Stereotactic body radiation therapy

Four years ago the leadership of the American Association of Physicists in Medicine (AAPM) formed a task group to investigate the efficacy and safety of a new kind of radiation therapy for treating cancer. Chaired by Stanley Benedict of the University of Virginia and Kamil Yenice of the University of Chicago, the task force has now published its report (S. H. Benedict et al. Med. Phys. 37, 4078 (2010). ).

The new treatment is called stereotactic body radiation therapy. Like earlier radiation-based therapies, SBRT relies on the ability of x or gamma rays to damage or destroy cancer cells’ DNA. Without intact DNA, cancer cells are unable to do what makes them so deadly: Multiply and spread unchecked.

What sets SBRT apart from previous radiation therapies are the high radiation dose used in each treatment and the precision with which the dose is delivered to the tumor, thereby sparing nearby healthy tissue from harm.

In writing its report, the SBRT task group aimed to provide a set of best practices for medical physicists, clinicians, and therapists who are using, or who want to use, what is emerging as an effective weapon in the battle against cancer.

Fewer, stronger doses

In conventional radiation therapy, tumor cells are destroyed over time by irradiating them repeatedly with small amounts of radiation at regular intervals. The process, called fractionation, is needed because of the imprecise targeting of the most common radiation therapy systems. To make sure that no part of a tumor is left untreated, radiation oncologists include a margin of healthy tissue in the target volume.

The margin compensates for several targeting uncertainties, including misalignment of the patient in the treatment machine, changes in the position of the patient’s anatomy between treatments and during treatments, and imprecision in the machine’s delivery of the radiation field itself. Another source of uncertainty arises from imprecision in the measured tumor volume.

Fractionation works because healthy tissue and tumors recover from radiation at different rates. After receiving a modest dose of radiation, healthy cells within the radiation margin will have recovered more than the tumor cells by the time of the next radiation session, typically about a day later. Eventually, the accumulated damage to the DNA of the tumor cells destroys their ability to reproduce, and the tumor dies.

In conventional radiation therapy, the tumor will receive a dose of 2 gray each session, over a course of 20–40 sessions. (In radiation therapy, the absorbed dose to tissue is described in units of grays; 1 Gy is the amount of ionizing radiation that deposits 1 joule of energy in 1 kg of matter.) A typical course of radiation therapy would deliver up to 80 Gy to the tumor.

Despite helping to spare healthy tissue, fractionation has drawbacks. Patients need multiple visits at evenly spaced times, which could be difficult to schedule. Worse, during the protracted treatment regimen, cancer cells could spread to establish metastases or repair themselves sufficiently to survive and multiply anew.

But with SBRT’s more accurate targeting, higher doses can be safely delivered in one session, reducing by an order of magnitude both the number of sessions and the size and margin of healthy tissue needed to ensure adequate tumor coverage. Rapid advances in five interconnected areas led to improved performance and with it greater confidence in the precision of the radiation treatment:

• Tumor imaging and identification
• Design and modeling of three-dimensional radiation patterns in human tissue
• Technologies for immobilizing patients
• Techniques for delivering radiation to moving targets
• Image-guidance during treatment to help direct radiation beams on the tumor

The new therapy evolved from a combination of two existing technologies: stereotactic radiosurgery and intensity-modulated radiation therapy (IMRT). In stereotactic radiosurgery, which is used to treat brain tumors, a large number of narrow radiation beams target the tumor with heavy doses of radiation. The brain is simpler to treat than other organs because it and the surrounding skull can be regarded as rigid and are easily immobilized. In IMRT, beam shapes and intensities are changed to help the 3D radiation dose match the shape of the target, but without SBRT’s high precision.

The first step in SBRT is to create a 3D image of the tumor using computer-assisted tomography, magnetic resonance imaging (MRI), positron emission tomography, or all three. Radiation dosimetrists, medical physicists, and radiation oncologists then use a sophisticated radiation treatment planning system to model the relative dose deposition in various tissue types and to determine an optimized plan for delivering radiation to the tumor.

Typically, SBRT uses a large number of beam trajectories to optimize the geometric placement of the 3D dose pattern on the tumor and to minimize normal tissue exposure. The beams’ duration, profile, and direction can all be adjusted more or less arbitrarily by the treatment planning system.

Dividing the dose among numerous beams that hit the same target but enter the body at different angles can be more effective than dividing the dose among a few beams. The advantage arises because the combined dose at the target where all the beams converge is significantly higher than the individual doses along any of the beams’ separate trajectories. As a result, the target receives a heavy, focused dose while healthy tisse receives a light, distributed dose.

On its own, the ability of SBRT to accurately define a radiation dose distribution around the tumor would be useless without the complementary ability to accurately deliver the intended dose. In both IMRT and more traditional radiation therapy, treatment margins of up to a centimeter are defined around the tumor in all directions.

By contrast, SBRT requires a margin of only a few millimeters. Given that margins are linear not cubic, the volume of healthy tissue that SBRT spares is considerable. Thanks to its greater geometric precision, SBRT can deliver a more toxic dose to the tumor in smaller number of fractions (1–5) than IMRT can (10–40).

Guiding light

Image guidance at the time of treatment is essential to SBRT’s increased precision and to ensuring that the tumor is in the planned treatment position. By imaging the patient in the treatment room and by using sophisticated image registration algorithms, the radiation therapist can adjust either the patient’s position or the treatment plan to account for changes in the tumor’s size, shape, or location in near real time.

Even with a perfect map of the tumor at the onset of treatment, millimeter-level precision cannot be sustained without managing the patient motion, monitoring his or her internal organs in real time, or both. Various mechanical positioning and motion-limiting systems have been designed for SBRT and evolved out of the simpler immobilization techniques successfully applied to radiosurgery for brain tumors.

Current techniques include vacuum cushions and moldable plastic mask systems to limit motion, gating systems that track internal organ motion and turn off the beam whenever the target is out of optimum position, and 4D imaging technologies to help define the extent of tumor motion.

Because SBRT requires such sustainably high precision, the AAPM task group recommends a host of safety measures, including the simulation of treatment plans, the use of high spatial resolution in imaging and dose calculations and the continual evaluation of dose tolerances for healthy tissue located near high-dose targets.

The task group emphasizes that ongoing training of personnel is essential. Referring to a set of guidelines published jointly by the American Society for Therapeutic Radiology and Oncology and the American College of Radiology, the task group wrote:

Clinical results have been impressive so far. References cited in the task group’s report describe success in treating tumors in a large variety of locations, including lung, liver, and spine.

Because SBRT is usually applied to relatively small tumors, and the overall toxicity of the treatment is lower than traditional radiation treatments, SBRT is more suitable than either conventional radiation therapy or IMRT for use in concert with chemotherapy, an approach known as systemic therapy.

Whether SBRT saves many lives will probably depend as much on its cost as on its effectiveness. A typical SBRT system costs between $4 and 5 million, about twice as much as an MRI scanner.

Charles Day

Stereotaxis is a method in neurosurgery for locating points in the brain with respect to an external coordinate system. ‘Stereotactic body’ refers to the method’s extension to the entire human body.