Variables For Overall Survival Research Articles

The Long-Term Prognostic Outcomes of Emergent Colon Cancer Surgery: A Single-Center Experience.

Colorectal cancer (CRC) ranks as the second most diagnosed and third most deadly cancer worldwide. Despite advances in early diagnosis and treatment, CRC remains a leading cause of cancer-related deaths. Up to 30% of CRC patients are diagnosed during emergency department visits, leading to surgical procedures that may not adhere to oncological principles due to complications like obstruction, bleeding, or perforation. This study aims to compare postoperative complications and long-term oncological outcomes between emergent and elective colon cancer surgeries. Retrospective analysis was performed on patients who underwent surgery for colonic adenocarcinoma from January 2018 to December 2021. Patients included were those diagnosed with colonic adenocarcinoma, excluding those under 18 years old or with other pathological results. Patients were examined under the elective and emergent surgery groups. The study investigated demographic data, tumor localization, operation type, postoperative complications, and long-term oncological outcomes. A Cox proportional hazard model was used to perform multivariate analysis in order to identify prognostic variables for overall survival (OS) and disease-free survival (DFS). A total of 318 patients were included, with 62 undergoing emergent surgery and 256 undergoing elective surgery. Patient demographics were similar between the groups. The emergent surgery group had a significantly lower OS rate at 50 months compared to the elective surgery group (51% vs. 62%, p = 0.002). DFS at 50 months was also lower for the emergent surgery group compared to the elective surgery group (43% vs. 59%), but this difference did not reach statistical significance (p = 0.202). Independent poor prognostic factors included stage N, stage M, tumor diameter, neural invasion, and emergent surgery status. Emergency surgery for colon cancer is associated with poor long-term outcomes due to shorter OS and DFS, highlighting the need for increased awareness and screening to reduce emergency colon cancer surgery.

Treatment patterns and clinical outcomes of resectable central non-small cell lung cancer patients undergoing sleeve lobectomy: a large-scale, single-center, real-world study.

In the treatment of central-type non-small cell lung cancer (NSCLC), sleeve lobectomy (SL) has emerged as the surgical treatment of choice over pneumonectomy (PN). This retrospective study evaluates the clinical profiles and prognostic elements impacting survival and recurrence rates in patients who underwent SL. We retrospectively analyzed 288 patients who underwent SL from January 2010 to December 2023. Survival analysis was performed using the Kaplan-Meier method, and survival curves were subsequently drawn. Factors predicting SL outcomes were investigated through univariate and multivariable Cox regression analyses. Univariate and multivariable analyses consistently demonstrated significant variations in overall survival (OS) and disease-free survival (DFS) among subgroups receiving neoadjuvant therapy (NT), which also stood out as independent prognostic factors. Patients undergoing NT showed enhanced OS [hazard ratio (HR) =0.4652, 95% confidence interval (CI): 0.3042-0.7116, P=0.004] and DFS (HR =0.5182, 95% CI: 0.3243-0.8279, P=0.01). Earlier pT stages were associated with better prognosis (P<0.05). Significant differences in both OS and DFS were noted across pN stages, with earlier stages indicating improved prognosis; this was a significant independent factor for DFS (P<0.001). Similar significant trends were observed across pathological Tumor-Node-Metastasis (pTNM) stages, with earlier stages linked to better outcomes. Additionally, body mass index (BMI) was identified as an independent prognostic factor for both OS and DFS. Clinical T stage independently influenced DFS. No significant prognostic disparities were observed in other clinical characteristics (P>0.05). NT significantly improves the prognosis for NSCLC patients undergoing SL. Pathological staging is proven to be more indicative of prognosis than clinical staging. Understanding the staging of lymph nodes (LNs) is crucial for predicting the long-term recurrence risk in patients with NSCLC who undergo SL treatment. Mediastinal and hilar LN dissection is especially important in minimizing this risk and improving prognosis.

