Radiation therapy

Image:Clinac 2100 C with patient.JPG Radiation therapy (or radiotherapy) is the medicaluse of ionising radiationas part of cancertreatmentto control malignant cells(not to be confused with radiology, the use of radiation in medical imagingand diagnosis). Radiotherapy may be used for curative or adjuvant cancer treatment. It is often used as a palliative treatment, where cure is not possible and the aim is for local disease control or symptomatic relief. Total body irradiation(TBI) is a special radiotherapy technique used to prepare the body to receive a bone marrow transplant. Radiotherapy has a few applications in non-malignant conditions, such as the treatment of severe thyroid eye disease, pterygium, prevention of keloidscar growth, and prevention of heterotopic boneformation. The use of radiotherapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers.

Application

Radiotherapy is commonly used for the treatment of malignant tumours(cancer.) It may be used as the primary therapy. It is also common to combine radiotherapy with surgeryand/or chemotherapyand/or hormone therapy. Most common cancer types can be treated with radiotherapy in some way. The precise treatment intent (radical, adjuvant, 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 gross 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.

In order to spare normal tissues (such as skin or organs which radiation must pass through in order to treat the tumour) several angles of exposure are utilised such that the radiation beams overlap on top of each other at the tumour, providing a much larger absorbed dose there than in the surrounding, healthy tissue.

Side effects

Radiotherapy is in itself painless. Many low-dose palliativetreatments (e.g. radiotherapy to bony metastases) cause minimal or no side effects. Treatment to higher doses causes variable side effects during treatment (acute side effects) or in the months to years following treatment (long term side effects). The nature of the side effects depends on the site which receives the radiation, and the treatment schedule (type of radiation, dose, fractionation, concurrent chemotherapy). Individuals differ somewhat in their radiation reaction. Retreatment of previously irradiated sites can cause particular problems: any tissue has a maximum lifetime tolerance for radiation, so retreatment of a site which received a maximum safe dose years before can cause problems.

Most side effects are predictable and expected. 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.

Acute side effects

Damage to epithelial surfaces (skin, oral, pharyngeal and bowel mucosa, urothelium)

The rate of onset and recovery is related to the rate of turnover of the epithelial cells. Typically the skin starts become pink and sore one week to ten days into treatment. The reaction may become more severe during the treatment and for up to about one week following the end of radiotherapy, and there may be moist desquamation(where the skin breaks down). Although this is uncomfortable, recovery is usually quite 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.

Similarly, the lining of the mouth, throat, esophagus, and bowel will be affected by radiation. If the head and neck area is treated, temporary soreness and ulceration commonly occur in the mouth and throat. If severe, this can affect swallowing, and the patient may need painkillers and nutritional support. The esophagus can also get sore if it is treated directly, or if, as commonly occurs, it receives a dose of radiation during treatment of lung cancer.

The lower bowel may be treated directly with radiation (treatment of rectal or anal cancer) or be exposed as an inevitable side effect of radiotherapy to other pelvic structures (prostate, bladder, female genital tract.) Apart from soreness, diarrhea is commonly seen, and nausea may be a problem.

Swelling (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, and also where the tumour is causing near-total obstruction of a lumen(eg: trachea or main bronchus). Surgical intervention may be considered prior to treatment with radiation. If surgery is not felt necessary or appropriate, the patient may receive steroidsduring radiotherapy in order to reduce swelling.

Infertility

The gonads(ovaries and testicles) are very sensitive to radiation. They will be unable to produce gametesfollowing direct exposure to most normal treatment doses of radiation.

Generalised fatigue

Medium and long-term side effects

These may be minimal and depend on the tissue which received the treatment.

Fibrosis

Tissues which have been irradiated tend to become less elastic over time due to a diffuse scarring process.

Hair loss

This may be pronounced in patients who have received radiotherapy to the brain. For the most part, hair loss is limited to the area treated by the radiation. Unlike the hair loss seen with chemotherapy, radiation-induced hair loss is more likely to be permanent.

Dryness

The salivary glands and tear glands have a radiation tolerance of about 30Gyin 2Gy fractions, a dose which is exceeded by most radical head and neck cancer treatments. Dry mouth (xerostomia) and dry eyes (xerophthalmia) can be an irritating long-term problem. 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 cause of cancer, and secondary malignancies are seen in a small minority of patients, generally many years after they have received a curative course of radiation treatment. In the vast majority of cases, this risk is greatly outweighed by the reduction in risk conferred by treating the primary cancer.

