Purpose The aim of this study is to ascertain the subsequent radiobiological impact of using a consensus guideline target volume delineation atlas. and reduced variance in NTCP for the bowel. In Phase 2 the atlas group had increased TCP relative to the control for CTV (p = 0.03). Conclusions Visual atlas and consensus treatment guidelines usage in the development of rectal cancer IMRT treatment plans reduced the inter-observer radiobiological variation with clinically relevant TCP alteration for CTV and PTV volumes. DKK1 study was deemed exempt and was conducted under the auspices of the University of Texas Health Science Center at San Antonio institutional review board. Pilot data from the study have been presented previously [6]. Briefly thirteen radiation oncologist observers from eight SWOG-affiliated institutions were recruited and were asked to contour a standardized case (an anonymized patient with Stage T3N0M0 adenocarcinoma of the rectum) with instructions from an (at that time) in-development SWOG protocol AEE788 (S0713: “exploratory contour surface variability analysis [8 9 was previously reported [6]. In this analysis the statistical significance of the presented results is investigated. Treatment Planning Treatment planning was performed using a commercial treatment planning software (Pinnacle Philips Medical Systems Inc.). A volumetric modulated arc technique (VMAT) which employs 2 arcs of 6 MV photons was AEE788 applied. The organs-at-risk were delineated as ROIs by a single observer [CDF]. The individual treatment plans were produced by a single physicist [DG] using the dosimetric constraints for the target volumes and organs at risk that were specified in the AEE788 SWOG S0713 protocol (Supplementary Table B). The individual treatment plans were produced using the first set of delineations of each observer. The same treatment plans were subsequently applied on the second sets of delineations of each observer (no re-planning took place only renormalization) in order to determine the impact of delineation/segmentation alone upon plan quality. Radiobiological measures for treatment plan evaluation Secondary radiobiological evaluation was performed using previously defined literature-derived metrics [10]. Tumor response was calculated using the Poisson model with parallel tumor structural organization assumed (i.e. 100% clonogenic kill required for tumor control). Thus tumor control probability (TCP) for a tumor volume is given by the expression: is the total number of voxels or sub-volumes in the target. Response of a normal tissue to a non-uniform dose distribution was obtained using the relative seriality model with normal tissue complication probability expressed as [3]: is the probability of injuring organ and having the reference volume and being irradiated to dose compared to the reference volume (is the total number of voxels or subvolumes in the organ is the relative seriality parameter that characterizes the internal organization of that organ. AEE788 Complication-free tumor control probability (is the relative seriality which … Statistical analysis Statistical analysis was performed using the JMP software package (SAS Insititute Cary NC USA). The one-sided Wilcoxon Signed-Rank test was used as a non-parametric measure for matched pair analysis (e.g. Phase 1 vs. Phase 2). The Wilcoxon Rank Sums Test was used to assess distributional equivalence/nonequivalence between post-intervention cohorts for both groups. The Brown-Forsythe test was used as a non-parametric measure to determine whether variance in TCP/NTCP changed across an ROI for both interventions. Results Table 2 presents an outline of dosimetric and radiobiological measures that evaluate treatment plan efficacy. In this table for every observer’s treatment plan and organ delineation set the values the different measures were derived. Fig. 1 shows normalized cumulative DVHs of the targets GTV CTV and both PTVs for the expert the atlas-assisted group and the control group. Fig. 1 The normalized cumulative dose volume histograms (DVHs) of the GTV CTV PTV1 and PTV2. The DVHs are based on the first (Phase 1) and.