Radiation therapy
From Wikipedia, the free encyclopedia
Radiation therapy of the
pelvis. Lasers and a mould under the legs are used to determine exact position.
Radiation therapy (in
North America), or
radiotherapy (in the
UK and
Australia) also called
radiation oncology, and 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). Radiotherapy may be used for
curative or
adjuvant cancer 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 radiotherapy technique used to prepare the body to receive a
bone marrow transplant. Radiotherapy 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 radiotherapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers.
Radiotherapy is used for the treatment of malignant
tumors (
cancer), and may be used as the primary therapy. It is also common to combine radiotherapy with
surgery,
chemotherapy,
hormone therapy
or some mixture of the three. Most common cancer types can be treated
with radiotherapy in some way. The precise treatment intent (curative,
adjuvant,
neoadjuvant, therapeutic, or
palliative) will depend on the tumour type, location, and stage, as well as the general health of the patient.
Radiation therapy is commonly applied to the cancerous tumour. The
radiation fields may also include the draining lymph nodes if they are
clinically or radiologically involved with tumour, 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 tumour 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 tumour position.
To spare normal tissues (such as skin or organs which radiation must
pass through in order to treat the tumour), shaped radiation beams are
aimed from several angles of exposure to intersect at the tumour,
providing a much larger
absorbed dose there than in the surrounding, healthy tissue.
[edit] Mechanism of action
Radiation therapy works by damaging the
DNA of cells. The damage is caused by a
photon,
electron,
proton,
neutron, or
ion beam directly or indirectly
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 most common forms of
radiation therapy, most of the radiation effect is through free
radicals. Because cells have mechanisms for repairing DNA damage,
breaking the DNA on both strands proves to be the most significant
technique in modifying cell characteristics. Because 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. The DNA damage is inherited through cell division, accumulating
damage to the cancer cells, causing them to die or reproduce more
slowly.
One of the major limitations of radiotherapy 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.
[1]
Much research has been devoted to overcoming this problem including the
use of high pressure oxygen tanks, blood substitutes that carry
increased oxygen, hypoxic cell
radiosensitizers such as
misonidazole and
metronidazole, and hypoxic cytotoxins, such as
tirapazamine. There is also interest in the fact that high-LET (
linear energy transfer)
particles such as carbon or neon ions may have an antitumor effect
which is less dependent of tumor oxygen because these particles act
mostly via direct damage.
The amount of radiation used in radiation therapy is measured in
gray
(Gy), and varies depending on the type and stage of cancer being
treated. For curative cases, the typical dose for a solid epithelial
tumor ranges from 60 to 80 Gy, while lymphoma tumors are treated with
20 to 40 Gy.
Preventative (adjuvant) doses are typically around 45 - 60 Gy in 1.8
- 2 Gy fractions (for Breast, Head and Neck cancers respectively.) Many
other factors are considered by
radiation oncologists
when selecting a dose, including whether the patient is receiving
chemotherapy, whether radiation therapy is being administered before or
after surgery, and the degree of success of surgery.
Delivery parameters of a prescribed dose are determined during
treatment planning (part of
dosimetry).
Treatment planning is generally performed on dedicated computers using
specialized treatment planning software. Depending on the radiation
delivery method, several angles or sources may be used to sum to the
total necessary dose. The planner will try to design a plan that
delivers a uniform prescription dose to the tumor and minimizes dose to
surrounding healthy tissues.
[edit] Fractionation
The total dose is fractionated (spread out over time) for several
important reasons. Fractionation allows normal cells time to recover,
while tumor cells are generally less efficient in repair between
fractions. Fractionation also allows tumor cells that were in a
relatively radio-resistant phase of the cell cycle during one treatment
to cycle into a sensitive phase of the cycle before the next fraction
is given. Similarly, tumor cells that were chronically or acutely
hypoxic (and therefore more radioresistant) may reoxygenate between
fractions, improving the tumor cell kill. Fractionation regimes are
individualised between different radiotherapy centres and even between
individual doctors. In North America, Australia, and Europe, the
typical fractionation schedule for adults is 1.8 to 2 Gy per day, five
days a week. In the northern United Kingdom, fractions are more
commonly 2.67 to 2.75 Gy per day, which eases the burden on thinly
spread resources in the
National Health Service.
