Independent Prognostic Factor Research Articles

Predicting pan-cancer immune-checkpoint therapy and prognosis with a chromatin-accessibility-related alternative splicing signature: a retrospective study

Background: This study examines alternative splicing (AS) events in genes linked to chromatin accessibility in various cancers and their relation to the tumor immune microenvironment. Methods: Data from the Cancer Genome Atlas Database (TCGA) were used to identify independent prognostic factors for pan-cancer. We explored the correlation between differentially expressed genes and tumor immunity, including immune checkpoint genes, tumor development, and immune cells. A regulatory network diagram of alternative splicing-splicing factors (AS-SFs) was constructed to find potential immunotherapy targets. Results: IRF5 and E2F8 genes showed significant differential expression in pan-cancer. Age, cancer grade, primary tumor, cancer lymph nodes, and distant metastasis were independent prognostic factors. The risk model achieved good predictive performance, with AUC values of 0.705, 0.746, 0.743, and 0.743 for 1-year, 3-year, 5-year, and 10-year survival predictions, respectively. Positive correlations were found between IRF5/E2F8 and CD274/CTLA4 in certain cancers using TIMER and CIBERSORT software. Conclusions: AS events in chromatin accessibility genes (IRF5 and E2F8) have significant predictive value in pan-cancer prognosis. Our model assesses patient survival probability and highlights the synergistic impact of immune checkpoints and the AS-SF regulatory network on tumor immunotherapy.

Overestimation of clinical N-staging in microsatellite instable gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics

Abstract Background Microsatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation. Materials and methods We conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors. Results Multivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts. Conclusion Frequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options.

NETosis in pulmonary pleomorphic carcinoma

AbstractPulmonary pleomorphic carcinoma (PC) is a rare non‐small‐cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil‐specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy‐six patients with pulmonary PC who underwent complete resection were enrolled. Tumor necrosis was evaluated using digitally scanned resected specimens. The regions of NETosis were quantified using citrullinated histone H3 (citH3)‐ and myeloperoxidase‐positive regions. We examined the association between the NETosis area and the prognostic outcomes and assessed the correlation between the NETosis area and systemic inflammation. Tumor necrosis was observed in 70 patients (92%). In all the cases, the TN region was accompanied by a citH3‐positive region. The patients with high NETosis area (n = 54) had significantly shorter overall survival than those with low NETosis area (n = 16) (p = 0.013). Furthermore, a high NETosis area was an independent poor prognostic factor in the multivariate analyses. Systemic inflammatory markers, including C‐reactive protein (CRP), CRP‐to‐albumin ratio, and neutrophil‐to‐lymphocyte ratio, were significantly higher in patients with high NETosis area than in those with low NETosis area. Furthermore, the levels of these inflammatory markers were significantly decreased postsurgery. This study shows that in surgically resected pulmonary PC, patients with high NETosis areas have higher systemic inflammation and worse prognosis.

A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery

Background: Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery. Methods: In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared. Results: Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p<0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K/Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival. Conclusion: Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Of 586 eligible patients, 393 underwent DPS and had a CRSreported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95-4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14-0.91; P = 0.0291). Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.

Senescence cell signature associated with poor prognosis, epithelial-mesenchymal transition, solid histology, and spread through air spaces in lung adenocarcinoma.

Cellular senescence is involved in critical processes in tumor progression. Despite this potential relationship, the relationship between tumor cell senescence, prognostic significance, spread through air spaces (STAS), and tumor histology has not been investigated in lung adenocarcinoma (LUAD). We used the LUAD PanCancer Atlas dataset to assess senescence cell signature (SCS) based on the SenMayo gene set. We examined the relationship between SCS, prognostic significance, STAS, and tumor histology. This relationship was confirmed in independent LUAD datasets by validation using immunohistochemical senescence markers. In the LUAD PanCancer Atlas dataset, patients with high SCS expression had a higher prevalence of solid histology and STAS patterns than those with low SCS expression. In the independent LUAD datasets, high p21 expression and low HMGB1 expression were correlated with solid histology or STAS patterns. SCS level was also independent prognostic factor in four different LUAD datasets. The HMGB1 expression was an independent prognostic factor in the independent LUAD dataset in multivariate analysis. The expression of p21 and the presence of solid histology were linked to the epithelial-mesenchymal transition (EMT) phenotype. In LUAD cell lines, inducing senescence with a DNA-damaging agent led to an increase in EMT marker expression. Our findings suggest a strong link between senescence, EMT, and solid histology, offering valuable insight into how cancer cell senescence may promote tumor progression through particular pathways.

