Image guided radiation therapy (IGRT) is bringing with it a lot of buzz to the field of radiation therapy. IGRT captures real-time images minutes before treatment is delivered to the patient. Clinicians compare the images to treatment plans and make any necessary positioning adjustments so that the tumor is directly in the path of the beam. With IGRT, radiation oncology teams are better hitting the target, all the while gaining the confidence they need to increase doses, permeate the tumor and significantly decrease the side effects of radiation treatment.
As more and more cancer treatment centers throughout the United States add newer hardware and software capabilities to their arsenal of radiotherapy devices, treatment options for patients are expanding and rates of complications due to the side effects of radiotherapy are falling. Advancements in both the planning and the delivery stages of radiation oncology are giving radiotherapy teams the clinical confidence they need to go after the toughest of tumors; including masses intertwined with critical structures and tumors that have unsuccessfully undergone some other form of treatment.
Perhaps one of the most talked-about radiation oncology technologies on the market today is image guided radiation therapy (IGRT). IGRT allows images - created via ultrasound, x-ray, fluoroscopic or cone beam computed tomography - to be acquired immediately before a patient receives treatment to confirm that the beam is going to hit the intended target. Regardless if the patient is repositioned one, three or even seven millimeters back on target, IGRT enables radiation treatment to be delivered more accurately and at higher doses to eradicate the tumor.
In radiotherapy, doctors use ionizing radiation to kill cancer cells and shrink tumors. Intensity modulated radiation therapy (IMRT) takes external beam radiation therapy a step further than its predecessor, 3D conformal radiation therapy (3D-CRT). IMRT employs computer-generated images in an increased level of accuracy by matching radiation to the size and shape of a patient's tumor.
It's an iterative, time consuming process, but IMRT has the amazing ability to be exceedingly precise within millimeters, according to Michael Steinberg, MD, medical director at Santa Monica Cancer Treatment Center (SMCTC) in Santa Monica, Calif. "With conventional radiotherapy, we were precise within about 20 millimeters, meaning we had to put margins of two centimeters around the target just to make sure we were hitting it everyday," he says. "When 3D-CRT came along, precision got down to seven and 10 millimeters. IMRT is literally precise between one and three millimeters."
While IMRT has the potential to deliver high doses of radiation that permeate to the tumor while also missing critical structures, the addition of IGRT allows clinicians to carefully evaluate tumor motion throughout a patient's elongated treatment process. A significant problem in radiotherapy, tumor motion is attributed mostly to involuntary changes in patient anatomy that occur over the course of daily treatments and variation in patient set up.
To compensate for target movement in prostate cancer patients, clinicians at SMCTC are using NOMOS Radiation Oncology's BATCAM, an ultrasound image guidance tool, in conjunction with IMRT. The BAT combines ultrasound and a 3D tracking system with a touchscreen-based treatment room interface to non-invasively pinpoint tumor targets at the time of a radiation therapy treatment.
After patients are immobilized on the couch, Steinberg says that ultrasound images acquired via BATCAM are compared with fused MR/CT data sets that are acquired during treatment planning. "If the patient needs to be adjusted, the computer will actually [determine] how far off the patient is from the reference point from the original set up," says Steinberg. "The system will tell you to move the patient 4 millimeters in x direction, 5 millimeters in the y direction and 6 millimeters in the z direction.
"IMRT offers unprecedented precision and we add IGRT with the BATCAM, which localizes the prostate accurately each day of treatment to make sure that the highly precise dose gets to where it is intended," continues Steinberg. "With regards to dose escalation, it turns out that higher dose eradicates and cures more prostate cancer. The problem is that there are sensitive normal structures around the prostate like the bladder and rectum. By adding the precision afforded with the BAT, one is able to escalate dose higher because you can be more confident that you are hitting the target."
