HNSCC and was correlated with clinicopathological characteristics. According to survival analysis, BANF1 can be inversely correlated with patient survival and can act as a prognostic risk indicator. IC50 values for chemotherapeutic treatments indicated that the group with high BANF1 expression was more responsive to most antitumor treatments. Furthermore, higher TIDE scores were observed in the low BANF1 expression group, indicating a decline in the efficacy of immune checkpoint inhibitor therapy. Functionally, the malignant biological behavior of HNSCC cell lines was inhibited when BANF1 expression was knocked down. Conclusion: BANF1 can promote tumor progression in patients with HNSCC. BANF1 shows great promise as a potential biomarker to assess the prognosis. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breastconserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings. Methods: Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed. Results: A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5 cm for BC and 1.2 cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030). Conclusion: At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER-patients for IORT. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. Objective: This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. Methods: An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. Results: A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. Conclusion: This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it. [ABSTRACT FROM AUTHOR]

Objective: Nasopharyngeal carcinoma (NPC) patients frequently present with distant metastasis (DM), which is typically associated with poor prognosis. This study aims to develop and apply machine learning models to predict DM, overall survival (OS), and cancer-specific survival (CSS) in NPC patients to provide optimal tools for improved predictive accuracy and performance. Methods: We retrieved over 8,000 NPC patient samples with associated clinical information from the Surveillance, Epidemiology, and End Results (SEER) database. Utilizing two methods for handling missing values--imputation or deletion--we created various cohorts: DM-all, DM-slim, OS-all, OS-slim, CSSall, and CSS-slim. Five machine learning models were deployed for the binary classification task of DM, and their performance was evaluated using the area under the curve (AUC). For the survival prediction tasks of OS and CSS, we constructed 45 combinations using nine survival machine learning algorithms. The Concordance Index (C-index), 5-year AUC, and Brier score assessed model accuracy. Patients were stratified into two risk groups for survival analysis, and the survival curves were presented. Results: This study examines the relationships between clinical factors and survival in NPC patients. The analysis, visualized through forest plots, indicates that demographic and clinical variables like gender, marital status, tumor grade, and stage significantly affect metastatic risks and survival. Specifically, factors such as advanced stages increase metastasis and survival risks, while enhanced treatments improve survival rates. In the cohort for DM prediction, results revealed that the random forest model was the most effective, with an AUC of 0.687. In contrast, when predicting overall survival (OS), the random survival forest (RSF) model consistently showed superior performance with the highest mean C-index of 0.802, a 5-year AUC of 0.857, and a Brier score of 0.167. Similarly, for cancer-specific survival (CSS) prediction, the RSF model demonstrated a mean C-index of 0.822, a 5-year AUC of 0.884, and a Brier score of 0.165. An online Shiny server was developed to allow the models to be used freely and efficiently via http://npcml.shinyapps.io/NPCpre. Conclusion: This study successfully established an online tool by machine learning models for NPC metastasis and survival prediction, providing valuable references for clinicians. [ABSTRACT FROM AUTHOR]

