Katy Walter
Beginning in 2014, a particle accelerator derived from Lawrence Livermore National Laboratory’s nuclear weapons program may begin to appear in hospitals to deliver lifesaving proton therapy to cancer patients who would otherwise receive traditional and often-dangerous radiation treatments. The path to this success has been long and challenging but the payoff for patients is enormous.
Scientists recognized the benefits of radiation as a method for treating cancer in the late 1800s, even before X-rays were used as an imaging device. A medical student, Emil Grubbe, noted that his hands peeled when exposed to X-rays and recognized X-rays as a possible way to remove damaging tissue. His use of X-rays to treat a woman with advanced breast cancer slowed the tumor’s growth.
Today, radiation therapy can be a highly successful method of treatment but it also often damages healthy tissue around the tumor as the radiation beam passes through the body. Ever more sophisticated methods of delivering radiation have reduced collateral damage, but it is still virtually impossible to avoid. Enter proton therapy, whose properties are entirely different from X-ray or gamma-ray treatments.
Because of their relatively large mass, protons have minimal lateral side scatter in the tissue. The beam stays focused on the tumor and delivers only low-dose side effects to surrounding tissue. A proton beam of a given energy has a certain range, so very few protons penetrate beyond that distance. By calibrating the energy of the proton beam to the depth of the tumor, an accelerator can deliver the appropriate proton dose specifically to the tumor. Tissues closer to the surface of the body, above the tumor, receive less radiation and therefore less damage, while tissues around the tumor receive almost no protons. Proton therapy is considered especially effective for the treatment of eye cancer and for children who require radiation. It is also gaining ground as a method for treating prostate cancer because damage does not occur in the surrounding nerves that are important for maintaining sexual function.
Despite the effectiveness of protons, only 31 proton treatment centers exist in the world with just 9 in the U.S. The current delivery method requires what is essentially a giant bunker to house a cyclotron and patient treatment rooms. The cyclotron, weighing several hundred tons, is surrounded by concrete walls 10-feet thick to shield patients and operators from the heavy dose of neutrons that are a side effect of the huge magnets needed to guide the proton beam. Thick walls must also surround each therapy room, which are typically three stories high to accommodate the gantry vault that the patient lies in. Given that a proton treatment center is about the size of a basketball arena and costs more than $100 million, it comes as no surprise that few hospitals can afford one.
The proton therapy system based on laboratory technologies and being refined by Compact Particle Acceleration Corporation (CPAC) of Livermore, Calif., will revolutionize proton delivery. The system’s linear accelerator will be about four meters long, available for a small fraction of the cost of today’s systems, and use intensity-modulated proton therapy to treat the patient. CPAC’s system will deliver protons more directly to the patient than do typical scattered proton beams and thus will require no more shielding than an ordinary X-ray facility.
Given the low cost of the system and proven effectiveness of protons for the treatment of many cancers, the hope is that hospitals will retrofit one or more of their traditional radiation facilities to instead deliver protons.
In June, when CPAC completed the construction of its first precommercial prototype system, the company had taken a major step toward providing the world’s most precise and compact proton accelerator for treating cancer and other solid tumors.
The idea for the compact accelerator came from a team led by physicist George Caporaso, whose responsibilities include fundamental particle beam science and the development of advanced accelerators and technology. The novel design came about because of the potential benefits of performing proton radiography with a small accelerator to augment the X-ray radiographic capabilities of Livermore’s Flash X-Ray (FXR) and Los Alamos National Laboratory’s Dual-Axis Radiographic Hydrodynamic Tests (DARHT) Facility.
Proton radiography offers the potential for higher resolution and better discrimination between two similar materials. FXR and DARHT are enormous machines, tens of meters long. Both systems are essential tools of the National Nuclear Security Administration’s Stockpile Stewardship Program, which, in the absence of underground nuclear testing, must ensure that the nation’s existing warheads remain safe, secure and reliable well into the future.
An induction accelerator comprises a series of electrically independent modules, each pulsed in turn to push energetic particles forward, increasing their energy with every pulse. FXR and DARHT are long because of the need to deliver photons at very high energies. They are also long because their “acceleration gradient,” the relationship of energy increase over distance, is low, less than 1 megaelectronvolt per meter.
