Methods for categorizing a prognostic variable in a multivariable setting

Mazumdar, Madhu; Smith, Alex; Bacik, Jennifer

doi:10.1002/sim.1333

Cited by 113 publications

(98 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cut-off points of INHBA were evaluated in a multivariate Cox proportional-hazards model with prognostic factors that were significantly related to overall survival in the univariate analysis. "Optimal" cut-off points were selected by the minimum p-value method, whereas the internal validity of the cut-off points was evaluated with a two-fold cross-validation approach (7). Relations between gene expression and potential prognostic variables were evaluated using the χ 2 test.…”

Section: Quantitative Real-time Reverse-transcriptase Polymerase Chamentioning

confidence: 99%

Clinical Significance of INHBA Gene Expression in Patients with Gastric Cancer who Receive Curative Resection Followed by Adjuvant S-1 Chemotherapy

Katayama

Oshima

Sakamaki

et al. 2017

View full text Add to dashboard Cite

Gastric cancer is the third leading cause of cancer-related death in the world. In 2012, there were 723,000 deaths from gastric cancer (1). Although good treatment outcomes are being obtained after endoscopic therapy and surgery in patients with early gastric cancer, outcomes in patients with advanced gastric cancer remain inadequate despite progress in diagnostic devices, surgical techniques and chemotherapy. Standard treatment for stage II or III gastric cancer is surgery plus fluoropyrimidine-based postoperative adjuvant chemotherapy. In Japan, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) obtained a 5-year survival rate of 71.7% in patients with stage II or III disease who received oral S-1 for 1 year after curative resection with D2 lymph node dissection. In the subgroups of patients with stage IIIA or stage IIIB disease, the 5-year survival rates were 67.1% and 50.2%, respectively (2). These results remain unsatisfactory and hope has been placed on personalized therapy guided by biomarker analysis as a strategy that can potentially improve outcomes.We analyzed the expression ratios of approximately 30,000 genes in gastric cancer tissue and adjacent normal gastric mucosa by DNA microarray profiling in patients with stage II or III gastric cancer who received oral S-1 for 1 year after curative resection and had early recurrence and poor treatment outcomes. When we examined overexpressed genes in gastric cancer tissue, we found that inhibin βA (INHBA) gene expression was 12.8 times higher in cancer tissue than in adjacent normal gastric mucosa, indicating overexpression of the INHBA gene in gastric cancer tissue. INHBA is a member of the transforming growth factor (TGF)-β superfamily and recent studies have reported that the INHBA gene is overexpressed in various types of cancers, including lung (3), pancreatic (4) and colorectal cancer (5). In recent years, INHBA has been reported to have a role in cancer cell proliferation, invasion, metastasis and chemoresistance (6). 565

show abstract

Section: Quantitative Real-time Reverse-transcriptase Polymerase Chamentioning

confidence: 99%

Clinical Significance of INHBA Gene Expression in Patients with Gastric Cancer who Receive Curative Resection Followed by Adjuvant S-1 Chemotherapy

Katayama

Oshima

Sakamaki

et al. 2017

View full text Add to dashboard Cite

show abstract

“…To dichotomise prognostic variables, CD3, CD8, and CD45RO, a two-fold cross-validation methodology and a minimum P-value approach (Mazumdar et al, 2003) were used. The dataset was randomly divided into two subsets.…”

Section: Two-fold Cross-validation Approachmentioning

confidence: 99%

Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer

et al. 2008

View full text Add to dashboard Cite

The study aims to determine whether type and density of tumour-infiltrating lymphocytes (TILs) can predict the clinical course in gastric cancer. Gastric carcinomas (n ¼ 220) were immunostained for CD3, CD8, CD20, and CD45RO and evaluated for clinicopathologic characteristics. Number of TILs that immunostained positively for each marker were counted using NIH ImageJ software. Tumours were grouped into low-and high-density groups for each marker (CD3, CD8, CD45RO). The densities of CD3 þ , CD8 þ , and CD45RO þ TILs were found to be independent predictors of lymph node metastasis by multivariate analysis with odds ratios (95% CI) of 0.425 (0.204 -0.885), 0.325 (0.150 -0.707), and 0.402 (0.190 -0.850), respectively. Kaplan -Meier survival analysis revealed that patients in the high-density groups for CD3, CD8, and C45RO had a significantly longer survival time than the patients in the corresponding low-density groups, respectively. In multivariate survival analysis, the densities of CD3 þ , CD8 þ , and CD45RO þ TILs remained independent prognostic factors with hazard ratios (95% CI) of 0.549 (0.317 -0.951), 0.574 (0.347 -0.949), and 0.507 (0.298 -0.862), respectively. In conclusion, density of TILs was found to be independently predictive of regional lymph node metastasis and patient survival in gastric cancer.

show abstract

“…In the final multivariate model, a χ² test using the minimum p-value approach was used for all categorised variables associated with nephrolithiasis or SAR, in order to choose the more discriminating threshold among those best separating patients with nephrolithiasis or SAR from patients without (30). To avoid biased relative risk, it was followed by a cross validation (31). SAS software (version 8.2 ; SAS Institute Inc, Cary, NC, USA) was used for statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

Indinavir Trough Concentration as a Determinant of Early Nephrolithiasis in HIV-1-Infected Adults

Collin

Chêne²,

Retout³

et al. 2007

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Indinavir plasma levels are associated with antiretroviral efficacy however few data is available regarding toxicity. We assessed the relationship between indinavir pharmacokinetic (PK) characteristics and severe nephrolithiasis as well as other severe or serious adverse reactions (SAR). Patients included in the ANRS CO8 APROCO-COPILOTE cohort and receiving indinavir 800 mg thrice daily as first line protease inhibitor, were eligible for this study. To be included in the analysis, their plasma sample at month 1 (M1) had to be available (n=282) to estimate, using population PK modelling, indinavir PK characteristics, i.e. maximum (C max ) and trough plasma (C res ) concentrations, area under the curve (AUC) and observed/predicted concentrations ratio (CR). A Cox model was used to estimate the independent effect of C max , C res , AUC and CR on the hazard of severe nephrolithiasis and SAR. At M1, median C max was 6 205 ng/mL, C res : 631 ng/mL, AUC: 24 242 ng.h/mL and CR: 0.6. After a median follow-up of 12 months, 11% of patients (30/282) had experienced at least one SAR among which 12 were nephrolithiasis.In the multivariate analyses, early high indinavir C res (i.e. ≥ 1000 ng/mL at M1) was associated with a higher rate of severe nephrolithiasis (HR=6.7; 95% confidence interval=1.8-25.2; p<0.01) and was also associated with a higher rate of all SAR but only when nephrolithiasis were included among those cases. Prospective and early indinavir C res determination should be recommended in the patient's care management and dosage adjustments.

show abstract

Methods for categorizing a prognostic variable in a multivariable setting

Cited by 113 publications

References 19 publications

Clinical Significance of INHBA Gene Expression in Patients with Gastric Cancer who Receive Curative Resection Followed by Adjuvant S-1 Chemotherapy

Clinical Significance of INHBA Gene Expression in Patients with Gastric Cancer who Receive Curative Resection Followed by Adjuvant S-1 Chemotherapy

Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer

Indinavir Trough Concentration as a Determinant of Early Nephrolithiasis in HIV-1-Infected Adults

Contact Info

Product

Resources

About