Background and objectives: Following nephrectomy with curative intent, a subset of patients diagnosed with non-metastatic renal cell carcinoma (nmRCC) will present late recurrences, with metastatic relapses after 5 years from the surgical intervention. The aim of this study is to evaluate the prevalence of late recurrences in Romanian patients with nmRCC that have undergone surgery and to assess the clinicopathological characteristics prognostic for late-relapse RCC. Materials and methods: This is a single-center, retrospective and observational study that analyzed patients with nmRCC with clear cell histology who underwent surgical resection of the primary tumor with curative intent. The patients included in the study were treated and further surveilled according to a personalized follow-up plan between January 2011 and December 2012 in The Oncology Institute "Prof. Dr. Ion Chiricuţă", Cluj-Napoca, Romania. Study endpoints included median disease-free survival (DFS), median overall survival (OS), as well as evaluation of possible prognostic factors indicative of late relapse. Results: In the study cohort (n=51), the median DFS was 46 months and median OS was 130 months. DFS was significantly correlated with the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (p=0.04, HR=2.48; 95% CI [1.02, 6.01]), neutrophil to lymphocyte ratio (NLR) (a higher NLR value was associated with a poorer DFS, p=0.035), tumor size (T4 tumors vs. T1 p<0.05, HR=9,81; 95% CI [2.65, 36.27]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=4,16; 95% CI = [1.13,15.22]). Fifty one percent of the patients included experienced disease relapse. From this subgroup, a significant percentage of 42% patients presented disease recurrence after 60 months from nephrectomy. OS was correlated to IMDC score (p=0.049, HR=2.36; 95% CI [1, 5.58]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=3,97; 95% CI [1.08, 14.54]). Conclusions: The results of this study support the previously presented biological behavior of RCC, demonstrating that late recurrences in RCC are not uncommon occurrences and patients with localized RCC should be followed up for a longer interval after the surgery for the primary tumor. In addition, the study strengthens the data supporting certain biomarkers as valuable prognostic factors determining survival outcomes of patients with RCC. [ABSTRACT FROM AUTHOR]

Background: DNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort. Methods: We evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression. Results: GEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p=0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p=0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p=0.008). Conclusions: Our results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA). [ABSTRACT FROM AUTHOR]

