Purpose: We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT).Method and Materials: Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly.Results: In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume-planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3 degrees (mean of means), standard deviation of means +/- 4.9 degrees, maximum at 30.7 degrees. Three-dimensional vector translations relative to skin markings were 9.3 +/- 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 +/- 1.5 min (maximum, 15.1 min) between kV imaging and last beam's electronic portal images showed further L-R rotations of 2.5 degrees +/- 2.3 degrees (maximum, 26.9 degrees), and three-dimensional vector translations of 3.0 +/- 3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm.Conclusion: We demonstrated the clinical feasibility of an online adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of internal organ motion, allowing safe and straightforward implementation of margin reduction and dose escalation. (C) 2012 Elsevier Inc.