One of the fundamental concepts of radiation therapy is this: if you can increase the dose to targeted areas, you can increase the cure rate. While this cause-and-effect relationship is easily stated and understood, in practical application it becomes a little more complicated. The most obvious consideration is the effect on adjacent normal tissue. Therefore, to avoid severe side dffects, physicians have historically restricted radiation doses.

In recent years, three-dimensional conformal radiation therapy (3D-CRT) has made it possible to improve turmor localization and, thus, minimize doses to surrounding, healthy tissue. The technique has allowed the escalation of dosages to the targeted area nad improve local tumor control. Ongoing research and evolving technology are combining to make 3D-CRT even more effective. Specifically, the advancements involve safe dose escalation and more precise targeting methods.

Steven A. Leibel, MD, FACR, chairman of the department of radiation oncology at Memorial Sloan-Kettering Cancer Center in New York, N.Y., says that an advanced form of 3D-CRT, intensity modulated radiation therapy (IMRT), has been developed which precisely shapes the high-dose radiation volume to cancerous areas and sculpts it arund adjacent normal tissues. This makes it possible to deliver higher doses to tumors without increasing side effects. (IMRT involves the utilization of radiation beams of varying intensity as opposed to beams of uniform intensity. Both 3D-CRT and IMRT uses less.)

Leibel reports that the feasibility of dose escalation was demonstrated by a recent study involving 1,100 patients with localized prostate cancer. Researchers set out to determine the maximum radiation dose that could be delivered. With conventional radiotherapy techniques, the dose level was limited to 68.4 Gy to 70 Gy, says Leibel. When the dose was increased to above 70 Gy, the rate of serious complications essentially doubled. S o we set out to determine what we could do.

According to Leibel, the researchers started out by determining what the side effects of 3D-CRT were at the traditional dose levels. Once this was determined, they began to increase the dose, raising the level to 75.6 Gy. When this was determined to be safe, it became the standard dose. Then the dose was increased to 81 Gy. When we gave 81 Gy, the incidence of rectal bleeding with the standard three-dimensional con-formal techniques was about 17%, Leibel points out. We thought that by increasing the dose to the next level of 86.4 Gy, we would see more complications. This stimulated our development of IMRT. We used that same dose of 81 Gy and found that the incidence of rectal bleeding decreased from 17% to 3%. With the IMRT approach, we were able to safely increase the dose to the prostate to 86.4 Gy. Leibel says that, with the standard dose now increased to 86.4 Gy, they are developing new approaches to increase the dose to 91.8 Gy.

MORE TUMOR SITES

Research on the effectiveness of 3D-CRT and IMRT is not restricted to prostate cancer, Leibel notes. Three-dimensional CRT and IMRT are being tested in a variety of different types of tumors to see where the advantages are, although, as time goes by, the only way you will be able to plan treatment is with 3-D systems and IMRT systems. Currently the advantages are being tested in a number of different tumors. For example, for 3D-CRT and IMRT, the big sites of testing are not only the prostate, but head and neck, brain and liver tumors, and lung and breast cancer, he explains.

During the past five years, physicians at St. Vincents Comprehensive Cancer Center in New York have been using 3D-CRT to treat a variety of tumors, according to Richard Emery, MS, the centers chief physicist. We use it on nearly 100% of our patients because the reasons 3D-CRT makes sense for prostate cancer are the same reasons that make sense for breast cancer, lung cancer, and just about anything else, he notes. Emery says that 3D-CRT was first used on prostate patients at the center. Then, as we have developed and evolved, we saw the benefit of using it for probably 95% to 96% of our patients, he adds.

3D-CRT PLANNING AND DELIVERY

As its name implies, conformal radiation therapy involves the delivery of a radiation dose that conforms to the shape of the target volume the prostate for instance allowing for a 3-D and volumetric visualization of the target volume and normal tissues. Treatment planning involves acquiring a volumetric CT with the patient immobilized in a position that will be identical to the one used for radiation treatment. Positioning is a critical part of the process; there fore, immobilization devices are used to hold patients in place. We position them on the CT table, and they are immobilized in some manner that is reproducible, explains Emery. That is extremely important because, when the patients later come for their treatments, we want to be able to position them in the same way they were positioned on the CT scanner every day.

