Current Techniques in Three-Dimensional CT Simulation and Radiation Treatment Planning

The modern CT simulator is capable of interactive three-dimensional (3D) volumetric treatment planning; this allows radiation oncology departments to operate without conventional x-ray simulators. Treatment planning is performed at the time of virtual simulation by contouring the organs or volumes of interest and determining the isocenter. A digitally reconstructed radiograph (DRR) provides a beam's-eye-view display of the treatment field anatomy and contoured areas of interest. Conformal and noncoplanar teletherapy is facilitated for patients with prostate cancer, lung cancer, and brain tumors. Ongoing developments include 3D dose calculation, dose-volume histogram analysis, and tumor dose escalation.

Introduction

With the advent of high-speed, high-capacity computers, commercial CT simulators are now available that permit three-dimensional (3D), volumetric, conformal radiation therapy techniques to be used on a routine basis in busy, modern radiation therapy departments. Three-dimensional radiation therapy simulation allows multiple cross-sectional CT slices to be inputted into the treatment planning equation as part of a large, complex data set. With these sophisticated computers, the cross-sectional slices can be synthesized into a unified 3D volume [1].

Furthermore, interactive 3D treatment planning at the time of CT simulation provides a graphic display of the 3D anatomy of both normal tissue and a discrete tumor or tumor-bearing region. Consequently, complex relationships between structures can be appreciated within the treatment display; this facilitates the design of an optimal treatment plan through the rapid scanning of various treatment beams and field arrays.

Most significantly, the use of noncoplanar beams can now be quickly assessed and integrated into the treatment plan, and the radiation oncologist is no longer confined to simple coplanar anterior-posterior (AP) or opposed lateral fields. A third dimension is readily and clinically available with superior and inferior, as well as superior-oblique and inferior-oblique, fields. These new fields may be used to optimize the therapeutic plan and to minimize the dose to normal tissue structures [2-4].

Another important feature of 3D CT simulation is the ability to generate a digitally reconstructed radiograph (DRR), or beam's-eye-view display, which allows for verification of the treatment field using conventional port film techniques [5]. CT simulation permits multiplanar reconstruction, so that virtually any planar treatment field can be calculated using standard two-dimensional (2D) treatment planning systems.

Three-dimensional treatment planning techniques are now approved by the FDA, which will facilitate the use of multiple noncoplanar fields. Three-dimensional treatment planning technology also allows for dose-volume histogram analysis. This is a more accurate and optimal way of comparing (in a 3D sense) one treatment plan to the other, which compares the tumor volume and the volume of normal tissue that are irradiated by displaying the dose received according to the percent volume of tissue [6].

This article will briefly describe the 3D CT simulation procedure and the various types of images it can produce. (Table 1 defines key terms used in the article.) Clinical results to date with conformal radiation therapy in various carcinomas, including prostate, lung, and brain tumors, will also be summarized, as well as recent technologic developments.

3D CT Simulation Procedure

CT Data Acquisition

Computed tomographic scanning is performed with a 70-cm ring aperture and flat couch, which is integrated into a computer-based virtual simulator capable of 3D volumetric reconstruction and multiplanar reconstruction for treatment planning. A laser isocenter projection system is mounted in the room; the system combines two fixed and one movable sagittal laser with a variance of only 2 mm over a 6-month period. Digitally reconstructed radiographs (DRRs) with superimposed target volume information are generated by the computer and transferred to a commercially available CT film processor. Analysis of DRRs reveals acceptable bone detail and anatomic agreement with port films taken on the treatment unit.

The best quality DRRs are obtained with a nonspiral CT slice thickness of 2 mm and table increment of 2 mm. A slice thickness of 5 mm and table increment of 3 mm also yield DRRs of excellent quality. For larger fields up to 40 cm in length, a 5-mm slice with 5-mm table increment is used most commonly, and results in lesser detail but clinically acceptable positioning accuracy and results. For patients who cannot stay in position for more than 15 to 20 minutes, a 10-mm slice and 10-mm table increment provide acceptable quality for treatment of bone metastases and other simple treatment set-ups. Plastic mask immobilization facilitates brain, head, and neck positioning and stability.

The average length of CT simulation, including patient positioning; CT data acquisition with an average of 40 cuts; physician contouring of the target organ, volume of interest, or isocenter definition; and projection of the isocenter on the patient, is less than 1 hour. The amount of time that the patient spends on the CT table is consistently less than with conventional simulators for intact breast or prostate.

We have developed CT urethrography, which improves definition of the relationship of the prostate apex to the urogenital diaphragm and external urethra. An average of three CT simulation procedures daily, with a maximum of eight, have been performed. The ring aperture of 70 cm requires special arm positioning for breast and mantle simulation and treatment. Patients up to 350 pounds have been simulated on the rated couch.