In some cancer types, prolongation of the fraction schedule over too
long can allow for the tumor to begin repopulating, and for these tumor
types, including head-and-neck and cervical squamous cell cancers,
radiation treatment is preferably completed within a certain amount of
time. For children, a typical fraction size may be 1.5 to 1.8 Gy per
day, as smaller fraction sizes are associated with reduced incidence
and severity of late-onset side effects in normal tissues.
In some cases, two fractions per day are used near the end of a
course of treatment. This schedule, known as a concomitant boost
regimen or hyperfractionation, is used on tumors that regenerate more
quickly when they are smaller. In particular, tumors in the
head-and-neck demonstrate this behavior.
One of the best-known alternative fractionation schedules is
Continuous Hyperfractionated Accelerated Radiotherapy (CHART). CHART,
used to treat lung cancer, consists of three smaller fractions per day.
Although reasonably successful, CHART can be a strain on radiation
therapy departments.
Implants can be fractionated over minutes or hours, or they can be
permanent seeds which slowly deliver radiation until they become
inactive.
[edit] Effect on different types of cancer
Different cancers respond differently to radiation therapy.
[2][3][4]
The response of a cancer to radiation is described by its
radiosensitivity. Highly radiosensitive cancer cells are rapidly killed
by modest doses of radiation. These include
leukaemias, most
lymphomas and
germ cell tumours. The majority of
epithelial cancers
are only moderately radiosensitive, and require a significantly higher
dose of radiation (60-70Gy) to achieve a radical cure. Some types of
cancer are notably radioresistant, that is, much higher doses are
required to produce a radical cure than may be safe in clinical
practice.
Renal cell cancer and
melanoma are generally considered to be radioresistant.
It is important to distinguish the radiosensitivity of a particular
tumour, which to some extent is a laboratory measure, from the
radiation "curability" of a cancer in actual clinical practice. For
example, leukaemias are not generally curable with radiotherapy,
because they are disseminated though the body. Lymphoma may be
radically curable if it is localised to one area of the body.
Similarly, many of the common, moderately radioresponsive tumours are
routinely treated with curative doses of radiotherapy if they are at an
early stage. For example:
non-melanoma skin cancer,
head and neck cancer,
non-small cell lung cancer,
cervical cancer,
anal cancer,
prostate cancer.
Metastatic cancers are generally incurable with radiotherapy because it is not possible to treat the whole body.
Before treatment, a CT scan is often performed to identify the tumor
and surrounding normal structures. The patient is then sent for a
simulation so that molds can be created to be used during treatment.
The patient receives small skin marks to guide the placement of
treatment fields.
[5]
The response of a tumour to radiotherapy is also related to its
size. For complex reasons, very large tumours respond less well to
radiation than smaller tumours or microscopic disease. Various
strategies are used to overcome this effect. The most common technique
is surgical resection prior to radiotherapy. This is most commonly seen
in the treatment of
breast cancer with
wide local excision or
mastectomy followed by
adjuvant radiotherapy. Another method is to shrink the tumour with
neoadjuvant
chemotherapy prior to radical radiotherapy. A third technique is to
enhance the radiosensitivity of the cancer by giving certain drugs
during a course of radiotherapy. Examples of radiosensiting drugs
include:
Cisplatin,
Nimorazole, and
Cetuximab.
[edit] History of radiation therapy
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.
[6]
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.
[6] Radium was used in various forms until the mid-1900s when
cobalt and
caesium units came into use.
Medical linear accelerators have been used to 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). These advances have resulted in better treatment outcomes and fewer side effects.
[edit] Types of radiation therapy
Historically, the three main divisions of radiotherapy are
external beam radiotherapy (EBRT or XBRT) or teletherapy,
brachytherapy or sealed source radiotherapy, 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 radiotherapy where the particles are
protons or heavier
ions. Introperative radiotherapy
[7]
is a special type of radiotherapy that is delivered immediately after
surgical removal of the cancer. This method has been employed in breast
cancer (TARGeted Introperative radioTherapy), brain tumours and rectal
cancers.
