Independent Predictor Of Survival Research Articles

Neutrophil-to-Lymphocyte Ratio is Associated with Clinical Outcomes in Patients Treated with Mechanical Thrombectomy for Posterior Circulation Large Vessel Occlusion

To investigate the potential of composite inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), in predicting outcomes in patients with posterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). We included patients who underwent MT for posterior circulation large vessel occlusion between February 2016 and December 2021. We then assessed composite inflammatory markers on day 1 post-MT. The primary outcome was the modified Rankin Scale score at 3 months (favorable score: 0 -3). The primary safety measure was 3-month mortality. Receiver operating characteristic (ROC) curve analysis determined each marker's predictive values and optimal cutoff values. Multivariable regression analysis assessed the relationship between markers and outcomes. We included a total of 137 patients (median age: 71 years, 26% females, median National Institutes of Health Stroke Scale [NIHSS] score: 23). NLR demonstrated the best predictive value for the prognosis of patients with posterior circulation large vessel occlusion who underwent MT. ROC analysis identified an optimal NLR cutoff of 12.5 (area under curve [AUC]: 0.741, 95% confidence intervals [CIs]: 0.652-0.830) for favorable outcomes and 14.1 (AUC: 0.764, 95% CIs: 0.662-0.865) for predicting death. Multivariate analysis determined an NLR <12.5 as an independent predictor of favorable post-MT outcomes (odds ratio [OR]: 10.43, 95% CIs: 3.85-28.29, p <0.001), and NLR <14.1 as an independent predictor of post-MT survival (OR: 0.09, 95% CIs: 0.03-0.25, p <0.001). Among the assessed markers, NLR emerged as the strongest predictor of clinical outcomes following MT for posterior circulation large vessel occlusion.

Sleep Disturbances in Amyotrophic Lateral Sclerosis and Prognostic Impact—A Retrospective Study

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with sleep disturbance, namely insomnia and sleep-disordered breathing. This study aims to evaluate the overall sleep characteristics of ALS patients, their association with lung function tests, and possible predictive survival factors. We conducted a retrospective observation study among ALS patients monitored during a pulmonology consultation. Type one polysomnography (PSG) and lung function tests were performed once the patients presented with sleep-related symptoms, and the relationship between their parameters was assessed, as well as a survival analysis. We included 35 patients, with an overall diminished sleep efficiency, a partially conserved forced vital capacity (FVC), and low maximal inspiratory pressure (MIP). A positive correlation between FVC and REM sleep percentage was observed. A survival analysis showed that a normal rapid eye movement (REM) sleep percentage and respiratory disturbance index (RDI) ≥ 15/h were independent predictors of survival. We observed a trend for higher sleep quality in patients with conserved lung function. A better sleep quality was associated with a higher survival. Obstructive events (reduced or absence of airflow associated with continued or increased inspiratory effort) did not seem to impact survival.

Epigenetic landscape reorganisation and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma

Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological grading is challenging, and aside from CDKN2A/B homozygous deletions in IDH-mutant astrocytomas, there are no other objective molecular markers used for grading. RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n = 138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide. We integrated the RNA-sequencing data with matched DNA-methylation and NGS data. We also used multi-omics data from IDH-mutant astrocytomas included in the TCGA dataset and validated results on matched primary and recurrent samples from the GLASS-NL study. Since discrete classes do not adequately capture grading of these tumours, we utilised DNA-methylation profiles to generate a Continuous Grading Coefficient (CGC) based on classification scores from a CNS-tumour classifier. CGC was an independent predictor of survival outperforming current WHO-CNS5 and methylation-based classification. Our RNA-sequencing analysis revealed four distinct transcription clusters that were associated with (i) upregulation of cell cycling genes; (ii) downregulation of glial differentiation genes; (iii) upregulation of embryonic development genes (e.g. HOX, PAX, and TBX) and (iv) upregulation of extracellular matrix genes. The upregulation of embryonic development genes was associated with a specific increase of CpG island methylation near these genes. Higher grade IDH-mutant astrocytomas have DNA-methylation signatures that, on the RNA level, are associated with increased cell cycling, tumour cell de-differentiation and extracellular matrix remodelling. These combined molecular signatures can serve as an objective marker for grading of IDH-mutant astrocytomas.

Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors.

For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement. Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method. One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively). Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

A Clinico-Genetic Score Incorporating Disease-Free Intervals and Chromosome 8q Copy Numbers: A Novel Prognostic Marker for Recurrence and Survival Following Liver Resection in Patients with Liver Metastases of Uveal Melanoma

Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (&gt;3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment.

IGFL2 expression and surgical volume: Independent predictors of survival in gastric cancer.

This study aimed to assess the impact of surgeons' annual volume and insulin-like growth factor-like family member 2 (IGFL2) expression on gastric cancer prognosis. Clinicopathological data from 475 patients who underwent D2 lymph node dissection were analyzed. IGFL2 expression was evaluated using immunohistochemistry. Patients were divided into training (70%) and validation (30%) groups. Univariate and multivariate Cox regression identified risk factors for overall survival (OS) and disease-free survival (DFS), leading to a clinical prediction model. Model performance was evaluated using C-index. High IGFL2 expression and low surgical volume independently predicted poorer OS and DFS (hazard ratio = 2.13, 2.17, all P < .01). Surgeons performing >26 cases annually had higher OS and DFS (hazard ratio = 1.65, 1.58, all P < .01). Nomograms integrating surgical volume, IGFL2 expression, grade, TNM staging, and carcinoembryonic antigen showed superior predictive accuracy for OS and DFS compared to TNM alone, with robust C-indices and area under the curve values. Surgeons' annual volume and IGFL2 expression independently predict gastric cancer prognosis, emphasizing the need for specialized training and further research on IGFL2's molecular mechanisms to enhance patient outcomes.

Epidemiological Study of Adenoid Cystic Carcinoma and Its Outcomes: Insights from the Surveillance, Epidemiology, and End Results (SEER) Database

Objective: Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mainly arises in the head and neck area. We aimed to compare the long-term survival of patients with ACC based on their geographic regions within the United States using the Surveillance, Epidemiology, and End Results (SEER) registry data. Methods: We queried the SEER database to evaluate the geographic distribution of ACC patients based on inpatient admissions. The states included in the study were divided into four geographical regions (Midwest, Northeast, South, and West) based on the U.S. Census Bureau-designated regions and divisions. Demographic and clinical variables were compared between the groups. Kaplan–Meier curves and Cox regression were used to assess late mortality. Results: A total of 5150 patients were included (4.2% from the Midwest, 17.2% from the Northeast, 22.5% from the South, and 56.1% from the West regions). The median follow-up was 12.3 (95% CI: 11.6–13.1 years). Median overall survival was 11.0 (95% CI: 9.2-NR years), 14.3 (95% CI: 12.4–16.4 years), 11.3 (95% CI: 9.7–14.8 years), and 12.0 (95% CI: 11.3–13.0 years) for Midwest, Northeast, South, and West regions, respectively. In multivariable analysis, older age, male sex, thoracic cancer, the presence of regional and distal disease, receiving chemotherapy, not undergoing surgical resection, and being treated in the West vs. Northeast region were found to be independent predictors of poor survival. We identified a significant survival difference between the different regions, with the West exhibiting the worst survival compared to the Northeast region. Conclusions: In addition to the well-known predictors of late mortality in ACC (tumor location, stage, and treatment modalities), our study identified a lack of social support (being unmarried) and geographic location (West region) as independent predictors of late mortality in multivariable analysis. Further research is needed to explore the causal relationships.

