scholarly journals A Comparative Study of Cox Regression vs. Log-Logistic Regression (with and without its frailty) in Estimating Survival Time of Patients with Colorectal Cancer

2017 ◽  
Vol 6 (1) ◽  
pp. 35-43
Author(s):  
A.H. Hashemian ◽  
M. Garshasbi ◽  
M.A. Pourhoseingholi ◽  
S. Eskandari
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Logistic Model ◽  
Cox Regression ◽  
Cox Model ◽  
Logistic Models ◽  
Individual Characteristics ◽  
Parametric Models ◽  
Biomedical Sciences ◽  
Non Parametric

Colorectal cancer is common and lethal disease with different incidence rate in different parts of the world which is taken into account as the third cause of cancer-related deaths. In the present study, using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of patients with colorectal cancer were evaluated and the models efficiency were compared to provide the best model. This study is conducted on medical records of 1,127 patients with colorectal cancer referred to Taleghani Medical and Training Center of Tehran between 2001 - 2007 and were definitely diagnosed with cancer, pathologically. Semi-parametric Cox model and parametric log-logistic model were fitted. Akaike’s criterion of Cox Snell graph was used to compare the models. To take into account non-measured individual characteristics, frailty was added to Cox and log-logistic models. All calculations were carried out using STATA software version 12 and SPSS version 20.0, at the 0.05 level of significance. From a total of 1,127 patients studied in this research, there were 690 men and 437 women. According to non-parametric Kaplan-Meier method, chances of surviving for 1, 3, 5 and 7 years were 91.16, 73.20, 61.00, and 54.94, respectively. Addition of frailty parameter did not change the model outcome. The results of fitting classified Cox and log-logistic models showed that body mass index (BMI), tumor grade, tumor size, and spread to lymph nodes, were the factors affecting survival time. Based on comparisons, and according to Cox Snell residuals, Cox and log-logistic models had almost identical results; however, because of the benefits of parametric models, in surveying survival time of patients with colorectal cancer, log-logistic can be replaced, as a parametric model, with Cox model.Journal of Medical and Biomedical Sciences (2017) 6(1), 35-43Keywords: Colorectal cancer, Cox regression, Log-logistic model, Cox Snell residual

scholarly journals HHLA2 and NEBL as novel prognostic biomarkers based on Rayleigh survival model in colorectal cancer

2021 ◽  
Author(s):  
Altaf Khan ◽  
Mohammed Azhar Aziz ◽  
Ghada T Alatar ◽  
Amal AlGhamdi ◽  
Mohammed A Hussein ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Cox Model ◽  
Parametric Models ◽  
Prognostic Biomarkers ◽  
Survival Models ◽  
Diagnostic Tools ◽  
Brier Score ◽  
Small Subset ◽  
Parametric Survival

Abstract Background The primary focus for this study was investigation of prognostic biomarkers in colorectal cancer (CRC), since biomarkers are instrumental in clinical decision making and patient management as well as playing pivotal roles in precision medicine.Methods We analyzed indigenous dataset from colorectal cancer patients. Exon microarray dataset was used and 135 genes were identified as novel candidate biomarkers. 135 genes were further split into two groups: low and high gene expression values via ’maxstat’ algorithm, they were analyzed using Kaplan-Meier (K-M) analysis and univariate Cox model, and a set of 33 genes were identified as statistically significant (p¡0.05). Furthermore, using the ’VARCLUS’ algorithms (a SAS software procedure) which is a useful tool for variable reduction, based on the divisive clustering techniques, a small subset of 5 genes were selected out of 33 significant genes as potential candidates to build survival models. Both parametric and semi-parametric survival models were utilized to assess whether these 5 genes could be used as prognostic biomarkers.Results HHLA2 (p < 0.01) and NEBL (p < 0.01) genes emerged as potential biomarkers, based on the para- and semi-parametric models such as: Rayleigh, Exponential probability distributions, and Cox models and were also validated on independent datasets, apart from validation with qPCR test as well as with the cell lines patients data in the laboratory. A rigorous statistical evaluation for model’s performance were done via Harrell’s index, Brier score, Shoenfeld residual plots as well as with comparing several predictive model plots. We also made the comparison of Akaike and Bayesian Information(AIC and BIC) criteria as well as log-likelihood estimates. The Tukey-Anscome plot and Quantile-Quantile plot as diagnostic tools were applied to validate the parametric survival models. Conclusion Based on predictive models HHLA2 and NEBL novel biomarkers were found as statically significant.

