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.

• The inherent radiosensitivity of the tumour is important in achieving a cure or control of tumour. Some tumours are very radiosensitive (e.g. lymphoma and seminoma) whereas others are relatively radioresistant (e.g. melanoma, sarcoma). Most tumours are moderately radiosensitive. Cure can be achieved with a smaller dose of radiotherapy in very radiosensitive tumours (e.g. germinoma, p. 275)

• Repair of sublethal damage – reducing the dose per fraction helps to repair damage of normal tissues more effectively than tumours. Normal tissue may be able to repair sublethal damage if the interval between two fractions of radiotherapy is at least 6 hours. However, some types of cancers also have quick ability to repair radiation damage leading to radioresistance (e.g. melanoma).

• Repopulation – fractionation helps rapidly populating normal tissues such as skin and gut to repopulate and hence recover from radiotherapy damage. Again, cancer cells also have the capacity to repopulate especially when radiation treatment is very prolonged or interrupted (gap correction, see later).

Radiotherapy planning and delivery

Position and immobilization

Radiotherapy aims to deliver a uniform (homogenous) therapeutic dose of radiation to the tumour and areas of microscopic spread with minimal possible dose to the adjacent organs. This necessitates accurate reproduction of treatment position on a daily basis. Patients are positioned and immobilized to ensure optimal beam delivery while maintaining a comfortable position. The common positions are either supine or prone.

Immobilization depends on the site of treatment and intent. Radical treatment needs better immobilization techniques as the dose delivered is often very high. Examples of site specific immobilization devices used are as follows:

• Brain tumours – for radical treatment: Perspex shell or stereotactic frame and for palliative treatment: thermoplastic shell.

• Head and neck cancers – Perspex shell.

• Breast cancer – chest board with cross bar to fix the arms above the head.

• Chest – head support and knee support or stereotactic body frame.

• Abdomen and pelvis – knee support or stereotactic frame or vacuum bags.

• Limbs – vacuum bags.

Localization of tumour is to define various treatment volumes (Box 3.6). Conventional localization (2-dimensional, 2D) is with orthogonal X-rays using special treatment planning machines called simulators. These are diagnostic X-ray machines, which can mimic all the positions and movements of a treatment machine (Figure 3.6A) and some of these machines have a CT scan facility. 2D localization is appropriate for palliative treatment. Radical radiotherapy utilizes a planning CT scan or advanced techniques to define the various tumour volumes in 3-dimensions. Modern computer software allows co-registration of the planning CT scan with an MRI or PET scan (Figure 3.6B), which improves the accuracy of GTV delineation. Planning CT scan is usually taken at a slice interval of 1.5–5 mm. A slice thickness of <3 mm helps to get better resolution of digitally reconstructed images (DRRs) which are used to check accuracy of treatment delivery (see later in Box 3.12).

Box 3.6
Volumes in radiotherapy (Figure 3.5)

The following are the volumes in radiotherapy:

• GTV – Gross tumour volume – is the gross disease or radiologically visible tumour – this area has 10⁹ cancer cells. In the figure, the T2W MRI shows hyperintense low grade brain tumour.

• CTV – Clinical target volume – is the volume which contains GTV and/or subclinical microscopic disease (10⁶ cells) which need to be treated to an adequate dose to achieve the aim of treatment. The CTV depends on the pattern of local spread of specific tumours. In the figure, note the outer border of CTV merges with that of PTV as there is no possibility of microscopic spread beyond the inner layer of the skull.

• PTV – Planning target volume – is a geographical concept which denotes the CTV and margins for geographic variations and inaccuracies during treatment. The margin added to CTV to derive PTV depends mainly on the immobilization device (e.g. 2–3 mm with stereotactic frame). PTV has two components:

• IM (internal margin) – is a margin added to CTV to compensate for normal anatomical movements and variations in size, shape and position of CTV during treatment. In the figure, there is very little anatomic movement of CTV and hence IM is almost zero, whereas in a lung tumour, it may be around 1–4 cm depending on the location of the tumour and depth of breathing.

• SM (set up margin) – a number of factors can cause uncertainties such as daily variation in position of the patient, mechanical uncertainties of the equipment, transfer set up errors etc. In brain tumour treatment, if a Perspex shell is used a 5 mm margin is added.