Systemic inflammatory markers: Predictors of survival in mucinous appendix cancer patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionInflammatory markers have been investigated as predictors of prognosis in various malignancies, but their role in mucinous appendix cancer (MAC) remains controversial. We evaluated the association between complete blood count-derived markers and survival in MAC patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). MethodsWe conducted a retrospective analysis of a single-center database (1998–2023) including newly diagnosed MAC patients who underwent complete (CC-0/1) CRS/HIPEC. Preoperative values of neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelets-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated. For markers strongly associated with survival, we used time-dependent ROC analysis to define cutoffs to predict 5-year overall survival (OS). The Kaplan-Meier method with and Cox regression were employed for survival analysis. ResultsOf 626 CRS/HIPEC cases, 211 were eligible. NLR (p=0.049), dNLR (p=0.049), and MLR (p<0.001) were significantly associated with OS, while PLR was not. MLR demonstrated the strongest prognostic power (AUC=0.682) with the optimal cut-off 0.29. There were no significant differences in age, grade, or peritoneal cancer index (PCI) between patients with MLR<0.29 and MLR≥0.29. Five-year progression-free (PFS) and OS were 72.2 % and 83.2 % for MLR<0.29 and 54.2 % and 66.6 % for MLR≥0.29, respectively. After adjusting for age, PCI, and grade, MLR≥0.29 was associated with worse 3-year PFS (hazard ratio [HR] 1.74, 95 % confidence interval [CI]:1.02–2.97, p=0.044) and 3-year and 5-year OS (HR 1.87, 95 %CI: 1.00–3.47, p=0.049). ConclusionMLR has emerged as an independent predictor of survival in MAC patients undergoing CRS/HIPEC. Along with other prognostic factors, MLR≥0.29 may be potentially used for preoperative risk stratification.

Positive Lymph Node Ratio as a new prognostic score in Geriatric patients with operated gastric cancer

ObjectiveThe pivotal prognostic determinant for recurrence and survival in surgically treated gastric cancer (GC) patients remains the lymph node status. Despite the adoption of D2 lymph node dissection as the standard approach in recent years, its association with increased morbidity in elderly patients raises concerns. This study aims to explore the prognostic significance of the Positive Lymph Node Ratio (PLNR) score in the context of recurrence and survival among elderly patients with surgically treated GC. Material and methodA retrospective review of files about surgically treated patients with GC was conducted. The prognostic impact of the PLNR score on overall survival (OS) was assessed through Receiver Operating Characteristic (ROC) analysis. ResultsThe cut-off value for the PLNR, determined through ROC analysis, was identified as 0.138. This value serves as a crucial threshold, as it distinguishes patients with a higher risk of poor outcomes. Patients with a PLNR score of 0.138 or below exhibited a median OS of 111 months, whereas those with a PLNR score above 0.138 had a significantly lower median OS of 22 months (p = 0.004). ConclusionOur findings revealed that the PLNR emerged as an independent predictor of survival and recurrence in patients undergoing GC resection.However, it's important to note that while valuable, the PLNR system has limitations. It does not encompass the T stage, a key factor in cancer staging. Therefore, it cannot be a direct substitute for the comprehensive information TNM staging provides. It should be used as a supplementary tool in predicting prognosis, particularly in elderly patients unsuitable for standard lymph node dissection.

Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with CCNU/TMZ.

Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The RANO resect group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyse the prognostic performance of binary EOR assessment compared to volumetric assessment. 78 patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and PFS was analysed using uni- and multivariable Cox regression analysis as well as two-sided log rank test. Patients were divided into RTV ≤1 cm³, >1 cm³ - ≤5 cm³ and >5 cm³ following the proposed criteria of the RANO resect group. Prolonged OS was associated with age <60 years, low RTV, and gross total resection (GTR). Residual tumor volume (RTV) had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI 46.94-not reached), with a 5-year survival rate of 49%. Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways “BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation” and “AMAN pathway”. In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Predicting prognosis in patients with stage IA lung adenocarcinoma with a micropapillary component using a nomogram based on computed tomography radiomics and clinicopathologic factors: a retrospective analysis.