[edit] External beam radiotherapy
The following three sections refer to treatment using x-rays.
[edit] Conventional external beam radiotherapy
Conventional external beam radiotherapy (2DXRT) is delivered via
two-dimensional beams using linear accelerator machines. 2DXRT mainly
consists of a single beam of radiation delivered to the patient from
several directions: often front or back, and both sides.
Conventional refers to the way the treatment is
planned or
simulated
on a specially calibrated diagnostic x-ray machine known as a simulator
because it recreates the linear accelerator actions (or sometimes by
eye), and to the usually well-established arrangements of the radiation
beams to achieve a desired
plan. The aim of simulation is to
accurately target or localize the volume which is to be treated. This
technique is well established and is generally quick and reliable. The
worry is that some high-dose treatments may be limited by the radiation
toxicity capacity of healthy tissues which lay close to the target
tumor volume. An example of this problem is seen in radiation of the
prostate gland, where the sensitivity of the adjacent rectum limited
the dose which could be safely prescribed using 2DXRT planning to such
an extent that tumor control may not be easily achievable. Prior to the
invention of the CT, physicians and physicists had limited knowledge
about the true radiation dosage delivered to both cancerous and healthy
tissue. For this reason, 3-dimensional conformal radiotherapy is
becoming the standard treatment for a number of tumor sites.
[edit] Stereotactic Radiation
Stereotactic radiation is a specialized type of external beam
radiation therapy. It uses focused radiation beams targeting a
well-defined tumor using extremely detailed imaging scans. Radiation
oncologists perform stereotactic treatments, often with the help of a
neurosurgeon for tumors in the brain or spine.
There are two types of stereotactic radiation.
Stereotactic radiosurgery (SRS) is when doctors use a single or several stereotactic radiation treatments of the brain or spine.
Stereotactic body radiation therapy (SBRT) refers to one or several stereotactic radiation treatments with the body, such as the lungs
[8].
Some doctors say an advantage to stereotactic treatments are they
deliver the right amount of radiation to the cancer in a shorter amount
of time than traditional treatments, which can often take six to 11
weeks. Plus treatments are given with extreme accuracy, which should
limit the effect of the radiation on healthy tissues. One problem with
stereotactic treatments is that they are only suitable for certain
small tumors.
Stereotactic treatments can be confusing because many hospitals call
the treatments by the name of the manufacturer rather than calling it
SRS or SBRT. Brand names for these treatments include Axesse,
Cyberknife,
Gamma Knife,
Novalis,
Primatom,
Synergy,
X-Knife,
TomoTherapy and
Trilogy.
[9] This list changes as equipment manufacturers continue to develop new, specialized technologies to treat cancers.
[edit] Virtual simulation, 3-dimensional conformal radiotherapy, and intensity-modulated radiotherapy
The planning of radiotherapy treatment has been revolutionized by
the ability to delineate tumors and adjacent normal structures in three
dimensions using specialized CT and/or MRI scanners and planning
software.
[10]
Virtual simulation, the most basic form of planning, allows
more accurate placement of radiation beams than is possible using
conventional X-rays, where soft-tissue structures are often difficult
to assess and normal tissues difficult to protect.
An enhancement of virtual simulation is
3-Dimensional Conformal Radiotherapy (3DCRT), in which the profile of each radiation beam is shaped to fit the profile of the target from a
beam's eye view (BEV) using a
multileaf collimator
(MLC) and a variable number of beams. When the treatment volume
conforms to the shape of the tumour, the relative toxicity of radiation
to the surrounding normal tissues is reduced, allowing a higher dose of
radiation to be delivered to the tumor than conventional techniques
would allow.
[5]
Intensity-Modulated Radiation Therapy (IMRT) is an advanced type of high-precision radiation that is the next generation of 3DCRT.
[11] IMRT also improves the ability to conform the treatment volume to concave tumor shapes,
[5] for example when the tumor is wrapped around a vulnerable structure such as the spinal cord or a major organ or blood vessel.
