Radiation therapy (in the USA),
radiation oncology, or radiotherapy (in the UK, Canada and Australia),
sometimes abbreviated to XRT, is the medical use of ionizing radiation
as part of cancer treatment to control malignant cells (not to be
confused with radiology, the use of radiation in medical imaging and
diagnosis). Radiation therapy may be used for curative or adjuvant
treatment. It is used as palliative treatment (where cure is not
possible and the aim is for local disease control or symptomatic relief)
or as therapeutic treatment (where the therapy has survival benefit and
it can be curative). Total body irradiation (TBI) is a radiation
therapy technique used to prepare the body to receive a bone marrow
transplant. Radiation therapy has several applications in non-malignant
conditions, such as the treatment of trigeminal neuralgia, severe
thyroid eye disease, pterygium, pigmented villonodular synovitis,
prevention of keloid scar growth, and prevention of heterotopic
ossification. The use of radiation therapy in non-malignant conditions
is limited partly by worries about the risk of radiation-induced
cancers.
Radiation therapy is used for the
treatment of malignant cancer, and may be used as a primary or adjuvant
modality. It is also common to combine radiation therapy with surgery,
chemotherapy, hormone therapy, Immunotherapy or some mixture of the
four. Most common cancer types can be treated with radiation therapy in
some way. The precise treatment intent (curative, adjuvant, neoadjuvant,
therapeutic, or palliative) will depend on the tumor type, location,
and stage, as well as the general health of the patient.
Radiation therapy is commonly
applied to the cancerous tumor. The radiation fields may also include
the draining lymph nodes if they are clinically or radiologically
involved with tumor, or if there is thought to be a risk of subclinical
malignant spread. It is necessary to include a margin of normal tissue
around the tumor to allow for uncertainties in daily set-up and internal
tumor motion. These uncertainties can be caused by internal movement
(for example, respiration and bladder filling) and movement of external
skin marks relative to the tumor position.
To spare normal tissues (such as
skin or organs which radiation must pass through in order to treat the
tumor), shaped radiation beams are aimed from several angles of exposure
to intersect at the tumor, providing a much larger absorbed dose there
than in the surrounding, healthy tissue.
Brachytherapy, in which a
radiation source is placed inside or next to the area requiring
treatment, is another form of radiation therapy that minimizes exposure
to healthy tissue during procedures to treat cancers of the breast,
prostate and other organs.
Radiation therapy works by
damaging the DNA of cancerous cells. This DNA damage is caused by one of
two types of energy, photon or charged particle. This damage is either
direct or indirect ionizing the atoms which make up the DNA chain.
Indirect ionization happens as a result of the ionization of water,
forming free radicals, notably hydroxyl radicals, which then damage the
DNA. In the older, most common form of radiation therapy,
Intensity-modulated radiation therapy (IMRT) (photons), most of the
radiation effect is through free radicals. Because cells have mechanisms
for repairing single-strand DNA damage, double-stranded DNA breaks
prove to be the most significant technique to cause cell death. Cancer
cells generally are undifferentiated and stem cell-like, they reproduce
more, and have a diminished ability to repair sub-lethal damage compared
to most healthy differentiated cells. This single-strand DNA damage is
then passed on through cell division, accumulating damage to the cancer
cell's DNA, causing them to die or reproduce more slowly.
One of the major limitations of
photon radiation therapy is that the cells of solid tumors become
deficient in oxygen. Solid tumors can outgrow their blood supply,
causing a low-oxygen state known as hypoxia. Oxygen is a potent
radiosensitizer, increasing the effectiveness of a given dose of
radiation by forming DNA-damaging free radicals. Tumor cells in a
hypoxic environment may be as much as 2 to 3 times more resistant to
radiation damage than those in a normal oxygen environment. Much
research has been devoted to overcoming hypoxia including the use of
high pressure oxygen tanks, blood substitutes that carry increased
oxygen, hypoxic cell radiosensitizer drugs such as misonidazole and
metronidazole, and hypoxic cytotoxins (tissue poisons), such as
tirapazamine.
