81 Radiotherapy and Chemotherapy for Head and Neck Cancer
Radiotherapy is treatment with ionising radiation. This may consist of high-energy electromagnetic radiation such as X-rays and gamma rays or particulate radiation such as electrons (beta particles) or protons.
• X-rays X-rays have a smaller wavelength (10–15 to 10–18 m) than ultraviolet light (between 4 × 10–12 and 10–13 m) and have high energy, from kilovolts (kV) to megavolts (MeV). The greater the energy, the greater its tissue penetration. They are produced when high-speed electrons expelled by thermionic emission from an electrically heated tungsten filament are arrested by a target anode of high atomic number, usually tungsten, converting their kinetic energy into heat and photons. The photon is simply a quantum or bundle of electromagnetic radiation. Megavoltage linear acceleration of the electrons produces X-rays in the energy range of 4 to 20 MeV. Orthovoltage machines produce X-rays with energy of about 300 kV. For the treatment of head and neck cancer, energy in the region of 4 to 6 MeV is used.
• Gamma rays Radioactive atoms disintegrate to form a more stable atom, releasing energy, which may be particulate (usually electrons) or uncharged electromagnetic radiation called gamma rays, having the same wavelength and energy as X-rays.
• Electrons External beam electrons produced by thermionic emission from an electrically heated tungsten filament in a linear accelerator can be used as an alternative to electromagnetic radiation. They give a uniform dose up to a certain depth which varies depending on the energy of the beam, with a rapid fall off in dose beyond this. They are used, in particular, to boost the dose to a neck lump lying in close approximation to the spinal cord. The technique is more skin sparing than orthovoltage radiotherapy and is the treatment of choice for irradiating the nose and pinna.
• Protons Protons are positively charged particles made by stripping an electron from a hydrogen atom. They are accelerated to high speed to form a proton beam. The difference between protons and photons is that protons deposit energy at a specific distance in tissue known as the Bragg peak. This means that there is very little energy passing into deeper tissues, allowing sparing of normal tissue structures deep to the tumour. Their exact role in head and neck cancer remains to be evaluated. The NHS has commissioned two proton centres in London and Manchester which should start treating patients in 2019 and 2020.
81.1.1 Biological Principles
Factors that affect the response of cells to a given dose of radiation include intrinsic radiosensitivity, cell repair, cellular oxygenation, linear energy transfer, relative biological effectiveness and position in the cell cycle.
• Radiosensitivity is an inherent characteristic of the cell (e.g., seminoma and leukaemia cells are exquisitely sensitive to radiation whereas glioma and melanoma cells are relatively radioresistant). This is to a certain extent dependent on cellular repair mechanisms, which are enhanced in melanoma cells. Squamous cell carcinoma is relatively sensitive to radiation.
• Oxygen is a potent sensitiser, due to its ability to form free radicals. Oxygen enhancement ratio (OER) is defined as the ratio between doses in hypoxic and euoxic cells to produce the same biological effect. OER for low energy X-rays is between 2.5 and 3, which means the dose required to kill hypoxic cells is three times greater than in oxygenated cells. Many head and neck tumours are thought to have necrotic and therefore hypoxic cores leading to radioresistance.
• Linear energy transfer (LET) is defined as the amount of energy deposited as the X-ray travels through matter. High LET radiation (e.g., neutrons) have a greater biological effect than low LET radiation (X-rays).
• The position that the cell occupies in the cell cycle also determines sensitivity to radiation. Cells in the S phase are relatively more resistant than cells in the G2 or M phase. DNA is most susceptible to lethal injury when the cell is dividing and is not able to repair DNA damage. Malignant cells have a greater proportion of actively dividing cells at any point in time (a larger growth fraction) and so a greater percentage of cells will die. Resting cells may also sustain DNA damage. Normal cells are better able to activate DNA repair factors such as p53 protein, which prolong the S phase (synthesis of DNA phase) of the cell cycle, allowing repair of damaged DNA before the next cell division. Resting malignant cells have much less capability to arrest in S phase, have a shorter cell cycle, are less likely to repair damaged DNA, and therefore more likely to undergo apoptosis before entering mitosis. A higher proportion of malignant cells will therefore die from radiotherapy compared to normal cells.
81.1.2 Clinical Principles
Radiotherapy should be defined in terms of type, method of application, number of fractions, fraction size, interval between fractions and volume treated. The principle is to provide a sufficient dose to the tumour to affect a cure or adequate palliation but deliver a minimal dose to the surrounding normal tissue to minimise complications. Each tissue has its own tolerance level beyond which radiation toxicity will occur, so that a small increase in dose may greatly increase tissue injury. Omission of one or two fractions of radiotherapy, perhaps because of concerns about acute side effects, can significantly reduce the chances of cure. Radiotherapy therefore should not be interrupted unless absolutely necessary.
Maximising the therapeutic ratio is the overriding principle of radiation therapy. This is the ratio between normal tissue complication rate and the tumour control rate. Many manoeuvres are utilised to maximise the ratio. These include the following:
• Fractionation of dose.
• Conformal (or focussed) radiotherapy.