Background: Programmed cell death 1 receptor (PD-1) inhibition as monotherapy followed by Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibition in case of progression or as upfront double co-inhibition has drastically improved the survival outcomes of metastatic melanoma. Still, many patients develop primary or acquired resistance to both agents, relapse soon, and survive less. For these patients, the therapeutic options are very limited, and for many years, conventional chemotherapy (CC) was the standard of care. Recently, the phase II LEAP-004 trial supported that pembrolizumab/lenvatinib could potentially overcome anti-PD-1/anti-CTLA-4 immunotherapy refractoriness. Materials and methods: In the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m2 i.v. Q3W) in melanoma patients who relapsed to both checkpoint inhibitors, either in combinatorial or in sequential setting, between July 2022 and January 2024. Baseline demographics, disease characteristics, and treatment outcomes (objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)) were recorded. Survival analyses were performed using the Kaplan-Meier method. All patients were also considered for safety analysis. Results: A total of 84 patients were included in the effectiveness and safety analysis (pembrolizumab/lenvatinib, n=39 and CC, n=45). The median age was 67 (45-87) years and 64 (34-87) years, and men were 33.3% and 46.7%, respectively. The distribution of their metastatic sites was comparable, including 12.8% and 20% with brain involvement. Most patients had a good PS<2 (69.9% and 56.5%), increased lactate dehydrogenase (LDH) (71.8% and 84.4%), BRAF-wild status (82.1% and 84.8%), and received ≥2 previous systemic therapies (61.5% and 53.3%). The median follow-up was 18 months. The ORR was 23.1% and 11.1% (p<0.0001), the median PFS was 4.8 months and 3.8 months [HR (95%CI), 0.57 (0.36-0.92); p=0.017], and the median OS was 14.2 months and 7.8 months [HR (95%CI), 0.39 (0.22-0.69), p=0.0009] in pembrolizumab/lenvatinib and CC arms, respectively. Grade 3-5 treatment-related adverse events were documented in 48.7% (pembrolizumab/lenvatinib) and 75.6% (CC) of patients (p=0.034), which led to treatment discontinuation in 10.3% and 17.8% of cases, respectively. Conclusions: This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly longer outcomes in cases treated with pembrolizumab/lenvatinib versus CC. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed. Methods: This retrospective study assesses the prognostic value of blood biomarkers in advanced and metastatic PDAC patients (n=96) from Spain. Cut-off points for hematological parameters were calculated and correlated with overall survival (OS) using Kaplan-Meier, log-rank test, robust Cox proportional hazards and logistic regressions. Results: In univariate analysis, individuals with low levels of GGT, LDH, ALP, leukocyte-, neutrophil- and monocyte counts showed significantly longer survival than patients with higher levels. In multivariate analysis, lower levels of GGT (HR (95%CI), 2.734 (1.223-6.111); p=0.014), LDH (HR (95%CI), 1.876 (1.035-3.400); p=0.038) and monocyte count (HR (95%CI), 1.657 (1.095-2.506); p = 0.017) remained significantly beneficial. In consequence, we propose a prognostic model based on logistic regression (AUC=0.741) of these three biomarkers as a pioneer tool to estimate OS in PDAC. Conclusion: This study has demonstrated that the joint use of GGT (<92.00), LDH (<220.00) and monocyte count (<800) are independent positive prognostic factors in PDAC that can predict one-year survival in a novel prognostic logistic model. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic value of 18F-FDG PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in diffuse large B-cell lymphoma (DLBCL) remains inadequately explored. This study aims to assess the correlation between these parameters and patient outcomes. Methods: A cohort of 156 DLBCL patients underwent 18F-FDG PET/CT imaging at baseline and after 3-4 cycles of R-CHOP or CHOP-like regimen. The third quartiles of liver uptake values were used as thresholds for calculating MTV and TLG. Patient outcomes were analyzed based on Ann Arbor staging and the 5-PS score. A nomogram was developed to predict overall survival (OS). Results: Patients with low baseline TLG exhibited significantly better outcomes compared to those with high baseline TLG in both Ann Arbor stages I-II and III-IV (1-year PFS: 78.9% vs. 40%, p=0.016; OS: 94.7% vs. 40%, p=0.005 for stage I-II; 1-year PFS: 74.1% vs. 46.8%, p=0.014; OS: 85.4% vs. 71.8%, p=0.007 for stage III-IV). In interim PET/CT patients with a 5-PS score >3, the high Î"TLG group had superior prognosis (1-year PFS: 82.3% vs. 35.7%, p=0.003; OS: 88.2% vs. 85.7%, p=0.003). The nomogram achieved a C-index of 0.9 for OS prediction. Discussion: The findings suggest that baseline TLG is a robust prognostic indicator for patients with DLBCL, particularly in early stages, while Î"TLG effectively distinguishes those with favorable outcomes in higher-risk groups. These metabolic parameters from 18F-FDG PET/CT could enhance treatment decision-making and patient management strategies. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the outcomes after stereotactic body radiotherapy (SBRT) for locally advanced primary liver cancer. Materials and methods: Patients with locally advanced liver cancer unsuitable for other loco-regional treatments were treated with SBRT with 50--60 Gy in 3--12 fractions in two consecutive prospective trials. Results: A total of 83 patients were included, of whom 14 were excluded, leaving 69 evaluable patients with 74 treated lesions. A total of 50 patients had hepatocellular carcinoma (HCC), and 11 patients had cholangiocarcinoma (CCC). Approximately 76% had a Child-Pugh (CP) score of A, while 54% had an albumin--bilirubin (ALBI) score of 1. With a median follow-up of 29 months, the median overall survival (OS) was 11 months, and the progression-free survival (PFS) was 18 months. The ALBI score was an important predictor of overall survival (HR 2.094, p = 0.001), which remained significant also in the multivariate analysis. Patients with an ALBI grade of ≥1 had an OS of 4 months versus 23 months in patients with an ALBI grade of 1 (p ≤ 0.001). The local control at 1 and 2 years was 91%. Thirteen patients developed grade ≥ 3 toxicities, of whom nine patients experienced liver toxicities. Patients with a higher ALBI score had a high risk for developing hepatic failure (OR 6.136, p = 0.006). Discussion: SBRT is a very effective treatment with low toxicity and should be considered as a local treatment option in patients with HCC and CCC. Patients with a higher ALBI grade are at risk for developing toxicities after SBRT and have a significantly lower survival rate. [ABSTRACT FROM AUTHOR]

