Principles of radiotherapy

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3 Principles of radiotherapy

Introduction

After surgery, radiotherapy is the most effective curative treatment for cancer, contributing up to 25–30% of cure. At least half of the patients with cancer require radiotherapy at some time in their illness of which about 60% are treated with curative intent, often in combination with surgery and chemotherapy. Radiotherapy involves use of various types of ionizing radiation, and X-ray is the commonest type of radiation used. Other forms of radiation include electrons, protons, neutrons and gamma radiations from radioactive isotopes. This chapter intends to review the principles of practical radiotherapy (Box 3.1) and a detailed discussion on radiobiology and mathematical modelling are beyond the scope of this chapter.

Box 3.1
Steps in practical radiotherapy

1 Indication for radiotherapy

2 Intent of radiotherapy

3 Which is the best way to deliver radiotherapy?

• External beam radiotherapy alone (e.g. head and neck cancer)

• Brachytherapy alone (e.g. early stage cervical cancer)

• External beam radiotherapy and brachytherapy (e.g. advanced stage cervical cancer)

• External beam radiotherapy with concurrent chemotherapy (e.g. squamous oesophageal cancer)

• External beam radiotherapy with target agents (e.g. advanced head and neck cancer)

• Radioisotopes (e.g. well-differentiated thyroid cancer)

4 Obtaining informed consent

• Benefit of radiotherapy

• Explaining the process

• Expected side effects – short-term and long-term

6 Supportive care during radiotherapy

7 Treatment modifications during treatment (e.g. bank holidays, toxicities and interruptions)

8 Care after radiotherapy and survivorship issues

Indications for radiotherapy

Radiotherapy is indicated if it cures or improves the chances of cure, improves local tumour control, achieves symptom control or improves the quality of life. There are already adequate data on these various indications for radiotherapy for different neoplasms. With current understanding of radiation biology and improved techniques, more indications are evolving, particularly for tumours previously thought to be radioresistant (e.g. liver and pancreatic cancer).

Intent of radiotherapy

Radiotherapy treatment is given with either curative or palliative intent. Curative treatment involves either radical radiotherapy (radiotherapy given either alone or in combination with chemotherapy or biological agents) or adjuvant radiotherapy (given after definitive treatment of tumour, usually surgery). Palliative radiotherapy is intended to improve symptoms (e.g. bone pain) or prevent tumour related complications (e.g. ulceration in breast cancer).

Methods of delivery of radiotherapy

Radiotherapy is either delivered by a radiation source placed away from the body (teletherapy or external beam radiotherapy), by placing a radiation source into the tumour (interstitial brachytherapy, e.g. small tongue cancer) or in a body cavity containing the tumour (intracavitary brachytherapy, e.g. cervical cancer) or by intravenous or oral administration of nonsealed radionuclides. Depending on the site and type of cancer, radiotherapy is delivered by either one of these techniques or a combination. Sometimes radiotherapy is delivered concurrently with chemotherapy or biological agents to improve the chances of cure (see below).

External beam radiotherapy (EBRT)

EBRT commonly utilizes X-rays and electrons. Before the 1950s, radiotherapy units were kilovoltage machines which produced X-rays with limited penetrability. These machines, which are still used in some centres, can be one of the following:

• Superficial X-rays – operate at a potential of 50–150 kVp and tube current of 5–10 mA and useful to treat superficial skin cancers.

• Deep (ortho – ‘orthodox’) X-rays – operate at a potential of 150–500 kVp and tube current of 10–20 mA. These are useful to treat thick skin cancers and rib lesions. In many centres, these machines are being replaced by electron beam treatment.

Modern radiotherapy is based on megavoltage X-rays (photons) and electrons. Megavoltage X-rays are produced by artificial acceleration of electrons through a vacuum to impact on a target in machines called linear accelerators (LINACs) (Box 3.2). The energy of the X-rays is proportional to the speed of electrons. Electrons are produced when the target in a linear accelerator is removed from the path of the electron beam (Box 3.2). Modern LINACs have facilities to produce both photons and electrons. Electrons have a predictable penetrability and hence are useful when it is important to limit the radiation dose to a deeper organ. Characteristics of photons that are useful in their clinical use are:

• Greater penetration compared to lower energy X-rays, which helps in delivering a higher proportion of dose to the deep tumour compared to the surface dose.

• Skin sparing effect – the maximum absorbed dose is deposited a few millimetres beneath the skin. This helps to deliver higher dose to depth without causing significant damage to skin and subcutaneous tissue (Box 3.3).

Box 3.2
Linear accelerator (Figure 3.1)

Electrons from gun are accelerated before they hit the target. The X-rays produced from the target are collimated by primary collimators in the direction of patient. This beam is further modified by flattening filter, secondary collimation and multileaf collimators before reaching patient’s surface.

Figure 3.1 A & B, Linear accelerator.

(Courtesy of Varian Medical Systems.)

Box 3.3
Choosing the energy (Figure 3.2)

Electrons have a definite range (range in centimeters is approximately half of beam energy in MeV) and selection of electron is based on the depth needed to treat (effective treatment depth in centimeters, as defined by 90% isodose in centre, is approximately one-third of the beam energy in MeV ). With increasing energy, the surface dose decreases and hence if higher dose is needed at the surface, a bolus is used (p. 23). Bolus is also used to bring up high dose region to surface to avoid radiation to underlying critical structure. Higher energy electron beams exhibit a lateral constriction of 90% isodose line (Figure 3.2B) which need to be taken into consideration while deciding the field size at surface.