Prognostic signature based on S100 calcium-binding protein family members for lung adenocarcinoma and its clinical significance

The S100 family proteins (S100s) participate in multiple stages of tumorigenesis and are considered to have potential value as biomarkers for detecting and predicting various cancers. But the role of S100s in lung adenocarcinoma (LUAD) prognosis is elusive. Transcriptional data of LUAD patients were retrieved from TCGA, and relevant literature was extensively reviewed to collect S100 genes. Differential gene expression analysis was performed on the LUAD data, followed by intersection analysis between the differentially expressed genes (DEGs) and S100 genes. Unsupervised consensus clustering analysis identified two clusters. Significant variations in overall survival between the two clusters were shown by Kaplan-Meier analysis. DEGs between the two clusters were analyzed using Lasso regression and univariate/multivariate Cox regression analysis, leading to construction of an 11-gene prognostic signature. The signature exhibited stable and accurate predictive capability in TCGA and GEO datasets. Subsequently, we observed distinct immune cell infiltration, immunotherapy response, and tumor mutation characteristics in high and low-risk groups. Finally, small molecular compounds targeting prognostic genes were screened using CellMiner database, and molecular docking confirmed the binding of AMG-176, Estramustine, and TAK-632 with prognostic genes. In conclusion, we generated a prognostic signature with robust and reliable predictive ability, which may provide guidance for prognosis and treatment of LUAD.

Analysis of prognostic factors and construction of prognostic models for invasive lobular carcinoma of the breast.

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling.

IL-17 expression and prognosis of laryngeal squamous cell carcinoma.

Objective: To investigate the roles of proinflammatory cytokine IL-17 in the prognosis of laryngeal squamous cell carcinoma (LSCC). Methods: In all, 67 LSCC patients were enrolled to evaluate the expression of IL-17, IL-23, CD8, CD31, and vascular endothelial growth factor by immunohistochemical staining. Cumulative survival time was determined by the Kaplan-Meier approach, and prognostic variables for overall survival (OS) were identified by Cox proportional-hazards models. Results: The expression of IL-17 and IL-23 was remarkably higher in LSCC tissue than in adjacent normal (AN) tissue (P < .001). The Kaplan-Meier analysis indicated that patients with cervical lymph node metastasis (CLNM), advanced tumor node metastasis (TNM) stage, poor-differentiated grade, high microvessel density (MVD) in LSCC tissues, and high IL-17 expression in AN tissues had poorer OS (all P < .05). Cox regression analysis revealed that CLNM (HR = 7.246; 95% CI: 2.598-20.208; P < .001), high MVD in tumor tissues (HR = 4.233; 95% CI: 1.482-12.092; P = .007), and low CD8 expression in AN tissues (HR = 3.996; 95% CI: 1.442-11.074; P = .008) were significantly associated with poorer OS in LSCC, while IL-17 expression in AN tissue was not. Conclusion: High IL-17 expression in AN tissues could indicate poor prognosis and may be a prognostic marker for LSCC. Low CD8 expression in AN tissues may represent poor frontline antitumor immunity and be associated with poor prognosis.

Surgical-decision making in the setting of unsuspected N2 disease: a cost-effectiveness analysis.

Identification of unsuspected nodal metastasis may occur at the time of operation for a stage I non-small cell lung cancer. Guidelines for this scenario are unclear. Our goal was to assess the cost-effectiveness of aborting the operation in an attempt to first provide neoadjuvant systemic therapy compared with upfront resection. A computer simulation Markov model with a lifetime horizon was constructed to compare the costs and clinical outcomes, as measured by quality-adjusted life-years (QALYs), of upfront resection at the time of identification of unsuspected N2 mediastinal disease vs. aborting initial resection and continuing with neoadjuvant therapy prior to resection. Input parameters for the model were derived from published literature with costs measured from the healthcare perspective. The incremental cost-effectiveness ratio (ICER) was evaluated with a willingness-to-pay (WTP) threshold of $150,000/QALY. Both deterministic (one-, two-, and three-way) and probabilistic sensitivity analysis (PSA) were performed to assess the impact of variation in input parameter values on model results. Aborting initial resection in favor of neoadjuvant therapy resulted in both higher costs ($40,415 vs. $29,873) and more QALYs (3.95 vs. 2.84) relative to upfront resection, yielding an ICER of $9,526/QALY. While variation in overall survival had a significant impact on the ICER, perioperative variables did not. As the annual mortality of best-case therapy in the abort group increased from a base-case estimate of 11% to 15%, the ICER exceeded the WTP threshold of $150,000/QALY. Subsequent one- and two-way sensitivity analyses did not find substantially alter the overall results. PSA resulted in aborting resection to be cost-effective in 99.7% of samples, with 13% of samples dominating upfront resection. Treatment of stage IIIa lung cancer requires the input of a multidisciplinary team who must consider cost, quality of life, and overall survival. As new treatments are developed, further analyses should be performed to determine optimal therapy.

Prognostic value of coagulation markers in patients with colorectal caner: A prospective study.

