Stage-specific prognostic value of molecular markers in colon cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60–00 trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4002-4002 ◽  
Author(s):  
A. D. Roth ◽  
S. Tejpar ◽  
P. Yan ◽  
R. Fiocca ◽  
D. Dietrich ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Molecular Markers ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Models ◽  
Clinical Predictors ◽  
Exon 2 ◽  
Translational Study ◽  
T Stage ◽  
N Stage

4002 Background: We compared the incidence of molecular markers in stage II (SII) and III (SIII) colon cancer and tested their prognostic value per stage, using PETACC 3, an adjuvant trial with 3,278 patients. We included expression of P53, SMAD4, thymidylate synthetase (TS) and hTERT, mutations of KRAS and BRAF, microsatellite instability (MSI) and 18qLOH. Methods: 1,564 formalin fixed paraffin embedded tissue blocks were prospectively collected and DNA from normal and tumor tissue was extracted after macrodissection. High P53, TS and hTERT expression and SMAD4 loss were assessed by immunohistochemistry. MSI was studied with 10 markers. KRAS exon 2 and BRAF exon 15 mutations were analyzed by allele specific real time PCR. 18qLOH was studied by pyrosequencing 7 SNPs. Prognostic value of the markers was analysed per stage by Cox regression for Relapse Free Survival (RFS). Results: marker frequencies and stage specific p-values in prognostic models in 420 SII and 984 SIII patients are listed in the table . Significant differences in frequency per stage were found for all markers except KRAS and BRAF. An interaction test for differences between marker prognostic value for SII and SIII was significant for MSI (p=0.04) and 18qLOH (p=0.04) in SII. Multivariate analysis including markers, T stage, N stage (for SIII), Tu grade, age <60, sex, treatment arm, and Tu site found T stage (p=0.0001) and MSI (p=0.02) as independently significant clinical predictors in SII; N stage (p<0.0001), T stage (p<0.0001), SMAD4 (p<0.0001) and P53 (p=0.01) in SIII. Conclusions: Molecular markers in colon cancer have a stage specific prognostic value. The possibility that the stages represent different diseases, rather than sequential steps in the evolution of a single disease, needs to be considered. [Table: see text] [Table: see text]

scholarly journals Exploration of a Modified Stage for pN0 Colon Cancer Patients

2021 ◽  
Author(s):  
Yunxiao Liu ◽  
Hao Zhang ◽  
Yuliuming Wang ◽  
Mingyu Zheng ◽  
Chunlin Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Validation Cohort ◽  
Predictive Accuracy ◽  
Model Fitting ◽  
Cancer Specific Survival ◽  
T Stage ◽  
N Stage ◽  
Medical University

Abstract Purpose: Exploring a modified stage (mStage) for pN0 colon cancer patients.Methods: 39637 pN0 colon cancer patients were collected from the SEER database (2010-2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011-2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software. LNE is combined with conventional T stage to form the mStage.Results: The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 10-25 and N0c: LNE < 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs 0.678, P < 0.001) and validation cohort (0.649 vs 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting.Conclusions: For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.

Prognostic value of KRAS exon 2 gene mutations in stage III colon cancer: Post hoc analyses of the PETACC8 trial.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3549-3549
Author(s):  
Julien Taïeb ◽  
Jean-François Emile ◽  
Karine Le Malicot ◽  
Aziz Zaanan ◽  
Josep Tabernero ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Value ◽  
Gene Mutations ◽  
Stage Iii ◽  
Exon 2 ◽  
Stage Iii Colon Cancer ◽  
Post Hoc ◽  
Kras Exon

scholarly journals Development and Validation of Prognostic Nomograms for Patients with Parotid Gland Adenocarcinoma Not Otherwise Specified: A SEER Analysis From 2004 To 2016

2021 ◽  
Author(s):  
Zi-Meng Wang ◽  
Zuo-Lin Xiang
Keyword(s):  
Parotid Gland ◽  
Prediction Models ◽  
Cox Regression ◽  
Clinicopathological Characteristics ◽  
Prognostic Indicators ◽  
Regression Analyses ◽  
Cancer Specific Survival ◽  
T Stage ◽  
Not Otherwise Specified ◽  
N Stage