Caporaso’s team sought to vastly increase the acceleration gradient and deliver equivalent energies across a distance of just a few meters. The solution was a high-gradient insulator (HGI), a sandwich of very thin layers of insulating and conducting materials across which large electric fields are applied to accelerate charged particles. HGI, which won an R&D 100 Award in 1997, forms the beam tube of a dielectric wall accelerator (DWA).
The DWA components were integrated into an accelerating module, but a complete accelerator was not built because the weapons application was not pursued. However, at about that time, fellow physicist Dennis Matthews asked Caporaso if the DWA could deliver protons instead of electrons. Matthews was leading a team developing biomedical devices at the laboratory and also working at the newly established University of California at Davis Cancer Center, in which Livermore was an active collaborator. Matthews knew that Ralph deVere White, a urological oncology specialist and director of the center, was on the hunt for a more compact method for proton therapy.
Both Matthews and deVere White were excited about the prospects for Livermore’s novel electron delivery methodology. However, much work remained for DWA to be modified for use as a proton delivery medical device.
The components developed for radiography had been designed to deliver electrons in long pulses. But effective proton therapy required very short pulses. In 2004, the Laboratory Directed Research and Development program funded a project to determine the feasibility of DWA technology for medical use. UC Davis matched subsequent investments by the laboratory, to the tune of millions of dollars.
Matthews notes that the goal of this project was to prove the technology’s value and make it attractive to investors, without whom DWA for proton therapy would never get beyond the laboratory gates. It was attractive enough to interest TomoTherapy, Inc., a company headquartered in Madison, Wis., and already active in the development and sale of traditional radiation treatment systems.
In a 2007 technology transfer agreement, TomoTherapy entered the proton therapy business with funding for the continued development of the new accelerator. With TomoTherapy’s financial and personnel backing, Livermore was able to develop and successfully test a prototype in December 2007, of which the DWA portion was about 2 centimeters long. According to Livermore engineer Jim Watson, who has been a member of the DWA team since 2007, this test proved the world’s first complete DWA accelerator, with particle injector and diagnostics.
By December 2008, the team had successfully demonstrated that the device could accelerate ions. DeVere White says that this technology is unique for proton therapy. No one else is working on anything that comes close to delivering a device with the small size, low cost and treatment effectiveness of DWA. Says deVere White, “Some cancer experts wonder whether the $150 million price tag is worth the advantages that proton therapy can provide.
This solution takes the cost issue away.”
In 2008, TomoTherapy announced its participation in a new venture called Compact Particle Acceleration Corporation, located just blocks from the laboratory. Today, CPAC has 10 employees. “Our entire effort here at CPAC is on the accelerator,” Anthony Zografos, the general manager, says. “The development of the rest of the system including the laser, high-voltage equipment, and fiber optics is outsourced.”
This prototype will not actually be used for treatment but rather to demonstrate that adding more modules does indeed increase output energy and that tthe machine can be scaled up to the energy levels needed to deliver therapeutic protons.
The third and final prototype, scheduled for testing in 2013, will combine both technical and clinical viability in an integrated system that could be installed in hospitals. Says Zografos, “We have to know whether the device can be reasonably priced and what the cost of ownership will be terms of maintenance, spare parts, and so on.”
Accuray, Inc, which acquired TomoTherapy in June, will likely handle final integration of all the system components. This particular system need only prove that it can deliver protons at therapeutic levels.
To facilitate a hospital’s transition from X and gamma-ray treatment to proton therapy, CPAC will deliver a fully integrated product that allows a hospital to easily begin implementing proton therapy.
CPAC holds the exclusive commercial rights to more than 30 DWA-related patents or patent applications and has the license for nonmedical uses for the optical switches and DWA. “The technology could be used for imaging and cargo inspection, for example,” says Zografos. Both are high on the Department of Energy’s list of important national security projects, so Livermore involvement will surely continue.
DeVere White observes that Livermore’s application of a stockpile stewardship technology to the medical field is a highly effective use of tax dollars. “It leverages monies spent on national security without diverting the laboratory from its primary mission,” says deVere White. “Without Livermore, the Cancer Center, TomoTherapy, and CPAC, this technology for cancer treatment would not exist. Cancer patients will be the unwitting beneficiaries of an exceptional partnership.”
Katie Walter is a science writer at Lawrence Livermore National Laboratory.