The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d-dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan-Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single-factor and multifactor cox regression analysis model. The following indicators (TM, TAT, PIC, t-PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination "TAT + PIC + DD + FDP + Fbg" can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.

Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model. Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets. Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets. Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.

Prognostic value of immune-inflammatory and nutrition indicators in non-metastatic nasopharyngeal carcinoma with negative plasma Epstein-Barr virus DNA.

Plasma Epstein-Barr virus (EBV) DNA has been identified as a significant prognostic marker for nasopharyngeal carcinoma (NPC), yet there is limited research on the prognosis of NPC patients with negative EBV DNA. We explore the prognostic value of comprehensive immune-inflammatory and nutritional indicators to offer personalized treatment recommendations and prognosis predictions for non-metastatic NPC patients with negative EBV DNA. This was a retrospective study. This study retrospectively analyzed 257 non-metastatic NPC patients with negative EBV DNA between January 2015 and December 2019. The Kaplan-Meier survival curves evaluated survival endpoints, and group discrepancies were assessed with log-rank tests. Principal component analysis (PCA) reduced data dimensionality. Univariate and multivariate Cox regression analyses identified significant prognostic variables. Risk stratification was performed based on recursive partitioning analysis (RPA). A robust prognostic model was constructed by nomogram and evaluated by calibration curves, decision curves, and the time-dependent area under the curve analysis. PCA was employed to compute the immune-inflammation index (III) and nutrition index (NI). Multivariate Cox regression analysis revealed lactate dehydrogenase, III, and NI as significant prognostic variables for overall survival (OS). Utilizing RPA, we stratified the risk into three categories: low-risk group (low III + high NI), middle-risk group (low III + low NI), and high-risk group (high III). Both the middle- (p = 0.025) and high-risk groups (p < 0.001) exhibited poorer OS compared with the low-risk group. The nomogram model exhibited superior predictive accuracy compared to tumor lymph node metastasis stage alone (C-index: 0.774 vs 0.679). Our study validated the prognostic significance of III and NI in non-metastatic NPC patients with negative EBV DNA. Additionally, a clinical risk stratification was constructed to offer valuable insights into the individualized treatment of these patients.

A review of the role of liver resection in the treatment of human immuno-deficiency virus-positive patients with hepatocellular carcinoma

Patients with human immune-deficiency virus (HIV) have increased risk of developing hepatocellular carcinoma (HCC); this neoplasm apparently behaves more aggressively in this population, leading to worse outcomes. Questions remain regarding the best treatment of HCC in these patients, mainly related to the role of surgical resection. Some studies show that, after transplantation, this group of patients has an overall survival rate comparable to that of uninfected patients. This integrative review assesses and summarize the survival outcome of resection in the treatment of HIV-positive patients with HCC. Integrative review of articles published in English, in PubMed and Scielo databases until October 2021, using the terms: HIV, HCC, and resection. Four publications were analyzed in relation to their content and relevance to the research question. We identified 54 patients who underwent surgical resection, with great variability in overall survival between studies (median between 18 and 72 months); only one study demonstrated disease-free survival. There was also great variability in morbidity and mortality rates after the procedure. All studies were non-comparable. Data regarding the impact of surgical resection on survival in HIV-positive patients with HCC are scarce, and questions remain about the best treatment options with curative intent. Further studies on the topic are needed, given the practical implications for decision-making. Therefore, we suggest that the treatment of these patients should still be conducted similarly to that indicated by the main guidelines on the treatment of patients with HCC, without distinction to HIV serology.

Development and validation of a prognostic model for esophageal cancer patients with liver metastasis: a cohort study based on surveillance, epidemiology, and end results database.

Our objective is to examine the independent prognostic risk factors for patients with Esophageal Cancer with Liver Metastasis (ECLM) and to develop a predictive model. In this study, clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was employed to identify independent prognostic factors and construct nomograms based on the results of multivariate regression. The predictive performance of the nomograms was assessed using several methods, including the consistency index (C-index), calibration curve, time-dependent receiver-operating characteristic curve (ROC), and decision curve analysis (DCA). Additionally, Kaplan-Meier survival curves were generated to demonstrate the variation in overall survival between groups. A total of 1163 ECLM patients were included in the study. Multivariate Cox analysis revealed that age, tumor differentiation grade, bone metastasis, therapy, and income were independently associated with overall survival (OS) in the training set. Subsequently, a prognostic nomogram was constructed based on these independent predictors. The C-index values were 0.739 and 0.715 in the training and validation sets, respectively. The area under the curve (AUC) values at 0.5, 1, and 2years were all higher than 0.700. Calibration curves indicated that the nomogram accurately predicted OS. Decision curve analysis (DCA) showed moderately positive net benefits. Kaplan-Meier survival curves demonstrated significant differences in survival between high- and low-risk groups, which were divided based on the nomogram risk score. The nomogram we developed for ECLM patients has demonstrated good predictive capability, allowing clinicians to accurately evaluate patient prognosis and identify those at high risk, thereby facilitating the development of personalized treatment plans.

