Radiation effects in speci \201c tissues Skin (cid:2) Erythema \200\224week 2 \200\2233 (cid:2) Desquamation \200\224later (cid:2) Ulcera tion \200\224later (cid:2) Shorter course increases severity of acute skin reaction (cid:2) Dose per fraction is less important in acute reaction (cid:2) Tolerance for late effects d ecreases with increasing dose per fraction Late effects include: (cid:2) Atrophy (cid:2) Contraction (cid:2) Radiation \201brosis (c id:2) Telangiectasia OHO-08(93-134) 11/16/02 11:19 AM Page 96 PRINCIPLES OF RADIATION ONCOLOGY 96 Oral mucosa (cid:2) Severe mucositis after a dose of 70 Gy in 6 weeks (cid:2) Severity relates to treat ment time and volume irradiated Gastrointestinal tract (cid:2) Acute mucositis causes diarrhea and gastritis; if occurs, cease treatment for a few days (cid:2) Late effects \200\224mucosal ulceration, atrophy, \201brosis, necrosis Nervous system (cid:2) Dose of 50 Gy \200\224low risk of injury (cid:2) Dose of 60 Gy \200\2245% risk of m ajor complications (cid:2) Early reaction (6 months) \200\224demyelination; brain (somnolen ce); spinal cord (Lhermitte \200\231s syndrome) (cid:2) Later reaction (1 \200\2232 years) \200\224radiation necrosis, initially in white matter; then telangiectasia, focal hemorrhage (cid:2) Peripheral nerves may be more radiore sistant Lung (cid:2) Responds late (cid:2) Radiation pneumonitis \200\2242 \200\2236 months after treatm ent (cid:2) Dose tolerance \200\22410 Gy in single treatment; 25 Gy in 2 Gy fractions (cid: 2) Lung \201brosis \200\2246 months to years Kidney (cid:2) Responds later (cid:2) Large reserve capacity, therefore effects occur up to 10 yea rs later (cid:2) Radiation nephropathy \200\224proteinuria, hypertension Heart (cid:2) Pericarditis (6 months \200\2232 years); settles spontaneously (cid:2) Cardiomyopat hy \200\224decreased ventricular ejection; conduction blocks (10 \200\22320 years) New developments High-precision or conformal radiotherapy A combination of new imaging technologies (MR, CT, portal imag- ing), new treatment planning approaches, and high-precision acceler- ators pe rmit higher radiation doses to more precisely delineated target volumes. By these high-prec ision techniques, smaller volumes of nor- mal tissue are irradiated, but to a higher dose. OHO-08(93-134) 11/16/02 11:19 AM Page 97 RADIOBIOLOGY OF NORMAL TISSUES 97 Normal tissue tolerance to re-treatment Recent studies have shown some tissues and organs h ave a substantial ability to recover from subclinical radiation injury, allowing the re- tr eatment of previously irradiated sites. The large capacity of long- term regeneration of th e CNS allows the possibility to re-treat parts of the brain or the spinal cord and offers n ew clinical possibilities for tumors recurring in or near these critical structures. Endovascular irradiation Although not strictly belonging to the \201eld of oncology, prev ention of restenosis by endovascular irradiation with small beta- or gamma- emitting radioa ctive sources is a rapidly expanding application of radiation in the cardiology clinic. Rad iation has been shown to prevent or delay the formation of new plaques by inhibition of pro - liferation of the vascular endothelium or smooth muscle cells. This immediate bene \201t needs to be counterbalanced by the risk of late complications. OHO-08(93-134) 11/16/02 11:19 AM Page 98 PRINCIPLES OF RADIATION ONCOLOGY 98 Radiotherapy fractionation Objective To choose the most appropriate combination of the number of treat- ments (fractio ns), overall time, and total dose to achieve the required level of effect on the tumor with the minimal effect to surrounding normal tissues. Basis of practice Mathematical models based on clinical and laboratory studies have been de veloped and the linear quadratic has now replaced Ellis as the preferred formula for relati ng dose and fractionation. At clinically relevant doses, tumors and early reacting tissues respond to ionizing radiati on with a linear relationship between dose and effect \200\224the linear or (cid:2)componen t. In the late reacting tissues, in the clinically relevant dose range, a large part of the effect is related to the square of the individual dose given \200\224the (cid:3)or quadrat ic element. The important implication of the linear quadratic model is that by giving radiotherapy in m any small doses, changes in the late reacting tissues should be spared, with little or no a lteration in the response of the early reacting normal tissues