scholarly journals An alternative method for assessing the equivalence among treatments in survival analysis

2013 ◽  
Vol 43 (9) ◽  
pp. 1553-1560
Author(s):  
Luiz Alexandre Peternelli ◽  
Flávia Sílvia Corrêa Tomaz ◽  
Diego Paiva Bernardes ◽  
Gilson Fernandes da Silva ◽  
Fabricia Gonçalves Lacerda
Keyword(s):  
Cluster Analysis ◽  
Logistic Model ◽  
Logistic Models ◽  
Parametric Models ◽  
Survival Curves ◽  
Multivariate Technique ◽  
Kaplan Meier ◽  
Log Normal ◽  
Adjusted Model ◽  
Nonparametric Procedure

This work aims to evaluate the use of parametric models instead of a nonparametric procedure to adjust survival curves related to different treatments, and to verify the equivalence among treatments by the multivariate method of cluster analysis. The dataset used to validate the method was obtained from a laboratory experiment with cutting ants. Eight colonies of cutting ants were used, each one receiving different treatments. The exponential, Weibull, log-normal, and logistic models were adjusted for each treatment, along with the usual Kaplan-Meier adjustment. The logistic model used was the best option for evaluating the survival of the ants. Therefore, this model was adjusted for each treatment. The estimates of the parameters of each adjusted model were clustered using Ward's method of multivariate technique of cluster analysis. Finally, heuristic techniques for choosing the number of clusters were applied in order to define the sets of equivalent treatments. For the dataset used, the proposed method was less laborious and as efficient as the logrank for the comparison of many survival curves.

scholarly journals A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaochen Chen ◽  
Huafeng Qiu ◽  
Yunwang Chen ◽  
Mingxing Wang ◽  
Pengfei Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Treatment Group ◽  
Metastatic Colorectal Cancer ◽  
Standard Treatment ◽  
Cox Regression ◽  
Cox Model ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Single Agent

BackgroundsAs a new oral chemotherapy drug, TAS-102 is currently recommended as the third-line treatment for metastatic colorectal cancer (mCRC). Recently, studies have reported the efficacy of TAS-102 combined with bevacizumab in colon cancer patients after standard treatment fails. Here, we evaluated the efficacy and safety of TAS-102 combined with bevacizumab versus TAS-102 as a single agent by a systematic review and a meta-analysis.MethodsPubMed, Web of Science and Cochrane libraries were searched. Studies involving bevacizumab combined with TAS-102 in mCRC were included. Study characteristics (author, year of publication, country et al.), efficacy (disease control rate(DCR), progression-free survival(PFS), overall survival(OS)) and adverse effects were extract from studies. Forest plots were created based on Cox model analysis.ResultsAfter screening 550 studies, a total of 3 studies were included, which compared the safety and effectiveness of TAS-102 with or without bevacizumab. Analysis based on Cox regression showed that the combined treatment group had advantages in 6-month (OR= 2.93, 95% CI: 1.72 to 5.00, P&lt;0.0001), 12-month(OR= 2.18, 95% CI: 1.24 to 3.81, P=0.006), and 18-month (OR=3.08, 95% CI: 1.34 to 7.12, P=0.008) OS. The combined treatment group demonstrated superiority in 6-month PFS rates (OR= 2.50, 95% CI: 1.18 to 5.31, P=0.02). The incidence of thrombocytopenia in the dual-drug treatment group was higher (OR= 1.96, 95% CI: 1.14 to 3.36 P=0.01). The proportion of serious adverse events were similar in tow groups (OR= 1.01, 95% CI: 0.76 to 1.34 P=0.93).ConclusionBevacizumab combined with TAS-102 could improve the prognosis of patients with mCRC who have failed standard treatment. In terms of side effects, the addition of bevacizumab did not increase serious adverse reactions, but the occurrence of thrombocytopenia was worth noting.

