Heart disease is the major cause of death in the United States. But there is another disease that we fear even more, because of the disability and suffering it causes. Cancer in its many forms, is one of the cruelest, most feared, and emotionally draining diseases ever experienced by mankind.
In 1990, after almost 20 years of research, Loma Linda University Medical Center, in cooperation with Fermi National Accelerator Laboratory and the Proton Therapy Cooperative Group, opened the world's first hospital-based proton-beam accelerator dedicated to the treatment of patients with cancer. Though not a cure for all forms of cancer, it has become a major advancement in the treatment of "localized cancer," a malignant tumor that is still in its original site and has not yet spread throughout the body.
Until 1990 all proton therapy was delivered in high-energy, physics-research laboratories. Loma Linda University Medical Center and James M. Slater, M.D., F.A.C.R., (Class of 1963) past Chair of the Loma Linda University Department of Radiation Sciences and Department of Radiation Medicine, changed that. Dr. Slater's major field of interest prior to becoming a physician was physics. Therefore, he was already aware of the clinical interest in protons and other heavy charged particles.
"In order for cancer radiation therapy to advance," says Dr. Slater, "we needed to improve our ability to focus a beam inside the body. The proton accelerator does that. It's a superior tool that's going to produce a major improvement in cancer therapy."
The $100 million, three-story facility is awesome. The equipment, including the accelerator and the proton guidance system, weighs 400 tons and produces up to 250 million electron volts of radiation. It is a giant weapon now being used to treat cancer and other diseases.
The accelerator itself, weighing 50 tons, is a ring of eight electromagnets, 60 feet in circumference and 20 feet in diameter. These electromagnets bend and focus the beam around a closed path within a vacuum tube. Protons are accelerated up to half the speed of light by applying a radio-frequency voltage in synchronization with the circulating beam. Thus the machine is called a "synchrotron." An extraction system removes protons as needed and carries them into the beam-transport system. The beam-transport system takes the "Beam of Hope" into one of five rooms: three having three-story-high rotating gantries, designed to aim the beam at the patient from any angle; one containing two fixed, horizontal beams; and a calibration/research room with three beams.
To prevent and cure cancer has been one of science's greatest challenges. Great progress has been achieved over the years. Unfortunately, some of the treatments that have succeeded in fighting cancer have caused pain and suffering also. What attacks the cancer cells usually causes some damage to good and healthy tissues.
Sufficient radiation can destroy any type of cancer. However, because of the inability to selectively irradiate the cancer with conventional means of treatment, a high radiation dose can also damage normal tissues. As a consequence, a less-than-optimal dose is frequently used in order to reduce damage to the normal tissue. This precaution reduces the likelihood of cure for many patients. The medical profession, knowing the limitations of its arsenal in the war against cancer, has to give the patient enough potential remedy to defeat the cancer, without causing too much damage to the patient. In some cases, that is not possible, and the patient is allowed to die.
In 1970 scientists at Loma Linda University Medical Center, under the direction of Dr. Slater, were not satisfied with the limitations they were experiencing from the most up-to-date radiation equipment available (a cobalt machine, betatron machine, and linear accelerator), machines that ranged in power from eight million up to 25 million electron volts of energy. They believed there must be a better way.
Even before coming to Loma Linda in 1970, Dr. Slater envisioned three major approaches to solving the problem: beam-shaping devices designed to shield normal tissues; a better way to visualize the distribution of radiation within the patient; and determination of the most appropriate subatomic particle for treatment. Under Dr. Slater's direction, LLUMC scientists have accomplished notable achievements in all three areas. They were supported by a broad base of people working together for a common cause: a large number of the world's scientists and high-energy physics laboratories, physicians, national agencies, local and federal political officials, University and Medical Center administrators, faculty, staff, and Boards of Trustees.
In 1971 Dr. Slater began assembling a team that would explore the possibilities of using charged particles from a machine designed to treat cancer, instead of using conventional radiation.