Improvements in imaging have included the development of electronic portal imaging (EPI) devices that produce megavoltage (MV) images so that target movement can be verified and patient positioning can be corrected. Newer versions of image guidance technology, such as Varian Medical Systems' On-Board Imager (OBI), produce real-time diagnostic quality radiographic images using kilovoltage (kV) energies. The advantages of kilovoltage imaging are that it produces high-quality digital images, and the imaging can be done more frequently since the dose the patient receives is lower.
The Josephine Ford Cancer Center (JFCC) is one of the largest cancer centers in Michigan that is affiliated with Detroit's Henry Ford Health System. JFCC has installed two Varian linear accelerators at its Downriver facility. One is outfitted with the OBI.
The On-Board Imager consists of robotic arms that operate along three axes of motion to position an x-ray tube and flat-panel image detector on opposite sides of the patient. Seconds after high-quality images are obtained, they are displayed in real-time on a control console so that physicians can compare them to reference images. In many cases, the patient needs to be repositioned to align the tumor with the radiation beam.
"We started taking electronic portal imaging two years ago," says Deepak Pradhan, MD, medical director at JFCC-Downriver. "Before that, our traditional practice has been to take treatment port images on x-ray plates at least once a week. But with electronic portal imaging, we could do megavoltage (MV) imaging everyday before treatment, especially for prostate cancer patients. Now with the kilovoltage (kV) arm of the OBI, the process is a little quicker because we obtain an MV image for AP and a kV image for the lateral right angle port without having to rotate the machine. We obtain those images and confirm the center position of the radiation field everyday before treatment for our prostate cancer patients."
According to Suzanne Schultz, chief medical physicist at the Radiation Oncology Department at Providence Medical Center in Kansas City, kV energies - compared with MV energies - produce a clearer image. "It is sort of like having something good versus something that is excellent," opines Schultz. Providence Medical Center recently installed Varian's Trilogy system, outfitted with an OBI, for image-guided radiosurgery.
"The images are crystal clear with the kV imaging," says Schultz. "For instance, with stereotactic in the brain, you need to be under a millimeter in terms of your accuracy. The [kV images] make you feel like you can really pinpoint it to that level. The other thing is that they are kilovoltage doses, which means lower dosage to the patient. He or she is already getting radiation treatment so it's not that the other images added a great deal to the treatment. It's further refinement of lowering the dose the patient receives, that is not the [actual radiation] treating the patient."
The Department of Radiation Oncology at Emory University School of Medicine also is equipped with Varian's OBI technology, which clinicians have been using since June 2004. "Kilovoltage energies result in improved image quality and lower patient dose compared with standard megavoltage imaging," says Tim Fox, PhD, director of the division of medical physics, radiation oncology, at Emory. "It is beneficial since we can take the images on a daily basis without increasing the dose to the patient. The improved image quality is better for matching the internal anatomic structures such as bony landmarks or implanted fiducial markers."
Improving the delivery
Fox believes that image guidance really refers to image guided radiation treatment delivery. "We are talking about images that guide the delivery of treatment," explains Fox. "The mid-'90s focused on CT simulation; next were improvements to treatment planning and 3D-CRT. We also saw the explosion of IMRT. Now the next wave is to look at delivery. One of the sources of error is set up uncertainty. Image guidance with the machine addresses that."
Emory's OBI is being used to manage two types of motion: inter- and intra-fraction motion. Inter-fraction are the changes that take place in patient anatomy on a daily basis, which can be significant in fractionalized treatments spanning the course of five to eight weeks. "For inter-fraction, we have used [the OBI] on prostate, head and neck, brain and breast cancer," says Fox. "Intra-fraction is the motion that happens when the patient is being treated. One of the causes of that is respiration. For intra, we have used it on lung, pancreatic and gall bladder cases."
Emory clinicians employ a technology called gating for intra-fraction motion. "With gating, we can turn the beam on and off according to the respiratory signal," says Fox.
The Radiation Oncology Department at the Providence Hospital in Mobile, Ala., is another center using the advanced gating application. Providence's radiation oncology team began using the technology after installing Varian's Trilogy with OBI. The department first started using the system to do stereotactic radiosurgery in the brain, and conventional radiotherapy treatments started on the Trilogy system in January.
