Proton therapy

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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.

[edit] 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]

[edit] Comparison with Surgery

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. ^[5]

The application of radiation is statistical in nature. This is because the cure rate of radiation therapy is based on the probability of cell kill within a geometric margin. Therefore surgery has a 100% success rate of removing tissue within a geometric margin. The only way to "know" if radiation is successful is if a cell does not multiply.

The decision to use surgery or proton therapy (or in fact any radiation therapy) is based on the tumor type, stage, and location. In some instances surgery is superior (e.g. cutaneous melanoma), in some instances radiation is superior (e.g. skull base chondrosarcoma), and in some instances they are comparable (e.g. prostate cancer). In some instances, they are used together (e.g. rectal cancer or early stage breast cancer). The main benefit of proton radiation is its dosimetric superiority over photon radiation in cases, where the use of radiation therapy is already indicated, rather than as a direct competition with surgery.

[edit] The Promises and Perils of Proton Radiotherapy - Using Children to Justify New Technology

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The justification for technological advances in medicine is often spearheaded by an appeal to human compassion. For example radiotherapy advertisements often use children to sway public opinion in the development and adoption of a costly technology. ^{[7] [8]}

It is worth noting that cancer in children is a rare disease. For every 120 adults who develop cancer, there is approximately one child. ^[9] The most common childhood cancer is leukemia, accounting for about one third of all cancers seen.

As a point of comparison note that proton therapy has its most profitable application in the treatment of well encapsulated tumours such as prostate cancer. ^[8] Statistics from one proton therapy center suggest that 64.3% of patients treated by proton therapy are prostate cancer patients. ^[6] Of the 1,437,180 new cancer cases diagnosed in the United States for one year

• 15% of these are prostate cancer diagnosis
• 0.05% (11,000) of these cancer cases are children.^[10]

Critically thinking with these statistical values assumes that a well informed pediatrician allows every child diagnosed with cancer to be treated with radiotherapy.

One article suggests that a possible estimate of 45 children, i.e. one third, were denied treatment due to limited resources at a proton center.^[7] It is worth noting that the care put into treating children involves 2-4 times the resources than more conventional cancer treatments. Therefore approximately 200 adults would have benefited over the 45 children. One proton therapy center has a capacity to treat 140-150 (adult) patients per day. This capacity averages out to a mixture of 1,000 patients in one year [1].

The success of this therapy for either patient population is yet to be established. In all likelihood any new benefit will be incrementally small as this treatment technique has been around since 1946. ^[11] This simple cost benefit analysis suggests that one proton center would have the capacity to treat every child in the United States rather than a dearth of centers. Therefore it is safe to conclude that the construction of multiple proton therapy centers is being done to treat adults and not children.

[edit] Early history of proton therapy

The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson^[11] 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^[12] before the Cyclotron was shut down in 2002. Following this pioneering work, the first hospital based proton treatment center of the world 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), where more than 13000 patients with 50 different types of tumor have been treated so far (end of 2008)^[12]. 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.

The first proton therapy center in Western Europe has been in operation at the Paul Scherrer Institute (PSI) in Villigen, Switzerland, since 1984.^[12].

[edit] 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][13] 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^[14].

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.^[15]

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.^[16]

[edit] 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.^[17]

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^[18].

With over 5000 patients, the largest number of ocular tumors have been treated since 1984 at the Paul Scherrer Institute in Switzerland^[12].

Im March, 2009, patient treatment has begun at the first commercial proton therapy center of Europe, the Rinecker Proton Therapy Center (RPTC)^[19] in Munich, Germany.

[edit] Future proton centers

The Particle Therapy Co-Operative Group^[12] 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).

[edit] 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^[20]
• 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.^{[21][22][23][24]}
• 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.

[edit] 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.^[25][26][27]
• Facilities are also planned or under construction^[12] in Austria, Italy, Germany, South Africa, France, Japan, Russia, Slovak Republic, China, Sweden and Turkey^[28].

[edit] 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^[20]. 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.

[edit] Therapy equipment suppliers

The following firms are currently supplying or developing proton therapy equipment:

• IBA (Belgium)
• Optivus Proton Therapy (USA)
• Hitachi (Japan)
• Sumitomo Heavy Industries (Japan)
• ACCEL (Germany, now acquired by Varian, USA)
• Mitsubishi Electric, (Japan)
• Siemens (Germany)
• Still River Systems (USA)
• ProTom International (USA/Russia)

[edit] References

Wikimedia Commons has media related to: Proton therapy

[edit] Further reading

• Greco C, Wolden S. Current status of radiotherapy with proton and light ion beams. Cancer. 2007 Apr 1;109(7):1227-38 PMID 17326046
• "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)
• Accelerator Physics: The Plasma Revolution, Nature 449 (2007) 133, by Navroz Patel