Proton therapy
Overview
 
Proton therapy is a type of particle therapy
Particle therapy
Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions for cancer treatment. The most common type of particle therapy as of 2009 is proton therapy. Although a photon, used in x-ray or gamma ray therapy, can also be considered a...

 which uses a beam of proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....

s to irradiate
Irradiation
Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve a specific purpose, rather than radiation exposure to...

 diseased tissue, most often in the treatment of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. The chief advantage of proton therapy is the ability to more precisely localize the radiation dosage when compared with other types of external beam radiotherapy
External beam radiotherapy
External beam radiotherapy or teletherapy is the most common form of radiotherapy. The patient sits or lies on a couch and an external source of radiation is pointed at a particular part of the body...

.
Proton therapy is a type of external beam radiotherapy using ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

. During treatment, a particle accelerator is used to target the tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 with a beam of protons.
Encyclopedia
Proton therapy is a type of particle therapy
Particle therapy
Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions for cancer treatment. The most common type of particle therapy as of 2009 is proton therapy. Although a photon, used in x-ray or gamma ray therapy, can also be considered a...

 which uses a beam of proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....

s to irradiate
Irradiation
Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve a specific purpose, rather than radiation exposure to...

 diseased tissue, most often in the treatment of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. The chief advantage of proton therapy is the ability to more precisely localize the radiation dosage when compared with other types of external beam radiotherapy
External beam radiotherapy
External beam radiotherapy or teletherapy is the most common form of radiotherapy. The patient sits or lies on a couch and an external source of radiation is pointed at a particular part of the body...

.

Description

Proton therapy is a type of external beam radiotherapy using ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

. During treatment, a particle accelerator is used to target the tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 with a beam of protons. These charged particle
Charged particle
In physics, a charged particle is a particle with an electric charge. It may be either a subatomic particle or an ion. A collection of charged particles, or even a gas containing a proportion of charged particles, is called a plasma, which is called the fourth state of matter because its...

s damage the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 of cells, ultimately causing their death or interfering with their ability to proliferate. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

 and their reduced abilities to repair DNA damage.

Due to their relatively large mass, protons have little lateral side scatter
Scattering
Scattering is a general physical process where some forms of radiation, such as light, sound, or moving particles, are forced to deviate from a straight trajectory by one or more localized non-uniformities in the medium through which they pass. In conventional use, this also includes deviation of...

 in the tissue; the beam does not broaden much, stays focused on the tumor shape and delivers only low-dose side-effects to surrounding tissue. All protons of a given energy have a certain range
Range (particle radiation)
In passing through matter, charged particles ionize and thus lose energy in many steps, until their energy is zero. The distance to this point is called the range of the particle...

; very few protons penetrate beyond that distance. Furthermore, the dose
Absorbed dose
Absorbed dose is a measure of the energy deposited in a medium by ionizing radiation per unit mass...

 delivered to tissue is maximum just over the last few millimeters of the particle’s range; this maximum is called the Bragg peak
Bragg Peak
The Bragg peak is a pronounced peak on the Bragg curve which plots the energy loss of ionizing radiation during its travel through matter. For protons, α-rays, and other ion rays, the peak occurs immediately before the particles come to rest...

.

To treat tumors at greater depths, the proton accelerator must produce a beam with higher energy, typically given in eV or electron volts. Tumors closer to the surface of the body are treated using protons with lower energy. The accelerators used for proton therapy typically produce protons with energies in the range of 70 to 250 MeV (Mega
SI prefix
The International System of Units specifies a set of unit prefixes known as SI prefixes or metric prefixes. An SI prefix is a name that precedes a basic unit of measure to indicate a decadic multiple or fraction of the unit. Each prefix has a unique symbol that is prepended to the unit symbol...

 electron Volts: million electron Volts). By adjusting the energy of the protons during application of treatment, the cell damage due to the proton beam is maximized within the tumor itself. Tissues closer to the surface of the body than the tumor receive reduced radiation, and therefore reduced damage. Tissues deeper within the body receive very few protons so that the dosage becomes immeasurably small.

