Radiation Therapy

What is Radiation Therapy?

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.

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 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.

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Side Effects of Radiation Therapy?

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.

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. 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.

Medium and long-term side effects

These depend on the tissue that received the treatment; they may be minimal.

Fibrosis Tissues which have been irradiated tend to become less elastic over time due to a diffuse scarring process. Hair loss This may be most pronounced in patients who have received radiotherapy to the brain. Unlike the hair loss seen with chemotherapy, radiation-induced hair loss is more likely to be permanent, but is also more likely to be limited to the area treated by the radiation. 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. Fatigue Fatigue is among the most common symptoms of radiation therapy, and can last from a few months to a few years, depending on the quantity of the treatment and cancer type. Lack of energy, reduced activity and overtired feelings are common symptoms. Cancer Radiation is a potential cause of cancer, and secondary malignancies are seen in a very small minority of patients, generally many years after they have received a 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. Death Radiation has potentially excess risk of death from heart disease seen after some past breast cancer RT regimens. Cognitive decline In cases of radiation applied to the head radiation therapy can cause cognitive decline

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.

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Radiation Therapy and Cancer

Different cancers respond differently to radiation therapy. 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.

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.

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Radiation Therapy Dosage

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.

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.

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