Systemic immune-related spleen radiomics predict progression-free survival in patients with locally advanced cervical cancer underwent definitive chemoradiotherapy.

Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity. This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters. Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001). Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity.

Microstomia is associated with functional impairment and is a poor prognostic factor in systemic sclerosis - a single center observational study with survival analysis.

Objectives were to assess the mouth opening ability (MOA) among patients with systemic sclerosis (SSc) in comparison to a healthy control population. The impact of microstomia (decrease in any of the MOA parameters) on physical performance and long-term survival was also investigated. Interincisal (ID), interlabial (LD), the intercommissural distances at both opened mouth and closed mouth (OW, CW) and the oral area (OA) and circumference (OC) all were assessed in 131 SSc patients. Microstomia was defined based on the oral aperture values of a healthy control group (n = 63) with similar median age and sex distribution. Tests evaluating functional performance were performed. Survival analysis by univariate and multivariate Cox regression analysis was performed. Microstomia was present in 56.5% of the entire SSc cohort. Patients with microstomia had higher number of contractures compared to those with preserved oral aperture parameters (median 10 vs. 7, p < 0.01). LD, OA and OC correlated negatively with the number of joint contractures, both in the entire SSc cohort and separately in the diffuse (dcSSc) and limited cutaneous subsets (lcSSc), (rho: between - 0.267 and - 0.516, p < 0.05). Reduced ID was associated with worse Health Assessment Questionnaire Disability Index (HAQ-DI) only in dcSSc while reduced LD was linked to increased HAQ-DI scores in both SSc subsets. Decreased OA upon enrollment was associated with an increased risk in mortality by multivariate Cox regression analysis (HR: 2.74; 95% CI, 1.15-6.53). Microstomia was associated with joint damage, and higher overall disability based on HAQ-DI. Interlabial distance was a beneficial, convenient measurable parameter to characterize oral aperture. Oral area was an independent poor prognostic factor regarding long-term survival.

Radiomics-based predictive model for preoperative risk classification of gastrointestinal stromal tumors using multiparametric magnetic resonance imaging: aretrospective study.

The aim of this study was to develop and assess aradiomics model utilizing multiparametric magnetic resonance imaging (MRI) for the prediction of preoperative risk assessment in gastrointestinal stromal tumors (GISTs). An analysis was performed retrospectively on agroup of 121 patients who received ahistological diagnosis of GIST. They were then divided into two sets, with85 in the training set and 36 in the validation set through random partitioning. Radiomics features from five MRI sequences, totaling 600 per patient, were extracted and subjected to feature selection utilizing arandom forest algorithm. The discriminatory efficacy of the models was evaluated through receiver operating characteristic (ROC) and precision-recall (P-R) curve analyses. Model calibration was assessed via calibration curves. Subgroup analysis was performed on GISTs with apathological maximum diameter equal to or less than 5 cm. Furtherly, Kaplan-Meier (K-M) curves and log-rank tests were used to compare the differences in survival status among different groups. Cox regression analysis was employed to identify independent prognostic factors and to construct aprognostic prediction model. The clinical model (ModelC) displayed limited predictive efficacy in the context of GIST. Conversely, aradiomics model (ModelR) incorporating five parameters exhibited robust discriminative capabilities across both the training and validation sets, yielding area under the ROC curve (AUC) values of 0.893 (95% confidence interval [CI]: 0.807-0.949) and 0.855 (95% CI: 0.732-0.978), respectively. The F1max scores derived from the P‑R curves were 0.741 and 0.842 for the training and validation sets, respectively. Noteworthy was the exclusion of the two-dimensional tumor diameter and tumor location when constructing ahybrid model (ModelCR) that amalgamated radiomics and clinical features. ModelR demonstrated asubstantially enhanced discriminative capacity in the training set compared with ModelC (p < 0.005). The net reclassification improvement (NRI) corroborated the superior performance of ModelR over ModelC, thereby enhancing diagnostic accuracy and clinical applicability. Patients in the high-risk group had significantly worse recurrence-free survival (RFS, p < 0.001) and overall survival (OS, p = 0.004), and the radiomics signature is an independent risk factor for RFS. The extended model incorporating the radiomics signature outperformed the baseline model in terms of risk assessment accuracy (p < 0.001). Our investigation underscores the value of integrating radiomics analysis in conjunction with machine learning algorithms for prognostic risk stratification in GIST, presenting promising implications for informing clinical decision-making processes as well as optimizing management strategies.

Modified Textbook Outcome was a Predictor for Early Mortality After Oral Cancer Surgery.