In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor. These Bragg peaks are shown as blue lines in the figure to the right. The total radiation dosage of the protons is called the Spread-Out Bragg Peak (SOBP), shown as a red line in figure to the right. It is important to understand that, while tissues behind or deeper than the tumor receive no radiation from proton therapy, the tissue in front of or shallower than the tumor receive radiation dosage based on the SOBP.

History

The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson
Robert R. Wilson
Robert Rathbun Wilson was an American physicist who was a group leader of the Manhattan Project, a sculptor, and an architect of Fermi National Laboratory , where he was also the director from 1967–1978....

 in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory
Harvard Cyclotron Laboratory
The Harvard Cyclotron Laboratory operated from 1949 to 2002. It was most notable for its contributions to the development of proton therapy....

 (HCL). The first treatments were performed with 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
Massachusetts General Hospital
Massachusetts General Hospital is a teaching hospital and biomedical research facility in the West End neighborhood of Boston, Massachusetts...

 (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. The world's first hospital-based proton therapy center was built in 1990 at the Loma Linda University Medical Center
Loma Linda University Medical Center
Loma Linda University Medical Center is a teaching hospital on the campus of Loma Linda University in Loma Linda, California, United States. The medical center serves as a level I trauma center for San Bernardino County and the rest of the Inland Empire. It is one of two closest trauma centers for...

 (LLUMC) in Loma Linda, California
Loma Linda, California
Loma Linda is a city in San Bernardino County, California, United States, that was incorporated in 1970. The population was 23,261 at the 2010 census, up from 18,681 at the 2000 census...

. Later, The Northeast Proton Therapy Center at Massachusetts General Hospital
Massachusetts General Hospital
Massachusetts General Hospital is a teaching hospital and biomedical research facility in the West End neighborhood of Boston, Massachusetts...

 was brought online, and the HCL treatment program was transferred to it during 2001 and 2002. By 2010 these facilities were joined by an additional seven regional hospital-based proton therapy centers in the United States alone, and many more worldwide.

Application

The types of treatments for which protons are used can be separated into two broad categories. The first are those for disease sites that favor the delivery of higher doses of radiation, i.e. dose escalation. In some instances dose escalation has been shown to achieve a higher probability of "cure" (i.e. local control) than conventional radiotherapy. These include (but are not limited to) uvea
Uvea
The uvea , also called the uveal layer, uveal coat, uveal tract, or vascular tunic, is the pigmented middle of the three concentric layers that make up an eye. The name is possibly a reference to its reddish-blue or almost black colour, wrinkled appearance and grape-like size and shape when...

l melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

 (ocular tumors), skull base and paraspinal tumors (chondrosarcoma
Chondrosarcoma
Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Chondrosarcoma is a member of a category of "soft tissue" malignancies known as sarcomas. About 30% of skeletal system cancers are chondrosarcomas...

 and chordoma
Chordoma
Chordoma is a rare slow-growing malignant neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors , the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the...

), and unresectable sarcomas. In all these cases proton therapy achieves significant improvements in the probability of local control over conventional radiotherapy.

The second broad class are those treatments where the increased precision of proton therapy is used to reduce unwanted side effects, by limiting the dose to normal tissue. In these cases the tumor dose is the same as that used in conventional therapy, and thus there is no expectation of an increased probability of curing the disease. Instead, the emphasis is on the reduction of the integral dose to normal tissue, and thus a reduction of unwanted effects. Two prominent examples are pediatric neoplasms (such as medulloblastoma
Medulloblastoma
Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...

) and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

. In the case of pediatric treatments there is convincing clinical data showing the advantage of sparing developing organs by using protons, and the resulting reduction of long term damage to the surviving child.

