is a type of particle therapy
which utilizes a beam of protons
diseased tissue, most often in the treatment of cancer.
Proton therapy, like all forms of radiotherapy, works by aiming energetic ionizing
particles (in this case, protons
accelerated with a particle accelerator
) onto the target tumor. These particles damage the DNA
of cells, ultimately causing their death. Cancerous cells, because of their high rate of division
and their reduced ability to repair damaged DNA, are particularly vulnerable to attack on their DNA.
Due to their relatively enormous size, protons scatter less easily in the tissue and there is very little lateral dispersion; the beam stays focused on the tumor shape without much lateral damage to surrounding tissue. All protons of a given energy have a certain range; no proton penetrates beyond that distance. Furthermore, the dosage to tissue is maximum just over the last few millimeters of the particle’s range; this maximum is called the Bragg Peak. This depth depends on the energy to which the particles were accelerated by the proton accelerator, which can be adjusted to the maximum rating of the accelerator. It is therefore possible to focus the cell damage due to the proton beam at the very depth in the tissues where the tumor is situated; tissues situated before the Bragg peak receive some reduced dose, and tissues situated after the peak receive none.
Early history of proton therapy
The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson
in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL). The first treatments were performed at Particle accelerators
built for physics research, notably Berkeley Radiation Laboratory
in 1954 and at Uppsala in Sweden in 1957. In 1961, a collaboration began between HCL and the Massachusetts General Hospital
(MGH) to pursue proton therapy. Over the next 41 years, this program refined and expanded these techniques while treating 9,116 patients before the Cyclotron was shut down in 2002. Following this pioneering work, the first hospital based proton treatment center in the United States was built in 1990 at the Loma Linda University Medical Center
in Loma Linda, California (LLUMC) (recently renamed the James M. Slater Proton Therapy Center). This was followed by The Northeast Proton Therapy Center at Massachusetts General Hospital (recently renamed the Francis H. Burr Proton Therapy Center), to which the HCL treatment program was transferred during 2001 and 2002.
Pros and cons
The treatment method is of interest because of its ability to accurately target and kill tumors, both near the surface and deep seated within the body, while minimizing damage to the surrounding tissue. For this reason, it is favored for treating certain kinds of tumors where conventional X-ray radiotherapy
would damage surrounding radio-sensitive tissues to an unacceptable level. This is of particular importance in the case of pediatric patients where long term side effects such as residual occurrence of secondary tumors
resulting from the overall radiation dose to the body are of great concern. Because of the lower dose to healthy tissue protons have less severe collateral side-effects than conventional radiation therapy
The logic for treating common cancers (for example lung, head/neck, etc) with proton therapy is the same as saying that surgery alone should cure most cancers, as surgery is the Definitive Local Treatment. Of course, surgery does not - because most cancers spread microscopically very early beyond the tumor ('local') site.
Historically, one area where proton therapy had considerable early successful application was in treating choroidal malignant melanomas, a type of eye cancer for which the only known treatment was enucleation (removal of the eye). Today, proton therapy is one of the techniques that are capable of treating this tumor without mutilation. Proton therapy is used on cancers that have not yet spread.
Proton therapy, however, needs heavy equipment - weighing into the hundreds of tons. For instance, the Orsay proton therapy center, in France, uses a synchrocyclotron weighing 900 tons in total. Such equipment was formerly only available within centers studying particle physics; and in the case of the Orsay installation, the treatment machine was converted from particle research usage to medical usage.
Proton therapy for ocular tumors is also available in Sacramento at the UC Davis Proton Facility, a facility operated exclusively by the UC San Francisco Department of Radiation Oncology. It is estimated that over 44,000 patients have been effectively treated with proton therapy. With nearly 5000 patients, the largest number of ocular tumors have been treated since 1984 at the Paul Scherrer Institute in Switzerland.
Now on line as well is the Midwest Proton Radiotherapy Institute at Indiana University In the summer of 2006 treatment started at two new facilities: the for-profit University of Texas M. D. Anderson Cancer Center proton center in Houston, Texas, and the University of Florida Proton Therapy Institute in Jacksonville, Fla. (This particular proton therapy center is unique in that it is the only facility that sits at grade, or at ground-level. In centers prior to this, the first floor which contains the proton cyclotron is situated below ground to aide in radiation shielding. Due to the high water table in Florida, the entire building was raised to ground level and the exterior walls thickened to 18 feet in some areas to obtain the same level of radiation shielding.) The University of Pennsylvania is slated to open the biggest proton therapy institute in the world (the Roberts Proton Therapy Center in the Perelman Center for Advanced Medicine) in 2009. The last three facilities were designed by the architecture firm Tsoi/Kobus and Associates and the proton therapy equipment supplier was Ion Beam Applications (IBA).