• TV – treated volume – is the volume enclosed by an isodose surface, selected and specified by the oncologist as being appropriate to achieve the purpose of treatment.

• IrV – irradiated volume – is that tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance.

• PRV – planning organ at risk volume – refers to the definition of margins around organs at risk for injury by radiation.

Please note, even if the actual tumour (GTV) is small, after adding various margins as above the irradiated volume is much bigger. This is one of the limiting factors in delivering a high dose to tumour without having significant irradiation to normal tissue. Studies show that a 4–5% increase in dose increases the tumour control probability by 10% and hence newer developments are aiming at better localization of tumour and reduction of various margins to increase the dose to the actual tumour.

Figure 3.5 Volumes in radiotherapy.

Figure 3.6 Localization of tumour. A, Simulator used for conventional localization as well as for plan verification (courtesy Varian Medical Systems). B, Co-registered planning CT with PET scan showing primary tumour (arrow head) and PET positive right paratracheal node (arrow).

Box 3.12
Verification of treatment (Figure 3.12)

DRR (Figure 3.12A) is used to verify treatment accuracy. This is commonly done by comparison of DRR with the treatment verification film (Figure 3.12B). The treatment set-up is checked by comparing the position of isocentre, bony landmarks and the positions of MLCs or beam shaping block for the same beams. If a systemic error is found during verification, it needs to be corrected before proceeding with further treatment and the corrected treatment plan should be verified for accuracy of treatment set-up.

Figure 3.12 A&B, Verification of treatment.

Planning technique

Conventional (2D) simulator planning uses simple beam arrangements such as single field radiotherapy or parallel opposed beams. In conformal (3D) planning various volumes and organs at risk (OAR) are delineated individually on every slice of cross-sectional imaging and a treatment plan produced by a planning computer. Intensity modulated planning (IMRT) is a further improvement of 3D planning, which is aimed at ensuring homogeneous dose to the tumour with less dose to organs at risk. This technique has particular advantage with concave-shaped target volumes with OAR located in the concavity. The technique is also useful in sparing critical organs from radiotherapy toxicity (e.g. parotid gland sparing in head and neck cancer).

Image guided radiotherapy (IGRT) is a further advance in radiotherapy planning and delivery where the real time position of the tumour is taken into consideration (Figure 3.7). 3D, IMRT and IGRT use multiple beams to obtain the optimal treatment plan.

Figure 3.7 A&B, IMRT and IGRT. A, IMRT is a conformal technique which helps to selectively avoid/limit radiotherapy dose to critical structures. This IMRT plan aims to give 70 Gy to ethmoid cancer (yellow line represents 70 Gy) while keeping the dose to the optic chiasma (arrow) to less than 50 Gy. B, IGRT – specialized radiotherapy machine with on-board imaging system (arrows) allows real time imaging and correction of error.

(Courtesy Varian Medical Systems.)

Treatment planning (Box 3.7)

Direction of beam

The direction of beam depends on the location of PTV and OARs. Generally beams are placed so that they are equi-angled, entering the body through the side of disease and avoiding passing directly through the OARs if possible.

Box 3.7
Radiotherapy planning (see Figure 3.8)

Three fields are used and the dose is prescribed at the intersection point as 100% of prescribed dose

Note the beam arrangement –

• Only one beam passes directly through the spinal cord so as to keep cord dose within tolerance

• Beams enter only through the side of disease. No beams are entering through the normal lung side

• Beams are sized according to the beam’s eye view and are of different dimension

Figure 3.8 Radiotherapy planning.

Beam size and shape

Conventional radiotherapy uses either rectangular or square fields with appropriate blocking of beams over critical organs (by shields, see below). Conformal radiotherapy shapes every beam according to the ‘beam’s eye view’ (BEV). The exact shaping of the beam used to be attained by shaped blocks. With the advent of multileaf collimators (MLC), shaping of beams becomes increasingly easy (Box 3.8).

Box 3.8
Beam shaping (Figure 3.9)

In the early 1950s radiotherapy beams used to be either square or rectangular. There was an option to shield part of the field with lead or equivalent material. When conformal radiotherapy started evolving, individual blocks were made based on the BEV of individual beams to shape the radiotherapy fields using cerrobend (an alloy of bismuth, lead, tin and cadmium with a melting point of 70°C and hence easy to make different shapes). Currently beam shaping is achieving with MLCs (see Figure 3.9).