©
Beginning in 2014, a particle accelerator derived from Lawrence Livermore National Laboratory’s nuclear weapons program may begin to appear in hospitals to deliver lifesaving proton therapy to cancer patients who would otherwise receive traditional and often-dangerous radiation treatments. The path to this success has been long and challenging but the payoff for patients is enormous.
Scientists recognized the benefits of radiation as a method for treating cancer in the late 1800s, even before X-rays were used as an imaging device. A medical student, Emil Grubbe, noted that his hands peeled when exposed to X-rays and recognized X-rays as a possible way to remove damaging tissue. His use of X-rays to treat a woman with advanced breast cancer slowed the tumor’s growth.
Today, radiation therapy can be a highly successful method of treatment but it also often damages healthy tissue around the tumor as the radiation beam passes through the body. Ever more sophisticated methods of delivering radiation have reduced collateral damage, but it is still virtually impossible to avoid. Enter proton therapy, whose properties are entirely different from X-ray or gamma-ray treatments.
Because of their relatively large mass, protons have minimal lateral side scatter in the tissue. The beam stays focused on the tumor and delivers only low-dose side effects to surrounding tissue. A proton beam of a given energy has a certain range, so very few protons penetrate beyond that distance. By calibrating the energy of the proton beam to the depth of the tumor, an accelerator can deliver the appropriate proton dose specifically to the tumor. Tissues closer to the surface of the body, above the tumor, receive less radiation and therefore less damage, while tissues around the tumor receive almost no protons. Proton therapy is considered especially effective for the treatment of eye cancer and for children who require radiation. It is also gaining ground as a method for treating prostate cancer because damage does not occur in the surrounding nerves that are important for maintaining sexual function.
Despite the effectiveness of protons, only 31 proton treatment centers exist in the world with just 9 in the U.S. The current delivery method requires what is essentially a giant bunker to house a cyclotron and patient treatment rooms. The cyclotron, weighing several hundred tons, is surrounded by concrete walls 10-feet thick to shield patients and operators from the heavy dose of neutrons that are a side effect of the huge magnets needed to guide the proton beam. Thick walls must also surround each therapy room, which are typically three stories high to accommodate the gantry vault that the patient lies in. Given that a proton treatment center is about the size of a basketball arena and costs more than $100 million, it comes as no surprise that few hospitals can afford one.
The proton therapy system based on laboratory technologies and being refined by Compact Particle Acceleration Corporation (CPAC) of Livermore, Calif., will revolutionize proton delivery. The system’s linear accelerator will be about four meters long, available for a small fraction of the cost of today’s systems, and use intensity-modulated proton therapy to treat the patient. CPAC’s system will deliver protons more directly to the patient than do typical scattered proton beams and thus will require no more shielding than an ordinary X-ray facility.
Given the low cost of the system and proven effectiveness of protons for the treatment of many cancers, the hope is that hospitals will retrofit one or more of their traditional radiation facilities to instead deliver protons.
In June, when CPAC completed the construction of its first precommercial prototype system, the company had taken a major step toward providing the world’s most precise and compact proton accelerator for treating cancer and other solid tumors.
The idea for the compact accelerator came from a team led by physicist George Caporaso, whose responsibilities include fundamental particle beam science and the development of advanced accelerators and technology. The novel design came about because of the potential benefits of performing proton radiography with a small accelerator to augment the X-ray radiographic capabilities of Livermore’s Flash X-Ray (FXR) and Los Alamos National Laboratory’s Dual-Axis Radiographic Hydrodynamic Tests (DARHT) Facility.
Proton radiography offers the potential for higher resolution and better discrimination between two similar materials. FXR and DARHT are enormous machines, tens of meters long. Both systems are essential tools of the National Nuclear Security Administration’s Stockpile Stewardship Program, which, in the absence of underground nuclear testing, must ensure that the nation’s existing warheads remain safe, secure and reliable well into the future.
An induction accelerator comprises a series of electrically independent modules, each pulsed in turn to push energetic particles forward, increasing their energy with every pulse. FXR and DARHT are long because of the need to deliver photons at very high energies. They are also long because their “acceleration gradient,” the relationship of energy increase over distance, is low, less than 1 megaelectronvolt per meter.
