PROTONS: A ray of hope in oncology

Christina T. Loguidice
Published: Wednesday, May 05, 2010
Radiation therapy has been used to treat cancer for more than 100 years, and was made possible by the discovery of X-rays in 1895 by German physicist Wilhelm Conrad Röntgen, which allowed tumors to be detected more easily and noninvasively. In the early 1900s, the field of radiation therapy began to expand, especially after Marie Curie discovered the radioactive elements polonium and radium; however, once the ill effects of radium became apparent in the mid-1900s, radium isotopes were largely replaced by cobalt and caesium, which were found to be safer and more effective.
The first clinical use of X-ray radiation therapy was undertaken in 1937 to treat a patient with leukemia at the University of California at Berkeley. Since then, there have been considerable advances in radiation therapy. Some of the most recent include three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic radiotherapy, brachytherapy, and radioimmunotherapy, all of which have improved radiation targeting by limiting radiation exposure of healthy tissues. One of the most promising recent advances, however, is the use of proton beam therapy. There are currently seven institutions in the United States that offer proton therapy, and several more centers are in development.
Protons are heavy, positively charged subatomic particles that were first discovered by British physicist Ernest Rutherford in 1919. Proton therapy is an external beam radiotherapy in which protons are accelerated in a particle accelerator to almost the speed of light and then slowed down to the target speed before hitting the tissues. Unlike conventional radiation therapy, which uses photons, protons can be manipulated to release their energy at a precise point. The depth of their penetration into the human body depends on how much energy the protons acquire, which is carefully calculated before therapy is administered. The peak of the radiation dose, referred to as the Bragg Peak, conforms to the back of the tumor; thus, almost no radiation is administered beyond that point, ensuring the healthy tissue behind the tumor is spared. Although the healthy tissue in front of the tumor is exposed to the protons, the treatment conforms so closely to the tumor that the effects of this exposure are minimized, and the procedure is painless and without side effects in most patients.
In contrast to proton therapy, conventional photon therapy does not permit the irradiation pattern to conform to the cancer as accurately; thus, the surrounding healthy tissues and organs often receive a similar dose and may become damaged in the process. To spare healthy tissues and prevent any untoward side effects, radiation oncologists often administer a lower dose of photons than is desired, which may reduce the efficacy of treatment. Because of how well protons conform to the tumor, higher doses of radiation can be used to control and manage the cancer while significantly reducing damage to healthy tissues and vital organs. Proton beam therapy also does not affect the bone marrow, allowing chemotherapy agents to be used that previously could not be administered in the setting of radiation therapy; thus, this modality expands the available treatment options for certain patients.
While it is unclear whether proton therapy offers a survival benefit compared with photon therapy, a study presented in 2008 at the 50th Annual Meeting of the American Society for Radiation Oncology (formerly known as the American Society for Therapeutic Radiology and Oncology, but still referred to as ASTRO) in Boston reported that patients treated with proton therapy had a two-fold decreased risk of developing a secondary cancer compared with those treated with standard photon therapy. This may be an especially important finding for pediatric patients, who are at greater risk of developing secondary tumors.
Proton therapy has been found to be effective in treating brain, head and neck, central nervous system, lung, and prostate tumors, and with considerably fewer side effects than conventional photon therapy. For instance, a 2006 report by Metz found that less than 2% of patients who received proton therapy for head and neck cancer became blind versus 15% of those who received conventional radiotherapy. This modality may also be beneficial in treating tumors that are unresectable or close to vital organs, and its precise targeting offers considerable benefits to pediatric patients, who are especially sensitive to the effects of radiation.
As the technology behind proton therapy continues to evolve, more tumors will become treatable using this modality. In February 2009, the University of Florida Proton Therapy Institute in Jacksonville announced the availability of uniform scanning, which allows the proton beam to cover a wider treatment area and penetrate deeper into the body than the more commonly used scattering method. As a result, the institution is now able to treat sarcomas larger than 9.4 inches and prostate cancer in patients with a hip circumference of more than 50 inches.
Because of the limited number of proton treatment facilities worldwide, physicians have focused on using the therapy for a small number of patients with diagnoses that make proton therapy especially beneficial, such as cancers and other tumors in children and tumors that are near vital organs or structures. The indications for proton therapy will continue to expand as more treatment centers open and become involved in clinical research. Currently, numerous clinical trials are being conducted to investigate proton therapy, including for rarer cancers, such as chondrosarcomas. See the sidebar on the right for a list of some of the proton therapy clinical trials that are currently recruiting patients.
Building a proton therapy center is costly, ranging from $100 to $250 million, and once up and running, there are substantial operating costs. It is estimated that a $125 million facility may generate operating costs between $15 million and $25 million annually. These facilities require a tremendous amount of space, approximately that of a football field, contributing to the cost. Because of the expense of building and running these facilities, the costs of administering this therapy are substantially higher than that of conventional radiotherapy. Currently, one treatment can range from $1500 to $2000, and patients typically require between 20 and 40 treatments, depending on the location and size of the tumor; thus, complete treatment may range from $30,000 to $80,000. Many US insurance providers cover proton therapy, as does the US Medicare program and many state Medicaid programs. It is also anticipated that the costs of treatment will go down as more centers are built.
The latest proton therapy center to come on the scene is the ProCure Proton Therapy Center in Oklahoma City, which was built in just 27 months. The facility opened its doors to patients on July 8, 2009, and this marks the first time proton therapy will be available in a community hospital setting, outside of an academic center. The ProCure facility measures 60,000 square feet and is the first to feature inclined beam rooms, which allow the proton beam to be delivered from two angles (horizontal and 60 degrees inclined from horizontal), replacing the need for multiple full-gantry treatment rooms. These rooms allow 80% of tumors to be treated without a gantry, cutting treatment costs by 50%.
Other innovations at the Oklahoma facility include the use of image-guided radiotherapy and a robotic patient positioning system (PPS). The PPS is a computer-controlled robotic system that moves patients precisely into the treatment position, eliminating the need to create body pods to hold patients in place during treatment. This system received FDA approval in spring 2009, and the Oklahoma center is the first one to use this technology; however, ProCure has shared these innovations with IBA in Belgium and other centers. For more on this center and proton therapy, turn to page 38 to read our interview with John Cameron, PhD, founder of the ProCure Treatment Centers.
More than 60,000 people worldwide have received proton therapy at centers in the United States, Europe, and Asia. While it is estimated that more than 250,000 US patients with cancer may benefit from proton therapy, the centers that are currently in operation can only handle about 6,000 treatment slots per year; however, as more facilities continue to open, the technology continues to improve, and costs are cut, considerably more patients will be able to fight their cancer using the power of protons, another effective weapon in the oncology arsenal and a ray of hope for patients.  

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