scholarly journals Microvascular density assessed by CD31 predicts clinical benefit upon bevacizumab treatment in metastatic colorectal cancer: results of the PassionATE study, a translational prospective Phase II study of capecitabine and irinotecan plus bevacizumab followed by capecitabine and oxaliplatin plus bevacizumab or the reverse sequence in patients in mCRC

2020 ◽  
Vol 12 ◽  
pp. 175883592092863
Author(s):  
Daniela Bianconi ◽  
Merima Herac ◽  
Florian Posch ◽  
Margit Schmeidl ◽  
Matthias Unseld ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Microvessel Density ◽  
Cox Regression ◽  
Cox Model ◽  
Predictive Biomarkers ◽  
Prognostic Impact ◽  
Bevacizumab Treatment ◽  
Reverse Sequence

Background: Targeted therapies offer novel opportunities to explore biomarkers based on their mode of action. Taking this into consideration, we evaluated six angiogenesis-related proteins as potential predictive biomarkers, which expression might predict the benefit of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). Methods: This was a phase II multicenter, two-armed, randomized study, in which patients with mCRC were treated with XELIRI (capecitabine and irinotecan) plus bevacizumab followed by XELOX (capecitabine and oxaliplatin) plus bevacizumab (Arm A) or the reverse sequence (Arm B). Tissue expression level of six prespecified candidates [microvessel density assessed by CD31, PTEN, αV integrin, CD98hc, uPAR and NRP-1] was analyzed via immunohistochemistry. The prognostic impact on survival was quantified using the Cox regression model. The predictive potential for benefit from Arm A versus Arm B treatment was investigated by fitting an interaction between the biomarkers and treatment assignment within a multivariable Cox model. Results: In total, 74 out of 126 patients were included in the analysis. The expression of PTEN, αV integrin, uPAR and NRP-1 was not associated with progression-free survival (PFS) or overall survival (OS). For the first time, we identified that patients with tumors expressing CD98hc had a longer PFS than patients without CD98hc-expression ( p = 0.032). More importantly, and in accordance with previous studies, low microvessel density was found to be associated with a reduced PFS [adjusted HR per doubling of CD31-expression ( p = 0.53, 95% confidence interval: 0.30–0.95, p = 0.034)]. Conclusions: These results can contribute to the development of a personalized strategy for the treatment of mCRC with bevacizumab.

scholarly journals A Comparison of Epidural Analgesia and Traditional Pain Management Effects on Survival and Cancer Recurrence after Colectomy

2012 ◽  
Vol 116 (4) ◽  
pp. 797-806 ◽  
Author(s):  
Kenneth C. Cummings ◽  
Fang Xu ◽  
Linda C. Cummings ◽  
Gregory S. Cooper
Keyword(s):  
Colorectal Cancer ◽  
Epidural Analgesia ◽  
Cox Regression ◽  
Surgical Stress ◽  
Cox Model ◽  
Conditional Logistic Regression ◽  
Cancer Recurrence ◽  
Epidural Group ◽  
Recurrence Rates ◽  
Anesthetic Drugs