Treatment Planning

Computed tomographic simulation requires a different perspective and expectations of simulation. With conventional simulation, the physician determines the edges of a field, whereas with CT simulation, the physician contours the treatment volume, and the computer determines the isocenter of a field. As such, with CT simulation and interactive 3D treatment planning, the physician identifies an organ or target of interest, such as the prostate or a brain tumor, along with a ring of normal tissue to account for patient positioning and microscopic extension of disease beyond the enhancing lesion seen on CT scan. When contouring of a discrete volume is performed, computerized selection of an isocenter can be performed at the time of virtual simulation and an isocenter placed into the middle of a 3D volume. In radiation therapy, however, a discrete organ or tumor nodule is not always treated with a small field. Therefore, a volume of interest must be defined, such as the intact breast, a long bone (Figure 1), a lymph node region, or multiple lymph node regions, such as a mantle field (Figure 2).

Three-dimensional CT simulation with accurate positioning and immobilization allows for rapid data acquisition, contouring of key structures, the selection of an isocenter, either manually or calculated by the computer, and 3D reconstruction, with the generation of a DRR in which the target volume is superimposed on the film. Once the isocenter has been determined, treatment planning can take minutes or hours, depending on the complexity desired. Exact field angles can be determined after the patient has left the simulation room with an isocenter marked on the patient's skin.

Digitally Reconstructed Radiograph

Using traditional simulation, the radiation oncologist obtains a radiograph from the region in which radiation is to be given. The simulator allows a field size with an isocenter to be projected upon the patient's skin, which can also be drawn on the skin. Once the radiograph with this information is obtained, specialized metal (cerrobend) blocking can be produced from the film and custom shape the radiation beam for daily treatment.

A disadvantage of conventional simulation is that it provides detail only of bone. In the case of the lung, conventional simulation can visualize soft-tissue masses if they are within the lung parenchyma. However, this type of simulation generally does not visualize mediastinal and hilar involvement as well as does a 3D CT simulation rendering (Figure 3). When conventional simulation is used for the abdomen or pelvis, contrast agents may allow the organ to be delineated more precisely. When treating the brain, the surgeon occasionally will leave a bone flap, which may help localize the tumor volume. If the treatment volume cannot be visualized, a larger field may be required than if CT simulation were utilized.

With a DRR, the contoured tumor volume is superimposed on the radiograph [7]. This radiograph takes into account beam divergence, and is an accurate representation of the treatment beam as it can be imaged with a port film [8]. Traditional simulation allows for radiographs to be obtained in anterior-posterior (AP), posterior-anterior (PA), oblique, or lateral directions. Treatment with superior or inferior fields, such as a vertex field in therapy for brain tumors (Figure 4) or inferior-oblique fields in therapy for prostate cancer, is difficult to simulate unless optimized with 3D simulation (Figures 5A and5B). This therapeutic approach, termed "noncoplanar therapy," refers to treatment that is given in anything other than the standard transaxial or CT plane.

Using interactive virtual simulation, beams can now be established from virtually any direction or angle. This allows critical structures, such as the spinal cord, kidney, eyes, or liver, to be shielded, and consequently, higher doses to be delivered to the tumor volume [9]. While noncoplanar therapy allows for the use of multiple beams (in fact, there has been a tendency for radiation oncologists to use multiple beams to treat a lesion), we have been surprised at the ability of just three noncoplanar fields to dramatically reduce doses to crucial structures. An example is opposed lateral and anterior-inferior oblique fields for treating the prostate. Using dose-volume histograms and comparing a three-field set-up with a six-field coplanar set-up, one can achieve a dramatic reduction in the rectal dose with the use of an anterior-inferior field (see "Dose-Volume Histogram" below).

3D Dose Calculations

Using 3D CT simulation, it is possible to do multiplanar reconstruction through virtually any plane of treatment. In this way, it is possible to obtain very good dose calculation using standard 2D treatment planning systems that are FDA approved and have a proven track record for clinical use. With currently available 3D treatment planning systems, one can look through the entire volume being treated and plan the superior and inferior aspects, rather than just the mid-plane dose calculation that a 2D system facilitates for noncoplanar treatment. Most 3D planning systems still display the isodoses on a slice through the treatment plane, although 3D isodose renderings are now available in which an isodose can be selected; ie, if a portion of the tumor volume is being underdosed, it projects through the 3D rendering of the isodose [10].

Dose-Volume Histogram

Dose-volume histograms display the dose received according to the percent volume of tissue and can be generated by the computer looking at the target volume and comparing it to tissues that are at risk and that are also contoured at the time of treatment planning [11]. Three-dimensional treatment planning allows for volumetric analysis of the area being treated, and as such, can aid in field design that may be difficult to visualize at the time of virtual simulation [12,13]. A dose-volume histogram can compare a six-field coplanar prostate set-up with a three-field noncoplanar prostate set-up and reveal a significant reduction in dose to a portion of the rectal volume (Figures 6A and 6B).

