s02a.jpg (12818 bytes)It’s amazing what a few great ideas can bring. And radiation therapy is benefitting these days from some dramatic improvements thanks to the combining of some medical imaging modalities and improvements in tried-and-true existing linear accelerator technologies.

Amongst the imaging technologies joining forces with linear accelerators to better target cancer are CT, PET and SPECT. Similarly, intensity modulated radiation therapy (IMRT) and intensity modulated arc therapy (IMAT) are stepping up with increased precision in conformal radiation therapy, too.

Siemens Medical Systems Inc.’s Oncology Group (Concord, Calif.) has combined a linear accelerator with a CT scanner to enable physicians to visualize tumors immediately prior to radiation treatment.

IMRT, a more automated and advanced form of conformal radiation therapy (CRT), relies on CT scans as well as positron emission tomography (PET) or single photon emission computed tomography (SPECT) scans prior to radiotherapy to more precisely locate cancerous tumors. Using several beams of varying intensity, IMRT systems can increase radiotherapy dosage to the tumor, and, at the same time, decrease dosage to the surrounding healthy tissue. One of the leading companies in IMRT is Varian Medical Systems Inc. (Palo Alto, Calif.).

Another new method of delivering conformal treatments is intensity modulated arc therapy. IMAT is a technology and process patented by Elekta Inc. (Norcross, Ga.). IMAT continuously changes multileaf collimator field shapes during gantry rotation and irradiation. While it is not yet commercially available in the United States, IMAT — like the CT/Linac combination and IMRT — meets the ultimate goal of radiation oncology — increasing dosage to the tumor, while sparing healthy tissue.

Each of these technological developments enables image-guided radiation therapy or treatment that uses medical imaging to better localize tumor volumes. Image-guided radiation therapy lends itself to faster and more effective treatment.

Integrating CT
For decades, radiation treatment has relied on skin landmarks to determine where to target treatment. Yet, every day there are slight variations in the location of the skin, and these skin variations occur more frequently and are more pronounced with age and weight.

“Relying on skin landmarks is not accurate,” says James Wong, M.D., chairman of the department of radiation oncology at the Carol G. Simon Cancer Center at Morristown (N.J.) Memorial Hospital. “While the skin’s location can vary externally, organs also can shift internally. The location, size, and shape of the prostate, for example, are affected by the amount of urine and feces.”

Wong and Minoru Uematsu, M.D., a colleague of Wong’s, began asking the questions that every radiation therapy patient asks: Are we missing the tumor? How do we know we are hitting the tumor?

The answer, the doctors felt, was to combine CT and a linear accelerator. So they took the idea to Siemens.

“It seems like a simple concept, but it took four years to develop,” says Wong.

This “simple concept” entails taking a formerly stationary CT and connecting it to a robotic arm. The modification represents a breakthrough in image-guided radiation therapy and allows physicians to pinpoint the tumor prior to radiation treatment to increase the radiation dosage to the tumor.

The Primatom CT/Linac system was the result of a single technological breakthrough. Traditional CTs, which drive a table through a bore during image acquisition, would not work in a radiation therapy room. Wong and Siemens reversed the traditional CT mechanism to meet the particular needs of radiation oncologists. With the Primatom, the bore moves in a very controlled way upon rails, while the patient and table remain stationary. Treatment is delivered on the same table immediately after the image is taken.

Wong describes the implications of this advance as tremendous. “Cancers that were barely curable before can now be cured,” he adds.

The first prototype for the Primatom was built in Japan. Today, Uematsu is using the CT/Linac to treat lung cancer patients.

According to Wong, when conventional radiotherapy is used on early stage lung cancer, 40 treatments yield a 20 percent cure rate. Japanese data with the CT/Linac show that five treatments can result in an 80 percent cure rate.

In the United States, Wong began using the Primatom with prostate cancer patients in July. Approximately one-third of the 20 prostate cancer patients treated with the Primatom had to be moved prior to radiotherapy because the CT scan revealed that the prostate had moved.

While the prostate results have been promising, Wong says the biggest implication is for the treatment of lung cancer. He plans to use the CT/Linac to treat lung cancer patients during clinical trials this fall. After that, he will use the device to treat liver cancer, as well as other cancers in other parts of the body.

“Right now, there are only three people in the United States who know how to use the machine,” he adds. “There will be a learning curve. Nevertheless, in a few years this will be a standard piece of equipment.”

The Primatom is designed to eliminate inaccuracies associated with acquiring CT data on a different table at a different time and allow oncologists to increase radiotherapy doses to the tumor. It also is designed to facilitate CT-to-CT comparisons over the course of treatment and to boost treatments that may be delivered with improved localization of the target.

The price tag for this up-to-the-minute tumor visualization is approximately $1.8 million.