To explore prognostic factors for early mortality among patients undergoing surgery for oral cavity cancer (OCC) and identify valuable strategies to improve patient outcomes. A total of 397 patients treated by primary tumor resection and neck dissection between 2017 and 2021 were retrospectively analyzed. Univariate and multivariate Cox regression analysis were used to explore the relationships between the study factors and early death (within 12months). Predictors were further incorporated into a nomogram for estimation of 1-year overall survival (OS). The mean age was 57.2 (SD, 9.8)years and 92.9% patients were male. The early death rate was 12.6% overall, 35.6% in patients with pN2-3, 22.3% in patients with tumor size > 3 cm, and 36.2% in patients with lymphovascular invasion. A non-modified textbook outcome (mTO), pN2-3, tumor size > 3 cm, and lymphovascular permeation were independent prognosticators for early mortality. A nomogram with the above-mentioned four factors were created with good discrimination and calibration. Among the pN2-3 or tumor size > 3 cm subgroup, a non-mTO, cancer resource center (CRC) visits, perineural invasion, and lymphovascular permeation were independent prognostic factors for early death. In addition to traditional clinicopathological features, a non-mTO and CRC visits could serve as prognostic factors for early death in OCC. A novel nomogram had good discrimination and calibration. Quality improvements in terms of mTO and patients demanding resource support could improve survival outcomes in OCC.

Integrating 18F-FDG PET/CT radiomics and body composition for enhanced prognostic assessment in patients with esophageal cancer.

This study aimed to develop a predictive model utilizing radiomics and body composition features derived from 18F-FDG PET/CT scans to forecast progression-free survival (PFS) and overall survival (OS) outcomes in patients with esophageal squamous cell carcinoma (ESCC). We analyzed data from 91 patients who underwent baseline 18F-FDG PET/CT imaging. Radiomic features extracted from PET and CT images and subsequent radiomics scores (Rad-scores) were calculated. Body composition metrics were also quantified, including muscle and fat distribution at the L3 level from CT scans. Multiparametric survival models were constructed using Cox regression analysis, and their performance was assessed using the area under the time-dependent receiver operating characteristic (ROC) curve (AUC) and concordance index (C-index). Multivariate analysis identified Rad-scorePFS (P = 0.003), sarcopenia (P < 0.001), and visceral adipose tissue index (VATI) (P < 0.001) as independent predictors of PFS. For OS, Rad-scoreOS (P = 0.001), sarcopenia (P = 0.002), VATI (P = 0.037), stage (P = 0.042), and body mass index (BMI) (P = 0.008) were confirmed as independent prognostic factors. Integration of the Rad-score with clinical variables and body composition parameters enhanced predictive accuracy, yielding C-indices of 0.810 (95% CI: 0.737-0.884) for PFS and 0.806 (95% CI: 0.720-0.891) for OS. This study underscored the potential of combining Rad-score with clinical and body composition data to refine prognostic assessment in ESCC patients.

Development and validation of a dynamic nomogram for individualized prediction of survival in patients with colon cancer.

Current tools for predicting survival outcomes in colon cancer patients predominantly rely on clinical and pathologic characteristics. However, accumulating evidence demonstrates a significant correlation between nutritional status and patient outcomes. This study aimed to establish a new dynamic nomogram for individualized prediction of postoperative overall survival (OS). The clinicopathological and nutritional data of colon cancer patients undergoing radical resection were retrospectively collected and randomly divided into the primary and validation cohorts. Risk factors on OS rates were investigated by Cox analyses and, the nomogram was constructed using significant predictors. Among 1,024 patients, 341 deaths were observed after median follow-up of 54months. Five independent prognostic factors, including nutritional status assessments, were incorporated into the nomogram. The C-index regarding 1-, 3-, and 5-year OS were 0.830, 0.859, and 0.757 in the primary cohort and 0.843, 0.870, and 0.773 in the validation cohort, respectively. Calibration curves for the probability of OS exhibited an optimal agreement. Decision curve analyses revealed the greater application value of the nomogram than the TNM staging system. Based on the nomogram, patients could be stratified into three scenarios with significant prognostic classification (P < 0.0001). In conclusion, we developed and validated an easy-to-use dynamic nomogram for predicting postoperative OS in colon cancer patients.

Contemporary comparative surgical outcomes of type A aortic dissection in US and China: an analysis of the national inpatient sample database and a Chinese multi-institutional registry.