Figure 3.9 Beam shaping using BEV (A) and MLCs (B&C).

Energy of the beam

For superficial lesions and lesions lying within a limited depth, electrons are used and energy of the electron beam depends on the depth which needs to be treated (Box 3.3). For deep seated tumours, megavoltage energy is used, usually 6 MV photons; in some patients a higher energy with high penetration is necessary to improve the dose homogeneity.

Wedges, shields and bolus

In multifield radiotherapy, wedges are necessary to alter the beam profile, thereby ensuring a homogeneous dose to the target volume (Box 3.6). Wedges also act as a tissue compensator for sloping external surface.

Shields are used to avoid irradiation of part of the radiotherapy field. In the modern machines it is achieved by individual leaves of multileaf collimators.

Bolus (a tissue-equivalent material placed directly on the patient’s skin surface) is used to bring up the radiation dose to the surface. The commonly used tissue equivalent materials are slabs of paraffin wax, gauze coated with petrolatum or synthetic-based substances. Megavoltage radiotherapy has a skin sparing effect (i.e. delivering maximum dose at a point deep to the skin) which may be a disadvantage when treating a superficial PTV (e.g. chest wall after mastectomy). Hence in order to bring up the maximum dose to the surface bolus is placed on the surface of the treatment volume. Bolus is also used to bring up the high dose radiation towards the surface to avoid higher doses to the deeply situated OARs.

Evaluation of treatment plan

Once treatment is planned, it is necessary to evaluate the treatment plan before it is accepted for treatment. In difficult situations, such as when an OAR is lying near the PTV, the planning physicists come up with more than one plan for the oncologist to evaluate and choose one for treatment. Evaluation of the plan takes the following steps (Box 3.9):

• Homogenous dose to the PTV – ideally, the whole of the PTV should be covered by 95% isodose and the recommendation is that PTV dose should be within –5% and +7% of the prescribed dose. This is confirmed by looking at the dose distribution at every slice of plan or looking at the dose volume histogram (DVH). DVH plots the total dose against the percentage of target volume or OAR irradiated (Box 3.9). Hotspots are areas outside the PTV which receive a dose >100% of the specified PTV dose. Hotspots are considered significant only if they exceed >15 mm in diameter, except in small organs (e.g. eye, optic nerve) where <15 mm diameter has to be considered significant.

• Dose to OAR – dose to the OAR should not exceed their tolerance dose. Tolerance dose (TD) is the dose beyond which there is a risk of dose limiting toxicity. TD is stated as TD5/5 (dose at which there is 5% risk of occurring dose limiting toxicity at 5 years) and TD5/50 (dose at which there is 50% risk of occurring dose limiting toxicity at 5 years. The aim of treatment plan evaluation is to limit the dose to OAR below TD5/5. Table 3.1 gives the approximate TD of various organs.

• Dose to other normal tissue – it is important to check that there is no increased dose to the entry and exit of the beam and there are no sensitive structures in the path of the radiation beams.

Box 3.9
Evaluation of a treatment plan (Figure 3.10)

Treatment plan evaluation is to ensure that the PTV receives a homogenous dose and the doses to the OAR are within tolerance. Spatial distribution displays ensure that 95% isodose encloses the PTV (Figure 3.10A & B). Dose volume histogram (Figure 3.10C) is helpful to indicate underdosage to PTV as well as excessive dose to OAR.

Figure 3.10 A–C, Evaluation of a treatment plan.

Table 3.1 Normal tissue radiation tolerance dose (treated with 2 Gy per fraction)

Dose prescription for radiation treatment

The prescription point of radiotherapy depends on the type of plan. For a single beam, the prescription point either lies in the point of maximum dose (d_max) or at a depth. For parallel opposed beams the prescription point is mid-plane whereas for all 3D and 4D planning the prescription point is often at the isocentre or at the intersection of points.

For electrons, dose is prescribed at 100%; however, it is necessary that 90% isodose covers the PTV.

