The Power of Protons
Saturday, March 01, 1997
Proton Treatment Center remains first, largest, and most comprehensive such facility in the world
I was chair of the Board of Trustees when Loma Linda University Medical Center embarked on a mission far beyond that ever undertaken by an American medical institution. We began a project which would transform how cancer patients will be treated. We sought a better, more humane, and less damaging manner to cure those afflicted with cancer....
“I never dreamed that almost a decade later I would personally benefit from this miracle. I was diagnosed with prostate cancer. As everyone knows who has had his doctor tell him this news, confusion as to what to do is always a major concern. But not for a minute did I doubt my course of action. I know the promise of protons, I was involved with the team dedicated to realizing the power of protons, and I know what I wanted: cure without the devastating side-effects commonly associated with prostate treatment....
“Today, my PSA is normal—better than normal—and my life and my work continue. I am a testimony to the success of proton treatment at LLUMC. I thank God that I had a small role to play in bringing this potential to many others.....”
Neal C. Wilson
Immediate past president
General Conference of Seventh-day Adventists
Loma Linda University Medical Center’s Proton Treatment Center, founded by James M. Slater, MD, FACR, chair of the department of radiation sciences in the School of Medicine, is celebrating its seventh anniversary this spring. The Center remains the largest and most comprehensive proton treatment facility in the world; however, since its opening in April, 1990, two other clinically based centers are now under construction: one nearing completion at Harvard University’s Massachusetts General Hospital in Boston, and another as part of the National Cancer Institute in Tsukuba, Japan. Additional centers are under review in the United States and other countries.
Patients at the Proton Treatment Center undergo treatment both for benign and malignant diseases in approximately 20 sites in the body, including such areas as the brain, head and neck, chest, abdomen, and pelvis (prostate). More than 2,000 patients have received proton treatment at the Loma Linda University Proton Treatment Center from 40 states, and several foreign countries. Globally, more than 20,000 patients have received the benefits of proton treatment.
First medical use of protons proposed in 1940s
Proton therapy fulfills a well-practiced and documented path of medicine begun early in the 20th century. After the end of the Second World War, building on discoveries made during the Manhattan Project and other activities, groups of physicists developed higher-energy particle accelerators.
The first proposal for the medical use of protons was made in 1946, in a paper by physicist Robert Wilson, PhD. By 1954, proton beams from a high-energy physics research accelerator were first used to treat humans.
Research and laboratory applications increased rapidly in the next three decades. It was not until the opening of the proton treatment facility at Loma Linda University Medical Center in 1990, however, that the full benefits of this new treatment modality could be offered to patients with a wide variety of cancers.
Much of the research to develop and enhance the clinical applications for proton medicine took place around the world, including work in physics laboratories in Belgium, Canada, England, France, Japan, Russia, South Africa, and Switzerland. But the greatest attention and financial investment in the development of clinical applications was done in the United States.
Many hundreds of millions of dollars of U.S. federal funding went into the development of the technology to accelerate protons, with much of that work being done at the U.S. Department of Energy’s Fermi National Accelerator Laboratory. Additionally, the Loma Linda University Proton Treatment Center received Congressional support to assist in this federal demonstration project.
Congressman Jerry Lewis said in 1990, “Loma Linda is taking a very courageous step by being the first medical institution in the world to bring the practical medical treatment to what has been—up until now—highly scientific research…. I believe this state-of-the-art facility at Loma Linda will be a model for the world medical community to emulate in future years.”
One of the vital tools
Proton-beam therapy is a type of radiation therapy that has some superior properties over other forms of radiation therapy. Protons have superior qualities for delivering radiation to specific targeted tissues and thus are one of the vital tools at the disposal of the radiation oncologist.
New technology, including the use of protons, has been the primary factor leading to the stature of radiation in modern medicine for diagnostic and therapeutic purposes. Major improvements in diagnostic radiology, for example, continue to appear as new technology provides a means of minimizing the dose of radiation received by the patient and maximizing the quality of the image produced. This concept has been strongly supported by the American Cancer Society (ACS), as exemplified by the directives used for mammography in detecting early breast cancer.
The concerns of repeated mammographies have diminished as new technology has significantly reduced the dose of radiation needed for the procedure. The medical community, along with the ACS, worked to clear radiology departments of their antiquated mammography equipment and replace it with new technology to maintain minimum doses of radiation to the breast as well as improving the images obtained. The potential of unnecessary radiation to the breast was a primary factor in establishing the ACS guidelines for mammography.
Radiation for therapeutic purposes has experienced this same benefit. New technology has allowed the physician to significantly improve x-ray beam therapy by providing the means to minimize radiation to the normal tissues and maximize the dose to the tumor; this procedure is now called “conformal therapy.” Protons provide even more control over the placement of the high doses of radiation in a threedimensional volume, thereby further reducing the integral dose of radiation to normal tissues by factors of two to three.
Superior controllability
Proton beam therapy is an accepted, proven form of radiation therapy, one that uses established radio-biological principles and adds significantly increased precision to this major modality of cancer therapy. The biologic effects of protons on human cells, tissues, and organs are the same as those of x-rays and electron beams and thus are well known and understood. Its new feature is superior controllability; this feature makes it possible for the physician to more accurately concentrate the radiation on the desired target than is possible with x-rays or electrons.
However, there is a significant distinction between standard radiation treatment and proton therapy. If given in sufficient doses, conventional radiation therapy techniques will control many cancers. However, conventional x-rays always irradiate healthy tissue in front of and behind the tumor site, and because of this fundamental characteristic, are limited in the amount of dosage available for destroying the cancerous cells. Consequently, a less-than-desired dose is frequently used in order to reduce damage to healthy tissues and avoid subsequent unacceptable side effects.