To investigate the contemporary comparative inpatient prognosis among US and Chinese patients with type A aortic dissection (TAAD). Data from Chinese multi-institutional TAAD registry and the US National Inpatient Sample databases were analyzed. We used multivariable logistic regression models to compare in-hospital mortality and perioperative complication rates between the US and China. Length of stay and overall costs were fitted with quantile regression models. Independent prognostic factors associated with post-operative survival were assessed via Cox proportional hazards models. Among 3,121 eligible TAAD patients, 1,073 were from China (25.0% female; mean ± SD age, 53.9 ± 12.4) and 2,048 were from the US (31.2% female; mean ± SE age, 59.8 ± 0.3). During the study period, the in-hospital mortality rates in China and the US were 15.5% and 13.3%, yet the difference was insignificant after adjustment (aOR, 1.16; 95% CI, 0.69-1.97). While there was no significant difference in overall perioperative complications (aOR, 1.07; 95% CI, 0.52-2.18), the patterns of complications differed between two cohorts. While Chinese TAAD patients experienced significantly longer duration of hospitalization (median difference, + 10.4 days; 95% CI, 9.2-11.5), the US TAAD cohort had significantly greater overall hospitalization costs (49.9; 95% CI, 55.4-44.5, in 1000 USD). Notwithstanding significant differences in demographic and clinical characteristics, TAAD patients from China and the US demonstrated comparable in-hospital mortality and overall perioperative complication rates. Future initiatives should focus on expanding surgical eligibility to the elderly Chinese TAAD patients and optimizing the duration of hospitalization without undermining meaningful clinical outcomes. KY20220425-05, April 5th 25 2022.

Prognostic impact of adipose tissue loss at 1month after surgery in patients with gastric cancer.

The postoperative impact of short-term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1month after surgery in determining postoperative survival and recurrence rates in patients with GC. We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v-ATL), and subcutaneous ATL (s-ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v-ATL and s-ATL measurements. Patients with higher v-ATL and s-ATL had lower overall survival (OS) and recurrence-free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16-4.42; and P=0.02) and RFS (HR 2.51; 95% CI 1.34-4.71; and P=0.004) rates. A reduction in adipose tissue volume shortly after surgery (1month) could potentially indicate an increased risk of recurrence and mortality in patients with GC.

Risk factors of surgical compliance and impact on survival in patients with kidney cancer: a population-based, propensity score matching study.

To identify the impact of surgical compliance on survival in patients with kidney cancer and to explore the factors that influence surgical compliance. Clinical date of kidney cancer patients were identified from the SEER databases, and the patients were divided into surgical compliance group and surgical noncompliance group. Cox survival analysis and Kaplan-Meier curves were used to evaluate the effect of surgical compliance on overall survival (OS) and cancer-specific survival (CSS). A diagnostic nomogram was constructed to quantify individual differences in compliance, and receiver operating characteristics (ROC) curves and calibration curves were used to assess the accuracy of the nomogram. Propensity score matching (PSM) was performed to balance potential baseline confounding factors. Of the 133,950 patients eligible for surgical resection, 2,814 (2.1%) patients did not opt for surgery ultimately. Surgical noncompliance was associated with poor prognosis. In all patients, Cox regression analysis showed that surgical noncompliance was an independent predictor for OS [before: HR = 2.490, 95% CI 2.374-2.612, p < 0.001; after: HR = 2.380, 95% CI 2.202-2.573, p < 0.001] and CSS [before: HR = 2.490, 95% CI 2.318-2.675, p < 0.001; after: HR = 2.035, 95% CI 1.813-2.285, p < 0.001] of kidney cancer patients before and after PSM. Multivariable logistic regression revealed that older age, afro-american origin, lower household income, and advanced tumor grade were associated with surgical noncompliance. The ROC and calibration curves showed that the diagnostic nomogram had high predictive accuracy. Surgical compliance was an independent prognostic factor for OS and CSS in patients with kidney cancer, and surgical noncompliance was associated with poor survival.

The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance. Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis. Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23-0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25-0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41-0.79, P = 0.001) were favorable prognostic factors for OS in PR patients. In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

Predicting the prognosis of Wilms tumor by peripheral blood cells: a real-world study of more than 30years.

