//Development and Research Issues

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Development and Research Issues

IMRT can really be considered an extended form of 3D-CRT with use of a large number of segmented fields. At the core of clinical implementation is the computer optimization and 3-D patient imaging, usually with CT, but more and more often augmented by PET, MRI, and other functional imaging studies. This 3-D patient imaging enables the physician to accurately contour the PTV plus normal tissues of interest, which, when coupled with BEV design of treatment portals, permits delivered dose distributions to conform to the shape of the PTV while sparing normal tissues to a level not approachable during the era of conventional radiotherapy. There is significant interest in developing methods to verify the delivery of IMRT beams. These efforts are benefiting greatly from the gradual maturation of the EPID technology, particularly amorphous silicon detectors and onboard volumetric imaging systems. [120] The ability to directly verify the intensity pattern of the delivered intensitymodulated beams will greatly enhance confidence in the use of IMRT and lead to wider acceptance of this modality. At present, the electromechanical monitoring of leaf positions during radiation delivery provides similar assurance, albeit indirectly. With the availability of onboard cone beam CT (CBCT), it is now possible to obtain the patient's on-treatment geometric model. Combined with the MLC log file or EPID-captured delivery segments, this allows us to retrospectively reconstruct the delivered dose distribution to the patient. [74,121-124] An example of reconstructed dose distribution is shown in Fig. 10-21 for a head and neck cancer case. In this example, CBCT 1, CBCT 2, and CBCT 3 were taken at 1 day, 15 days, and 30 days, respectively. For illustration purposes, the fluence maps used in this calcualtion were reconstructed using a simple ray-tracing algorithm. The DVH comparison of the four different dose distributions is also presented.

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FIGURE 10-21 An example of reconstructed dose distribution for a head and neck cancer case. In this example, cone beam computed tomography (CBCT) 1, CBCT 2, and CBCT 3 were taken at 1 day, 15 days, and 30 days, respectively.

IMRT offers a valuable tool for dose escalation and radiation toxicity reduction, and shows significant potential to improve therapeutic ratio. In reality, however, the efficacy of IMRT can only be fully exploited with an effective means of dealing with the uncertainties in beam targeting. To ensure the delivery of exquisite IMRT dose distribution, image guidance becomes an important issue, as evidenced by the intense research effort in imageguided radiation therapy (IGRT). [120] The overarching goal of IGRT is to eliminate or reduce the uncertainties associated with target volume definition and intrafractional and interfractional organ motion. Various novel imaging techniques, such as 4D-CT, [125-128] 4D-PET, [129-131] and 4D-CBCT[132-135] are applied to radiotherapy guidance and verification. With integration of these state-of-the-art imaging technologies and time-resolved IMRT (such as respiration-gated IMRT), it is anticipated that we will be able to treat moving targets with much reduced safety margins and with high confidence in the near future. Adaptive IMRT is an active research area that is currently being pursued at a number of institutions to overcome issues related to setup errors and interfractional anatomy changes. [25,136-139] Despite the fact that these uncertainties are inevitable during a course of radiotherapy, up to this point, almost all research efforts have been focused on reducing the adverse effects of organ movement and deformation by attempting to reposition the patient more accurately. Indeed, the conventional approach treats the patient as a rigid dummy and tacitly ignores the multidimensional nature of the beam-targeting problem in radiotherapy. The integration of CBCT in linear accelerators opens a new avenue of volumetric image-guided adaptive therapy, in which the patient's on-treatment imaging data is used as feedback for adaptive modification of the treatment plan to ensure full dose coverage of the tumor target while sparing the sensitive structures. To realize this new paradigm of radiotherapy, a number of enabling computational tools, such as replanning, [137],[140] contour propagation, [22,23,141] and deformable image registration,* must be developed and their potential benefit must be evaluated. The use of biologic models of tumor tissue response as criteria for plan optimization has attracted much attention. [15,42,112,144-147] In general, biology-based score functions typically consist of some weighted combination of biologic indices such as NTCP [114] and TCPs.[118],[119] These indices condense structure-specific dose-distribution data to yield relative figures of merit for the respective objects of interest. However, both of these indices are based on rather rudimentary models with simplistic assumptions. Importantly, clinical data for validating the models and deriving the model parameters are lacking. Nevertheless, the advent of 3D-CRT and the accrual of patients treated with this modality are beginning to provide clinical outcome data for which DVH data are available. For example, analysis has been performed on clinical complication data of the liver, prostate, and optic pathways[7,12,67,148-154] using specific DVH information. Such studies promise to improve the present biologic models and provide better estimates for the model parameters. It is hoped that the iterative process of generating clinical data and refinement and validation of the models will incrementally improve the predictive power of the biologic indices and facilitate the quantitative evaluation of 3-D treatment plans. The ability of IMRT to deliver nonuniform dose patterns brings to the fore the question of how to dose paint or sculpt, leading to the suggestion that biologic images may be of assistance.* In contrast to the conventional radiologic images that primarily provide anatomic information, biologic images reveal metabolic, functional, physiologic, genotypic, and phenotypic data. Important for radiotherapy, the new and noninvasive imaging methods may yield 3-D radiobiologic information. Studies are urgently needed to identify genotypes and phenotypes that affect radiosensitivity, and to devise methods to image them noninvasively. Incremental to the concepts of GTV, CTV, and PTV, we suggest the concept of biologic target volume (BTV) and hypothesize that BTV can be derived from biologic images and that their use may incrementally improve target delineation and dose delivery.
[89],[156]

* References 23, 120, 129, 131, 133-135, 137, 142, and 143. * References 7, 15, 32, 42, 57, 89, 146, 147, 149, 150, and 155-158.

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