Treating 600 patients annually with radiotherapy, Cheryl Atchison, chief therapist at Providence Hospital, explains that nearly 10 to 15 percent of patients are treated daily with IMRT. IGRT is being added to treatments for lung and prostate cancers. "When using OBI with our respiratory gating cases, these are lung cases who are patients with some sort of respiratory problems or they have had previous treatment in the area," explains Atchinson. "We need to make sure that when the patient is breathing, the tumor is not moving in and out of the beam."
Before any treatment is delivered, a CT scan is acquired of the patient and radiation oncologists use gating software to determine the most appropriate treatment plan. "When we start [treatment], patients are verified by the OB imaging," says Atchinson. "We can look at it to make sure that it is within the planned tumor volume. Before, all we used [as a reference] was anatomy. This is a huge leap for patients who need small fields and have some sort of respiratory disease."
In November 2004, Varian announced FDA clearance for cone-beam CT (CBCT) imaging using its OBI device for IGRT with the Clinac and Trilogy linear accelerators. Cancer treatment centers, such as the radiation oncology department at Duke University Medical Center, are in the very early stages of utilizing CBCT imaging to quickly acquire a high-quality 3D image of tumor and surrounding anatomy. Just before treatment, clinicians compare the new 3D images to reference images and make necessary adjustments to a patient's position so that is matches the treatment plan.
According to Fang Fang Yin, PhD, physicist, professor of radiation oncology and director of Duke's Radiation Physics Department, the information obtained from CBCT imaging allows clinicians to better see where they are treating and identify patient variations, as well as modify treatment plans. The technology works by acquiring more than 660 projection images as the gantry rotates 360 degrees around the patient. The software then uses the projection images to calculate CT images. "It can reconstruct up to 62 slices of axial images," says Yin.
"We can use CBCT data in two ways," continues Yin. "One is to match the bony structure in 3D to identify not only the shifts but also the rotation. In this way the patient reposition will be based on bony structures. The other way is to use CBCT data to match soft tissues between simulation CT and localization CBCT. The patient repositioning will then be based on soft tissue information. This could not be done by 2D matching."
Adding volume to treatment
The radiation therapy department at Princess Margaret Hospital in Toronto implemented IGRT with Elekta's Synergy. The hospital is one of four medical facilities initially involved in the clinical development of the Elekta Synergy image guided platform. Thus far, the centers have been successful at using Synergy's imaging platform to acquire online static x-rays, fluoroscopic images or 3D volume data sets to more accurately treat cancers in the prostate, liver, bladder, lung, head and neck, breast, brain, pancreas and rectal cancer.
Princess Margaret Hospital installed the system in 2002 and clinicians have been using it in clinical studies since 2003, according to David Jaffray, PhD, chief of radiation physics at Princess Margaret's radiation therapy department. "[Synergy] allows us to generate an image of a patient's internal anatomy by rotating the gantry around the patient about 360 degrees," says Jaffray. "Over that 360 degrees, more than 300 to 600 high-quality radiographic projections are taken and they are reconstructed into a volume that is substantial enough to encompass the patient with about 25 centimeters of superior-inferior field of view."
The system's software tools allow for imaging registration and comparison. The 3D image sets are reviewed by the radiation oncology team to see if adjustments need to made to the patient's position. Jaffray says the process, once refined, won't take longer than early electronic portal imaging. "Right now, it is about an extra five minutes," Jaffray says.
"IGRT increases the overall quality of radiotherapy as well as the ability to more precisely place radiation. One of the observations that the technology provides is let people pursue tighter margins knowing that the geometric component is increased confidence in the daily placement of the radiation field. However, what this will do in the long term is not yet well understood."
From ultrasound to radiographic to CBCT imaging, IGRT is the wave of the future in radiotherapy. The technology compensates for tumor motion, allowing clinicians to reduce their planning target volume and increase doses. Clinicians using IGRT with IMRT and other radiotherapy delivery devices are hoping to see reductions in complications for patients and significant improvement in tumor control.