Eective management of intrafraction organ motion during radiotherapy has historically been considered a “holy grail” that, when viewed in the context of improvements in image-guided radiotherapy (IGRT), may now be achievable in the common practice of clinical radiation therapy (Shirato et al. 2007). Intrafraction motion has many physiological sources, including the motion of organs associated with cardiac, gastrointestinal, and respiratory function. Even before the introduction of advanced, computer-aided diagnostic-quality imaging as the basis for 3D treatment planning, clinicians and physicists were well aware of and considered the consequences of organ motion for the placement and planning of radiotherapy portals. For much of the modern history of external beam radiotherapy, the delivery of radiation to targets in the thoracic cavity involved the planning of relatively simple, large treatment portals because of a lack of quality methods for assessing and quantifying disease in situ over the course of therapy. is method of delivering radiation prescriptions attempted to balance the need to deliver therapeutic doses of radiation to cancer cells while acknowledging the tradeo of limiting doses to the critical structures. e resulting suboptimal delivery associated with this still recent era of radiotherapy is evident in the historically low local control rates for certain cancers of the lung and abdomen associated with convention fractionated radiotherapy when compared with dramatically improved local control provided by new, highly focused hypofractionated dose schemes (Fakiris et al. 2009). e

opportunity for hypofractionated radiotherapy and other delivery schemes that leverage favorable radiobiology, however, have only been possible because of a technological evolution in imaging and image-guided interventions. While improvements in diagnostic imaging have increased the ability of clinicians to detect disease, the targeting of tumor targets remains fraught with uncertainties including target delineation variability, daily setup uncertainty and, to a lesser degree, intrafraction motion, that greatly inuence the optimal dosimetric delivery of radiotherapy. e common usage of PET/CT imaging has paid dividends toward the addressing the challenge of improving target delineation variability (Greco et al. 2007; Senan et al. 2005). With IGRT rapidly becoming the standard of care in radiotherapy, many of the challenges related to daily setup uncertainty are also being addressed (Bissonnette et al. 2009a, 2009b; Dawson and Jaray 2007; Xing et al. 2006). Intrafraction motion assessment has beneted in many ways from the advances and investment in IGRT technology, thus making the attempt to manage the uncertainties desirable as well as feasible (Sonke et al. 2009).