Background Cancer recurrence after surgery may be affected by immunosuppressive factors such as surgical stress, anesthetic drugs, and opioids. By limiting exposure to these, epidural analgesia may enhance tumor surveillance. This study compared survival and cancer recurrence rates for resection of colorectal cancer between patients who received perioperative epidurals and those who did not. Methods The linked Medicare-Surveillance, Epidemiology, and End Results database was used to identify patients ages 66 yr or older with nonmetastatic colorectal cancer diagnosed between 1996 and 2005 who underwent open colectomy. Recurrence was defined as chemotherapy 16 months or more after surgery and/or radiation 12 months or more after surgery. Patients were followed for at least 4 yr. To account for hospital effects, overall survival was estimated via marginal Cox regression. Recurrence was estimated by conditional logistic regression. Results A cohort of 42,151 patients, of whom 22.9% (n = 9,670) had epidurals at the time of resection, was identified. 5-yr survival was 61% in the epidural group and 55% in the nonepidural group. There was a significant association between epidural use and improved survival (adjusted Cox model hazard ratio = 0.91, 95% CI = [0.87, 0.94]). Adjusting for covariates, there was no significant reduction of recurrence in the epidural group (odds ratio = 1.05, 95% CI = [0.95, 1.15]). Several covariates, including blood transfusion, were predictive of mortality and cancer recurrence. Conclusion This large cohort study found that epidural use is associated with improved survival in patients with nonmetastatic colorectal cancer undergoing resection but does not support an association between epidural use and decreased cancer recurrence.

scholarly journals Prognosis of Colorectal Cancer in Tikur Anbessa Specialized Hospital, the Only Oncology Center in Ethiopia

2019 ◽  
Author(s):  
Eyob Kebede Etissa ◽  
Mathewos Assefa Assefa ◽  
Birhanu Teshome Ayele
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Adjuvant Therapy ◽  
Survival Time ◽  
Cancer Patients ◽  
Cox Regression ◽  
Addis Ababa ◽  
Specialized Hospital ◽  
Tikur Anbessa Specialized Hospital

Abstract BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females worldwide. According to Addis Ababa cancer registry, it is the first in male and fourth in female in Ethiopia. However, there have not been studies on prognostic factors and survival of colorectal cancer. Hence, this study aimed to estimate survival time and identify prognostic factors. METHODS: In this institution based retrospective study, medical records review of 422 colorectal cancer patients and telephone interview was used as sources of data. Survival time was estimated using Kaplan-Meier estimator. Prognostic factors were identified using the multivariable Cox regression model. RESULTS: The median survival time was 39 months. The overall five years survival rate was 33%. Patients diagnosed with rectal cancer had 76% (HR: 1.761, 95% CI: 1.173-2.644) increased risk to die compared to colon cancer patients. Node positive patients were 3.146 (95% CI: 1.626-6.078) times likely to die compared to node negative and metastatic cancer were 4.221 (95% CI: 2.788-6.392) times likely to die compared to non-metastatic patients. Risk of death was 36.1% lesser (HR: 0.639 (95% CI: 0.418-0.977)) among those who received adjuvant therapy compared to patients who had only surgical resection. CONCLUSION: The overall survival rate is low and majority of patients were young adults at presentation. Patient’s survival is largely influenced by advanced stage at presentation and delays in administration of adjuvant therapy. Adjuvant therapy was among the good prognostic factors. Implementation of colorectal cancer screening program and early detection with timely and advanced treatment are crucial to increase patients’ survival time. KEY WORDS: Colorectal cancer, survival, prognostic factor, Cox regression, Tikur Anbessa Specialized Hospital, Addis Ababa.

scholarly journals Prevalence of colorectal cancer biomarkers and their impact on clinical outcomes in Riyadh, Saudi Arabia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0249590
Author(s):  
Amjad Alharbi ◽  
Haifa Bin Dokhi ◽  
Ghadir Almuhaini ◽  
Futoon Alomran ◽  
Emad Masuadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Saudi Arabia ◽  
Survival Time ◽  
Cox Regression ◽  
Demographic Data ◽  
Response To Treatment ◽  
Treatment Modalities ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Increased Risk

