Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The effect of matrix components and the urocortin family of peptides on chondrocyte survival

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CAMERA CALIBRATION COMBINING IMAGES WITH TWO VANISHING POINTS

Single image calibration is a fundamental task in photogrammetry and computer vision. It is known that camera constant and principal point can be recovered using exclusively the vanishing points of three orthogonal directions. Yet, three reliable and well-distributed vanishing points are not always available. On the other hand, two vanishing points basically allow only estimation of the camera constant (assuming a known principal point location). Here, a camera calibration approach is presented, which exploits the existence of only two vanishing points on several independent images. Using the relation between two vanishing points of orthogonal directions and the camera parameters, the algorithm relies on direct geometric reasoning regarding the loci of the projection centres in the image system (actually a geometric interpretation of the constraint imposed by two orthogonal vanishing points on the ‘image of the absolute conic’). Introducing point measurements on two sets of converging image lines as observations, the interior orientation parameters (including radial lens distortion) are estimated from a minimum of three images. Recovery of image aspect ratio is possible, too, at the expense of an additional image. Apart from line directions in space, full camera calibration is here independent from any exterior metric information (known points, lengths, length ratios etc.). Besides, since the sole requirement is two vanishing points of orthogonal directions on several images, the imaged scenes may simply be planar. Furthermore, calibration with images of 2D objects and/or ‘weak perspectives ’ of 3D objects is expected to be more precise than single image approaches using 3D objects. Finally, no feature correspondences among views are require