The prescription should indicate the total dose, number of fractions, dose per fraction, and duration of treatment (e.g. 50 Gy in 20 fractions over 4 weeks). Conventional fractionation is to deliver one radiotherapy fraction per day for 5 days a week. There are a number of alternate fractionation regimes (Box 3.10). The total dose of radiotherapy depends on the type of cancer, site and bulk of disease (Box 3.11). Gray (Gy) is the usual measure of radiotherapy which is defined as 1 joule of energy per 1 kg of material. The subunit is centigray (cGy) which is 1/100 of a Gray. Radiotherapy alone for cure needs a dose of >60–65 Gy as 1.8–2 Gy per day whereas adjuvant radiotherapy uses 50–60 Gy. Most studies indicate a direct relation between the dose and chances of control and cure.

Box 3.10
Fractionation schedules

• Conventional fractionation – delivers 1.8–2 Gy single fraction per day, 5 times weekly.

• Accelerated fractionation – aims to shorten the treatment time by delivering larger than standard size fractions five times weekly or more than five fractions per week of 2 Gy. Multiple fractions may also be given daily. The acute toxicity is greater with this and late toxicity is either the same as (if complete repair of sublethal damage occurs) or greater than conventional fractionation. It is useful for tumours with a rapid growth rate.

• Hyperfractionation – aims to improve tumour control probability with the same late effects as conventional fractionation. It delivers a larger number of smaller than conventional dose fractions per day and the total dose is 10–20% higher than standard fractionation while total treatment time remains the same. It is useful for tumours with slow growth.

• Accelerated hyperfractionation – combines the principles of hyperfractionation and accelerated fractionation.

• Continuous accelerated hyperfractionation (CHART) – treatment is given as 1.5 Gy per fraction, three times daily 6 hours apart for 12 continuous days. Proved to improve local control in lung cancer.

• Hypofractionation – delivers more than 2 Gy per fractions and less than five fractions per week.

Box 3.11
Tumour control probability (TCP), normal tissue complication probability (NTCP) and therapeutic ratio (Figure 3.11)

For many types of cancer, a higher dose of radiotherapy produces better tumour control. After fractionated radiotherapy, the total number of cancer cells surviving depends on the initial number of cells and the proportion of cancer cells killed with each treatment. Studies show that visible disease needs more dose than microscopic disease (to pathologically detect microscopic disease, cell aggregates of ≥10⁶/cm³ are needed) and subclinical disease (cannot be detected microscopically). For example a dose of >65 Gy is needed to control visible epithelial tumours, whereas the dose needed to control microscopic disease is 60–65 Gy and 50–60 Gy for subclinical disease.

The aim of radiotherapy is to deliver a dose of radiation to destroy the tumour without leading to serious normal tissue complications. Therapeutic ratio is used to represent this concept where it is the ratio of the tumour control probability (TCP) and normal tissue complication probability (NTCP) at a specified level of response (usually <5% or 0.05) for normal tissue.

The probability of tumour control without normal tissue complications is highest in the therapeutic window. The further the NTCP curve to the right of the TCP (see Figure 3.11) cure it is easier to achieve a tumour control with minimal toxicity (A) and a larger therapeutic ratio. When NTCP and TCP (C) get closer the therapeutic ratio gets smaller.

In practical radiotherapy a better therapeutic ratio can be achieved by:

• Advanced treatment planning (3D, IMRT or IGRT)

• Accurate target localization which helps to reduce safety margins

• Sophisticated dose delivery

Figure 3.11 TCP and NTCP (see Box 3.11).

Treatment verification and corrections

Accurate position and immobilization during planning and treatment are important in accurate delivery of radiotherapy. In spite of this, treatment delivered can be different from the planned treatment. Hence it is important to ensure that treatment delivery is within the tolerance limit of accepted variation from the planning. The accepted tolerance generally depends on the immobilization method; e.g. a variation of <5 mm is acceptable with Perspex. The accuracy of planned treatment can be verified by:

• Verification of treatment position before treatment using simulator – the simulator X-rays are compared with DRRs for accuracy in terms of isocentre and comparison of bony landmarks if feasible and comparison of individual fields (Box 3.12).

