Dr. Marks and his colleagues at Duke University have summarized their experience in implementing three-dimensional conformal radiation therapy (3D CRT) at their clinic. Their article emphasizes that introducing this technology into a busy department comes at significant cost. The biggest costs may not be the price of the software and the hardware necessary to carry out the treatment procedures, but rather, the costs related to the learning curve that accompanies implementation of this technology. Just as the authors have documented the additional time required to treat patients with 3D CRT, we too have published data indicating 3D CRT requires additional time, effort, and other resources.
The time and effort involved in treating prostate cancer patients with 3D CRT has decreased significantly since our initial experience and is now equivalent to the time spent using older conventional methods. We are currently collecting data on time and effort to make validated comparisons to our historical experience.
Moreover, we are in the midst of transitioning from conventional 3D CRT to intensity-modulated radiation therapy (IMRT) to treat our prostate cancer patients and will likely face another learning curve, as the planning and treatment methods for this type of conformal therapy is strikingly different from our current method. Programs that are considering implementing these new technologies should not be dissuaded by the learning curve. Eventually, the new technologies will be as efficient as existing therapy, but will offer considerable advantages to patients by reducing toxicity or improving tumor control.
Gross Tumor Volume
The importance of accurately defining target volume for 3D CRT cannot be overemphasized. The International Commission on Radiation Units and Measures (ICRU) Report Number 50 has defined a set of terms that help to standardize communication among radiation oncologists. This language has recently been updated in a supplementary report, ICRU 62.  The gross tumor volume is any tumor that can be imaged on a diagnostic study or palpated or visually appreciated on physical examination. Unfortunately, translating information from a diagnostic study or physical exam to a treatment planning computed tomography (CT) scan is a very complicated process.
Software tools are now available commercially to help radiation oncologists fuse information from divergent imaging modalities such as magnetic resonance imaging (MRI) and CT. Although these tools are helpful, they still fall short of being complete solutions. For example, what signal abnormalities truly represent gross tumor on an MRI scan? Should it only be the contrast-enhanced area, or low signal on a T2-weighted image? How do we accommodate imaging modalities that provide conflicting information, such as MRI, CT, and positron emission tomography (PET)?
In addition, how should information from the physical examination be used to estimate gross tumor volume? For example, CT scanning poorly visualizes seminal vesicle extension from a prostate cancer felt on digital rectal examination. Therefore, we generally include both seminal vesicles entirely in the definition of the gross tumor volume for any patient with palpable extraprostatic extension. This may be an overestimate of the true gross tumor in patients with clinical stage T3 cancers.
Clinical Target Volume
The clinical target volume is an especially challenging target to define. It encompasses both the gross tumor and any microscopic extensions into adjacent normal tissues or lymph node regions. The clinical target volume requires a working knowledge of the natural history and behavior of the primary tumor. This behavior may be dependent not only on the site of the primary tumor, but also on its histopathology and local extent.
The margin one sets for subclinical extensions needs to account for the statistical probability of tumor extension. The clinician needs to balance the risk of missing potential disease against encompassing unnecessary amounts of normal tissue. Thus, he needs to weigh the risk of causing complications against tumor recurrence when defining the margin for the clinical target volume.
In the future, we may rank regions of the clinical target volume according to risk of tumor involvement. We can do this currently to a limited degree by defining multiple clinical target volumes, and assigning each a separate prescription dose. Eventually, we may wish to describe the clinical target volume by probable tumor cell density, with risk decreasing according to a linear or logarithmic scale as we move away from the primary tumor.
Variable radiosensitivity of a heterogeneous tumor may also require differential clinical target volumes. New imaging modalities may help clinicians define the clinical target volume. Positron emission tomography or functional MRI imaging will allow us to capitalize on a tumors physiology to assess regions at risk that should be encompassed in the clinical target volume and may even allow us to predict relative radiosensitivity.
Planning Target Volume
The ICRU 62 report describes the planning target volume with greater detail than the original ICRU 50 report. The planning target volume is intended to account for uncertainties related to patient setup and internal organ motion. It has been argued that these two components of geometric uncertainty are mostly independent and that management of each requires different strategies.
Two new terms have been introduced to the practice of 3D CRT: the internal margin and the setup margin. The internal margin accounts for variations in size, shape, and position of the clinical target volume in relation to anatomic reference points (eg, filling of stomach or bladder, movements due to respiration, and so forth). The setup margin accounts for uncertainties in patient-beam positioning, which may include technical factors such as patient immobilization or the mechanical stability of the machine.
The magnitude of the margin used for the planning target volume is undergoing substantial change. A growing body of literature has characterized the nature of internal organ motion that may assist clinicians in defining the internal margin of a variety of tumor sites. Even more intriguing are interventions that may reduce internal margins by controlling simple physiologic processes such as bladder or rectal filling for pelvic tumors or gating or active control of the ventilatory cycle for thoracic or abdominal tumors.
The setup margin is being reduced by the use of careful patient positioning that has been aided by electronic portal imaging and new immobilization devices. One goal of many radiation oncologists is to reduce the setup margin to less than a few millimeters with devices such as stereotactic body frames or direct, real-time visualization of tumors with ultrasound or CT.
Evolving Standards of Care
As treatment methods move away from conventional beams with flat intensity profiles to noncoplanar or intensity-modulated beams, the usual methods of ensuring adequate treatment will be taken away from the radiation oncologist. We will rely increasingly on treatment verification methods that lack two-dimensional anatomic information. Therefore, we need to be confident in our definition of clinical and planning target volumes on treatment planning CT scans. In the future, the single most important task of the radiation oncologist in planning treatment will be to define appropriate target volume.
The new technologies of 3D CRT and IMRT are gradually becoming accepted as evolving standards of care. As a community, we should not forsake the independent evaluation of these technologies or their impact on patient outcome. The Radiation Therapy Oncology Group (RTOG) has nearly completed its first three cooperative group clinical trials in cancers of the prostate, lung, and brain. RTOG trial 9406, a dose-escalation study of localized prostate cancer, demonstrated a significant reduction in late toxicity despite higher radiation doses.  These favorable results are due in part to the strict quality assurance exercised in this trial.
Clinical trials such as these may provide important data that justify the use of new technology in radiation oncology. We encourage the radiation oncology community to continue to support clinical research in the implementation of new innovative technologies in our specialty, including 3D CRT, IMRT, and even brachytherapy. Whether or not your practice is a participant in these studies, the outcome of this research will have a significant impact on all clinical practices.
The RTOG 3D QA center website (rtog3dqa.wustl.edu) contains valuable information about participant credentialing and treatment planning systems that support the exchange of data for participants. Practices interested in RTOG participation (or its support) should review the guidelines for involvement as they consider purchasing treatment planning software.