One potential application of the Primatom is in radiosurgery. Commonly used to treat brain lesions, radiosurgery requires accurate positioning and localization the target can be time-consuming as well as very uncomfortable for the patient. With the Primatom, it may be possible to localize brain lesions immediately prior to treatment, with the patient in the treatment position.

Mark McCarthy, Siemens’ senior product manager, says the company now needs to establish a process for using the technology. The process for using the Primatom will include new software tools. Siemens will modify and build on existing software tools for use with the Primatom.

One Primatom currently is being installed at Christiana Healthcare (Wilmington, Del.).

s02b.jpg (12227 bytes)The IMRT way
IMRT is a relatively young cancer treatment tool.

(left) Varian’s IMRT system can help target radiotherapy dose to the tumor, sparing nearby healthy tissue.

“What we’re seeing now are different technologies converge in a desktop environment,” notes Calvin Huntzinger, Varian’s IMRT product manager. “In the past, radiation oncologists may have had only a few CT images and few, if any, functional [PET or SPECT] images. They were trying to build a 3D image [of the tumor] in their mind. Now they can visualize the entire volume on their personal computer.”

A few short years ago, radiotherapy was relatively generic. The one-size-fits-all treatment plan failed to fit anyone very well and it resulted in side effects when healthy tissue was exposed to radiation.

IMRT, Huntzinger says, allows treatment to be highly personalized for individual patients. The radiotherapy dose can be sculpted to the area clinicians want to treat. IMRT also can be delivered with beams the size of 2-by-5 pixels, each with varying intensity.

During an IMRT treatment plan, a physician can “see” the cancer by overlaying a structural image — a CT scan — with a functional image via PET or SPECT. MRI also may be used to help image the tumor.

One benefit of functional imaging technology is that it more accurately predicts areas of tumor growth, areas of hypoxia and where the tumor is necrotic. IMRT weds this new 3D view of the tumor to a very individualized radiotherapy treatment plan.

As in 3D conformal radiation therapy, a multileaf collimator on the linear accelerator contains up to 120 leaves and enables clinicians sculpt the beams to conform to the size and shape of the tumor. With IMRT; however, clinicians can vary the intensity of very small radiation beams and aim them at the tumor from many angles to deliver a complete 3D attack; reduced doses are delivered to the surrounding tissue to eradicate outlying cancer cells while protecting healthy tissue.

This is made possible by dynamic wedge beam shaping, a computer-controlled technique introduced by Varian in 1991, which makes it possible to vary the dose within a treatment field.

The final component of IMRT technology is software. Image processing software takes the diagnostic images and creates the 3D view of the tumor and anatomical structures. Next, inverse treatment planning software allows physicians to dictate their clinical objectives mathematically. The computer reviews thousands of treatment options to determine an optimal arrangement for the beams.

Treatment delivery software controls and drives the radiation beams, and finally, quality assurance software verifies that treatment was delivered according to the plan. Hardware and software for implementing IMRT was totally integrated by Varian in 1999.

Because of its high degree of accuracy, IMRT is most useful for tumors adjacent to critical structures. IMRT has been used to treat prostate, brain, head and neck cancers.

Michael Zelefsky, director of brachytherapy services at Memorial Sloan-Kettering Cancer Center (New York City), has treated 600 to 700 prostate cancer patients with IMRT.

“In the last two to two-and-a-half years, IMRT has become the standard mode of radiation treatment delivery [for prostate cancer] at our center,” he states. “IMRT allows us to deliver higher doses of radiation safely than in the past with standard 3D therapy.”

With prostate cancer, higher doses are critical for achieving optimal outcomes. Zelefsky’s research at Memorial Sloan-Kettering shows that higher radiation doses (81 Gy) improve local tumor control from 55 to 94 percent over lower doses (64.8 to 72 Gy). IMRT enables clinicians to deliver these higher doses, while concurrently reducing the rate of normal tissue complications from 10 percent to 2 percent.

A complementary treatment
Intensity modulated arc therapy (IMAT) is similar to IMRT. While IMRT changes the field shape while the radiation beam is in multiple fixed positions, IMAT changes the field shape while the gantry rotates.

Carl Mansfield, professor and chairman of the department of radiation oncology at the University of Maryland (UM of Bethesda), says both modalities accomplish essentially the same objectives. In fact, IMAT is useful for the same types of tumors as IMRT.

At the University of Maryland, researchers are in phase two clinical trials using IMAT to treat head and neck tumors, prostate cancer and tumors located near radiosensitive structures, such as the optic nerve, brain stem or spinal cord. Researchers compare IMAT to other treatment plans, including IMRT.

One difference between the two modalities is the shared radiation dose to normal tissue. Because IMAT cross-fires from more angles than fixed-gantry IMRT, normal tissue receives a greater dose of radiation with IMAT. In some cases, it is preferable for a larger dose to be delivered to a smaller volume, and thus IMRT is preferable. In other cases, such as the brain or gastrointestinal tract, it is preferable for the normal tissue burden to be distributed to a larger area, which favors IMAT.