• Verification of treatment during treatment with portal imaging – a comparison is made with DRR to assess the position of isocentre in at least two views (anterior and posterior), position of beam in relation to bony or other visible landmarks (Box 3.12) and shape of individual fields.

• Real time verification of treatment with correction for variation is the back bone of image guided radiotherapy.

During the process of verification two types of errors in treatment set up can occur:

• Systemic Σ – error between planning and treatment. This needs correction before proceeding with further treatment.

• Random ∂ – variations and uncertainties that arise between each fraction of treatment. It is difficult to correct this error as this does not occur consistently.

During determination of PTV, these errors are taken into consideration to add a margin to PTV. The suggested margin is 2.5 Σ + 0.7∂.

Supportive care during radiotherapy

It is important to follow up patients regularly during radiotherapy to assess and manage radiotherapy toxicities, to monitor nutritional status and check blood counts. Studies have shown that during radical radiotherapy of head and neck, lung, oesophageal and cervical cancer, it is important to maintain a haemoglobin level of >12 gm/dl (a level lower than this may result in 10–12% less chance of disease control). The importance of level of haemoglobin is less clear in other cancers. However, symptomatic anaemia needs to be corrected. It is also important to make sure that the blood counts remains safe (i.e. platelet count of >100 × 10⁹/dL and neutrophil count of >1.5 × 10⁹/dL) during radiotherapy especially when it is given concurrently with chemotherapy or when a significant amount of bone marrow bearing area is being irradiated. Blood counts below the safe threshold necessitate either withholding chemotherapy or suspending chemotherapy until the blood count recovers.

Treatment modifications during treatment

Gap correction

One of the common situations is an interruption during radiotherapy due to holidays, non-attendance or intolerable toxicity. This might need modification of treatment. Studies have shown that tumours exhibit accelerated repopulation during radiotherapy. Accelerated repopulation implies an increase in multiplication of cancer cells which often starts with partial shrinkage of tumour after radiotherapy or chemotherapy. Prolonged interruption of radiotherapy results in decreasing efficacy of radiotherapy due to accelerated repopulation. Using modelling analysis, an increase of total treatment duration by 1 day may reduce local control by 1.4%. Hence attempts should be made to avoid prolongation of overall treatment. Still, occasionally treatment gets prolonged, when adjustment should be made to complete the treatment in the planned overall time by:

• delivering twice daily fractions, at a minimum of a 6-hour interval

• treating over the weekend

• use of biologically equivalent dose in fewer fractions to achieve planned overall time.

If treatment still cannot be completed within the planned overall time additional fractions may be considered. A rough estimate is an additional dose of 0.6 Gy per every day of increase in overall treatment time.

Care after radiotherapy and survivorship

Some patients have persistent acute radiotherapy side effects up to 3 months after completion of radiotherapy. Management of these side effects is multidisciplinary, involving a number of healthcare professionals including an oncologist, nurse specialists, therapeutic radiographers, dietician and speech and language therapists (SALT).

In the long term, there are a number of side effects needing special attention. Patients receiving radiotherapy to whole or part of the brain are at risk of cognitive impairment, cerebrovascular accidents, hormonal deficiency and second cancer (p. 58, late effects). Radiotherapy to the chest is associated with increased risk of second cancer and radiation damage to heart, particularly in patients receiving radiotherapy for left breast cancer. Pelvic radiotherapy often results in menopause and infertility in women and sexual dysfunction and infertility in men. Radiotherapy induced or promoted second cancer is an important survivorship issue. After cancer treatment, people often face an array of challenges including psycho-social functioning and economic well-being. As physicians, our triumph is not just in curing or controlling cancer, but also in helping cancer survivors to lead a high quality life in the society. For a detailed discussion on cancer survivorship, see p. 58.

Advances in radiotherapy

Based on experimental studies, there is a direct correlation between the radiation dose and chances of control of cancer, though not linear. However, various uncertainties in the radiotherapy planning process often lead to a large treatment volume (see Box 3.6). Advances in radiotherapy are aimed at understanding and controlling these uncertainties in radiotherapy planning. By doing so, we will be able to give a much higher dose to the tumour and areas of possible spread with minimal dose to the surrounding normal organs. The areas under research include advanced immobilization, improved radiotherapy with image guidance and incorporation of molecular imaging for tumour volume delineation.