Contact:
Charlie Osolin
Phone: (925) 422-8367
E-mail: osolin1@llnl.gov |
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April 28, 2006
SF-06-04-02 |
Next-generation radiation therapy at a cancer clinic near you.
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| Engineer Mark Rhodes (seated) and physicist George Caporaso adjust a prototype Blumlein transmission-line generator, which will supply power to the high-gradient insulators forming the beam tube dielectric walls in LLNL's compact proton accelerator. |
That’s the goal of an ambitious partnership between Lawrence Livermore National Laboratory (LLNL) and the UC Davis Cancer Center – one of more than two dozen joint research projects involving the two institutions that promise breakthroughs in the detection, treatment and prevention of cancer.
LLNL and UC Davis have committed more than $3 million to develop a compact, relatively inexpensive proton-beam therapy system that can effectively zap tumors with powerful, focused radiation, while causing minimum collateral damage to nearby healthy tissue and organs.
An outgrowth of the Laboratory’s weapons research, the technology is being developed by an LLNL team led by George Caporaso of the Laboratory’s Physics and Advanced Technologies Directorate. LLNL is currently seeking commercial partners to help construct a compact proton-beam therapy system that could be clinically tested at the UC Davis Cancer Center.
Proton-beam therapy, available in hospitals only since 1990, is expected to become the “next big thing” in radiation treatment for many localized cancers, including those of the head and neck, eye and orbit, prostate, abdomen and lung.
Traditional x-ray and gamma ray therapy can damage the tissue the radiation passes through on the way to a target, limiting the amount that can be delivered to a deep-seated tumor. Protons, however, because of their positive charge and high mass, retain most of their energy until they reach the cancer site. Using sophisticated software algorithms, radiation oncologists can control the penetration depth and shape of the protons in three dimensions, fitting the radiation dose precisely to the shape of the tumor. This allows them to focus more potent doses on the cancer cells without endangering surrounding healthy cells.
Conventional proton therapy systems, however, are large – occupying as much space as a basketball court – and cost as much as $150 to $200 million to build, Caporaso said. “They have to be surrounded by concrete walls to protect against the radiation they generate,” he added.
Because of their size and cost, there are only a few proton therapy centers in the United States and only about 20 in the world. Several more are under construction or being planned, but availability of the treatment will remain limited for some time.
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| Above: Engineer John Harris prepares the vacuum test chamber used to subject high-gradient insulators (HGIs) to high-voltage electric fields. The HGI is the candidate dielectric wall material that will be used for the beam tube in LLNL’s compact proton-beam accelerator. Since it can sustain a very high electric field parallel to its surface, it will be able to provide a high accelerating gradient for the proton beam. Below: A time-integrated open-shutter photo of an HGI flashing over in a 150,000- to 200,000-volt-per-centimeter electric field. Elevating the flashover threshold of these insulators is key to the success of the project. |
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On the other hand, if the huge accelerators could be made compact enough to fit in a single room – a significant technical challenge – and built for less than one-tenth the cost, the therapy could be offered in radiation oncology clinics across the country.
That’s where the LLNL-UC Davis Cancer Center partnership comes in. One of the first projects the two institutions launched after they agreed to collaborate in 2000, the compact proton accelerator would use an LLNL-developed technology called the dielectric wall accelerator (DWA) that enables protons to be accelerated to the required energies – as much as 100 million electron volts per meter – without using bending magnets or other techniques that take up space and generate unwanted radiation.
The dielectric wall uses a high-voltage-gradient insulator to handle high electric-field stresses, enabling a proton therapy accelerator to successfully operate without being short-circuited.
Today’s hospital proton radiotherapy machines generate from 70 million volts for eye tumors to 250 million volts for tumors deep in the body. A dielectric wall only 2.5 meters long could withstand the 250 million volts required to treat deep-seated tumors. The LLNL researchers have successfully tested a small (3-millimeter-long) dielectric wall sample that withstood an electric field of 100 million volts per meter.
Caporaso said the idea of using the DWA technology for cancer treatment “really started moving when Dennis Matthews (director of LLNL’s Center for Biotechnology, Biophysical Sciences, and Bioengineering) approached me with the vision that if you could make (a proton accelerator) really, really small, it might be able to go into existing x-ray therapy clinics”in place of conventional x-ray machines.
“We had been developing the accelerator for a long time for radiography and other defense applications, but Dennis helped us put together an LDRD (Laboratory-Directed Research and Development) proposal that was approved for funding,” Caporaso said. He noted that Ralph DeVere White, director of the UC Davis Cancer Center, “has been a rock-solid, enthusiastic supporter” of the project. “His support has been key to our progress so far.”
The project’s initial funding, which ended last September, enabled the team to push the system’s components to 50 percent of their performance targets. Additional funds from the Lab and UC Davis will “allow us to work toward a subscale (20-centimeter-long) prototype – a kind of a proof of principle device,” Caporaso said. “We think we can build enough of the accelerator to demonstrate the operating principles and characteristics within the next 18 months.