The concept was first proposed in 1946 by Dr. Robert Wilson, now professor emeritus of physics at Cornell University. In 1946 Dr. Wilson published a landmark research paper entitled "Radiological Use of Fast Protons," which proposed the use of protons for therapeutic purposes.
But physics research did not develop accelerators that were powerful enough to do this until the 1950s. Then there were limitations in imaging techniques. It wasn't until the development of computerized tomography (CT) and magnetic resonance imaging (MRI), that these limitations were overcome and the concept of precision radiation treatment by protons came of age.
Developed in 1973, CT scans provided a way to visualize the radiation within the patient's anatomy and thereby shape and finely adjust the beams on the computer to much closer tolerances for radiation treatment planning processes prior to the actual delivery of radiation. Dr. Slater's computer-assisted radiation treatment planning technology was accepted immediately and spread virtually world-wide with several international awards.
In time Dr. Slater and his colleagues decided that the proton was the optimal particle for a clinical heavy-charged particle treatment center. Dr. Slater had already decided that such a facility should be hospital-based where patients would have ready access to supporting services necessary to deliver optimal high-quality care.
In 1984 Dr. Slater recruited John O. Archambeau, M.D., F.A.C.R. as the first faculty member to help LLUMC develop a hospital-based proton treatment system. Dr. Archambeau, one of the pioneers of proton radiation therapy, having participated in proton-treatment-related investigations at Brookhaven National Laboratory, wrote classic papers about proton therapy in the early and mid-1970s. He and Dr. Slater began to work together when Dr. Archambeau chaired the department of radiation oncology at City of Hope Medical Center in Duarte, California. In 1984 Dr. Archambeau resigned his departmental chairmanship at City of Hope to join Dr. Slater's program at LLUMC.
In January 1985, a group of scientists from around the world, spearheaded in part by Slater, met to study the design of potential proton accelerators, facilities, and clinical trials. The Proton Therapy Cooperative Group discussed various machine designs and proton delivery systems.
How does proton therapy compare with traditional radiation therapy, called "conventional radiation"? Conventional radiation (gamma rays, and Xrays) travels completely through a patient's body, causing damage wherever it goes. In fact, conventional radiation deposits more energy just under the surface of the skin than it does in a deep-lying tumor, which may be near the center of the patient's body. Electrons, also considered to be conventional radiation, are used to treat superficial tumors (near the body's surface) only.
In order to increase the effectiveness of conventional radiation treatments, radiation oncologists (physicians who treat cancer with radiation) plan radiation treatments that enter the body from two, three, or even four different angles. This is done to bypass vital organs and good tissues, as much as possible, and to concentrate the radiation on the tumor. Still, because physicians cannot focus the radiation enough to avoid the surrounding tissues, they fail to control the local disease in hundreds of thousands of patients every year in the United States.
The proton beam dramatically reduces these negative factors by decreasing injury to the healthy tissues it passes through, and by penetrating no farther than the tumor. Protons are subatomic, positively charged particles, found in the nuclei of atoms. In contrast to conventional radiation, they enter the body at a very low absorption rate and go through good tissues rapidly. Their energy deposition increases sharply at a specific point, called the Bragg Peak (named after its discoverer), where they release most of their energy. By focusing the Bragg Peak on a patient's tumor, the deadly radiation causes most of its damage to the tumor.
Damage to the tissues in front of the tumor is significantly reduced in comparison to the damage caused by conventional radiation. There is no measurable damage to normal tissues beyond the tumor. The superior controllability of the proton beam has allowed for the delivery of higher radiation doses than is possible with conventional radiation and provides, therefore, better results.
The precision made possible by Loma Linda's Proton Treatment Center, as well as the reduced treatment time, with minimal side effects, also reduces patient fear and anxiety. This factor alone encourages some patients and families to seek early detection and treatment that they otherwise might avoid.
The new facility at Loma Linda uses state-of-the-art electronic advances to increase the precision and efficiency of treatment planning and beam transport. Treatments are planned with new imaging techniques that produce three-dimensional pictures of the interior of the body, including precisely identifying the boundary between the tumor and healthy tissues. The optimum irradiation technique for each patient is planned by computer simulation prior to the start of each treatment series.