Despite established excellent treatment strategies for Wilms tumor (WT), effective prognostic evaluation methods were lacking. This study aims to examine prognostic factors for WT through real-world peripheral blood cell profiling. Basic data and pre-treatment laboratory indices from WT and non-WT children underwent Wilcoxon test analysis. Chi-square tests assessed the correlation between blood cells and the overall survival (OS) and event-free survival (EFS) of WT. Further the Log-rank test and multivariate Cox were used to identify independent prognostic factors for OS. Traditional accepted factors were included in multi-Cox and the nomogram was constructed to further validate the outcome. Blood cells significantly differed between WT and non-WT groups (P < 0.05). Univariate analysis revealed that NLR above 1.380, stage IV, M below 0.325 × 103/μL were linked with lower OS, and PLR below 94.632, LB above 3.570 × 103/μL, stage IV, M above 0.325 × 103/μL,age ≤ 3years were meaningful for higher EFS (P < 0.05). While in the multifactorial COX, only M (HR:0.220, HR95%CI: 0.080 ~ 0.620, P = 0.004 and HR: 0.437, HR95%CI: 0.202 ~ 0.947, P = 0.036, respectively) and stage IV (HR: 7.890, HR95%CI: 1.650 ~ 37.770, P = 0.010 and HR: 3.720, HR95%CI: 1.330 ~ 10.408, P = 0.012, respectively) were independent prognostic factors for OS and EFS. These two variables also were significant after including recognized risk factors, and were demonstrated the predictability via nomogram. OS and EFS were poorer in WT children with M below 0.325 × 103/μL, suggesting the potential as a prognostic predictor for WT.

Prognostic significance and risk factors of mediastinal lymph node metastasis in esophagogastric junction cancer: a single-center, retrospective study.

Although the optimal extent of lymph node dissection in esophagogastric junction cancer (EGJC) has been reported, the efficacy of mediastinal lymph node dissection remains unclear. We aimed to identify risk factors for mediastinal lymph node metastasis and its prognostic impact in patients with EGJC. A total of 100 consecutive patients who underwent curative surgery for EGJC were eligible. We examined the rates of metastasis, prognosis, and therapeutic value index at each mediastinal lymph node station. In addition, multivariate analyses were performed to identify risk factors for mediastinal lymph node metastasis. The rates of upper, middle, and lower mediastinal lymph node metastases were 12.0%, 20.7%, and 13.2%, respectively. The 5-year overall survival rate was lower in patients with mediastinal lymph node metastasis than in those without mediastinal lymph node metastasis (11.1% vs. 59.2%, p < 0.01). The therapeutic value index was 0 in patients with upper/middle mediastinal lymph node metastasis, and mediastinal lymph node metastasis was an independent prognostic factor (hazard ratio 6.59, 95% confidence interval [CI] 2.48-17.9, p < 0.01). Additionally, the length of esophageal invasion and the presence of hiatal hernia were independent predictors of mediastinal lymph node metastasis (odds ratio 8.21, 95%CI 1.44-46.8, p = 0.02 and odds ratio 7.13, 95%CI 1.22-41.8, p = 0.03). No survival benefit of mediastinal lymph node dissection was observed. Intensive multidisciplinary treatment could be considered in patients with predicted mediastinal lymph node metastasis, such as those with longer esophageal invasion and those with hiatal hernia.

Peripheral Eosinophil Count May Be the Prognostic Factor for Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Treatment

(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and &lt;0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I–III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I–III, EOS &lt; 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS &lt; 0.1 G/l group: 5.0 months. EOS &lt; 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, p = 0.035 and HR = 1.57, p = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC.

Significance of the geriatric nutritional risk index and neutrophil-to-lymphocyte ratio as prognostic indicators in older patients with gastric cancer: a retrospective cohort study.

The number of older patients with cancer is increasing with the progression of aging societies. In the current study, we sought to clarify the prognostic values of the geriatric nutritional risk index (GNRI) as a nutritional index and the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory index in older patients with gastric cancer. Between January 2007 and December 2016, a total of 197 consecutive gastric cancer patients aged ≥ 75 years who underwent radical gastrectomy were enrolled in this study. The prognostic values of preoperative GNRI and NLR were assessed using time-dependent receiver operating characteristic curve analysis, log-rank tests, and Cox regression analysis. The areas under the curve (AUCs) predicting 5-year overall survival (OS) were 0.668 for GNRI and 0.637 for NLR. The 5-year OS rates in the groups with low GNRI and NLR were 40.1% and 74.1% (p < 0.001), and those with high GNRI and NLR were 70.7% and 41.5% (p < 0.001), respectively. Multivariate analysis showed that GNRI (hazard ratio (HR): 0.584; 95% confidence interval (CI): 0.356-0.960; p = 0.034) and NLR (HR: 2.470; 95% CI: 1.503-4.059; p < 0.001) were independent predictors for OS. The GNRI-NLR score constructed with GNRI and NLR had a higher AUC (0.698) than those of GNRI or NLR alone and was an independent prognostic factor (HR, 0.486; 95% CI: 0.363-0.651; p < 0.001). GNRI and NLR are useful prognostic biomarkers in older patients with gastric cancer aged≥75 years. The GNRI-NLR score could contribute to a more personalized and holistic approach to cancer treatment in this patient population.