Patients with stage IA lung adenocarcinoma (ADC) with an micropapillary (MIP) component are at a higher risk of recurrence after radical surgical resection; however, adding adjuvant chemotherapy (ACT) to their postoperative course remains controversial. This study determined the predictive factors that influence the prognosis of these patients and identified those at high risk of recurrence. Between January 2012 and December 2018, 254 eligible patients with stage IA lung ADC with an MIP component were categorized into training (n=169) and validation (n=85) cohorts. Clinicopathological and radiomics features were included in univariate and multivariate analyses, and statistically significant predictors were used to develop the nomogram. Area under the curve (AUC) of receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the model. The calculated risk scores for each patient were risk-stratified using the X-tile procedure, and survival analyses were performed among the different risk subgroups. T1c stage, MIP ≥1%, spread through air space (STAS), carcinoembryonic antigen (CEA) >5 µg/L, and radiomics features were independent predictors of overall survival (OS) and disease-free survival (DFS) in patients with lung ADC with an MIP component at stage IA. Incorporating this into the nomogram, the AUCs of the nomogram predicting 3-, 5-, and 7-year OS and DFS were 0.910, 0.914, and 0.904 and 0.868, 0.838, and 0.848, respectively, in the training cohort and 0.879, 0.895, and 0.899 and 0.817, 0.805, and 0.811, respectively, in the validation cohort, showing good differentiation. The OS and DFS survival analyses among different risk subgroups showed that the nomogram could well distinguish between low- and high-risk groups. We developed and validated a nomogram based on clinicopathological factors and radiomics features, which can be used as a powerful tool for predicting postoperative recurrence and survival in patients with stage IA lung ADC containing an MIP component.

Evaluation of glucocorticoid-related genes reveals GPD1 as a therapeutic target and regulator of sphingosine 1-phosphate metabolism in CRPC

Prostate cancer (PCa) is an androgen-dependent disease, with castration-resistant prostate cancer (CRPC) being an advanced stage that no longer responds to androgen deprivation therapy (ADT). Mounting evidence suggests that glucocorticoid receptors (GR) confer resistance to ADT in CRPC patients by bypassing androgen receptor (AR) blockade. GR, as a novel therapeutic target in CRPC, has attracted substantial attention worldwide. This study utilized bioinformatic analysis of publicly available CRPC single-cell data to develop a consensus glucocorticoid-related signature (Glu-sig) that can serve as an independent predictor for relapse-free survival. Our results revealed that the signature demonstrated consistent and robust performance across seven publicly accessible datasets and an internal cohort. Furthermore, our findings demonstrated that glycerol-3-phosphate dehydrogenase 1 (GPD1) in Glu-sig can significantly promote CRPC progression by mediating the cell cycle pathway. Additionally, GPD1 was shown to be regulated by GR, with the GR antagonist mifepristone enhancing the anti-tumorigenic effects of GPD1 in CRPC cells. Mechanistically, targeting GPD1 induced the production of sphingosine 1-phosphate (S1P) and enhanced histone acetylation, thereby inducing the transcription of p21 that involved in cell cycle regulation. In conclusion, Glu-sig could serve as a robust and promising tool to improve the clinical outcomes of PCa patients, and modulating the GR/GPD1 axis that promotes tumor growth may be a promising approach for delaying CRPC progression.

Neoadjuvant Chemotherapy for Borderline Resectable Head and Neck Cancers: A Comparative Study of Three-Drug and Two-Drug Regimens in a Low- and Middle-Income Country (LMIC) Context.

