Proton therapy (Arip Nurahman)

Proton therapy is a type of particle therapy which uses a beam of protons to irradiate diseased tissue, most often in the treatment of cancer.

Description

Proton therapy is a type of external beam radiotherapy. It works by aiming energetic ionizing particles (in this case, protons accelerated with a particle accelerator) onto the target tumor.^[1][2] 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 large mass, protons do not scatter much in the tissue; the beam does not broaden much and stays focused on the tumor shape without much damage to surrounding tissue. All protons of a given energy have a certain range; no proton penetrates beyond that distance. Furthermore, the dose delivered to tissue is maximum just over the last few millimeters of the particle’s range; this maximum is called the Bragg peak.^[3] 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 (typically 70 to 250 MeV). 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 only a reduced dose, and tissues situated after the peak receive none.^[4]

Comparison with conventional x-ray radiotherapy

The dose from protons to tissue is maximum just over the last few millimeters of the particle’s range, quite different from electrons or x rays.

Irradiation of nasopharyngeal carcinoma by photon therapy (left) and proton therapy (right).

The figure on the left shows how beams of electrons, x rays or protons of different energies (expressed in MeV) penetrate human tissue. Electrons have a short range and are therefore only of interest close to the skin. Bremsstrahlung x rays penetrate more deeply, but the dose absorbed by the tissue then shows the typical exponential decay with increasing thickness. For protons, on the other hand, the dose increases with increasing thickness up to the Bragg peak that occurs near the end of the particle's range.

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.^[2] 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.^[2][14] 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 side-effects than conventional radiation therapy^[15].

One area where proton therapy has had considerable success is 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.^[16]

Proton beam radiation therapy has also had remarkable success in the treatment of many other 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.^[17]

Present Proton Therapy Centers

2005 image of the control panel of the synchrocyclotron at the Orsay proton therapy center

Proton therapy needs heavy equipment.^[2] For instance, the Orsay proton therapy center, in France, (see figure) uses a synchrocyclotron weighing 900 tons in total. Such equipment was formerly only available within centers studying particle physics. In the case of the Orsay installation, the treatment machine was converted from particle research usage to medical usage.

Presently (end of 2008), there are proton therapy centers in Canada, China, England, France, Germany, Italy, Japan (5 centers), Korea, Russia, South Africa, Sweden, Switzerland, and USA (6 centers), altogether 26 installations, and over 60000 patients have been treated so far.^[18]

Proton therapy for ocular tumors is a special case since this treatment requires only a comparably low energy (about 70 MeV). In the United Kingdom, it is currently only available at the Clatterbridge Centre for Oncology in Bebington on the Wirral, Merseyside. In China, the only proton therapy machine is located in the Wanjie Proton Therapy Center in Zibo, Shandong. In the USA, it is available in Sacramento, California at the University of California, Davis, the UC Davis Proton Facility which is operated exclusively by the UC San Francisco Department of Radiation Oncology. Since 2004, the Midwest Proton Radiotherapy Institute at Indiana University, and, in 2006, the University of Texas M. D. Anderson Cancer Center in Houston TX, and the University of Florida Proton Therapy Institutein Jacksonville, FL^[19].

With over 5000 patients, the largest number of ocular tumors have been treated since 1984 at the Paul Scherrer Institute in Switzerland^[13].

Im March, 2009, patient treatment has begun at the first commercial proton therapy center of Europe, the Rinecker Proton Therapy Center (RPTC)^[20] in Munich, Germany.

Future proton centers

The Particle Therapy Co-Operative Group^[13] keeps a list of planned therapy facilities which is updated continually. At present (March 2009), it lists 21 projects in various stages of progress, from all over the world (see below).

Future centers in the United States

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 Proton Therapy Institute in Hampton, Virginia, planning a $225 million facility due for completion in 2009^[21]
• 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 (the Roberts Proton Therapy Center in the Perelman Center for Advanced Medicine), 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 cancer treatment and research center in Chicago that will provide proton therapy.^{[22][23][24][25]}
• 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. Patient treatment is expected to begin at CDH by 2010.
• [2]Procure Treatment Centers in Oklahoma City, due for completion in 2009.
• Barnes-Jewish Hospital in St. Louis, Missouri
• Robert Wood Johnson University Hospital in New Brunswick, New Jersey
• Broward General at Ft. Lauderdale and Orlando Regional at Orlando, Florida, are planning smaller units (about $20 million).
• 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.

Future centers in other countries

• 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.
• The National Health Service of Great Britain estimates that creating fully-equipped proton therapy centres in Britain would cost between £50-100m each.^[26][27][28]
• Facilities are also planned or under construction^[13] in Austria, Italy, Germany, South Africa, France, Japan, Russia, Slovak Republic, China, Sweden and Turkey^[29].

Future technical development

One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or synchrotron equipment necessary. Several industrial teams are working on development of comparatively small cyclotron or synchrotron systems to deliver the proton therapy to patients^[21]. 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.