Immobilization devices typically are made of foam or a plastic substance that hardens around the patients positioning. With the patient in this individualized device, CT scans are acquired, and treatment is planned We typically scan in intervals of 3 millimeters to 5 millimeters in the region of interest, says Emery. Following the scanning, the therapist may mark the patients skin and immobilization device to help in subsequent treatment sessions. The scans are then reconstructed and displayed on a computer screen. The virtual simulation computer creates a 3-D rendering of the patient, says Emery, and, while the patient is still in position, we perform the first step in the design of the radiation treatment. The first step, Emery explains, is the placement of the isocenter. That will be our primary reference point for the treatment of the patient, says Emery. So we need to define that point at that time. It is localized on the patient with external lasers and markers that will help reposition the patient each day, he adds. We then transfer that CT information to a 3-D treatment planning workstation, and we can spend hours or days, depending on the complexity working on the optimization of the treatment plan for that patient, says Emery. The radiation oncologist defines normal and target volumes on each slice of the CT scan. The oncologist chooses various beam arrangements to cover the tumor with radiation and minimize exposure to the normal structures. Images can be manipulated, and the oncologist can use various computer tools to design the best radiation beam geometry. The radiation therapy is then delivered in small fractions for several weeks, which allows normal tissue to recover between treatments. Generally, side effects from radiation therapy delivered with 3D-CRT are not too serious. In the case of prostate cancer, they may include bladder and rectal irritations. It depends on the site we are treating, says Emery, but side effects can include a skin reaction similar to a sunburn. However, this is common and goes away after a couple weeks of treatment. In the head and neck region, side effects can be a dry mouth or sore throat.

RESPIRATORY GATING

Because repositioning is a crucial element of treatment, methods are being developed to reduce patient movement. Emery reports that, at St. Vincents, they are working on ways to minimize the effects of internal organ motion during treatment delivery. The idea is that, if movement can be minimized, an even more tightly shaped conformal dose distribution is possible. One way this is being achieved is with respiratory gating. This is something we have been using for several months now and have been very excited about, says Emery. Currently, few places in the world have this technology.

Essentially, respiratory gating, a device developed by Varian Medical Systems, Inc., synchronizes the radiation therapy with a patients breathing patterns. It addresses the problem of internal organ movement as it relates to a patients respiration. The problem when we do a 3D-CRT treatment plan, especially with patients with lung cancer, is that the patient is breathing during simulation and, later, during the treatment, explains Emery. When a patient breathes, the target volume the tumor moves. So, essentially, we are dealing with a moving target. In the past, Emery says, this problem was dealt with by increasing treatment field margins to account for the movement. You cant see the movement on a CT scan because that is an image frozen in time, he points out. Respiratory gating, Emery says, allows therapists to track the patients respiratory cycle both at the time of the CT scan and at the time of treatment. In effect, we are able to isolate the position of the target during one specific phase of the respiratory cycle, either during exhale or inhale, says Emery. Thus, by isolating the target position, therapists can decrease the size of the radiation fields and, hopefully, involve smaller amounts of normal tissue.

This is accomplished by using a computer and linear accelerator to monitor the patients normal breathing pattern. Lets say we decided to deliver on exhale, explains Emery. Every time the patient exhales, the radiation beam comes on instantly for half a second. The moment the patient starts to inhale, the radiation beam goes off. It is pulsed like that repeatedly until the entire radiation dose has been delivered. The one drawback, Emery says, is that it increases the time of the treatment, but the additional time is not all that significant. It is much more significant that we can shrink the size of our radiation fields, he says.

Emery says the other technique the center has been working with is electronic patient tracking, a system complementary to respiratory gating that utilizes markers on a patients skin surface. It, too, allows for better targeting. Typically, the patient has a set of tattoos on the skin, and the therapist positions the patient, trying to align them according to t hose t att oos, explains Emery. This is a difficult process, and you have the element of human error in positioning. Emery adds that, with patient tracking, cameras that locate and monitor the markers in 3-D space are set up in the CT and the treatment room. This camera tracking system localizes each marker to less than 1 millimeter precision of variance which, Emery says, allows us to position the patient to the isocenter, which everything revolves around, with a greater level of accuracy. Now we can set up and position the patient more accurately than weve been able to do in the past.

CONCLUSIONS

Imaging and computer technologies continue evolving at a rapid pace. The possibilities that the advancements offer, when integrated into various treatment methods, are fascinating and medically significant. In radiation therapy, computers have made it possible to target are as of treatment with higher radiation doses while minimizing the risks to the healthy tissue, making radiation therapy even more effective in the ongoing battle against cancer in its various forms. New treatments like 3D-CRT and IMRT have improved ways in which radiation therapy can be delivered. Researchers have already developed new ways to minimize internal organ motion during treatment and deliver more effective dose distribution. All of this has happened in only the past decade. It is intriguing to speculate about what the next decade will bring.