Dosage

Radiation therapy, like drugs, has biological effects. It is therefore useful to distinguish the total dose from the fractionation schedule. Radiation therapy is usually given daily, the dose depends primarily on tumour type, but many other factors such as whether radiation is given alone or with chemotherapy, before or after surgery, the success of surgery and its findings and many other reasons that are considered by the treating doctor (known as a radiation oncologist). For Radical (curative) cases the typical dose for a solid epithelial tumour may range from 50 to 70 grays(Gy, a unit of radiation dose) or more, while lymphomas (white cell) tumours might receive doses closer to 20 to 40 Gy given in daily doses (a daily dose is a fraction); in adults fraction doses are typically 1.8 to 2 Gy per fraction. These small frequent doses allow healthy cells time to grow back, repairing damage inflicted by the radiation. In short, total dose can be given in daily fractions using external beam radiation or the total dose can be given via other methods such as implants that deliver radiation continuously over a given timeframe. Depending on the implant type, it may be given as a fraction (e.g. High Dose Rate HDR) over minutes or hours or as another example permanent seeds may be implanted (such as in the prostate) which slowly deliver radiation until the seeds become inactive. In Palliative cases a single dose of 6-10Gy may be given to painful superficial tumours i.e. a rib metastasis to relieve pain.

Fractionation schedules

As mentioned above, the typical fractionation schedule (in the USA and Europe) is 1.8 to 2 Gy per fraction, with 1 fraction per day. The typical treatment schedule is 5 days per week (no weekends). This schedule is also common in the South of England, whereas in the North of the UK fraction sizes are quite commonly 2.67–2.75 Gy per fraction (treating daily Monday–Friday), with a lesser number of total fractions. The reason for this is mainly a resource issue within the NHS, with Clinical Oncology departments having a much greater workload (secondary to fewer machines for more patients; i.e, a lack of physical resources) than the private clinics in Europe and the USA. Both fractionation schedules are effective, individual clinician preference and availability of resource are the deciding factors. (Longer schedules are common where payment is made to the clinic according to the number of treatment fractions delivered; however, to be balanced, higher dose/fraction, known as hypofractionation, can be associated with greater late normal tissue effects. Accordingly, large fraction size is more typically applied in the palliative setting where life expectancy is expected to be short and the late consequences of treatment less likely since the patient often does not survive his malignancy sufficiently long to manifest the late effects.) There are other alternative fractionation schedules that have been tried. One of the best-known was the CHART (Continuous Hyperfractionated Accelerated RadioTherapy) regimen for lung cancer, which uses 3 smaller fractions per day in the treatment of lung cancer. Although reasonably successful, this can impose strains on the departments delivering the service, as it required multiple treatments everyday, including weekends. With an international shortage of qualified Radiation Therapists this is often difficult to sustain. Twice a day treatments have been tried for other sites, such as head and neck cancers. A special case of twice a day radiotherapy is the concomitant boost regimen. The concomitant boost regimen was pioneered at the MD Anderson Cancer Center in Houston, TX and applied initially to head and neck sites where there is a particular concern of accelerated tumour repopulation, especially during the final few weeks of treatment. Accelerated repopulation probably occurs as tumour bulk diminishes and the surviving tumour cells find themselves in a more favorable growth environment, less competition for oxygen and nutrients. With the concomitant boost technique, a second fraction is added to "boost" the gross disease during the final approximate 2 weeks of treatment. The addition of multiple fractions in a day with the additional fraction usually comprising a somewhat decreased fraction size (e.g, 1.2–1.5 Gy, rather than 1.8–2.0 Gy) is termed hyperfractionation. If the multiple fractions otherwise shorten the overall treatment time (such as concluding seven weeks worth of radiation in six weeks elapsed time), then the schedule is also considered "accelerated."

In some paediatric cancers, fractionation schedules tend to give 1.5–1.7 Gy/fraction. The reason for this is that fractionation effects the balance between acute and late toxicity, and with smaller fractions late effects are less likely to occur and are less severe. Obviously late effects are of more concern in paediatric patients than adults.

How it works

Radiation therapy works by damaging the DNAof cells. The damage is caused by a photon, electron or proton beam directly or indirectly ionizingthe atoms which make up 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 breakage, where the DNA is broken on both strands of the DNA are the most significant 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 differentiatedcells. The DNA damage is inherited through cell division, accumulating damage to the cancer cells, causing them to die or reproduce more slowly. Proton radiotherapy works by sending protons with varying kinetic energyto precisely stop at the tumour.