Objectives KRAS, NRAS, and BRAF mutations are commonly present in colorectal cancer (CRC). We estimated the frequency of KRAS, NRAS, and BRAF mutations and assessed their impact on survival and other clinical variables among Saudi patients. Design Retrospective cohort study design. Settings Oncology department of a tertiary hospital in Riyadh, Saudi Arabia. We gathered information from 2016 to 2018. Participants Cohort of 248 CRC patients to assess the demographic data, pathological tumour features, response to treatment modalities, disease progression, and metastasis. Statistical analysis used Correlation analysis using the chi-square test. Survival analysis using a Kaplan Meier method. Cox regression analysis to calculate the hazard ratios. Results Demographic data revealed that 84% of patients were diagnosed with CRC above the age of 50 years. Only 27% of patients presented with distant metastasis. KRAS mutations were the most prevalent (49.6%), followed by NRAS mutations (2%) and BRAF mutations (0.4%). Wild type tumours were found among 44.4% of patients. KRAS mutation showed no significant correlation with the site, type, pathological grade, and stage of the tumour. The mean survival time was shorter among patients with KRAS mutations than among patients with wild type KRAS tumours (54.46 vs. 58.02 months). Adjusted analysis showed that the survival time was significantly affected by patients’ age at diagnosis (P = 0.04). Male patients had an increased risk of mortality by 77% (hazard ratio: 1.77). Conclusions Saudi CRC patients had a high frequency of KRAS mutations and a low frequency of BRAF mutations. The KRAS mutation status did not affect the patients’ survival.

scholarly journals The effect of individual-level factors in survival prognosis for colorectal cancer in Malaysia

2019 ◽  
Vol 6 (6) ◽  
pp. 2313 ◽  
Author(s):  
Anis K. Ghazali ◽  
Thomas J. Keegan ◽  
Mohd R. Abu Hassan ◽  
Benjamin M. Taylor
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Individual Characteristics ◽  
Treatment Modalities ◽  
Cancer Site ◽  
Survival Prognosis ◽  
Individual Level ◽  
Risk Of Death ◽  
Colorectal Cancer Patients

Background: In Malaysia, colorectal cancer is the second most common type of cancer for both sexes, represents 10.2% of total cancer cases in Malaysia. This study aims to identify the effect of individual-level factors on survival prognosis for patients with colorectal cancer in Malaysia.Methods: The study involved 4412 of colorectal cancer patients in Malaysia with histologically verified primary colorectal cancer, diagnosed between 2008 and 2013 (ICD-10, C18-C20), recorded in the database of National Cancer Patient Registry- Colorectal Cancer (NCPR-CC) Malaysia. We investigated the effect of individual characteristics such as age, gender, education as well as clinical characteristics such as cancer staging, cancer site and treatment modalities on survival prognosis after a diagnosis of colorectal cancer using a Cox regression survival model.Results: Patients diagnosed at stage IV had an almost 6-fold greater risk of dying from colorectal cancer than those with stage I. Age, third-degree education, poor tumour differentiation, the presence of distant metastases and receiving ‘other’ treatments were the other factors that increased the risk of death for colorectal cancer patients in Malaysian population.Conclusions: Our analysis revealed that the severity of the disease lead to poor prognosis in colorectal cancer in the population after adjusting for other individual characteristics. Health education programs targeting high risk group and emphasizing the importance of early detection of cancer as well as knowledge on the importance of cancer treatment should be implemented. Formulation of a better screening program needs to be extended so that it is a genuinely national program.

scholarly journals High-expression of LncRNA MAFG-AS1 is associated with the prognostic of patients with colorectal cancer

2020 ◽  
Vol 66 (11) ◽  
pp. 1530-1535
Author(s):  
Weichun Cui ◽  
Yong Wang ◽  
Xiangji Shen ◽  
Xudong Wu ◽  
Hui Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Expression ◽  
Rank Test ◽  
Depth Of Invasion ◽  
Chi Square ◽  
Potential Biomarker ◽  
Chi Square Test

