Purpose Cone-beam computed tomographic images (CBCTs) are increasingly used for set up correction, soft tissue targeting and image-guided adaptive radiotherapy (IGART). However, CBCT image quality is limited by low contrast and imaging artifacts. This analysis investigates the detectability of soft tissue boundaries in CBCT by performing a multiple-observer segmentation study. Material and Methods In 4 prostate cancer patients prostate, bladder and rectum were repeatedly delineated by 5 observers on CBCTs and fan beam CTs (FBCTs). A volumetric analysis of contouring variations was performed by calculating coefficients of variation (COV: standard deviation/average volume). The topographical distribution of contouring variations was analyzed using an average surface mesh-based method. Results Observer- and patient-averaged COVs for FBCT/CBCT were 0.09/0.19 for prostate, 0.05/0.08 for bladder and 0.09/0.08 for rectum. Contouring variations on FBCT were significantly smaller than on CBCT for prostate (p<0.03) and bladder (p<0.04), but not for rectum (p<0.37) (intermodality differences). Intraobserver variations from repeated contouring of the same image set were not significant for either FBCT or CBCT (p<0.05). Average standard deviations of individual observers’ contour differences from average surface meshes on FBCT versus CBCT were 1.5 versus 2.1 mm for prostate, 0.7 versus 1.4 mm for bladder, and 1.3 versus 1.5 mm for rectum. The topographical distribution of contouring variations was similar for FBCT and CBCT. Conclusion Contouring variations were larger on CBCT than FBCT, except for rectum. Given the well-documented uncertainty in soft tissue contouring in the pelvis, improvement of CBCT image quality and establishment of well-defined soft tissue identification rules are desirable for image-guided radiotherapy.

Although no dose-limiting events were noted in the first two courses of LU79553, cumulative muscular toxicity precluded repetitive treatment with LU79553 at doses above 18 mg/m(2)/d, which is the recommended dose for subsequent disease-directed evaluations. The preliminary antitumor activity noted is encouraging, but the qualitative and cumulative nature of the principal toxicities, as well as the relatively small number of patients treated repetitively, mandate that rigorous and long-term toxicologic monitoring be performed in subsequent evaluations of this unique agent.

The zinc metalloendopeptidase EC3.4.24.15 [EP24.15, thimet oligopeptidase], a neuropeptide processing enzyme, is central to the formation and degradation of many bioactive peptides in the neural proteome, and is highly expressed in normal prostate. EP24.15 actions are increased in androgen-dependent prostate cancer compared to androgen-independent; augmented by androgen treatment, and inhibited by clinical GnRH analogs. The "neural" prostate includes: neuropeptides, cognate receptors and processing enzymes regulating signaling of peptide-mediated neural inputs.

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