Abstract Background Parotid gland adenocarcinoma not otherwise specified (PANOS) is a rare malignancy, and the characteristics and prognosis of this disease remain unclear. This study aims to characterize PANOS and establish prognostic prediction models for patients with PANOS. Methods Cases from 2004–2016 were retrieved from the Surveillance, Epidemiology, and End Results Program database (SEER database). Univariate and multivariate Cox regression analyses, Gray's test and propensity score matching (PSM) were conducted to analyze demographics, treatments, and survival outcomes . Results The 446 patients ( 289 men) selected for analysis had a median age of 66 (19–95) years, and 307 patients were diagnosed with stage III/IV disease. The median survival of all patients was 66 months, with a 51.8% 5-year overall survival (OS) rate. Surgical treatment clearly improved survival time (p < 0.001). In the subgroup analysis, radiotherapy showed survival benefits in patients with advanced-stage disease (III/IV) (p < 0.001). Multivariate Cox regression analyses revealed that age, T stage, N stage, M stage and surgery were independent prognostic indicators for OS;T stage, N stage, M stage and surgery were independent risk factors for cancer-specific survival(CSS).In addition, age was independently associated with noncancer-related death. Two nomograms were established based on the results of the multivariate analysis, which was validated by the concordance index (C-index) (0.747 and 0.780 for OS and CSS, respectively) and the area under the time-dependent receiver operating characteristic(ROC) curve(0.756, 0.764 and 0.819 regarding for nomograms predicting 3-, 5- and 10- year OS, respectively and 0.794, 0.789 and 0.806 for CSS, respectively). Conclusions Our study clearly presents the clinicopathological characteristics and survival analysis of patients with PANOS. In addition, our constructed nomogram prediction models may assist physicians in evaluating the individualized prognosis and deciding on treatment for patients.

scholarly journals Survival prediction in mesothelioma using a scalable Lasso regression model: instructions for use and initial performance using clinical predictors

2018 ◽  
Vol 5 (1) ◽  
pp. e000240 ◽  
Author(s):  
Andrew C Kidd ◽  
Michael McGettrick ◽  
Selina Tsim ◽  
Daniel L Halligan ◽  
Max Bylesjo ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Computational Models ◽  
White Cell Count ◽  
Performance Status ◽  
Area Under The Curve ◽  
Clinical Information ◽  
Prognostic Models ◽  
Survival Prediction ◽  
Lasso Regression ◽  
Clinical Predictors

IntroductionAccurate prognostication is difficult in malignant pleural mesothelioma (MPM). We developed a set of robust computational models to quantify the prognostic value of routinely available clinical data, which form the basis of published MPM prognostic models.MethodsData regarding 269 patients with MPM were allocated to balanced training (n=169) and validation sets (n=100). Prognostic signatures (minimal length best performing multivariate trained models) were generated by least absolute shrinkage and selection operator regression for overall survival (OS), OS <6 months and OS <12 months. OS prediction was quantified using Somers DXY statistic, which varies from 0 to 1, with increasing concordance between observed and predicted outcomes. 6-month survival and 12-month survival were described by area under the curve (AUC) scores.ResultsMedian OS was 270 (IQR 140–450) days. The primary OS model assigned high weights to four predictors: age, performance status, white cell count and serum albumin, and after cross-validation performed significantly better than would be expected by chance (mean DXY0.332 (±0.019)). However, validation set DXY was only 0.221 (0.0935–0.346), equating to a 22% improvement in survival prediction than would be expected by chance. The 6-month and 12-month OS signatures included the same four predictors, in addition to epithelioid histology plus platelets and epithelioid histology plus C-reactive protein (mean AUC 0.758 (±0.022) and 0.737 (±0.012), respectively). The <6-month OS model demonstrated 74% sensitivity and 68% specificity. The <12-month OS model demonstrated 63% sensitivity and 79% specificity. Model content and performance were generally comparable with previous studies.ConclusionsThe prognostic value of the basic clinical information contained in these, and previously published models, is fundamentally of limited value in accurately predicting MPM prognosis. The methods described are suitable for expansion using emerging predictors, including tumour genomics and volumetric staging.

scholarly journals Analysis of Clinical Characteristics and Prognosis of Patients With Stages I-III Colon Cancer Based on Seer Data

2021 ◽  
Author(s):  
Fuqiang Zhao ◽  
Ying Sun ◽  
Jie Ge ◽  
Chunlei Zheng ◽  
Kepeng Ning ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Marital Status ◽  
Tumor Grade ◽  
The United States ◽  
Related Factors ◽  
Web Based ◽  
Factors Affecting ◽  
T Stage ◽  
N Stage ◽  
The Web