Proton treatments are fundamentally distinct: the energy of the radiation is released at the site of the tumor, with virtually no significant deposits in front of the site, and none at all beyond the tumor site. Furthermore, the power of the radiation can be increased without negative effects to healthy tissues or vital organs near the tumor site.
An important therapeutic gain
Clinical application is currently underway with dose escalation. The anticipated results should be: further enhancement of the cure rate; reduced treatment times; and greater hospital efficiency allowing for increased numbers of patients to be treated in the same facility.
Previous studies on radiation therapy for prostate cancer have demonstrated improved local control rates as the dose to the prostate is increased. A Loma Linda University Medical Center prostate study, accepted for publication in the International Journal of Radiation Oncology, Biology and Physics, supports that there is a decrease in the severity of post radiation treatment complications observed in patients treated with protons. Physicians and oncologists believe this represents an important therapeutic gain through the use of proton therapy. Further, conformal proton radiation at the Proton Treatment Center has been shown to be able to deliver higher doses of radiation with fewer side effects than conventional x-ray radiation techniques, resulting in a higher patient tolerance.
Because of the inability of conventional x-rays to selectively irradiate the cancer, however, the dose response of adjacent normal structures, including the bladder and rectum, becomes the dose-limiting factor. As a consequence, a sub-optimal total tumor dose is frequently used to reduce the incidence of unacceptable normal tissue damage.
Development of new methods of delivery using conformal techniques allows higher doses of x-rays to potentially be delivered to the prostate without significantly increasing the treatment-related morbidity. In a recent study led by Dr. Gerald Hanks at the Fox Chase Cancer Center, for instance, conformal x-ray radiation at high doses improved disease control in patients with high initial PSA values and increased toxicity only slightly.
Conformal x-rays, however, have a distinct disadvantage in that each individual x-ray beam delivers the majority of its radiation to normal tissues and not the prostate. The definitive advantage of protons is that each beam conforms to the target volume in all three dimensions.
Protons can be shaped to deliver homogeneous doses of radiation to a three dimensional target while delivering no radiation within millimeters beyond. This permits delivery of higher doses of radiation to the prostate while minimizing treatment-related morbidity.
Complications significantly lower
Beginning in October, 1991, proton beams were used for the treatment of prostate carcinoma at Loma Linda University Medical Center. Through December, 1995, 543 prostate cancer patients had accrued in one protocol in which patients received a dose 10 to 15 percent higher than normally delivered with conventional techniques. Follow-up ranged from 3 to 58 months (with a mean of 28 months). The overall clinical disease free survival was 92 percent and 89 percent at 3 and 4 years respectively, which compares favorably with other published studies. Of prime importance to the patient, as well as to reducing the overall cost of health care, gastrointestinal and genitourinary complications are significantly lower in the Loma Linda University Medical Center proton study than might be expected using equivalent doses with other modalities.
Age-related macular degeneration
While proton therapy has demonstrated extensive benefits for the treatment of various cancers, another recent Loma Linda University Medical Center study has shown that protons can also benefit the estimated 745,000 Americans aged 65 years and older who have severe visual impairment in one or both eyes secondary to age-related macular degeneration. Age related macular degeneration is a retinal disease involving degenerative changes which leads to a very high possibility of legal blindness.
In a paper presented by Jerry Slater, MD, clinical director of the Proton Treatment Center, at the annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) and accepted for publication in 1996, the use of protons to treat macular degeneration has demonstrated that a high of nearly 75 percent of the patients who were treated had improved or stable visual acuity following a single, one-day treatment with protons.
It is well understood that improvements in conforming the high-dose region of the radiation beam to the targeted volume is the primary reason radiation therapy has succeeded in improving the cure rate of localized and regional spread of cancer while reducing side effects of the treatment. Proton beam therapy includes the benefits of what are currently associated with conformal radiation therapy, but has the added advantages of limiting the scatter, as well as having three-dimensional control of each beam (port of entry), thus limiting adverse penetration, thereby reducing the side effects associated with photons (conventional x-rays).
Technology hurdles
Proton radiation therapy is not new; rather, it began with the discovery of protons in 1919. They were first accelerated to megavoltage energies at Berkeley in the early 1930s. Studies of the properties of protons at the Berkeley laboratories led Dr. Wilson, a physicist and later the first director of Fermi National Accelerator Laboratory (Fermilab), to pursue the idea of using protons for treating patients with cancer. This pursuit stimulated the clinical use of protons at Berkeley in the 1950s and the development of the Harvard cyclotron and its clinical use in the 1960s for treating patients with protons.
The delay between the first use of protons for clinical purposes in the ’50s and ’60s, and the comprehensive proton centers today in operation or being built, was caused by three technology hurdles which needed to be overcome:
First, computer technology was insufficient to handle the critical clinical needs of a patient-based center. This has obviously been overcome in many technological areas, including medical technology and the precise use of protons;
Second, the imaging technology to precisely determine the boundaries of a target site was insufficient until the early 1980s. This has also been overcome and is the basis for all conformal radiation technology in use today;
Third, the focusing technology to precisely deliver the proton beam did not exist until Loma Linda University Medical Center began this project in the early 1970s. Much of this aiming technology was developed by the engineering expertise at Loma Linda University Medical Center, for which the institution received international recognition. These three technological advances permitted proton therapy to become a hospital-based treatment modality.
In the U.S., approximately 180 third party payors (insurance companies and HMOs) have reimbursed the Proton Treatment Center patients for proton treatment. Medicare, through the Blue Cross intermediary of Southern California, approved proton therapy as an advanced form of conventional x-ray in 1990. The Food and Drug Administration approved the proton device for medical treatment in 1987.