Monocyte-to-lymphocyte ratio as a determinant of survival in patients with gastric cancer undergoing gastrectomy: A cohort study.

The monocyte-to-lymphocyte ratio (MLR) is an important prognostic determinant of various malignancies. However, the prognostic role of MLR in patients with gastric cancer undergoing gastrectomy remains unclear. Patients with stage I to III gastric cancer who underwent curative-intent gastric resection were enrolled in this study. Cox regression analysis was used to determine the independent variables for overall survival (OS) and disease-free survival (DFS). The established models were validated internally. Inter-model comparisons were performed using the integrated area under the receiver operating characteristic curve and the concordance index. Multivariate Cox regression analysis revealed that age, tumor-node-metastasis (TNM) stage, perineural invasion, serum albumin level, and MLR were prognostic factors for OS and DFS and constituted the full model. The full model was internally validated using calibration curves and decision curve analysis. The integrated area under the curve and concordance index of the full model outperformed those of TNM stage. The full model was a significant determinant of OS and DFS. Additionally, the full model was suggested to outperform TNM stage in predicting patient survival outcomes.

EGFR is a potential therapeutic target for highly glycosylated and aggressive pancreatic neuroendocrine neoplasms.

pNENs are relative indolent tumors with heterogeneous clinical presentation at diagnosis. It is important to establish aggressive subgroups of pNENs and identify potential therapeutic targets. Patients with pNEN (322 cases) were included to examine the association between glycosylation biomarkers and clinical/pathological traits. The molecular and metabolic features stratified by glycosylation status were assessed by RNA-seq/whole exome sequencing and immunohistochemistry. A considerable proportion of patients had elevated glycosylation biomarkers (carbohydrate antigen [CA] 19-9, 11.9%; CA125, 7.5%; carcinoembryonic antigen [CEA], 12.8%). CA19-9 (hazard ratio [HR]=2.26, P=.019), CA125 (HR=3.79, P=.004) and CEA (HR=3.16, P=.002) were each independent prognostic variables for overall survival. High glycosylation group, defined as pNENs with elevated level of circulating CA19-9, CA125 or CEA, accounted for 23.4% of all pNENs. High glycosylation (HR=3.14, P=.001) was an independent prognostic variable for overall survival and correlated with G3 grade (P < .001), poor differentiation (P=.001), perineural invasion (P=.004) and distant metastasis (P < .001). Epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival (P=.020). A clinical trial focusing on EGFR expressed pNENs was initiated (NCT05316480). Thus, pNEN with aberrant glycosylation correlates with a dismal outcome and suggests potential therapeutic target of EGFR.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma

Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. To create an effective survival nomogram for patients with primary gastric GML. All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

Proposed prognostic subgroups and facilitated clinical decision-making for additional locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a retrospective study based on recursive partitioning analysis

BackgroundThe high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups.MethodsThe study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables.ResultsAfter pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein–Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort.ConclusionsThe novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.

Post-weaning survival in kangaroos is high and constant until senescence: Implications for population dynamics.

Large herbivores typically have consistently high prime-aged adult survival and lower, more variable, juvenile, and senescent survival. Many kangaroo populations undergo greater fluctuations in density compared with other large herbivores, but age- and sex-specific survival of kangaroos and their response to environmental variation remain poorly estimated. We used long-term capture-mark-recapture data on 920 individuals to investigate the survival component of eastern grey kangaroo (Macropus giganteus) population dynamics. Forage availability and population density were monitored quarterly and included as predictors of survival in Bayesian Cormack-Jolly-Seber models. Annual survival probabilities were estimated for five age classes: 0 years (juveniles), 1-2 years (subadults), 3-6 years (prime-aged adults), 7-9 years (presenescent adults), and ≥10 years (senescent adults). Survival of juveniles varied widely during our 12-year study, ranging from 0.07 to 0.90 for females and 0.05-0.92 for males. Subadult survival was 0.80-0.93 for females and 0.75-0.85 for males, while that of prime-aged adults was ≥0.94 for females and ≥0.83 for males, despite large fluctuations in forage and density. The survival of presenescent adults spanned 0.86-0.93 for females and 0.60-0.86 for males. Senescent survival was variable, at 0.49-0.90 for females and 0.49-0.80 for males. Male survival was significantly lower than female survival in prime-aged and presenescent adults, but not in other age classes. Although most of the models supported by Watanabe-Akaike Information Criterion selection included at least one environmental covariate, none of these covariates individually had a discernible effect on survival. Temporal variability in overall survival appeared mostly due to changes in the survival of juvenile and senescent kangaroos. Kangaroo survival patterns are similar to those of ungulates, suggesting a strong role of sex-age structure on population dynamics.