Photons have a skin sparing effect and maximum dose is deposited at a depth from surface. Dose at a depth increases with energy of photos. 6–10 MV is generally used, however in large patients with very deep seated tumours >10 MV yields a better dose distribution.

Figure 3.2 A, The percentage of depth dose of electrons (MeV) and photons (MV). B, Electron beam isodose curves – Note the constriction of 90% isodose at depth which necessitates addition of wider margins to beam width for adequate coverage of tumour at depth.

Brachytherapy

Brachytherapy involves placing radioactive sources at a very short distance from or in contact with, the tumour. Rapid fall off of radiation dose at increasing distance from the source permits delivery of a high dose of radiotherapy to the tumour with sparing of surrounding normal tissue. Short half life and high specific activity of isotopes allow delivery of the dose over a short period of time. The spatial distribution of sources is based on a complex set of rules.

The previous problems of radiation safety for patients and staff, and prolonged treatment time, have become history with modern brachytherapy machines (Figure 3.3). Clinical applications of brachytherapy are as follows:

• Curative treatment as a single modality – e.g. prostate cancer, cervical cancer.

• Adjuvant after surgery – e.g. breast cancer.

• Curative treatment with external beam radiotherapy – e.g. cervical cancer, prostate cancer, anal cancer.

• Palliative treatment – e.g. intracavitary treatment for bronchial cancer and oesophageal cancer.

Figure 3.3 Brachytherapy machine and its application. A, High dose rate (HDR) afterloading brachytherapy machine which is fully computer controlled and completes treatment in a few minutes. B, Interstitial brachytherapy in breast cancer

(Courtesy of Varian Medical Systems).

Radionuclide treatment

Systemic administration of radionuclides, which emit gamma-radiation, is a useful treatment for cancer. In well differentiated thyroid cancer, ¹³¹I is given to patients after thyroidectomy (p. 282). Strontium-89 and samarium-153 are used for palliation of bone metastases, particularly from prostate cancer.

Informed consent

Once a decision is made to treat with radiotherapy, this decision should be communicated to the patient. The patient should be informed of the intention of treatment, potential benefits and side effects, both short term and long term. It is also an obligation to explain to the patient the potentially serious short and long term consequences of treatment in order to obtain truly informed consent. Often patients would like to know details of how radiation works (Box 3.4), dose and length of treatment, rationale for a number of treatments (fractionation – the process of giving the total dose of radiation as small doses over a period of time) (Box 3.5) and side effects (p. 348). Side effects of radiotherapy depend on the area of treatment, total dose and dose per fraction. These can be acute (occurring during radiotherapy and within 3 months of completion of radiotherapy) or chronic (occurring 3 months after completion of radiotherapy).

Box 3.4
How does radiation work?

Therapeutic use of radiotherapy is born out of empiricism. Science caught up with empirical clinical use later to provide explanations for various patterns of response to treatment. The cancer cell has an unlimited capacity to multiply and radiotherapy is aimed to prevent this unlimited multiplication. The conventional explanation of radiation effect is based on radiation damage to DNA caused directly by photons and indirectly by free radicals which are produced when photons interact with water molecules in the tissue (see Figure 3.4). There are three different types of radiation damage to DNA:

• Lethal – irreversible, irreparable leading to cell death.

• Sublethal – under normal circumstances cells can be repaired in a few hours unless additional sublethal damage (another dose of radiation) occurs which makes the damage lethal.

• Potentially lethal – the component of radiation damage can be modified by the post radiation environment.

However, DNA damage is not the only mechanism of radiotherapy action. Radiotherapy can also influence genes controlling the cell cycle (e.g. RB gene, p53) and alter the expression of various genes resulting in expression of cytokines, growth factors, structural proteins or enzymes. Radiation damage to cell membrane sends signals to the nucleus and these signals affect cell behaviour.

Figure 3.4 Mechanism of radiation induced cell damage.

Box 3.5
Rationale for fractionation

Radiotherapy usually results in equal damage to both normal cells and cancer arising from them. However, normal cells and cancer cells differ in their ability to recover from radiation damage. This differential capacity of normal cells to repair and re-grow is exploited in eradication of tumour cells. Radiation sensitivity of cells is dependent on the phase of cell cycle they are in: G2 and M are radiosensitive whereas S phase is radioresistant. At the time of radiotherapy, the cancer cells are in various phases of cell cycles; some of them will be in the sensitive phase when there is a good chance of cell kill and some will be in the resistant phase.

Rationale of fractionation is explained by 5 Rs. Some of the Rs lead to more cancer cell kill, whereas others lead to better repair of normal cells.

• Redistribution of cells – delivering radiotherapy as multiple treatments allows tumour cells to reassort into more radiosensitive phase leading to more cancer cell damage.

• Reoxygenation – many cancers have hypoxic areas within the tumour and normal cells do not have any hypoxic areas. Hypoxic areas are relatively resistant to radiotherapy. With each fraction, radiotherapy reduces the number of cancer cells and allows some of the hypoxic areas to become more oxygenated leading to better cancer cell radiation damage.

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