In the case of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

 the issue is not so clear. Some published studies found a reduction in long term rectal and genitio-urinary damage when treating with protons rather than photons (also known as X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...

 or gamma ray
Gamma ray
Gamma radiation, also known as gamma rays or hyphenated as gamma-rays and denoted as γ, is electromagnetic radiation of high frequency . Gamma rays are usually naturally produced on Earth by decay of high energy states in atomic nuclei...

 therapy). Others showed the difference is small, and limited to cases where the prostate is particularly close to certain anatomical structures. The relatively small improvement found may be the result of inconsistent patient set-up and internal organ movement during treatment, which offsets most of the advantage due to increased precision. One source suggests that dose errors around 20% can result from motion errors of just 2.5 mm, and another that prostate motion is between 5–10 mm.

However, the number of cases of prostate cancer diagnosed each year far exceeds those of the other diseases referred to above, and this has led some, but not all, facilities to devote a majority of their treatments slots to prostate treatments. For example two hospital facilities devote roughly 65% and 50% of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%

Current overall world wide numbers are hard to compile, but one example in the literature shows that in 2003 roughly 26% of proton therapy treatments world wide were for prostate cancer. Proton therapy for ocular (eye) tumors is a special case since this treatment requires only a comparatively low energy (about 70 MeV). Owing to this low energy requirement, some particle therapy centers only treat ocular tumors. Proton, or more generally, hadron
Hadron
In particle physics, a hadron is a composite particle made of quarks held together by the strong force...

 therapy of tissue close to the eye affords sophisticated methods to assess the alignment of the eye that can vary significantly from other patient position verification approaches in image guided particle therapy. Position verification and correction have to ensure that sensitive tissue like the optic nerve is spared from the radiation in order to preserve the patient’s vision.

Comparison with other treatment options

The issue of when, whether, and how best to apply this technology is controversial. As of 2009 it is not yet known whether proton therapy yields better clinical outcomes than other types of radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

 for people with many common cancers. Proton therapy is far more expensive than conventional therapy. It requires a large capital investment (roughly $100M to $150M) for 2009 technology.

Preliminary results from a three-year 2009 study, including high dose treatments, show very few side effects.

X-ray radiotherapy

The figure at the right of the page shows how beams of x-rays (IMRT) left frame and beams of protons right frame, of different energies, penetrate human tissue. A tumor with a sizable thickness is covered by the IMPT spread out Bragg peak (SOBP) shown as the red lined distribution in the figure. The SOBP is an overlap of several pristine Bragg peaks (blue lines) at staggered depths.

X-ray therapy may be described as having more "skin sparing potential" than proton therapy: x-ray radiation at the skin and at very small depths is lower than for proton therapy. One study estimates that passively scattered proton fields have a slightly higher entrance dose at the skin (~75%) compared to therapeutic megavoltage (MeV) photon beams (~60%). X-ray radiation dose falls off gradually, causing unnecessary damage to tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The X-ray advantage of reduced damage to skin at the entrance is partially counteracted by damage to skin at the exit point. Since X-ray treatments are usually done with multiple exposures from opposite sides, each section of skin will be exposed to both entering and exiting X-rays. In proton therapy, skin exposure at the entrance point is higher, but tissues on the opposite side of the body than the tumor receive no radiation. Thus, x-ray therapy causes slightly less damage to the skin and surface tissues, and proton therapy causes less damage to deeper tissues in front of and beyond the target.

Surgery

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 benefit of external beam proton radiation lies in the dosimetric difference from external beam x-ray radiation and brachytherapy
Brachytherapy
Brachytherapy , also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment...

 in cases, where the use of radiation therapy is already indicated, rather than as a direct competition with surgery.

Side effects and risks

Proton therapy is a type of external beam radiotherapy, and shares risks and side effects
Side Effects
Side Effects is an anthology of 17 comical short stories written by Woody Allen between 1975 and 1980, all but one of which were previously published in, variously, The New Republic, The New York Times, The New Yorker, and The Kenyon Review. It includes Allen's 1978 O...

 of other forms of radiation therapy. Proton therapy has been in use for over 40 years, and is a mature treatment technology. However, as with all medical knowledge, understanding of the interaction of radiation (proton, X-ray, etc.) with tumor and normal tissue is still imperfect.

