Where do we go from here? The increasing use of IMRT and IGRT will be refined to allow radiation oncologists to increase doses while limiting toxicities, improving quality of life for patients.

By Jeffrey Feinstein, MD

Radiation oncology has made great strides in the treatment of cancer patients in the last decade, significantly improving patient management and outcomes. New methods of controlling the radiation beam are being combined with imaging and computing technology to give radiation oncologists unprecedented precision. The ultimate goal of these converging technologies is to allow radiation oncologists to adjust radiation doses based on real-time images of the tumor. Physicians will be able to see the location of the tumor, compare how much radiation has been delivered vs. how much was planned, and adjust the dose accordingly.

Radiation is one of the oldest treatment modalities in cancer, and according to the American Society of Therapeutic Radiation Oncology, is currently used to treat nearly two-thirds of all cancer patients. Since its beginnings, the challenge of radiation therapy has been to deliver the strongest possible dose of radiation to the tumor tissue, while sparing the healthy tissue around it to reduce associated morbidity and toxicity.

In the past this effort was limited by the available technology. X-rays gave a limited view of tumors and the images represented a static view of the tumor. As treatment progressed, the tumor changed shape and position. To account for this variation, a larger area of tissue would have to be irradiated. In addition, the accuracy of the radiation beam was limited by linear accelerator technology that consisted of a single beam from one to four directions.

These limitations have largely been overcome by the development of a more sophisticated means of beam control, known as intensity modulated radiotherapy (IMRT), and the application of ever-improving imagery techniques, generically referred to as image-guided radiotherapy (IGRT). Other significant developments include improving computer algorithms that guide treatments and new electronic medical record (EMR) systems that allow everyone on the increasingly multidisciplinary oncology team to view the latest images of the tumor.

IMRT and IGRT

As the name implies, IMRT allows radiation oncologists to modulate the intensity of each radiation beam, so each field has multiple areas of high- and low-intensity radiation within the same field. The use of multi-leaf collimators provides for high-resolution IMRT. This ability to modulate the radiation dose provides almost limitless possibilities to customize each patient's treatment. Improved treatment planning software also helps determine the optimal distribution of beam intensities across the treatment area.

IMRT, which has been used in the clinical setting for over a decade now, gave radiation oncologists a powerful tool for treatment. However, IMRT was limited by the increased potential for treatment errors due to organ movement or errors in patient positioning. Radiation oncologists needed a better way to view their targets to optimally deliver this powerful treatment. Fortunately, advances in imaging that capture soft tissue as well as skeletal structure — such as computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) — provided the technology to acquire the more accurate images that IMRT required. This combination of electronic portal imaging devices (EPIDs) to provide accurate, powerful radiation therapy is referred to as IGRT.

New IGRT technologies

Although the use of advanced imagery technologies gave radiation oncologists unprecedented control of radiation treatments, some limitations remained. Most of the images were obtained outside of the radiation treatment room prior to treatment. During the planning phase, the images — port films — were used to determine treatment areas, which were then marked by tattoos on the skin. Because image reading and treatment occurred in different rooms, there was a potential for error in delivering the beam to the targeted area. In addition, tumor size and location often changed during treatment. To account for those variations, physicians included a sizable margin around the tumor.

The use of three-dimensional (3D) imagery with improved beam technology reduced the area of normal tissue being irradiated and allowed for more powerful doses to be targeted on the tumor. What has revolutionized the field in the last two or three years, however, is the practice of incorporating imaging tools onto linear accelerators. The X-ray source, imaging array and positioning systems may be part of the same unified system. This merger of technologies allows the radiation oncologist to target the beam on the tumor as it exists immediately prior to treatment, position the patient exactly as needed, and deliver a powerful, precise dose to the tumor. Innovative advancements that have emerged in the last year or two include cone-beam CT, kV imaging and gated CT.

Cone-beam CT brings the power of CT into the treatment room, providing up-to-date images showing soft tissue, organs, bony anatomy and alignment in three dimensions. As the name implies, the 3D volume imaging functionality of CT is integrated with the linear accelerator using a secondary, lower energy X-ray source than used for treatment delivery. The volumetric CT data set, which is reconstructed in a single gantry motion, allows an image of the tumor site to be acquired and displayed right before treatment begins. Differences of tumor location and size between the CT planning images and the current images are noted automatically by advanced software. The treatment couch is adjusted automatically before the treatment begins. Such precision allows the margin around the tumor to be minimized and helps limit set-up and positioning errors.

Planar kV imaging works in a similar fashion to cone-beam CT, providing high-quality, high-resolution X-ray images. The same kV X-ray tubes that are used for cone beam CT acquisition are attached to the linear accelerator and operate in a plane orthogonal to the megavoltage beam and its associated imager. This system provides quick low-dose radiographic images that can used to view high-contrast lung tumors and bony landmarks that don't overlay other bony features. Again, computer software adjusts treatment based on these nearly real-time X-ray images and images obtained during the planning stage. This planar technology also allows for derived 3D localization through stereoscopic (orthogonal imaging) visualization.