[12]
Computer-controlled x-ray accelerators distribute precise radiation
doses to malignant tumors or specific areas within the tumor. The
pattern of radiation delivery is determined using highly-tailored
computing applications to perform
optimization and treatment simulation (
Treatment Planning).
The radiation dose is consistent with the 3-D shape of the tumor by
controlling, or modulating, the radiation beam’s intensity. The
radiation dose intensity is elevated near the gross tumor volume while
radiation among the neighboring normal tissue is decreased or avoided
completely. The customized radiation dose is intended to maximize tumor
dose while simultaneously protecting the surrounding normal tissue.
This may result in better tumor targeting, lessened side effects, and
improved treatment outcomes than even 3DCRT.
3DCRT is still used extensively for many body sites but the use of
IMRT is growing in more complicated body sites such as CNS, head and
neck, prostate, breast and lung. Unfortunately, IMRT is limited by its
need for additional time from experienced medical personnel. This is
because physicians must manually delineate the tumors one CT image at a
time through the entire disease site which can take much longer than
3DCRT preparation. Then, medical physicists and dosimetrists must be
engaged to create a viable treatment plan. Also, the IMRT technology
has only been used commercially since the late 1990s even at the most
advanced cancer centers, so radiation oncologists who did not learn it
as part of their residency program must find additional sources of
education before implementing IMRT.
Proof of improved survival benefit from either of these two
techniques over conventional radiotherapy (2DXRT) is growing for many
tumor sites, but the ability to reduce toxicity is generally accepted.
Both techniques enable dose escalation, potentially increasing
usefulness. There has been some concern, particularly with 3DCRT, about
increased exposure of normal tissue to radiation and the consequent
potential for secondary malignancy. Overconfidence in the accuracy of
imaging may increase the chance of missing lesions that are invisible
on the planning scans (and therefore not included in the treatment
plan) or that move between or during a treatment (for example, due to
respiration or inadequate patient immobilization). New techniques are
being developed to better control this uncertainty—for example,
real-time imaging combined with real-time adjustment of the therapeutic
beams. This new technology is called
image-guided radiation therapy (IGRT) or four-dimensional radiotherapy.
[edit] Particle Therapy
In particle therapy (
Proton therapy), energetic ionizing particles (protons or carbon ions) are directed at the target tumor.
[13] The dose increases while the particle penetrates the tissue, up to a maximum (the
Bragg peak) that occurs near the end of the particle's
range,
and it then drops to (almost) zero. The advantage of this energy
deposition profile is that less energy is deposited into the healthy
tissue surrounding the target tissue.
[edit] Radioisotope Therapy (RIT)
Systemic radioisotope therapy is a form of targeted therapy.
Targeting can be due to the chemical properties of the isotope such as
radioiodine which is specifically absorbed by the thyroid gland a
thousand-fold better than other bodily organs. Targeting can also be
achieved by attaching the radioisotope to another molecule or antibody
to guide it to the target tissue. The radioisotopes are delivered
through
infusion (into the bloodstream) or ingestion. Examples are the infusion of
metaiodobenzylguanidine (MIBG) to treat
neuroblastoma, of oral
iodine-131 to treat
thyroid cancer or
thyrotoxicosis, and of hormone-bound
lutetium-177 and
yttrium-90 to treat
neuroendocrine tumors (peptide receptor radionuclide therapy). Another example is the injection of radioactive glass or resin microspheres into the
hepatic artery to radioembolize liver tumors or liver metastases.
A major use of systemic radioisotope therapy is in the treatment of
bone metastasis from cancer. The radioisotopes travel selectively to
areas of damaged bone, and spare normal undamaged bone. Isotopes
commonly used in the treatment of bone metastasis are
strontium-89 and
samarium (153Sm) lexidronam.
[14]
In 2002, the
United States Food and Drug Administration (FDA) approved
ibritumomab tiuxetan (Zevalin), which is an anti-
CD20 monoclonal antibody conjugated to yttrium-90.