Development of a novel transcription factor signature for accurate cervical cancer prognosis

Cervical cancer (CC) is a leading cause of cancer-related deaths in women. During tumor development, transcriptional factors regulate the transcription of proto-oncogenes and tumor suppressor genes. We examined the possibility of using transcription factors as prognostic biomarkers for patients with cervical cancer. Single-cell RNA-sequencing data were downloaded from the Gene Expression Omnibus database to identify specific activated transcription factors in different types of cells from CC. Publicly available bulk RNA-sequencing and clinical data of CC were obtained to identify associated prognostic transcription factors using survival analysis and the random survival forest methods. Accuracy and effectiveness of the established transcription factor-related predictive random survival forest model were verified using training and test datasets. We identified specific activated transcription factors in tissue cells of cervical cancer. A 3-transcription factors (PBX4 (PBX Homeobox 4), EBF2 (EBF Transcription Factor 2) and ZNF696 (Zinc Finger Protein 696)) prognostic signature for patients with cervical cancer was constructed showing good survival prediction. Gene function enrichment analysis indicated a correlation between the prognostic characteristics and different signaling pathways associated with cancer. Using the random survival forest model based on the 3-transcription factor signature, patients with cervical cancer were stratified into low- and high-risk groups with significant variations in overall survival (p &lt; 0.001). The area under the curve of the time-dependent receiver operator characteristic revealed a strong predictive accuracy for training and test datasets of the corresponding signature. CC has cellular heterogeneity of transcriptional activation. Our analyses provide a novel transcription factor-associated prognostic model for CC. These transcription factors could be used as effective prognostic biomarkers and potential therapeutic targets for patients with cervical cancer.

Regression Derived Staging Model to Predict Overall and Disease Specific Survival in Patients With Major Salivary Gland Carcinomas With Independent External Validation.

PURPOSEThe current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally.MATERIALS AND METHODSFrom SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into “Low Aggression” and “High aggression” groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019.RESULTSSix thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients.CONCLUSIONWe propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.

Evaluation of Prognostic Factors and Trastuzumab-based Treatments in HER2/Neu-positive Metastatic Gastric Cancer.

To determine the efficacy of trastuzumab-based treatment in patients with HER2/neu-positive metastatic gastric cancer. Observational study. Department of Medical Oncology, Istanbul University, Institute of Oncology, Istanbul, Turkey, between January 2014 and December 2020. The clinicopathological characteristic and treatment data of patients with HER2/neu-positive metastatic gastric cancer were recorded retrospectively. Kaplan-Meier analysis was performed to compare the chemotherapy regimens. Sixty-three patients were included in the study. The average age was 61. Female patients accounted for 27% of the total, while male patients accounted for 73%. De novo metastatic cases accounted for 44 (69.8%) of the total number of patients. The median survival time was 13.6 (8-19.3) months. Complete response was 6.3%, partial response was 39.7%, and the stable response was 9.5% with trastuzumab-based chemotherapy. The overall survival (p= 0.45) and progression-free survival (p=0.893) were similar for different chemotherapy regimens. The grade 1-2 to grade 3-4 toxicity ratio was 79.6% and 20.6%, respectively. The patients' performance (p<0.001) and the number of metastatic sites (p=0.001) were both shown to be unfavourable predictive variables for OS in multivariate analysis. The addition of taxane to trastuzumab-based combinations (with platinum and fluoropyrimidine) did not affect overall and progression-free survival in this research. Three or more metastatic sites and poor performance status were found as the unfavourable prognostic variables for overall survival. Gastric cancer, Trastuzumab, Chemotherapy, Prognostic factors.

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0–2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.