UM physicians have been using IMAT wherever possible because of another difference in the two modalities. The treatment time of IMAT is faster than that of IMRT. IMRT treatment takes about 30 minutes, while IMAT can be completed in 10 minutes. The same linear accelerator can be used to deliver both IMRT and IMAT.

Unlike IMRT, which is being used at more than two dozen sites in the United States, IMAT is not yet commercially available. It is in clinical use in the United States at the University of Maryland, William Beaumont Hospital (Detroit), and the University of Washington (Seattle) and in Europe at Royal Marsden Hospital (London), Christie Hospital (Manchester, England), Netherlands Cancer Institute (Amsterdam) and University Hospital (Gent, Belgium).

s02c.jpg (7887 bytes)Elekta Precise system features an integrated multileaf collimator. Precise’s radiation head — 60 cm — is the smallest commercially available.

Dee Mathieson, product manager for Elekta Oncology Systems (West Sussex, United Kingdom), expects IMAT to be commercially available some time in 2001.

She notes some drawbacks associated with IMAT. They include increased overhead and a need for the right skill levels among physicians and physicists for treatment planning and support. Similar drawbacks might also be encountered with IMRT.

The software is available to any institution that purchased an Elekta linear accelerator. A multileaf collimator is required to implement IMAT, and Elekta recommends training, which is offered at University Hospital in Gent.

If an institution is starting with an empty room and wanted to equip and install an IMRT system, Varian’s Huntzinger estimates a price tag between $1 and 2 million. The final cost depends on the range of capabilities required and pre-existing equipment.

Converging Technologies
IMRT and IMAT rely on the convergence of several different technologies. IMRT, for example, which allows clinicians to paint a precise radiation dose to the shape and depth of the tumor, relies on a digital linear accelerator, a multileaf collimator, and computer-driven imaging. Computer-driven imaging makes IMRT and IMAT practical.

When physicians relied on a few CT scans or X-rays to image the tumor, they could visualize the readily evident tumor and target radiation to that tumor volume. They could not, however, see the microscopic extent of the tumor, thus radiation treatment might miss these areas of growth.

Now, when physicians can combine structural images and functional images, they are able to visualize the entire tumor volume, including microscopic extent on their desktop. There is a direct correlation between the ability to say exactly where the tumor is and the ability to tighten up radiation fields and achieve greater accuracy and higher doses without incurring additional damage to normal tissue.

Both IMRT and IMAT are very complex, multi-step treatment plans that require computer control. The advent of highly sophisticated treatment planning software allows radiation oncologists to specify radiation dosage to the tumor and restrict dosage to healthy tissue. The computer analyzes hundreds of treatment options before selecting a treatment plan that will meet the oncologist’s objectives.

IMRT and IMAT systems are able to deliver dosage to precise targets via a computer-controlled multileaf collimator. The first computer-controlled multileaf collimators were introduced by Varian in 1989. The multileaf collimator, which is a series of metal plates added onto a linear accelerator, is more efficient and precise than the four leaf collimator which shaped only four fields and required custom-made blocking devices to shape the beam; with a four leaf system therapists also needed to move blocks between fields to shape the beam. The multileaf collimator eliminates this time-consuming step.

A glimpse at the future
As researchers, physicians, and physicists look to the future of radiation oncology, Mansfield does not believe healthcare has “even reached the ultimate form of treatment delivery.”

Over time, he anticipates more approaches increasing the radiation dose to the tumor and decreasing the dose to healthy tissue. One of the near-term possibilities he envisions is tagging antibodies with radioactive material to deliver radiation only to the tumor. This type of treatment might be available in three to five years, he opines.

Another future treatment modality is interstitial implants with which radioactive material is actually inserted into the tumor. Interstitial implants are available now. It is quite likely that future developments will also continue to combine treatment modalities, adds Mansfield.

Huntzinger points to the human genome project and expects to see efforts to take that understanding to an individual level.

“It’s not so far off in the future that we’ll be monitoring patients at the genetic level,” he adds. “Protocols are being developed to look at genetic markers and tailor treatment accordingly.”

Physiologic gating, which monitors physiologic symptoms of a patient during each treatment, will allow physicians to tailor treatment depending on a patient’s physiologic responses during treatment. According to Huntzinger, physiologic gating is currently being implemented at leading institutions and will be routine in the next few months.

Mathieson believes that one area that is still “exploding” is imaging guided radiotherapy. She says research using a linear accelerator with a cone-beam CT device at William Beaumont Hospital will be the basis of Elekta’s new products for the next decade. Many of Elekta’s new products will feature a kilovoltage source and amorphous silicon detector mounted on the gantry of a linac to allow clinicians to visualize the tumor. end.gif (810 bytes)