Image-Guided Radiotherapy for Localized Prostate Cancer: Treating a Moving Target Patrick A. Kupelian, MD, Katja M. Langen, PhD, Twyla R. Willoughby, MS, Omar A. Zeidan, PhD, and Sanford L. Meeks, PhD Prostate motion during external-beam radiotherapy can affect outcomes in patients with localized prostate cancer. Prostate motion and deformation are currently being character- ized with different techniques. There is significant individual variation among patients with respect to the observed motion and its dosimetric consequences. There is also significant difference in the accuracy of different localization methods currently used to adjust for prostate motion. The motion of the prostate gland can itself affect the accuracy of different localization methods. The dosimetric impact on target areas and organs at risk should be studied for different localization techniques, treatment plan margins, and treatment sched- ules. Such assessments will be increasingly important with smaller treatment margins, smaller fraction numbers, and higher radiation doses. Understanding and managing the consequences of anatomic variations within the lower pelvis should be a priority in designing and implementing future clinical trials. Semin Radiat Oncol 18:58-66 © 2008 Elsevier Inc. All rights reserved. T he need for high radiation doses for effective control of localized prostate cancer has resulted in the use of grad- ually smaller radiation field sizes. This, in turn, has necessi- tated a better understanding of the location and shape of the target areas (in this case, principally the prostate gland but also the surrounding normal tissues). During the past 10 years, imaging and localization techniques prior and during radiation delivery flourished and significantly contributed to this knowledge. The aim of the present review is 3-fold: (1) present our current understanding of these issues, (2) clarify how different current targeting methods attempt to address these issues, and (3) review the limited available clinical out- come data (tumor control and toxicity) resulting from the use of such targeting techniques. Historically, the term “organ motion” has been applied to describe mostly positional variations of target areas from one fraction to the other, often documented with “snapshots” (ie, static images obtained with different technologies before treatment delivery on each treatment day). However, ana- tomic changes within an individual patient are more complex in nature. The 2 main phenomena potentially affecting small- field radiation therapy are motion and deformation. These happen in 2 different timeframes generally described as in- terfraction (from day to day) and intrafraction (during a treat- ment session). The phenomenon least studied is intrafraction deformation. Only recent studies have indirectly addressed this issue by analyzing interfraction deformation. 1,2 Cur- rently, intrafraction deformation is difficult to assess and re- act to. The dosimetric impact of intrafraction deformation of the prostate gland is probably minimal. It is possible that this could be shown to be an important phenomenon to affect radiation delivery but is currently largely ignored. Therefore, 3 principal phenomena are relevant: interfraction motion, intrafraction motion, and interfraction deformation. The fo- cus of this communication is the analysis of interfraction and intrafraction motion. Imaging and localization techniques are crucial in the ac- quisition and use of the knowledge that we currently use in the treatment of localized prostate cancers. Therefore, it is important to understand how different imaging and localiza- tion techniques handle the three problems of interfraction motion, intrafraction motion, and interfraction deformation. It is also important to understand how these techniques affect the integrity or documentation of delivered doses. Ulti- mately, localization is performed for accurate radiation deliv- ered to areas intended to receive specified doses, not for an independent determination of the location (and/or shape) of the targeted areas at different points in time. This dosimetric aspect is, unfortunately, frequently ignored when localiza- Department of Radiation Oncology, M.D. Anderson Cancer Center, Or- lando, FL. Address reprint requests to Patrick A. Kupelian, MD, Department of Radia- tion Oncology, M.D. Anderson Cancer Center Orlando, 1400 South Orange Avenue, Orlando, FL 32806. E-mail: patrick.kupelian@orhs.org 58 1053-4296/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.semradonc.2007.09.008