Direct damage to cancer cell DNA
occurs through high-LET (linear energy transfer) charged particles such
as proton, boron, carbon or neon ions which have an antitumor effect
which is independent of tumor oxygen supply because these particles act
mostly via direct energy transfer usually causing double-stranded DNA
breaks. Due to their relatively large mass, protons and other charged
particles have little lateral side scatter in the tissue; the beam does
not broaden much, stays focused on the tumor shape and delivers small
dose side-effects to surrounding tissue. They also more precisely target
the tumor using the Bragg peak effect. See proton therapy for a good
example, with photos, of the different effects of IMRT vs. charged
particle therapy. The cyclotron's, dielectric wall accelerator (DWA), or
Still River Systems's super conducting high field magnet (two new
compact protron replacements) provide the energy source for charged
particle therapy. These particles can be charged to different amounts to
provide the desired tissue penetration. This procedure reduces damage
to healthy tissue between the charged particle radiation source and the
tumor and sets a finite range for tissue damage after the tumor has been
reached. In contrast, with IMRT using uncharged particles (photons),
its energy is deposited differently such that it is still damaging
healthy cells when it exits the body. This exiting damage is not
therapeutic, can increase treatment side effects, and increases the
probability of secondary cancer induction. This difference is very
important in cases where the close proximity of other organs makes any
stray ionization very damaging (example: head and neck cancers). This
x-ray exposure is especially bad for children, due to their growing
bodies, and they have a 30% chance of a second malignancy after 5 years
post initial RT.
Radiation therapy has been in
use as a cancer treatment for more than 100 years, with its earliest
roots traced from the discovery of x-rays in 1895 by Wilhelm Röntgen.
The field of radiation therapy
began to grow in the early 1900s largely due to the groundbreaking work
of Nobel Prize-winning scientist Marie Curie, who discovered the
radioactive elements polonium and radium. This began a new era in
medical treatment and research. Radium was used in various forms until
the mid-1900s when cobalt and caesium units came into use. Medical
linear accelerators have been used too as sources of radiation since the
late 1940s.
With Godfrey Hounsfield’s
invention of computed tomography (CT) in 1971, three-dimensional
planning became a possibility and created a shift from 2-D to 3-D
radiation delivery; CT-based planning allows physicians to more
accurately determine the dose distribution using axial tomographic
images of the patient's anatomy. Orthovoltage and cobalt units have
largely been replaced by megavoltage linear accelerators , useful for
their penetrating energies and lack of physical radiation source.
The advent of new imaging
technologies, including magnetic resonance imaging (MRI) in the 1970s
and positron emission tomography (PET) in the 1980s, has moved radiation
therapy from 3-D conformal to intensity-modulated radiation therapy
(IMRT) and image-guided radiation therapy (IGRT) Tomotherapy. These
advances allowed radiation oncologists to better see and target tumors,
which have resulted in better treatment outcomes, more organ
preservation and fewer side effects.
Historically, the three main
divisions of radiation therapy are external beam radiation therapy (EBRT
or XRT) or teletherapy, brachytherapy or sealed source radiation
therapy, and systemic radioisotope therapy or unsealed source
radiotherapy. The differences relate to the position of the radiation
source; external is outside the body, brachytherapy uses sealed
radioactive sources placed precisely in the area under treatment, and
systemic radioisotopes are given by infusion or oral ingestion.
Brachytherapy can use temporary or permanent placement of radioactive
sources. The temporary sources are usually placed by a technique called
afterloading. In afterloading a hollow tube or applicator is placed
surgically in the organ to be treated, and the sources are loaded into
the applicator after the applicator is implanted. This minimizes
radiation exposure to health care personnel. Particle therapy is a
special case of external beam radiation therapy where the particles are
protons or heavier ions. Intraoperative radiation therapy or IORT is a
special type of radiation therapy that is delivered immediately after
surgical removal of the cancer. This method has been employed in breast
cancer (TARGeted Introperative radiation therapy or TARGIT), brain
tumors and rectal cancers.
Radiation therapy is in itself
painless. Many low-dose palliative treatments (for example, radiation
therapy to bony metastases) cause minimal or no side effects, although
short-term pain flare up can be experienced in the days following
treatment due to oedema compressing nerves in the treated area.
Treatment to higher doses causes varying side effects during treatment
(acute side effects), in the months or years following treatment
(long-term side effects), or after re-treatment (cumulative side
effects). The nature, severity, and longevity of side effects depends on
the organs that receive the radiation, the treatment itself (type of
radiation, dose, fractionation, concurrent chemotherapy), and the
patient.
Most side effects are
predictable and expected. Side effects from radiation are usually
limited to the area of the patient's body that is under treatment. One
of the aims of modern radiation therapy is to reduce side effects to a
minimum, and to help the patient to understand and to deal with those
side effects which are unavoidable.
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