One of the major limitations of radiotherapy is that the cells of solid tumours become deficient in oxygen. This is because solid tumours usually outgrow their blood supply, causing a low-oxygen state known as hypoxia. The more hypoxic the tumours are the more resistant they are to the effects of radiation because oxygen "fixes" or makes permanent the radiation damage to DNA. 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 misonidazoleand metronidazole, and hypoxic cytotoxins, such as tirapazamine. Interestingly, recent data has indicated that patients ingesting excess amounts of antioxidant vitamins (such as C or E) may actually diminish the effectiveness of the radiation treatment.

Kinds of radiation therapy

Three main divisions of radiotherapy are external beam radiotherapy(XBRT) or teletherapy, brachytherapyor sealed source radiotherapyand unsealed source radiotherapy. The differences relate to the position of the radiation source; external is outside the body, while sealed and unsealed source radiotherapy has radioactive material delivered internally. Brachytherapy sealed sources are usually extracted later, while unsealed sources may be administered by injection or ingestion. Proton therapyis a special case of external beam radiotherapy where the particles are protons.

Roughly half of the 2500 worldwide radiotherapy clinics are in the US (as of 2001).

Conventional external beam radiotherapy

This is the mainstay of external beam radiotherapy in most of the world. Conventional refers to the way the treatment is planned or simulated on a specially calibrated conventional diagnostic x-ray machine (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 localise 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 to normal structures which lay close to the target volume. An example of this problem is seen in radical radiotherapy to the prostate gland, where the sensitivity of the adjacent rectum can limit the dose which can safely be prescribed to such an extent that tumour control may not be achievable with any degree of confidence. For this reason, conformal radiotherapy is becoming the standard treatment for a number of tumour sites.

Virtual simulation, 3-dimensional conformal radiotherapy, and intensity-modulated radiotherapy

The planning of radiotherapy treatment has been revolutionised by the ability to delineate tumours and adjacent normal structures in 3 dimensions using a specialised CT scanner and dedicated computer planning software. In its most basic form, virtual simulation, this process allows more accurate placement of conventional radiotherapy fields than is possible using conventional X-rays, where soft-tissue structures are often difficult to assess clearly.

3-Dimensional Conformal Radiotherapy (3DCRT) is an elaboration of this process, whereby the profile of each radiation beam is sculpted to fit the profile of the target from that Beam's eye view(BEV) using a multileaf collimator (MLC) and a variable number of beams. The aim of this process is to improve the therapeutic index of the radiotherapy. By conforming the radiotherapy treatment volume closely to the shape of the tumour, the relative toxicity of radiation to the surrounding normal tissues can be reduced, allowing a higher dose of radiation to be delivered to the tumour than would be possible using conventional techniques.

Intensity-modulated radiotherapy (IMRT) is an iteration of 3DCRT that employs dynamic multileaf collimation to shape not only the profile of the beam, but also to vary the intensity of the beam over its area. This may allow greater conformality than standard 3DCRT. It also provides the novel ability to conform the treatment volume to concave surfaces. This may be useful if the tumour is wrapped around a vulnerable structure such as the spinal cord, where a therapeutic dose of radiation might otherwise cause unacceptable damage.

3DCRT is used extensively. IMRT is becoming more widely used but is limited by the fact that it is a very resource-intensive process, in terms of manpower and computing time. The proven benefits from both of these modalities over conventional radiotherapy in terms of improved overall survival are limited to a few tumour sites. There has been some concern about increased exposure of normal tissues to radiation, particularly with IMRT, and the potential for secondary radiation-induced malignancy. The downside of tight conformality is that there is an increased chance of geographically missing disease, which may be invisible on the planning scans (and therefore not included in the treatment plan) or which may move between treatments, either because of internal organ movement (such as respiration) or because of inadequate patient immobilisation. Whatever the criticisms of conventional radiotherapy, it gives a wider margin for error than conformal techniques.

See also

• Cancer
• Chemotherapy
• Surgical oncology
• Radiosurgery
• Dosimetry
• Wikibooks: Radiation Oncology Textbook

External links

• American Society Therapeutic Radiology and Oncology – ASTRO: the official site for radiation oncologists
• The Radiation Therapy Oncology Group: an organisation for radiation oncology research
• European Society for Therapeutic Radiology and Oncology

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It uses material from the http://en.wikipedia.org/wiki/Radiation+therapy Wikipedia article Radiation therapy.