Background Borderline resectable head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge, particularly in low- and middle-income countries (LMICs) like India. Neoadjuvant chemotherapy (NACT) aims to downstage tumors to achieve operability, but the optimal regimen remains controversial due to varying efficacy and toxicity profiles. This study compares the efficacy and toxicity of a three-drug regimen (TPF: docetaxel, cisplatin, and 5-fluorouracil) with a two-drug regimen (taxane and platinum) in patients with borderline resectable HNSCC in an LMIC setting. Methods In this retrospective cohort study, a total of 90 patients with borderline resectable HNSCC were included. Forty-three patients received the TPF regimen (Arm A), while 47 received the taxane + platinum regimen (Arm B). The outcomes measured included conversion to operability, stage-specific outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Statistical analyses included chi-square tests for categorical variables, Kaplan-Meier survival analysis, and Cox proportional hazards modeling for multivariate analysis. Results The conversion to operability was significantly higher in the TPF group (72% vs. 51%, p=0.03). Patients in Arm A also exhibited a trend toward higher pathological complete response (pCR) rates compared to Arm B (60% vs. 43%, p=0.08). The overall survival and progression-free survival were improved in the TPF group, although the study did not reach statistical significance in these endpoints due to the limited sample size. However, the TPF regimen was associated with significantly higher toxicity. Grade 3-4 neutropenia occurred in 55% of the patients in Arm A compared to 32% in Arm B (p=0.01), and mucositis was observed in 47% of Arm A patients compared to 19% in Arm B (p=0.002). Febrile neutropenia was also more frequent in the TPF group (28% vs. 13%, p=0.04). Multivariate analysis identified the chemotherapy regimen (HR=1.45, 95% CI 1.05-2.01, p=0.02) and baseline nutritional status (HR=1.78, 95% CI 1.12-2.82, p=0.01) as independent predictors of overall survival. Conclusion While the TPF regimen offers superior efficacy in terms of tumor downstaging and conversion to operability, its higher toxicity profile limits its applicability in resource-constrained settings, such as LMICs. The taxane + platinum regimen, although less effective in downstaging, presents a more favorable toxicity profile, making it a viable alternative for patients with comorbidities or poor performance status. The choice between these regimens should be individualized, considering the patient's overall health, nutritional status, and the availability of supportive care. Further research is warranted to optimize NACT strategies for patients in LMICs.

Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma

Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.

Oncogenic mutations in the TP53 and PI-3 kinase/AKT pathway are independent predictors of survival for advanced thyroid cancer: Analysis from the Molecular Screening and Therapeutics (MoST) program

BackgroundThyroid cancers with mutations in the phosphatidylinositol-3 kinase/AKT pathway have a poorer prognosis. However, knowledge about the relationship between histology, mutation profile, and outcomes is still developing. This study assessed the prognostic value of genomic profiles for patients with advanced thyroid cancer who experienced progression on conventional treatment. MethodsPatients recruited to a national clinical oncology program for treatment-refractory locally advanced, recurrent or metastatic cancers were analyzed. Patients' archival tumor samples underwent comprehensive genomic profiling. Specific oncogenic mutations and the presence of cancer related pathways were correlated with overall survival. ResultsFrom 2018 to 2021, 4,955 patients were recruited, with 44 (0.9%) having a diagnosis of thyroid cancer with 4 medullary and the remaining follicular derived: 17 differentiated, 13 poorly differentiated, and 10 anaplastic thyroid cancers. Of the 40 follicular-derived thyroid cancer samples, 17 (42.5%) carried TP53 mutations, followed by 11 with BRAF V600E (27.5%), 9 with NRAS (22.5%), 9 with mutations in the phosphatidylinositol-3 kinase/AKT pathway (22.5%), and 7 with TERT promoter mutations (17.5%). Both TP53 and phosphatidylinositol-3 kinase/AKT pathway alterations were associated with reduced overall survival (hazard ratio, 5.19; 95% confidence interval, 1.59–16.70, P = .02 and hazard ratio, 10.12; 95% confidence interval, 1.61–63.76, P = .01). Cox regression showed histologic type anaplastic thyroid cancer (hazard ratio, 12.93, P = .004), poorly differentiated thyroid cancer (hazard ratio, 5.19, P = .039), and TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations (hazard ratio, 4.73, P = .017) were independently associated with overall survival. ConclusionTP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.

Exploiting the role of CSF NfL, CHIT1, and miR-181b as potential diagnostic and prognostic biomarkers for ALS.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by relentless and progressive loss of motor neurons. A molecular diagnosis, supported by the identification of specific biomarkers, might promote the definition of multiple biological subtypes of ALS, improving patient stratification and providing prognostic information. Here, we investigated the levels of neurofilament light chain (NfL), chitotriosidase (CHIT1) and microRNA-181b (miR-181b) in the cerebrospinal fluid (CSF) of ALS subjects (N = 210) as well as neurologically healthy and neurological disease controls (N = 218, including N = 74 with other neurodegenerative diseases) from a large European multicentric cohort, evaluating their specific or combined utility as diagnostic and prognostic biomarkers. NfL, CHIT1 and miR-181b all showed significantly higher levels in ALS subjects compared to controls, with NfL showing the most effective diagnostic performance. Importantly, all three biomarkers were increased compared to neurodegenerative disease controls and, specifically, to patients with Alzheimer's disease (AD; N = 44), with NfL and CHIT1 being also higher in ALS than in alpha-synucleinopathies (N = 22). Notably, ALS patients displayed increased CHIT1 levels despite having, compared to controls, a higher prevalence of a polymorphism lowering CHIT1 expression. While no relationship was found between CSF miR-181b and clinical measures in ALS (disease duration, functional disability, and disease progression rate), CSF NfL was the best independent predictor of disease progression and survival. This study deepens our knowledge of ALS biomarkers, highlighting the relative specificity of CHIT1 for ALS among neurodegenerative diseases and appraising the potential diagnostic utility of CSF miR-181b.