Treatment centers

As of June 2011, there were a total of 37 proton therapy centers in Canada, China, England, France, Germany, Italy, Japan, Korea, Poland, Russia, South Africa, Sweden, Switzerland, and USA; and more than 73800 patients had been treated.
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 accelerator systems to deliver the proton therapy to patients. Among the technologies being investigated are Superconducting synchrocyclotron
Synchrocyclotron
A synchrocyclotron is a cyclotron in which the frequency of the driving RF electric field is varied to compensate for relativistic effects as the particles' velocity begins to approach the speed of light...

s (also known as FM Cyclotrons), ultra-compact Synchrotron
Synchrotron
A synchrotron is a particular type of cyclic particle accelerator in which the magnetic field and the electric field are carefully synchronised with the travelling particle beam. The proton synchrotron was originally conceived by Sir Marcus Oliphant...

s and Dielectric wall accelerator
Dielectric wall accelerator
The Dielectric Wall Accelerator is a new compact particle accelerator designed at the Lawrence Livermore National Security, LLC , managed Lawrence Livermore National Lab LLNL, a DOE National lab. It has been turned over to the UC Davis Cancer center supported by the UC Davis Crocker Nuclear Lab...

s

See also

  • List of proton treatment centers currently operating in the United States
  • List of oncology-related terms
  • Proton
    Proton
    The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....

    , Hydrogen atom
    Hydrogen atom
    A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively-charged proton and a single negatively-charged electron bound to the nucleus by the Coulomb force...

    , Hydrogen ion
    Hydrogen ion
    Hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes.Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions....

    , ion beam
    Ion beam
    An ion beam is a type of charged particle beam consisting of ions. Ion beams have many uses in electronics manufacturing and other industries. A variety of ion beam sources exist, some derived from the mercury vapor thrusters developed by NASA in the 1960s.-Ion beam etching or sputtering:One type...

  • particle therapy
    Particle therapy
    Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions for cancer treatment. The most common type of particle therapy as of 2009 is proton therapy. Although a photon, used in x-ray or gamma ray therapy, can also be considered a...

    , Charged particle therapy, Hadron
    Hadron
    In particle physics, a hadron is a composite particle made of quarks held together by the strong force...

    , Microbeam
    Microbeam
    A microbeam is a narrow beam of radiation, of micrometer or sub-micrometer dimensions. Together with integrated imaging techniques, microbeams allow precisely defined quantities of damage to be introduced at precisely defined locations...

  • Fast neutron therapy
    Fast neutron therapy
    Fast neutron therapy utilizes high energy neutrons typically greater than 20 MeV to treat cancer. Most fast neutron therapy beams are produced from proton beams impinging upon beryllium targets.-Advantages:...

  • Boron neutron capture therapy
    Boron Neutron Capture Therapy
    Boron neutron capture therapy is an experimental form of radiotherapy that uses a neutron beam that interacts with boron injected into a patient...

  • Linear energy transfer
    Linear energy transfer
    Linear energy transfer is a measure of the energy transferred to material as an ionizing particle travels through it. Typically, this measure is used to quantify the effects of ionizing radiation on biological specimens or electronic devices....

    , Electromagnetic radiation and health
  • Dosimetry
    Dosimetry
    Radiation dosimetry is the measurement and calculation of the absorbed dose in matter and tissue resulting from the exposure to indirect and direct ionizing radiation...

    , Dosimeter
    Dosimeter
    Dosimeters measure an individual's or an object'sexposure to something in the environment — particularly to a hazard inflicting cumulative impact over long periods of time, or over a lifetime...

    , Ionizing radiation
    Ionizing radiation
    Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...


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)

External links

  • Proton therapy - MedlinePlus
    MedlinePlus
    MedlinePlus is a free Web site that provides consumer health information for patients, families, and Health care providers. The site brings together information from the United States National Library of Medicine, the National Institutes of Health , other U.S. government agencies, and...

    Medical Encyclopedia
  • Proton Therapy


The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK