Survivin mediates paclitaxel-resistance in prostate cancer cells. The inhibition of Survivin sensitizes prostate cancer cells to paclitaxel-induced apoptosis through a caspase-dependant mechanism in vitro and in vivo.
Purpose-We examined the prognostic value of nuclear and cytoplasmic Survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610.Methods and Materials-RTOG 8610 was a phase III randomized study comparing the effect of radiotherapy (RT) plus short-term androgen deprivation (STAD) with RT alone. Of the 456 eligible cases, 68 patients had suitably-stained tumor material for nuclear Survivin analysis and 65 patients for cytoplasmic Survivin.Results-Compared to patients with nuclear Survivin intensity scores ≤191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio (HR) = 0.45, 95% confidence intervals (CI) = 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear Survivin intensity scores >191.2 were significantly associated with improved overall survival (HR = 0.46, 95%CI = 0.25-0.86, p = 0.0156) and prostate cancer survival (HR = 0.36, 95%CI = 0.16-0.84, p = 0.0173). On univariate analysis, compared to patients with cytoplasmic Survivin integrated optical density ≤82.7, those with integrated optical density >82.7 showed a significantly increased risk of local progression (HR = 2.49, 95%CI = 1.03-6.01, p = 0.0421).Reprints requests to: Arnab Chakravarti, M.D., Massachusetts General Hospital, Department of Radiation Oncology, 100 Blossom Street, Cox 3, Boston, MA 02114. Telephone: 617-643-3427; Fax: 617-643-3229; Email: E-mail: achakravarti@partners.org. Conflicts of Interest Notification: none.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access
The aim of this study is to determine the gantry angle and multileaf collimator (MLC) gap error‐detection threshold of a diode helical array with an inserted microionization chamber in order to use this device for the pretreatment quality assurance (QA) of intensity‐modulated radiation therapy (IMRT) treatments. Implications on the dose‐volume histograms (DVHs) of the patient treatments will also be considered for the establishment of a QA protocol with a reasonable tolerance level. Three dynamic IMRT HN (head and neck) and prostate treatments were studied. Random and systematic variations of gantry angle and systematic errors in MLC gap width of the clinical treatments were analyzed in order to establish the detection sensitivity of the array. The associated clinical significance was studied introducing the same errors in the treatment plan based on the patients' computed tomography (CT) and calculating the corresponding DVHs. The Gamma (3%/3 mm) presented a 4% variation in failure rate for a rotation error of 1° for both types of treatment. Both systematic and random errors in gantry rotation angle have little effect on the patients' DVHs. MLC gap width errors of 1 mm and 2 mm in the prostate treatments imply a mean variation in isocenter‐measured absorbed dose of 2.1% and 4.1%, respectively. In the case of HN, these errors entail a change in measured isocenter dose of 4.7% and 8.6%, respectively. The variation observed in the DVHs of the patients was, basically, a global displacement of the curves proportional to the isocenter dose variation caused by the gap width error. According to the array sensitivity to the analyzed errors and its implication in patient DVHs, a tolerance of 95% point passing rate for the gamma criterion 3%/2 mm and an agreement of 2% in isocenter absolute dose have been established as tolerance criteria for our pretreatment IMRT QA protocol.PACS number: 87.56.Fc
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