To complement the machine's capability to treat localized cancer with precision, patients lie in a whole-body cradle, made before treatments begin. Technicians position patients into the gantries with the use of laser beams and X rays. The procedure not only helps align the patient with the proton guidance system, but also helps maintain the patient's position during the short treatments.
Treatments last from seconds to minutes. Some patients need only one treatment. Others may need up to 42 treatments--five a week.
One of the ultimate goals of proton therapy is to decrease the overall time the patient spends undergoing treatment. Proton therapy for cancer in limited sites already has a proven track record. The 8,000 patients already treated with protons had been treated on physics-research machines, some of which were designed as early as the 1940s. Since clinical trials first began in 1954 in Berkeley, California, at the Donner Laboratory (now known as the Lawrence Berkeley Laboratory) more than 40,000 patients have been treated with protons in Sweden, Switzerland, Japan, Russia, England, Belgium, Germany, France, South Africa, Italy, and the United States.
Loma Linda's machine is unique in several ways. It was the first proton accelerator in the world designed to treat cancer in a hospital setting, the first with continuously variable energy, the first being used to treat cancer with enough energy to reach deep tumors, and the first with isocentric, rotating gantries.
Continuously variable energy is a significant improvement over the energy of previously existing machines. With the capability of continuously variable energy, the Loma Linda machine is able to deliver a series of Bragg Peaks on the tumor and fill it with deadly radiation, from back to front, layer upon layer, with almost surgical precision.
With 250 million electron volts, the proton beam penetrates up to 15 inches, enough energy to reach deep tumors. The research machines had been useful in treating tumors that were not as deep, such as malignant tumors of the eye, head, neck, and spinal cord, and blood-vessel malformations in the brain.
One of the most dramatic results in proton treatment, already demonstrated on the research machines, is the treatment of ocular melanoma, an almost always fatal cancer of the eye. Using the old atom smasher at the Harvard Cyclotron Laboratory, scientists had been able to eliminate the cancer in more than 95 percent of the cases. Furthermore, they were able to save the vision in most of those cases. They were not been able to reach deep tumors. The Loma Linda machine, with increased power, does that.
The three gantries (part of the proton-delivery system), each weighing 95 tons and standing three stories high, look like little Ferris wheels. They aim the proton beam at an isocenter (a point in space, in the middle of the gantry). The patient is placed inside the gantry with the patient's tumor at the isocenter. The beam can be rotated 360 degrees on the gantry for the best angle of radiation. By varying the energy, the beam shape, and the number of protons accelerated, the dose of radiation can be formed to irregularly shaped, three-dimensional, tumor volumes.
The synchrotron was built and tested by Fermi National Accelerator Laboratory in Batavia, Illinois (near Chicago). Fermilab, one of America's largest and most powerful physics-research laboratories, is owned by the United States Department of Energy, and is operated by Universities Research Association, a consortium of 57 universities from around the world. The new accelerator has been an international effort to benefit mankind.
The design of the machine is based on well-developed technology. Proton accelerators have been in operation throughout the world for many years at physics-research laboratories, using higher energies and higher intensities. The unique design selected for the Loma Linda unit allows for operation with minimal maintenance and engineering attention.
Loma Linda's proton accelerator was funded in part by a $19.6 million grant from the United States Congress with the help of Representative Jerry Lewis (R-Redlands, CA), who believed in the project from an early date.
The facility has been in full operation since the summer of 1994. It is now capable of serving up to 200 patients a day--57,000 treatments per year. The synchrotron and its proton-delivery system were designed to improve with time. They are modified as new technology becomes available. Flexibility was built into the system to allow for easy installation of upgrades to keep the total system current with cutting-edge performance indefinitely. Loma Linda scientists are now developing robotic devices to position patients rapidly with sub-millimeter precision. With new positioning and scanning technology, the Center is projected to treat 320 patients a day-- 92,000 treatments per year--by the end of 2008. Almost 100 percent of the patients using the machine are outpatients.