Abstract Objective: This study analyzes the clinical features and prognosis of stages Ⅰ-Ⅲ colon cancer, and constructs a nomogram to predict the prognosis of patients. Methods: We included data from patients with stages Ⅰ-Ⅲ colon cancer confirmed by pathology after surgical treatment in the United States SEER (Surveillance, Epidemiology, and End Results) database from 2010-2015. The included patients are randomly divided into training cohorts and validation cohorts (ratio 1:1).The independent related factors of the prognosis of colon cancer patients were used to construct the nomogram and the web-based probability calculator.Concordance index (C-index) and calibration curve are used to evaluate the accuracy of the model. Results: After univariate and multivariate analysis, it was indicated that age, marital status, tumor grade, t-stage and n-stage were independent factors affecting prognosis of patients with stages Ⅰ-Ⅲ colon cancer. We built a nomogram and the web-based probability calculator based on this, and its C-index was 0.781 (95% CI: 0.77414–0.78786), and were superior to that of AJCC TNM Stage (C-index: 0.734, 95%CI: 0.72616–0.74184). The consistency test showed that the nomogram can effectively predict the prognosis of patients. The validation cohort confirms the reliability of the model. Conclusion: Age, marital status, tumor grade, t-stage and n-stage are independent factors affecting the prognosis of patients with stages Ⅰ-Ⅲ colon cancer. The nomogram we constructed in this way can better predict the prognosis of patients with stages Ⅰ-Ⅲ colon cancer.

scholarly journals Development and Validation of Nomograms to Predict Prognosis of Oral and Oropharyngeal Mucoepidermoid Carcinoma: A SEER-Based Study

2020 ◽  
Author(s):  
muyuan liu ◽  
Litian Tong ◽  
Manbin Xu ◽  
Xiang Xu ◽  
Bin Liang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Mucoepidermoid Carcinoma ◽  
Cox Regression ◽  
Seer Database ◽  
Disease Specific Survival ◽  
Cox Regression Analysis ◽  
T Stage ◽  
N Stage ◽  
Disease Specific

Abstract Background: Due to the low incidence of mucoepidermoid carcinoma, there lacks sufficient studies for determining optimal treatment and predicting prognosis. The purpose of this study was to develop prognostic nomograms, to predict overall survival and disease-specific survival (DSS) of oral and oropharyngeal mucoepidermoid carcinoma patients, using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Methods: Clinicopathological and follow-up data of patients diagnosed with oral and oropharyngeal mucoepidermoid carcinoma between 2004 and 2017 were collected from the SEER database. The Kaplan-Meier method with the log-rank test was employed to identify single prognostic factors. Multivariate Cox regression was utilized to identify independent prognostic factors. C-index, area under the ROC curve (AUC) and calibration curves were used to assess performance of the prognostic nomograms. Results: A total of 1230 patients with oral and oropharyngeal mucoepidermoid carcinoma were enrolled in the present study. After multivariate Cox regression analysis, age, sex, tumor subsite, T stage, N stage, M stage, grade and surgery were identified as independent prognostic factors for overall survival. T stage, N stage, M stage, grade and surgery were identified as independent prognostic factors for disease-specific survival. Nomograms were constructed to predict the overall survival and disease-specific survival based on the independent prognostic factors. The fitted nomograms possessed excellent prediction accuracy, with a C-index of 0.899 for OS prediction and 0.893 for DSS prediction. Internal validation by computing the bootstrap calibration plots, using the validation set, indicated excellent performance by the nomograms. Conclusion: The prognostic nomograms developed, based on individual clinicopathological characteristics, in the present study, accurately predicted the overall survival and disease-specific survival of patients with oral and oropharyngeal mucoepidermoid carcinoma.

Tumor site, clinicopathological characteristics, and survival of patients undergoing primary elective colorectal cancer resection.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 585-585
Author(s):  
James Hugh Park ◽  
Joanne Edwards ◽  
Campbell S.D. Roxburgh ◽  
Donald C. Mcmillan ◽  
Paul G. Horgan
Keyword(s):  
Colorectal Cancer ◽  
Splenic Flexure ◽  
Prognostic Value ◽  
Venous Invasion ◽  
Clinicopathological Characteristics ◽  
Advanced Age ◽  
Tumor Site ◽  
Margin Involvement ◽  
T Stage ◽  
N Stage

