Dataset for: Testing of Evaluation Bias for Progression Free Survival Endpoint in Oncology Clinical Trials

Progression free survival is an increasingly popular end point in oncology clinical trials. A complete blinded independent central review (BICR) is often required by regulators in an attempt to reduce the bias in PFS assessment. In this paper, we propose a new methodology that uses a sample-based BICR as an audit tool to decide whether a complete BICR is needed. More specifically, we propose a new index, the differential risk, to measure the reading discordance pattern, and develop a corresponding hypothesis testing procedure to decide whether the bias in local evaluation is acceptable. Simulation results demonstrate that our new index is sensitive to the change of discordance pattern; type I error is well controlled in the hypothesis testing procedure, and the calculated sample size provides the desired power

Data from: Testing of Evaluation Bias for Progression Free Survival Endpoint in Oncology Clinical Trials

Progression free survival is an increasingly popular end point in oncology clinical trials. A complete blinded independent central review (BICR) is often required by regulators in an attempt to reduce the bias in PFS assessment. In this paper, we propose a new methodology that uses a sample-based BICR as an audit tool to decide whether a complete BICR is needed. More specifically, we propose a new index, the differential risk, to measure the reading discordance pattern, and develop a corresponding hypothesis testing procedure to decide whether the bias in local evaluation is acceptable. Simulation results demonstrate that our new index is sensitive to the change of discordance pattern; type I error is well controlled in the hypothesis testing procedure, and the calculated sample size provides the desired power

Diurnal expression of <i>F. vesca PIP</i> aquaporins.

<p>Diurnal expression pattern of <i>FvPIP</i> genes in leaves of <i>F. vesca</i> on two consecutive days. Grey columns – control plants, black columns – drought-stressed plants. Data are means+SE, <i>n</i> = 3 biological replicates. Different letters annotate statistically significant differences determined by LSD following repeated measurements ANOVA (<i>P</i><0.05). The difference between treatments was significant for (a), (b), (c), and (d).</p

Deduced protein sequences of <i>F. vesca</i> PIP aquaporins.

<p>An alignment of <i>F. vesca</i> PIP deduced protein sequences. Blue – transmembrane domains (TM); red – NPA motif; green highlight – residues of the aromatic/arginine selectivity filter involved in determining water specificity. Asterisk denotes conserved sites. N stands for amino-terminal region and C stands for carboxy-terminal region of the protein.</p

<i>F. vesca</i> PIP isoform-specific and reference gene primers.

<p><i>F. vesca</i> PIP isoform-specific and reference gene primers.</p

Relative <i>PIP</i> expression in leaves and roots of <i>F. vesca</i> under different levels of drought stress.

<p>Expression of four <i>F. vesca PIP</i> aquaporin genes after six days of drought stress (a, c, e, g) and upon re-watering (b, d, f, h). C – control plants; D25– plants receiving 25% of the control irrigation; D0 − plants with no irrigation. Data are means+SE, <i>n</i> = 4 plants. Different letters denote statistically significant differences within each time point determined by LSD following one way ANOVA (<i>P</i><0.05).</p

Correlation between substrate moisture content and relative expression of <i>FvPIP</i> genes.

<p><i>FvPIP2;1</i> (a, b), <i>FvPIP2;2</i> (c, d), <i>FvPIP1;1</i> (e,f), <i>FvPIP1;2</i> (g, h) in leaves (a, c, e, g) and roots (b, d, f, h). Regression lines, correlation coefficients and probabilities are given for statistically significant relationships.</p

Prognostic Impact of FoxP3+ Regulatory T Cells in Relation to CD8+ T Lymphocyte Density in Human Colon Carcinomas

<div><h3>Background</h3><p>T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3⁺ regulatory T cells (Tregs) in relation to cytotoxic CD8⁺ T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR) status who participated in adjuvant chemotherapy trials.</p> <h3>Methods</h3><p>FoxP3⁺ and CD8⁺ densities in tumor epithelial and stromal compartments were analyzed by immunohistochemistry and quantified in resected, stage II and III colonic carcinomas (N = 216). Immune marker density was dichotomized at the median and categorized as high <em>vs</em> low. MMR status was classified as MMR deficient (dMMR) or proficient (pMMR). Cox models were adjusted for age, stage, and tumor grade.</p> <h3>Results</h3><p>The density of FoxP3+ infiltration was similar in tumor stroma and epithelia, whereas CD8+ was higher in stroma. The prognostic impact of FoxP3+ and CD8+ T cell infiltration was stronger in stroma <em>vs</em> epithelia, and the density of each marker in stroma was independently associated with improved overall survival (OS). However, the impact of FoxP3+ on survival was dependent upon CD8+ density (<em>P</em> interaction  = .040). Among CD8+_low tumors, FoxP3+_high cases had significantly improved OS compared to FoxP3+_low cases after adjustment for covariates (hazard ratio 0.43; 95% confidence interval 0.19 to 0.95; P = .030). In contrast, FoxP3+ was not prognostic among CD8+_high tumors. FoxP3+ remained prognostic in CD8+_low tumors after further adjustment for MMR or <em>BRAF</em>^V600E mutation status. Additionally, these immune markers identified a pMMR subgroup with a similarly favorable OS as for dMMR tumors.</p> <h3>Conclusions</h3><p>The prognostic impact of FoxP3+ and CD8+ T cell density are inter-dependent, whereby FoxP3+ exerts a favorable influence on survival only in colon cancers with low CD8+ infiltration.</p> </div

Clinicopathologic Characteristics of Study Population by Immune Marker Density (N = 216).

a<p>T cell densities were dichotomized at the median.</p>b<p>FoxP3+ (N = 156).</p>c<p>Histologic Grade: 1 or 2, well or moderately differentiated; 3 or 4, poor or undifferentiated.</p

Patient survival according to CD8+ and FoxP3+ T-cell density.

<p>Overall survival (OS) in resected colon carcinomas with (a) high <i>vs</i> (b) low density of cytotoxic CD8+ T-cell infiltration in tumor stroma according to FoxP3+ T-cell density in tumor stroma (<i>P</i> for interaction  = .040). Hazard ratios (HR) are adjusted for age, stage, and tumor grade.</p