[15] In 2003, the FDA approved the
tositumomab/iodine (
131I)
tositumomab regimen (Bexxar), which is a combination of an iodine-131
labelled and an unlabelled anti-CD20 monoclonal antibody.
[16] These medications were the first agents of what is known as
radioimmunotherapy, and they were approved for the treatment of refractory
non-Hodgkins lymphoma.
[edit] Side effects
Radiation therapy is in itself painless. Many low-dose
palliative treatments (for example, radiotherapy 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 radiotherapy 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.
The main side effects reported are fatigue and skin irritation, like
a mild to moderate sun burn. The fatigue often sets in during the
middle of a course of treatment and can last for weeks after treatment
ends. The skin irritation will also go away, but it may not be as
elastic as it was before. Patients should ask their radiation
oncologist or radiation oncology nurse about possible products and
medications that can help with side effects.
[17]
[edit] Acute side effects
Damage to the epithelial surfaces.
Epithelial surfaces may sustain damage from radiation therapy.
Depending on the area being treated, this may include the skin, oral
mucosa, pharyngeal, bowel mucosa and ureter. The rates of onset of
damage and recovery from it depend upon the turnover rate of epithelial
cells. Typically the skin starts to become pink and sore several weeks
into treatment. The reaction may become more severe during the
treatment and for up to about one week following the end of
radiotherapy, and the skin may break down. Although this
moist desquamation
is uncomfortable, recovery is usually quick. Skin reactions tend to be
worse in areas where there are natural folds in the skin, such as
underneath the female breast, behind the ear, and in the groin.
If the head and neck area is treated, temporary soreness and ulceration commonly occur in the mouth and throat.
[18]
If severe, this can affect swallowing, and the patient may need
painkillers and nutritional support/food supplements. The esophagus can
also become sore if it is treated directly, or if, as commonly occurs,
it receives a dose of collateral radiation during treatment of lung
cancer.
The lower bowel may be treated directly with radiation (treatment of
rectal or anal cancer) or be exposed by radiotherapy to other pelvic
structures (prostate, bladder, female genital tract). Typical symptoms
are soreness, diarrhoea, and nausea.
Swelling (edema or oedema). As part of the general
inflammation
that occurs, swelling of soft tissues may cause problems during
radiotherapy. This is a concern during treatment of brain tumours and
brain metastases, especially where there is pre-existing raised
intracranial pressure or where the tumour is causing near-total obstruction of a
lumen (e.g.,
trachea or main
bronchus).
Surgical intervention may be considered prior to treatment with
radiation. If surgery is deemed unnecessary or inappropriate, the
patient may receive
steroids during radiotherapy to reduce swelling.
Infertility. The
gonads (ovaries and testicles) are very sensitive to radiation. They may be unable to produce
gametes following
direct
exposure to most normal treatment doses of radiation. Treatment
planning for all body sites is designed to minimize, if not completely
exclude dose to the gonads if they are not the primary area of
treatment.
[edit] Late side effects
Late side effects occur months to years after treatment. They are
often due to damage of blood vessels and connective tissue cells. Many
late effects are reduced by fractionating treatment into smaller parts.
- Fibrosis
- Tissues which have been irradiated tend to become less elastic over time due to a diffuse scarring process.
- Epilation (Hair Loss)
- Epilation may occur on any hair bearing skin with doses above 1 Gy.
It only occurs within the radiation field/s. Hair loss may be permanent
with a single dose of 10 Gy, but if the dose is fractionated permanent
hair loss may not occur until dose exceeds 45 Gy.
- Dryness
- The salivary glands and tear glands have a radiation tolerance of about 30 Gy in 2 Gy fractions, a dose which is exceeded by most radical head and neck cancer treatments. Dry mouth (xerostomia) and dry eyes (xerophthalmia) can become irritating long-term problems and severely reduce the patient's quality of life. Similarly, sweat glands in treated skin (such as the armpit) tend to stop working, and the naturally moist vaginal mucosa is often dry following pelvic irradiation.