585 Background: Cancers arising in the proximal and distal colorectum differ in embryological origin, predisposing genetic and epigenetic mutations, clinicopathological characteristics and survival. However, the effect of tumor site on the prognostic value of clinicopathological characteristics and systemic inflammatory responses (SIR) is not known. The present study aims to examine the relationship between tumor site, clinicopathological characteristics and cancer-specific survival (CSS) in patients undergoing elective colorectal cancer (CRC) resection. Methods: Patients who had undergone elective, primary resection of stage I-III CRC (1997-2013) were included. Tumors were categorized as proximal (cecum to splenic flexure) or distal (splenic flexure to rectum) based on pathological reports. SIR was assessed using modified Glasgow Prognostic Score (mGPS; 0-CRP < 10mg/L, 1-CRP > 10mg/L, 2-CRP > 10mg/L and albumin < 35g/L). Results: 796 patients were included; 302 tumors were proximal and 494 were distal to the splenic flexure. Proximal location was associated with advanced age, T stage, poor differentiation, greater lymph node yield, peritoneal involvement and an increased mGPS (all P< 0.01). In all patients, on multivariate survival analysis, distal tumor site, advanced age, T stage, N stage, venous invasion, margin involvement and mGPS were independently associated with reduced CSS (all P< 0.05). In patients with proximal cancer, only age (HR 1.8, P= 0.001), T stage (HR 1.9, P= 0.009), N stage (HR 1.9, P< 0.001) and mGPS (HR 1.6, P= 0.004) were associated with CSS, whereas in patients with distal CRC, T stage (HR 1.4, P= 0.024), N stage (HR 1.5, P= 0.001), venous invasion (HR 1.5, P= 0.038), margin involvement (HR 4.1, P< 0.001) and mGPS (HR 1.5, P= 0.003) were associated with survival. Conclusions: In the present study, tumor site was associated with distinct clinicopathological characteristics. Furthermore, the prognostic value of pathological characteristics currently employed in tumor staging, such as venous invasion and margin involvement, differed with tumor site, whereas evaluation of the SIR was similarly prognostic in patients with proximal and distal CRC.

scholarly journals Systemic Inflammatory Response Syndrome in Patients Hospitalized for Acute Decompensation of Cirrhosis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Ariane Borgonovo ◽  
Caroline Baldin ◽  
Dariana C. Maggi ◽  
Livia Victor ◽  
Emilia T. O. Bansho ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Prognostic Value ◽  
Cox Regression ◽  
Beta Blockers ◽  
Univariate Analysis ◽  
Systemic Inflammatory Response ◽  
Prognostic Models ◽  
Cox Regression Analysis ◽  
Acute Decompensation

Background. Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results. SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan–Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions. SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

Validation of two gene-expression risk scores in a large colon cancer cohort and contribution to an improved prognostic method.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3509-3509 ◽  
Author(s):  
Arnaud Roth ◽  
Antonio Fabio Di Narzo ◽  
Sabine Tejpar ◽  
Fred Bosman ◽  
Vlad Calin Popovici ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cox Regression ◽  
Tnm Staging ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Models ◽  
Risk Scores ◽  
P Value ◽  
Prognostic Information

3509 Background: Prognosis prediction for resected primary colon cancer is currently based on the tumor, nodes, metastasis (TNM) staging system. Gene expression based risk scores have been proposed, but need to be validated and integrated with clinical and TNM variables. We performed an independent assessment of the individual recurrence signatures developed for commercial use by Veridex and Genomic Health. Methods: The Veridex (aVDS) and Genomic Health (aGHS) risk scores were applied to existing gene expression data of 580 stage III and 108 stage II tumors from the PETACC-3 trial. Association of the scores with relapse-free (RFS) and overall survival (OS) of the patients was assessed singularly, and in a combination with TNM and other clinico-pathological variables, by univariate and multivariate Cox regression models and logrank methods. Results: Both risk scores were significantly associated with RFS in univariate and multivariate models (Table) for the stage III cohort. The scores contributed different and additive prognostic information, and reached highest effect sizes (approximate p-value 0.001 and HR per interquartile range 1.4 each) in a combined model (Table) that includes both scores as well as T-stage, N-stage and MSI status as significant factors. Analysis in the stage II cohort gave similar effect estimates. Conclusions: This study confirms in an independent colon cancer patient cohort that gene expression based risk scores improve current prognostic models. The best prognostic model was obtained by using clinico-pathological variables and both gene-expression risk-scores. [Table: see text]

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