Loma Linda University Medical Center's new Proton Treatment Center is dedicated to medical service, cancer research, and education. It has become an international resource for the treatment of cancer, using charged particles. The calibration/ research room is made available to NASA and other institutions of higher education for physics and radiobiology research.
In 1992 a groundbreaking ceremony celebrated the $20.3 million building that would become the Chan Shun Pavilion and Coleman Pavilion. One half of the new four-story building contains laboratory space dedicated to proton-related cancer research and treatment, and to better understand the biological effects and capabilities of particle radiation. At the time, the University acknowledged Congressman Jerry Lewis for his dedicated work on behalf of proton radiation at Loma Linda: a floor at the research facility was named in his honor.
NASA Uses Proton Synchrotron
In 1993 Dr. Slater recruited Gregory A. Nelson, Ph.D., from NASA's Jet Propulsion Laboratory (JPL), in Pasadena, California, to direct molecular radiobiological research associated with NASA.
On Thursday, December 1, 1994, Loma Linda University Medical Center and the National Aeronautics and Space Administration signed a five-year Memorandum of Agreement to establish formal scientific collaboration between the Life and Biomedical Sciences and Applications Divisions within NASA's Office of Life and Microgravity Sciences Applications and Loma Linda University Medical Center.
NASA administrator, Daniel S. Goldin, said the agreement represented "the ultimate in technology transfer," and further stated that the Loma Linda facility was the only place on Earth where NASA could do everything it needs to do to learn how to protect its astronauts from the dangers of positively charged particles in space. He went so far as to claim that Loma Linda's proton facility was NASA's "gateway to Mars."
The space radiation environment consists of protons and electrons trapped in Earth's magnetic field. Of all the galactic cosmic rays, charged particles are the greatest danger to astronauts. Protons are of particular concern because they constitute the most abundant particle species in space. As such, protons contribute as much as half of the biologically significant radiation dose to which humans are exposed in space station missions and in future missions beyond low Earth orbit.
Unpredictable solar flares create the greatest source of protons in the solar system. NASA plans its low, Earth-orbit missions to avoid, as much as possible, solar flares. The manned trip to Mars will be unable to avoid solar flares.
According to the agreement, "the major goals of this collaboration are: (1) to enhance basic knowledge of living systems and their response to radiation exposure; in particular, utilizing the unique LLU accelerator, Proton Therapy Synchrotron, to simulate the proton component of the space radiation environment; (2) application of this knowledge to radiation protection, risk assessment, diagnosis, and treatment of cancer; and (3) to exploit the synergy between NASA research requirements and charged-particle therapy to establish a collaborative peer-reviewed research base which benefits the Loma Linda academic community."
The main objectives of this agreement are to provide access to accelerated proton beams and related research laboratories for NASA-sponsored investigators, to provide for a contribution of NASA-sponsored investigators to the academic and educational programs of LLU, and to facilitate the transfer of technical expertise between NASA and LLU in areas of radiation physics and radiation biology.
The scientific advances made at Loma Linda University Medical Center in the use of radiation therapy are of direct application to NASA's research into the biological action of energetic charged particles. Conversely, the results of the study of molecules, cells, and animals in space may lead to developments of importance to radiation medicine at LLUMC.
NASA investigators make research results available to LLU in the form of preprints and reprints. NASA, recognizing that its scientific research capabilities are of great relevance to medical education, also encourages investigators to participate in School of Medicine educational programs by giving lectures and seminars and by participating with the Loma Linda research community.
NASA investigator teams provide opportunities for students and resident physicians to participate in NASA's research.
This agreement benefits mankind in at least two ways. It provides improvements in the understanding of the biological action of space radiation and thus enables NASA to discharge its obligation to ensure the health, safety, and performance of its astronauts at a significantly reduced cost. It also provides a better understanding of the biological effects of protons, which is likely to lead to significant improvements in cancer therapy.