Introduction: Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. Methods: This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the riskadapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. Results: The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%- 3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). Conclusions: This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Despite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/ NF-kB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-kB and antiapoptotic activity. Methods: We conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide. Results: Results indicated that the PTX group exhibited higher apoptosis on day- 8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS. Conclusion: Our study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT02451774. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the relationship between the lymph node ratio (LNR) and the prognostic values of gynecological cancer. Materials and Methods: PubMed, Web of Science, Embase, and the Central Cochrane Library were used to search for studies on LNR and gynecological cancer published before 18 April 2024. The effect measure for meta-analysis of primary outcomes was the hazard ratio (HR) for overall survival (OS), progressionfree survival (PFS), and disease-free survival (DFS). Pooled HRs and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Sensitivity analysis was applied to evaluate the robustness of the results. The I2 statistic was used to measure heterogeneity. Subgroup analysis and meta-regression were chosen to illustrate the potential heterogeneity of the risk factors for outcomes. Publication bias was assessed using Egger's test and Begg's funnel plots. Results: A total of 34 studies with 23,202 cases were included in this metaanalysis. A meta-analysis found that higher LNR was associated with worse OS (HR = 2.42, 95% CI: 2.07-2.83; I2 = 77.4%, p < 0.05), PFS (HR = 1.97, 95% CI: 1.66-2.32; I2 = 0.00%, p > 0.05), and DFS (HR = 3.18, 95% CI: 2.12-4.76; I2 = 64.3%, p < 0.05). Moreover, meta-analysis revealed significant differences in the association between LNR and OS of cervical cancer (CC) (HR = 2.53, 95% CI: 1.94-3.31; I2 = 72.6%, p < 0.05), ovarian cancer (OC) (HR = 2.05, 95% CI: 1.66-2.54; I2 = 76.7%, p < 0.05), endometrial cancer (EC) (HR = 2.16, 95% CI: 1.48-3.16; I2 = 53.6%, p < 0.05), and vulvar cancer (VC) (HR = 8.13, 95% CI: 3.41-19.43; I2 = 57.2%, p < 0.05). Conclusion: We observed a clear association between higher LNR and poorer prognosis in our study of patients with gynecological cancer. Further prospective studies are warranted to determine the optimal LNR and whether LNR can guide adjuvant therapy use in gynecological cancer. It is essential to conduct further prospective studies to establish the optimal LNR threshold, determine the minimum threshold of lymph node removal, and investigate whether LNR can serve as a reliable marker for guiding adjuvant therapy choices in gynecological cancer. [ABSTRACT FROM AUTHOR]

Objective: To summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0. Results: A total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size =4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node = 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1. Conclusions: The migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions. [ABSTRACT FROM AUTHOR]

Background: The role of high-dose chemotherapy followed by autologous hematopoietic cell transplantation in the management of patients with relapsed/refractory germ-cell tumors has not been established in prospective studies. Our aim was to estimate the benefits and harm of this treatment in men with relapsed/refractory germ-cell tumors. Methods: Electronic databases, conference proceedings, and trial registers until April 30, 2023, were searched. Randomized and non-randomized prospective controlled trials were included. Risk of bias assessments were performed using either RoB2 or ROBINS-I tools. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Time-to-event data were analyzed using the hazard ratio. The primary outcome was overall survival, and a meta-analysis was not conducted to assess it because non-randomized trials were judged to have a critical risk of bias. Categorical data were analyzed using a risk ratio. All results are presented with the corresponding 95% confidence interval. Results: Four out of 3,824 records met the inclusion criteria, and three out of four were used to assess primary and secondary outcomes. Based on the IT94 study (N = 263 participants), single high-dose chemotherapy followed by autologous hematopoietic cell transplantation may have little to no effect on overall survival [hazard ratio (HR) 0.98, 95%CI 0.68 to 1.42; p = 0.916]. Non-randomized trials (N = 43 participants) showed contrasting results, which may be explained by the number of cycles of high-dose chemotherapy administered in each study. Regarding secondary outcomes, information was only provided for event-free survival, response rate, and acute toxicities. Conclusions: Based on prospective data, there is insufficient evidence to support or refute the proposal that high-dose chemotherapy with autologous hematopoietic cell transplantation improves survival in men with relapsed/refractory germ-cell tumors. If this treatment is considered essential, the choice should be made by experienced clinicians at high-volume cancer centers. [ABSTRACT FROM AUTHOR]