Medical Device Daily Washington Editor

WASHINGTON - It is no secret that more than one source of energy is available for radiological imaging and therapeutic purposes, but the proton has made few headlines in recent years as other energy sources have taken center stage. Still, recent events suggest that the relatively bulky proton may be staging a comeback that may threaten the status currently enjoyed by photon-producing Gamma Knife (GK).

Reinhard Schulte, assistant professor of radiation medicine at the Loma Linda School of Medicine (Loma Linda, California), gave participants at the second day of the fourth annual meeting of the International Brain Mapping and Intraoperative Surgical Planning Society (IBMISPS; West Hollywood, California) a look at the past, present and future of proton radiosurgery. Schulte said that despite the prominence of the photon, the particle used in the GK, there is still some debate as to which type of energy is ideal to treat many conditions. Schulte reminded the audience that Lars Leksell, PhD, the inventor of the GK, was also one of the first to propose the use of protons as a medical tool.

Other parties involved in early proton neurosurgery include Cornelius Tobias, PhD, and John Lawrence, PhD, who both worked at the physics labs at the University of California at Berkeley

Schulte said that Ernest Lawrence, PhD, John's older brother by four years, invented the cyclotron used to produce protons and the inspiration behind the naming of the Lawrence Livermore National Laboratory (Livermore, California).

In the 1950s, John Lawrence and Tobias used a cross-fire arrangement with multiple sources of proton beams on pituitary tumors to substantial effect. This advance gave medical science an alternative to the highly traumatic transcranial approach to pituitary tumor surgery, a procedure that entailed removal of portions of the front of the skull.

An alternate to the transcranial approach, the transsphenoidal approach, had lost favor among neurosurgeons in the second quarter of the 20th century due to several problems, including difficulty reaching all parts of a large, infiltrating tumor. The fact that the pituitary hangs almost like a punching bag from under the forebrain relieved researchers from concerns about collateral exposure of brain matter to radiation, making tumors of this gland the ideal candidates for development of novel radiosurgical techniques.

This first effort employed protons in a fairly raw fashion, however, and researchers saw the potential for greater efficacy if they could move beyond a simple cross-firing deployment.

In order to move the science along, however, researchers had to manipulate the energy levels of the protons so as to induce a peak effect in terms of depth that would maximize the hit on the tumor and minimize the exposure to surrounding tissues. Fortunately, Sir William Henry Bragg had already spelled out this peak effect for proton radiation in the 19th century.

"Raymond Kjellberg, an MD working at Harvard University (Cambridge, Massachusetts) in 1961, was the first to use the proton Bragg peak" to treat pituitary adenomas, Schulte said. Kjellberg is said to have teamed up with Robert Wilson, PhD, one of the leading particle physicists of the day, to develop a tabletop proton accelerator, but the effort apparently came to naught.

"Behind the Bragg peak, there's a rapid dose fall-off," which makes protons good "for spreading energies at a certain depth," Schulte said.

Schulte also said that protons delivered at an energy level of 250 million electron volts (MeV) "have a sharper penumbra" than gamma knife for depths below 10 cm, making this a potentially much more refined instrument for deep brain tumors as well as those nearer to the surface of the skull.

There was little argument at the IBMISPS gathering that proton beams can do some things much more effectively than gamma radiation, but conventional proton therapy systems can run as much as $200 million to build and a fair amount of floor space.

This problem may change fairly shortly, however.

Researchers at Lawrence Livermore have teamed up with the University of California-Davis Cancer Center (Sacramento, California) to come up with a system to collect and drive protons for less money and in a lot less space than currently required. The two institutions commenced work on a project in 2000 to develop a device known as a dielectric wall accelerator (DWA), which uses resistance to conduction to generate a flow of protons.

According to a July 16 article at Newswise.com, the Livermore DWA is a hollow tube insulated with ceramic and, when "most of the air is removed from the tube to create a vacuum, the tube can structurally withstand the very high electric-field gradations necessary for accelerating protons to high energies in a short distance." This type of device can "accelerate protons to up to 100 MeVs in just a meter," the article states.

The relationship between tube length and proton energy output is apparently a straight-line relationship, so a doubling of the length of the DWA would double the energy to as much as 200 MeVs, which would provide a Bragg peak that could treat the deepest tumors in the human body.

Another feature of the DWA that has captured the interest of researchers is the device's inherent ability to control the intensity of the proton beam as well as the beam's energy, a feature that would parallel the intensity-modulated radiation therapy that has generated so much interest of late in scientific circles with regard to the GK. With this kind of control, proton beams could well supplant other forms of radiation in treatment of tumors.

All this technology might fit into a tube six feet long, but Thomas Mackie, PhD, a professor of medical physics at the University of Wisconsin (Madison) is quoted in the article as saying that clinical trials may be five years off. On the other hand, Mackie and his colleagues at TomoTherapy (Madison) thought enough of the Livermore effort to help fund it.

TomoTherapy seems to have sufficiently deep pockets to make this a reality, given that its recent initial public offering in June brought in $186 million (Medical Device Daily, June 15, 2007).