SUMMARY OBJECTIVE: Long noncoding RNAs (lncRNAs) have been proven to exhibit distinct functions on the convoluted processes of tumor developments. Some studies on the biological functions of lncRNA MAFG-AS1 (MAFG-AS1) in cancers revealed that they may serve as an oncogene in some kinds of tumors, including colorectal cancer (CRC). However, little is known about the role of MAFG-AS1 in the prognostic of CRC. METHODS: A public dataset was mined for the screening of dysregulated lncRNAs in CRC. Quantitative real-time reverse transcription-polymerase chain reaction(qPCR) was used to compare the levels of MAFG-AS1 between paired MAFG-AS1 specimens and normal adjacent tissues. The correlations between MAFG-AS1 and clinic pathological features in CRC were analyzed using the chi-square test. The log-rank test and Kaplan-Meier test were carried out to compare the survival time of patients with high and low expressions of MAFG-AS1. Cox regression was applied for univariate and multivariate assays to validate whether MAFG-AS1 could be an independent factor in the prognosis of CRC. RESULTS: We found that the distinct upregulation of MAFG-AS1 in various tumors was a common event. MAFG-AS1 was distinctly up-regulated in CRC specimens compared to matched non-tumor specimens (p < 0.01). High MAFG-AS1 expressions were closely associated with depth of invasion (p = 0.011) and TNM stage (p = 0.022). Survival assays revealed that patients with high expression of MAFG-AS1 have a shorter overall survival (p = 0.0030) and disease-free survival (p = 0.0002). CONCLUSIONS: MAFG-AS1 can serve as a novel potential biomarker to predict CRC patients’ survival time.

Clinicopathological significance and prognostic value of EphA3 and CD133 expression in colorectal carcinoma

2011 ◽  
Vol 64 (6) ◽  
pp. 498-503 ◽  
Author(s):  
Hong-Qing Xi ◽  
Po Zhao
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Cox Regression ◽  
Mucosal Tissue ◽  
Ki 67 ◽  
Cd133 Expression ◽  
Clinicopathological Significance

AimsTo investigate clinicopathological significance and prognostic implications of EphA3, CD133 and Ki-67 expression in colorectal cancer.MethodsEphA3, CD133 and Ki-67 expression was assessed in 201 cases of paraffin-embedded colorectal carcinoma and 60 cases of distal normal mucosal tissue by immunohistochemistry. Medical records were reviewed and clinicopathological analysis was performed. The differential expression of EphA3 and CD133 protein was detected in 20 cases of fresh resected colorectal carcinoma and 20 cases of matched normal mucosal tissue adjacent to the carcinoma by western blot.ResultsThe expression of EphA3 and CD133 in carcinoma was significantly higher than that in normal mucosal tissue (p=0.008; p=0.004). EphA3 and CD133 were positively correlated with tumour size (p=0.029; p=0.017), histological grade (all p=0.001), infiltrative depth (all p=0.00), lymph node metastasis (all p=0.00), distant metastasis (p=0.017; p=0.030) and TNM stage (all p=0.001). Patients with high expression of EphA3 and CD133 had the lowest survival (all p=0.001) (median survival time of EphA3 positive and negative cases: 34.0 and 72.0 months; median survival time of CD133 positive and negative cases: 34.0 and 77.0 months). Multivariate survival analysis showed that EphA3 and CD133 expression was correlated significantly with shortened survival in patients with colorectal cancer (Cox regression: p=0.001, HR=4.722, 95% CI 2.667 to 8.361; p=0.001, HR=5.224, 95% CI 2.622 to 10.405). EphA3, CD133 and Ki-67 expression in colorectal cancer had positive correlations with each other (all p=0.001).ConclusionsEphA3 and CD133 may play an important role in the development and progression of tumours, and thus become useful indicators for clinical assessment of tumour biological behaviour and prognosis in patients with colorectal carcinoma.

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