Together, cone-beam CT and planar kV imaging allow radiation oncologists to compare planning images to images acquired right before treatment and adjust the location and frequency of the multiple beams of IMRT. But another important variable exists: the natural motion of the organs and tissue due to breathing. Some manual methods can be used to control the motion of the tumor during breathing, including voluntary breath hold, deep inspiration breath hold, and physical restraint. However, patient compliance limits the effectiveness of those methods. Controlling breathing is a difficult task for patients who may already have respiratory issues.

Gated CT is an electronic method of minimizing the effects of breathing during treatment. The gating system uses CT images acquired during the planning phase. Those CT images show the location of tumors and organs at different phases of the respiratory motion cycle. Using the gated CT or sequential imaging, the beam is adjusted so that it is turned on and off at specific intervals. This capability effectively "freezes" the tumor in one location, delivering radiation to this one area while the patient breathes normally.

These advances in beam delivery and imaging allow for higher doses to be targeted to tumors while avoiding normal tissue that previously had to be included in the radiation oncologists' extra margins. Not only can this method improve treatment, it also shortens treatment times. More important, more precise treatment increases the quality of life for patients.

In head and neck cancer, for example, the new technologies help avoid irradiating salivary glands, which in the past caused extremely uncomfortable side effects of xerostomia and its more serious complications such as mandibular osteoradionecrosis. In prostate cancer, improved imaging and beam control help to avoid impotence and incontinence by reducing the dose of radiation delivered to the bulb of the penis. The new method also limits the risk of rectal complications associated with traditional radiotherapy. Because of the recent nature of these advancements, limited data exist demonstrating improved survival; nonetheless, it is hoped that such data will be available in the near future.

Although these technologies are costly, reimbursement is good for this field, particularly for IMRT. Hospital, academic and freestanding facilities are expected to use IMRT and IGRT as described here in greater numbers as the technology becomes more affordable and the benefits of the treatments are seen in the long term. Future improvements include real-time imaging that can be used to adjust the radiation dose. We'll revisit that point after examining another crucial part of the new technology equation — tracking and monitoring all images and treatments.

Specialized EMR for oncology

EMRs have improved clinical efficiencies and limited treatment errors by providing a full record of a patient's treatments; the record can be viewed by anyone on the care team. Specialized EMRs for radiotherapy take this capability a step further. They not only help with scheduling, track treatments and outline future treatments, but also provide caregivers with the most up-to-date images of the tumor itself.

The images help guide the radiation treatments, but they also can be used by oncologists to view how the tumor is responding to treatments.

Cancer care has increasingly become multidisciplinary and the ability of the entire cancer team to view images of the tumor through the treatment process is invaluable. Two recent studies reported that concurrent chemoradiation with cisplatin showed a local control benefit, and the chemoradiation arm in one of the studies had improved overall survival. Another study found the combination of cetuximab (Erbitux) and radiation increased two-year survival over radiation therapy alone from 55 percent to 62 percent. Median survival increased from 28 months with radiation therapy alone to 54 months with the combination therapy.

Future technologies

In the near term, use of the newer technologies described thus far will become more prevalent, particularly cone-beam CT. Two new technologies — non-image-based positioning systems and megavoltage cone-beam CT (MVCT) — should become available in the next few years and will bring the field closer to the goal of real-time, dose-adaptive radiotherapy.

Although improved visual imagery has been behind the recent improvements in delivering radiotherapy, an exciting new possibility is the use of non-image based positioning systems such as implanted transponders. These transponders, about the size of a grain of rice, are excited by an AC electromagnetic field, the signals of which are captured on an interface that identifies the target before and during treatment. The system can provide real-time information about the location of the tumor without adding ionizing radiation (used by imaging systems).

MVCT uses the same megavoltage source of radiation to acquire the image of the patient, improving the integration between the imaging and treatment delivery and eliminating the delay in processing the images. This capability will allow radiation oncologists to reconstruct the actual daily-delivered dose in real time.

The ultimate goal of these technologies is to provide dose-adaptive radiotherapy. Essentially, radiation oncologists will be able to see in real time the delivered dose, compare it to the planned dose, and then adjust the dose during treatment to make up for any difference between the planned and actual dose. Such a system may be available commercially in the next three to five years.

Improvements and refinements

The use of IGRT to improve the control of IMRT will become more widespread, particularly if improved survival outcomes can be demonstrated as more data becomes available. The increasing use of these technologies will be refined to allow radiation oncologists to increase doses while limiting toxicities, improving quality of life for patients. In addition, decreases in treatment time will make these technologies more convenient. Ultimately, new technologies such as MVCT will allow for real-time dose adjustments, so there will be no difference between the planned dose and the actual dose.

Dr. Feinstein is medical director of radiation oncology at Hinsdale Hospital, Hinsdale, Ill. He is a clinical associate faculty member, Department of Radiation and Cellular Medicine, at the University of Chicago, and lecturer at University of Illinois, Chicago. Board-certified in radiation oncology, he is an active member of various organizations and oncology societies.