- Cancer
- Radiation is a potential cause of cancer, and secondary
malignancies are seen in a very small minority of patients - usually
less than 1/1000. It usually occurs 20 - 30 years following treatment,
although some haematological malignancies may develop within 5 - 10
years. In the vast majority of cases, this risk is greatly outweighed
by the reduction in risk conferred by treating the primary cancer. The
cancer occurs within the treated area of the patient.
- Heart disease
- Radiation has potentially excess risk of death from heart disease seen after some past breast cancer RT regimens.[19]
- Cognitive decline
- In cases of radiation applied to the head radiation therapy may cause cognitive decline
[edit] Cumulative side effects
Cumulative effects from this process should not be confused with
long-term effects—when short-term effects have disappeared and
long-term effects are subclinical, reirradiation can still be
problematic.
[20]
[edit] See also
[edit] References
- ^ Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D (2002). "Impact of tumor hypoxia and anemia on radiation therapy outcomes". Oncologist 7 (6): 492–508. doi:10.1634/theoncologist.7-6-492. PMID 12490737. http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=12490737.
- ^ CK Bomford, IH Kunkler, J Walter. Walter and Miller’s Textbook of Radiotherapy (6th Ed), p311
- ^ “Radiosensitivity” on GP notebook http://www.gpnotebook.co.uk/simplepage.cfm?ID=2060451853
- ^ “Radiotherapy- what GPs need to know” on patient.co.uk http://www.patient.co.uk/showdoc/40002299/
- ^ a b c Camphausen KA, Lawrence RC. "Principles of Radiation Therapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
- ^ a b "University of Alabama at Birmingham Comprehensive Cancer Center, History of Radiation Oncology" (from the Wayback Machine). http://web.archive.org/web/20080105043216/http://www3.ccc.uab.edu/show.asp?durki=68504.
- ^ Vaidya J. "TARGIT (TARGeted Intraoperative radioTherapy)". http://www.targit.org.uk. Retrieved 2009-09-27.
- ^ http://www.astro.org/PressRoom/PressKit/AnnualMeeting/documents/Timmerman.pdf
- ^ http://www.rtanswers.com/treatmentinformation/treatmenttypes/stereotacticradiation.aspx
- ^ Bucci M, Bevan A, Roach M (2005). "Advances in radiation therapy: conventional to 3D, to IMRT, to 4D, and beyond.". CA Cancer J Clin 55 (2): 117–34. doi:10.3322/canjclin.55.2.117. PMID 15761080. http://caonline.amcancersoc.org/cgi/content/full/55/2/117.
- ^ Galvin JM, Ezzell G, Eisbrauch A, et al.
(Apr 2004). "Implementing IMRT in clinical practice: a joint document
of the American Society for Therapeutic Radiology and Oncology and the
American Association of Physicists in Medicine". Int J Radiat Oncol Biol Phys. 58 (5): 1616–34. doi:10.1016/j.ijrobp.2003.12.008. PMID 15050343.
- ^ Intensity Modulated Radiation Therapy
- ^ Brain tumour patient 'unaware' treatment was available on NHS
- ^ Sartor O (2004). "Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease". Rev Urol 6 Suppl 10: S3–S12. PMID 16985930.
- ^ Fda Approves First Radiopharmaceutical Product To Treat Non-Hodgkin’S Lymphoma
- ^ Tositumomab and Iodine I 131 Tositumomab - Product Approval Information - Licensing Action
- ^ http://www.rtanswers.com/treatmentinformation/cancertypes/breast/possiblesideeffects.aspx
- ^ Hall, Eric J. (2000). Radiobiology for the radiologist. Philadelphia: Lippincott Williams Wilkins. p. 351. ISBN 0781726492, 9780781726498.
- ^ Taylor CW, Nisbet A, McGale P, Darby SC (Dec 2007). "Cardiac exposures in breast cancer radiotherapy: 1950s-1990s". Int J Radiat Oncol Biol Phys. 69 (5): 1484–95. doi:10.1016/j.ijrobp.2007.05.034. PMID 18035211.
- ^ Nieder C, Milas L, Ang KK (2000). "Tissue tolerance to reirradiation.". Semin Radiat Oncol 10 (3): 200–9. doi:10.1053/srao.2000.6593. PMID 11034631.