In July 2007, Central DuPage Hospital (CDH) in Winfield, Ill. announced its intent to enter a joint venture with ProCure Treatment Centers Inc. and Radiation Oncology Consultants, Ltd. to bring the future of cancer treatment to Illinois. Patient treatment is expected to begin at CDH by 2010. In a similar partnership, Procure is building a proton therapy center in Oklahoma City, OK which should be online in 2009-2010. Both sites are being designed by Tsoi/Kobus and use proton therapy equipment supplied by IBA.
However, there are now several dedicated proton therapy centers in operation or under construction in North America, Europe, and Asia. Proton beam radiation therapy has had remarkable success in the treatment of many types of cancer, including brain and spinal tumors, as well as prostate cancer. Some researchers have suggested that antiprotons may be even more effective at killing cancer cells than their proton counterparts. So far, only initial research with cell cultures has been performed.
Future proton centers
Highlighting the growing recognition, progress, and degree of potential for Proton Beam treatment, there are several new centers in the advanced planning stage within the U. S., most requiring an investment of $120 million to $200 million:
- Hampton University in Hampton, Virginia, planning a $183 million facility due for completion in 2011
- Seattle Cancer Care Alliance, planning a facility in Seattle, Washington, which will begin treatments in 2012
- University of Pennsylvania, planning a large new facility in Philadelphia (mentioned above), which is being partly funded by the United States Department of Defense in partnership with Walter Reed Army Hospital*
- Northern Illinois University, is building a world-class cancer treatment and research center in Chicago that will provide state-of-the-art proton therapy
- Procure Treatment Centers in Oklahoma City, due for completion in 2009.
- Barnes-Jewish Hospital in St. Louis, Missouri
- Broward General at Ft. Lauderdale and Orlando Regional at Orlando, Florida, are planning smaller units (about $20 million).
- National Taiwan University Hospital in Taipei City, Taiwan received US 400 million donation from Foxconn, proton therapy center due for completion in 2010.
- Chang Gung Memorial Hospital in Taipei County, Taiwan, proton therapy center due for completion in 2010.
- In Michigan, six health systems across the state have joined to form the Michigan Proton Therapy Consortium in an effort to build a new facility that will serve all Michiganders.
One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or synchrotron equipment necessary. The Massachusetts Institute of Technology (MIT) in collaboration with an industrial team, is working on development of a comparatively small accelerator system to deliver the proton therapy to patients. When perfected, an even more rapid expansion of proton facilities should almost immediately occur. The St. Louis, Missouri facility, and the two Florida hospitals mentioned above are each planning to use one of these systems. The Oklahoma City site will use a cyclotron developed by IBA.
Therapy equipment suppliers
Following firms are currently supplying or developing proton therapy equipment: the market leader is IBA
(Belgium), Still River Systems
USA, Optivus Proton Therapy
(Japan), Sumitomo Heavy Industries
(Germany, now acquired by Varian, USA),
- Accelerator Physics: Plasma Revolution, Nature (2007), Navroz Patel
- Greco C, Wolden S. Current status of radiotherapy with proton and light ion beams. Cancer. 2007 Apr 1;109(7):1227-38 PMID 17326046
- "Radiological Use of Fast Protons", R. R. Wilson, Radiology, 47:487-491 (1946)
- "Use of Protons for Radiotherapy", A.M. Koehler, Proc. of the Symposium on Pion and Proton Radiotherapy, Nat. Accelerator Lab., (1971)
- "Protons in Radiation Therapy: comparative Dose Distributions for Protons, Photons and Electrons, A.M. Koehler, W.M. Preston, Radiology, 104(1):191-195 (1972)
- "Bragg Peak Proton Radiosurgery for Arteriovenous Malformation of the Brain" R.N. Kjelberg, presented at First Int. Seminar on the Use of Proton Beams in Radiation Therapy, Moskow (1977)
- "Fractionated Proton Radiation Therapy of Cranial and Intracrainial Tumors" Austin-Seymor, M.J. Munzenrider, et al. Am.J.of Clinical Oncology 13(4):327-330 (1990)
- "Proton Radiotherapy", Hartford, Zietman, et al. in Radiotheraputic Management of Carcinoma of the Prostate, A. D'Amico and G.E. Hanks. London,UK, Arnold Publishers: 61-72 (1999)