Confidence intervals for the effect of a prognostic factor after selection of an ‘optimal’ cutpoint

Holländer, Norbert; Sauerbrei, Willi; Schumacher, Martin

doi:10.1002/sim.1611

Cited by 96 publications

(57 citation statements)

References 30 publications

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“…We used a multivariate Cox proportional hazards model to determine HRs. HRs were corrected as suggested by Holl€ ander and colleagues (20). All tests were two-sided, and a P < 0.05 was considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer

Aniţei

Zeitoun

Mlecnik

et al. 2014

Clinical Cancer Research

311

299

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Purpose: To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.Experimental design: The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3 þ ) and cytotoxic (CD8 þ ) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n ¼ 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.Results: The densities of CD3 þ and CD8 þ lymphocytes and the associated Immunoscore (from I0 to I4)were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3 þ and CD8 þ lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3 þ cells; Fisher exact test P ¼ 0.01). Conclusions:The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.

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Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer

Aniţei

Zeitoun

Mlecnik

et al. 2014

Clinical Cancer Research

311

299

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“…The efficiency of this strategy has already been illustrated [39], and presents the advantage of simplified computations and interpretation of results, in the case of a substantially large population sample. Some authors have suggested selecting optimal cut-points by the use of cross validation procedures [34], bootstrapping computations of an optimal cut-point effect confidence interval [40,41], adjusted significance level tests [34,42] and multivariate settings [43]. However, loss of power [34,43] and underestimated HR [34] have been reported in the case of the cross validation strategy.…”

Section: Discussionmentioning

confidence: 99%

Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points

Majed¹,

Moreau

Asselain³

2008

Breast Cancer Res Treat

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“…The serum GSTP1 hypermethylation status was coded as a categorical variable in this analysis. The optimal cut point for total DNA in the multivariable model was chosen using the minimum P value method with bootstrap resampling to correct for overfitting (18). For the multivariate analysis, we used the significant variables from the univariate model: total DNA level, surgical margin status, and lymph node status.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Value of Preoperative Serum Cell-Free Circulating DNA in Men with Prostate Cancer Undergoing Radical Prostatectomy

Bastian

Palapattu²,

Yegnasubramanian³

et al. 2007

Clinical Cancer Research

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Purpose: We evaluated the association of preoperative serum cell-free circulating DNA concentration in men with clinically localized prostate cancer who underwent radical prostatectomy with prostate-specific antigen (PSA) recurrence. Experimental Design: One hundred and ninety-two men with clinically localized prostate cancer, who underwent radical prostatectomy at the Johns Hopkins Hospital and had preoperative serum available for analyses constituted our study population. All serum samples were collected before prostate biopsy or at least 4 months after prostate biopsy. The total amount of serum cell-free circulating DNA from each sample was calculated using a standard curve generated via quantitative real-time PCR. PSA recurrence was defined as a single postoperative PSA level of z0.2. The natural logarithm (ln) of the DNA concentration was used for statistical analyses. Results: Of the 192 men in our study, 56 (29%) experienced PSA recurrence within the study period (median time to PSA recurrence 2 years). The median follow-up time for men free of disease at last follow-up was 3 years. The median serum cell-free DNA concentration of all men in the study was 5.3 ng/mL (mean 18.05 ng/mL; range 0.2-320 ng/mL). The mean serum DNA concentration for men who recurred and for those who did not was 3.8 F 34.1 and 13.7 F 33.6 ng/mL, respectively (P = 0.001). In a univariate analysis, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 1.49; 95% confidence interval, 1.3-1.8; P < 0.001). In the multivariate model, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 2.56; 95% confidence interval, 1.1-1.6; P = 0.003). Using bootstrap analyses, serum cell-free DNA concentrations z5.75 ng/mL were associated with an increased risk of PSA recurrence within 2 years of radical prostatectomy. Conclusion: Our study suggests that preoperative serum cell-free DNA concentration may be a useful prognostic biomarker for men with clinically localized prostate cancer treated with radical prostatectomy.

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Confidence intervals for the effect of a prognostic factor after selection of an ‘optimal’ cutpoint

Cited by 96 publications

References 30 publications

Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer

Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer

Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points

Prognostic Value of Preoperative Serum Cell-Free Circulating DNA in Men with Prostate Cancer Undergoing Radical Prostatectomy

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