Caporaso’s team sought to vastly increase the acceleration gradient and deliver equivalent energies across a distance of just a few meters. The solution was a high-gradient insulator (HGI), a sandwich of very thin layers of insulating and conducting materials across which large electric fields are applied to accelerate charged particles. HGI, which won an R&D 100 Award in 1997, forms the beam tube of a dielectric wall accelerator (DWA).
The DWA components were integrated into an accelerating module, but a complete accelerator was not built because the weapons application was not pursued. However, at about that time, fellow physicist Dennis Matthews asked Caporaso if the DWA could deliver protons instead of electrons. Matthews was leading a team developing biomedical devices at the laboratory and also working at the newly established University of California at Davis Cancer Center, in which Livermore was an active collaborator. Matthews knew that Ralph deVere White, a urological oncology specialist and director of the center, was on the hunt for a more compact method for proton therapy.
Both Matthews and deVere White were excited about the prospects for Livermore’s novel electron delivery methodology. However, much work remained for DWA to be modified for use as a proton delivery medical device.
The components developed for radiography had been designed to deliver electrons in long pulses. But effective proton therapy required very short pulses. In 2004, the Laboratory Directed Research and Development program funded a project to determine the feasibility of DWA technology for medical use. UC Davis matched subsequent investments by the laboratory, to the tune of millions of dollars.
Matthews notes that the goal of this project was to prove the technology’s value and make it attractive to investors, without whom DWA for proton therapy would never get beyond the laboratory gates. It was attractive enough to interest TomoTherapy, Inc., a company headquartered in Madison, Wis., and already active in the development and sale of traditional radiation treatment systems.
In a 2007 technology transfer agreement, TomoTherapy entered the proton therapy business with funding for the continued development of the new accelerator. With TomoTherapy’s financial and personnel backing, Livermore was able to develop and successfully test a prototype in December 2007, of which the DWA portion was about 2 centimeters long. According to Livermore engineer Jim Watson, who has been a member of the DWA team since 2007, this test proved the world’s first complete DWA accelerator, with particle injector and diagnostics.
By December 2008, the team had successfully demonstrated that the device could accelerate ions. DeVere White says that this technology is unique for proton therapy. No one else is working on anything that comes close to delivering a device with the small size, low cost and treatment effectiveness of DWA. Says deVere White, “Some cancer experts wonder whether the $150 million price tag is worth the advantages that proton therapy can provide.
This solution takes the cost issue away.”
In 2008, TomoTherapy announced its participation in a new venture called Compact Particle Acceleration Corporation, located just blocks from the laboratory. Today, CPAC has 10 employees. “Our entire effort here at CPAC is on the accelerator,” Anthony Zografos, the general manager, says. “The development of the rest of the system including the laser, high-voltage equipment, and fiber optics is outsourced.”
This prototype will not actually be used for treatment but rather to demonstrate that adding more modules does indeed increase output energy and that tthe machine can be scaled up to the energy levels needed to deliver therapeutic protons.
The third and final prototype, scheduled for testing in 2013, will combine both technical and clinical viability in an integrated system that could be installed in hospitals. Says Zografos, “We have to know whether the device can be reasonably priced and what the cost of ownership will be terms of maintenance, spare parts, and so on.”
Accuray, Inc, which acquired TomoTherapy in June, will likely handle final integration of all the system components. This particular system need only prove that it can deliver protons at therapeutic levels.
To facilitate a hospital’s transition from X and gamma-ray treatment to proton therapy, CPAC will deliver a fully integrated product that allows a hospital to easily begin implementing proton therapy.
CPAC holds the exclusive commercial rights to more than 30 DWA-related patents or patent applications and has the license for nonmedical uses for the optical switches and DWA. “The technology could be used for imaging and cargo inspection, for example,” says Zografos. Both are high on the Department of Energy’s list of important national security projects, so Livermore involvement will surely continue.
DeVere White observes that Livermore’s application of a stockpile stewardship technology to the medical field is a highly effective use of tax dollars. “It leverages monies spent on national security without diverting the laboratory from its primary mission,” says deVere White. “Without Livermore, the Cancer Center, TomoTherapy, and CPAC, this technology for cancer treatment would not exist. Cancer patients will be the unwitting beneficiaries of an exceptional partnership.”
Katie Walter is a science writer at Lawrence Livermore National Laboratory.
©