Clinical Results of Conformal Radiation Therapy

Prostate Cancer

Investigators have utilized conformal radiation therapy for the treatment of localized prostate cancer. Soffen, Hanks, and colleagues reported a reduction in acute morbidity with conformal therapy, as compared with nonconformal techniques [14]. Hanks et al further noted an average 14% reduction in rectal and bladder dose exposure with conformal therapy. Their experience using conformal therapy in 108 patients with localized prostate carcinoma revealed only 1% with Radiation Therapy Oncology Group (RTOG) grade 3 or 4 complications over a median follow-up of 16 months [15]. A recent report on this experience showed a 30% reduction in grade 2 urinary complications in the group receiving conformal therapy, as compared with a conventionally treated control group. Dose escalation to 75 to 79 Gy was achieved in 20 patients [16].

Leibel and coworkers described dose escalation using conformal therapy for localized prostate carcinoma in 123 patients. Doses ranged from 64.8 to 75.6 Gy. Only one patient experienced RTOG grade 4 toxicity, 67% of patients had normalized serum prostate-specific antigen (PSA) levels within 14 months of treatment (median, 4.5 months), and the early disease-free rate was 89% [17].

Our group has used conformal therapy to treat localized prostate carcinoma in 111 patients who did not receive hormonal manipulation. Treatment with radiation doses of 66.6 to 72.0 Gy resulted in normal PSA values (0 to 4.0 ng/mL) 6 weeks post-therapy in 49% of patients, and 88% (28 of 32) of patients achieved a normal serum PSA value of 0 to 4.0 ng/mL by 10 months after treatment. Eight patients experienced RTOG grade 3 toxicity, and none developed grade 4 toxicity [18]. Our block margin averaged 1.5 cm, which compares with Roach and associates [19], who have demonstrated that the ideal conformal block margin varies from 0.75 to 2.25 cm.

Lung Cancer

Conformal 3D radiation therapy may improve the therapeutic ratio of high-dose radiation therapy for lung cancer. Armstrong and associates analyzed nine patients treated with conformal 3D radiation therapy CT planning, and demonstrated that full radiation dose was delivered to nearly 100% of the target volume in all nine. Conventional treatment planning was equivalent to 3D coverage of the target volume in only two patients [20,21].

Emami and colleagues have shown that with 3D conformal radiation therapy the impact of inhomogeneity correction (x-ray scatter in surrounding tissue due to variations of tissue, air, and bone) on dose distribution can be significant and depends on anatomic factors and beam energy. Furthermore, they contend that 3D treatment planning has significant potential for optimization of treatment plans and will enable major progress toward better locoregional control of lung cancer with less complications [22,23].

Other Carcinomas

Preliminary analysis of the use of 3D conformal external irradiation for low-grade gliomas suggests potential increases in local control rates compared with conventional treatment techniques [24]. Robertson and associates have reviewed the clinical results of 3D conformal irradiation; in patients with unresectable hepatobiliary carcinoma treated with conformal therapy, median survival was 19.4 months, as compared with historical survival durations of 4 to 10 months with conventional therapy [25].

An NCI multi-institutional dose escalation study is currently evaluating the patient tolerance to higher doses of irradiation given with conformal techniques.

Summary

Three-dimensional CT simulation is FDA approved and commercially available for daily radiation therapy in patients. In fact, in our experience with 3D CT simulation, the conventional simulator is no longer clinically necessary [26]. The average amount of time required for simulation is under 1 hour.

Three-dimensional CT simulation has resulted in a dramatic increase in the effectiveness of radiation therapy planning. With this technique, it is possible to contour the target or volume of interest (Figure 7), superimpose it on DRRs, and treat patients with a high degree of accuracy (Figure 8). This would be very difficult to achieve with conventional simulation.

Furthermore, CT simulation allows for multiplanar reconstruction through any plane of treatment, which facilitates noncoplanar therapy. Possible advantages include safe administration of higher doses of radiation and minimization of the chances for toxicity and complications. Current developments include 3D intracavitary gynecologic implant planning using carbon fiber CT-compatible tandem and ovoids (Figure 9).

Clinical trials are attempting to determine whether dose escalation can be carried out with a favorable clinical result. In the meantime, 3D treatment planning results in reduced side effects and toxicity in patients treated with standard doses for their malignancies. The 3D CT simulation procedure has become rapid and accurate enough to be utilized on a routine clinical basis for patients with virtually any type of malignancy that can be treated with conventional simulation techniques (Figure 10).

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