Monitoring the Response of Cyclin-Dependent Kinase 4/6 Inhibitors with Mean Corpuscular Volume.

Currently, the combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy is a first-line treatment for hormone-receptor-positive and HER2-negative metastatic breast cancer. This study aimed to assess the impact of changes in Mean Corpuscular Volume (MCV) on predicting responses to treatment and survival in patients with hormone-receptor-positive, HER2-negative metastatic breast cancer receiving CDK4/6 inhibitors and endocrine therapy. Retrospectively, data on hemoglobin levels, MCV, B12, folate levels, and survival times were collected from 275 patients. Patients were categorized into two groups based on the degree of MCV change (delta MCV ≤ 10 vs. >10). Kaplan-Meier survival analysis was performed, with significance set at p < 0.05. The average age of the patients was 56.1 ± 12.1 years. In total, 72.7% received CDK4/6 inhibitors as first-line treatment, while 27.3% received them as second-line treatment. Before CDK4/6 inhibitor use, the median MCV level was 87.7 fL (IQR: 83-91), which increased to 98 fL (IQR: 92-103) after treatment (p < 0.001). ECOG performance score, CDK4/6 inhibitor treatment line, type of endocrine therapy, and MCV change were identified as independent predictors of progression-free survival in the Cox regression model. The median progression-free survival for the entire group was 28 months. Patients with MCV delta > 10 had a median progression-free survival of 33 months, compared to 23 months for those with MCV delta ≤ 10 (p = 0.029). There was no significant difference in median overall survival times between the two groups (p = 0.158). This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

Improve clinical feature-based bladder cancer survival prediction models through integration with gene expression profiles and machine learning techniques

BackgroundBladder cancer (BCa), one of the most common cancers worldwide, is characterized by high rates of recurrence, progression, and mortality. Machine learning algorithms offer promising advancements in enhancing predictive models. This study aims to develop robust machine learning models for predicting BCa survival using clinical and gene expression data. MethodsClinical data from BCa patients were obtained from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression models assessed the association between clinical variables and overall survival. Machine learning algorithms, including logistic regression, random forest, XGBoost, decision tree, and LightGBM, were employed to predict survival at 1, 3, and 5 years. The TAGO database, combined with the data from The Cancer Genome Atlas and four databases from the Gene Expression Omnibus, which have available genomic data and clinical data, were selected. Gene expression data were transformed into gene sets data, and the performance of models based on clinical data and gene sets data and their combination were compared. Furthermore, the impact of model-derived scores on overall survival was evaluated. ResultsAmong 138,741 BCa patients with available clinical data, key independent predictors of survival included age, race, marital status, surgery, chemotherapy, radiation, and TNM stages. Clinical data machine learning (CML) models used these clinical predictors to achieve AUC values of 0.860, 0.821, and 0.804 in the testing sets for predicting survival at 1, 3, and 5 years, respectively. In the TAGO database, which has 863 patients with clinical and genomic data, the integrated clinical and gene expression machine learning model (IML) outperformed the CML and gene expression machine learning (GML) models in survival prediction. Patients with higher IML and GML model scores exhibited poorer survival outcomes. ConclusionsThis study successfully identifies key clinical and genomic predictors, a significant step forward in BCa research. The development of predictive models for BCa survival underscores the potential of integrated data approaches in improving BCa management and treatment strategies.

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.