“There are a lot of technical challenges remaining,” he said. “We’ll see if we can push the components to 100 percent over the next year, but we can’t test the remaining issues until we build the prototype.
“So it remains to be seen if we can pull it off,” Caporaso said. “There are no guarantees, but progress has been good so far and we’re optimistic.”
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The UC Davis facility was the first major cancer center to team with a national laboratory, taking advantage of technology developed at LLNL for national and homeland security to carry out innovative anti-cancer research. The collaboration helped the cancer center become a National Cancer Institute-designated center in July 2002; that distinction, along with $14 million in new federal funding through the year 2010, was renewed last summer.
The partnership enables physicians and scientists to work together developing new cancer therapies, detection methods and prevention strategies. About forty Livermore scientists are actively engaged in cancer research through multi-locational appointments with the UC Davis Cancer Center research program. Dennis Matthews, director of the Lab’s Center for Biotechnology, Biophysical Sciences, and Bioengineering, is associate director of biomedical technology for the cancer center, while Jim Felton of the Lab’s Biosciences Directorate, a specialist in cancer causation and prevention, is associate director of cancer control.
Here is a sampling of some joint LLNL-UC Davis Cancer Center projects:
- LLNL physicist Stavros Demos is working with urologist Ralph deVere White, director of the cancer center, on instrumentation to help surgeons detect cancer and assess tissue injuries associated with transplant applications or trauma. Demos has developed optical spectroscopy-based imaging techniques that can detect and image cancer by taking advantage of the different ways light interacts with tissue at the microscopic level: malignant cells interact (scatter and absorb or emit) differently to light than healthy ones, giving rise to new ways to image cancer lesions and cancer cells. In one early application, a new imaging sensor has been built that simultaneously records and displays the spectroscopic cancer-specific image and the conventional color image. The sensor is placed at the end of a cystoscope, a device used to look inside the bladder, to detect bladder cancer without a surgical biopsy.
- Livermore scientists were the first to use accelerator mass spectrometer (AMS) technology for biological and cancer studies. Ultrasensitive pharmacokinetic studies using AMS can analyze how well drugs are absorbed in the body. This helps physicians to fine-tune chemotherapy dosages based on an individual’s metabolism, lessening toxicity and improving chemotherapy effectiveness. Earlier this month, LLNL and UC Davis scientists reported the development of a safer, more accurate AMS-based test for pernicious anemia and other conditions related to the poor absorption of vitamin B12. Another AMS study is looking at the causes of cancer in breast cancer cells and mice. “These studies couldn’t be done with any other technology,” said Paul Henderson of the Lab’s Defense Biology Division.
- Alice Yamada of the Lab’s Genome Biology Division is investigating the use of genetic techniques to lower the presence of lipids, such as fats and cholesterol, that are thought to promote the growth of prostate cancer cells. In another prostate cancer research project, Kris Kulp of the Biomedical Division and Ralph and Regina Gandour-Edwards of UC Davis are using time-of-flight secondary ion mass spectrometry to produce images of the chemical composition of single cells. The technique could lead to improved prognosis and treatment of prostate cancer.
- Several joint studies are looking at the relationship between food and cancer, including possible genetic predisposition toward certain cancers among African-Americans and Asian-Americans.
- Biochemist Rod Balhorn, division leader of LLNL’s Biomedical Division, and his collaborators at the cancer center are constructing tiny molecules called SHALs (synthetic high-affinity ligands) that bind to unique sites on the surfaces of proteins. Originally conceived as a way to detect and neutralize potential bioterror agents like botulism or anthrax, these “designer molecules” have the potential to selectively bind to tumor cells with particular proteins. Like Trojan horses, SHALs can be designed to carry a radioactive isotope or potent anti-cancer drug. After seeking out and binding to cancer cells, SHALs can unleash their weaponry locally, minimizing the risk to normal cells. “When I attended meetings with UC Davis Cancer Center researchers,” Balhorn said, “I saw the potential of SHALs to fit their needs.”
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LLNL’s Public Affairs Office (www.llnl.gov/pao/) UC Davis, LLNL researchers develop better, safer test for pernicious anemia
LLNL News Release, April 3, 2006 (www.llnl.gov/pao/news/news_releases/2006/NR-06-04-02.html) National Cancer Institute awards additional $14 million to UC Davis-LLNL Cancer Center
LLNL News Release, August 2, 2005 (www.llnl.gov/pao/news/news_releases/2005/NR-05-08-03.html) UC Davis Cancer Center (www.ucdmc.ucdavis.edu/cancer/) LLNL Center for Biotechnology, Biophysical Sciences and Bioengineering (www.llnl.gov/cbbb/) LLNL Physics and Advanced Technologies Directorate (www-pat.llnl.gov) LLNL Biosciences Directorate (www.llnl.gov/bio/) “Leading the Attack on Cancer”
Science & Technology Review, April 2001 (www.llnl.gov/str/April01/Felton.html) “Biomedical Research Benefits”
Science & Technology Review, July/August 2000 (www.llnl.gov/str/pdfs/07_00.2.pdf)
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