and of the tumor. Number of treatments Advantages of few fractions: (cid:2) Fewer attendances (cid:2) Sparing of resources (cid:2) Quicker response. Advantages of many fractions: (cid:2) Less severe acute and a lower incidence of late react ions (cid:2) Higher tumor doses can be achieved, so giving the greatest chance of cure. Expression of radiation dose The important elements of a course of radiotherapy \200\224fra ctionation, overall time, and total dose \200\224must always be considered together in orde r to assess the likely effect of a regime. The dose in the tumor target volume is normally prescribed at the center of the tumor where the beams employed usually intersect (the inter section dose), but the maximum and minimum levels also need consideration. OHO-08(93-134) 11/16/02 11:19 AM Page 99 RADIOTHERAPY FRACTIONATION 99 Radiosensitivity of tumors Some tumors, such as lymphoma and seminoma, may be controlled by doses approximately half that required for many carcinomas and sarcomas; others including gliomas and sarcomas, tend to be resistant. Radiosensitivity of normal tissues Some tissues are particularly radiosensitive and doses t o them must be limited in order to minimize the risk of late damage. If 2 Gy doses are give n, then total doses should not exceed 10 Gy to the lens of the eye; the whole kidney, 20 Gy ; whole lung, 20 Gy; the spinal cord, 50 Gy; the brain, 60 Gy; and the brachial plexus, 60 Gy. The risk of severe damage rises above 1% at these levels. The regime chosen must balance risk against likely bene \201t. The interfraction interval After a radiation treatment, some of the damage induced is compl ete but some can be repaired. With a single daily exposure, all or nearly all of the repair able damage is complete before the next treatment is given. If more than one treatment is g iven during a day, the duration of time between the fractions must be chosen with care to a llow for as much repair as possible in the normal tissues. If this is not followed, then th ere will be an increase in effect, most importantly, in the late reaction of normal tissues . Hyperfractionation By giving many small treatments, usually in a twice-a-day schedule, a hi gher total radiation dose may be achieved without an increase in the incidence of late morb idity. Such a regime was shown to be superior to conventional radiotherapy in a randomized controlled trial in oropharyngeal carcinoma. This is now being \200 tested more widely in head and neck tumors in a further EORTC trial in which cytotoxic chemotherapy is being inco rporated. Overall time and accelerated radiotherapy There is now evidence that squamous cell carcinom a in the head and neck and in the lung has the capacity to rapidly proliferate and, in some cases, the tumor cell numbers may double in a few days. This can occur during a course of treatment and be the cause of radiation failure. By shortening the overall duration, the op portunity for this to occur is reduced. \200 EORTC European Organization for Research and Treatment of Cancer OHO-08(93-134) 11/16/02 11:19 AM Page 100 PRINCIPLES OF RADIATION ONCOLOGY 100 In a randomized controlled trial, the CHART \200 regime, in which treatment is given 3 tim es on each of 12 consecutive days, proved superior to conventional radiotherapy in non-smal l cell lung cancer (NSCLC). A split course regime of accelerated radiotherapy was shown to be superior to conventional radiotherapy in head and neck cancer but there was some increas e in normal tissue morbidity. There is now evidence from randomized controlled clinical trials that a reduction of one we ek in the duration of radiotherapy in head and neck cancer gives major improvement without signi \201cant increase in late morbidity. The optimum regimen The clinical circumstances dominate the choice of regimen. In pallia- t ion, the fewer the attendances, the shorter the course, the sooner a response is achieved, the greater is the bene \201t for the patient. Regimens used for palliation generally carr y a low risk of morbidity and long-term effects are usually irrelevant. Where the highest d oses must be given to achieve tumor cure, as when radiotherapy alone is employed with the i ntention of cure, a low dose per fraction \200\224not exceeding 2 Gy \200\224should be empl oyed in order to minimize the risk of late radiation damage. A clinical oncologist should employ a wide range of schedules to best deal with all the sit uations where radiotherapy may bene \201t the cancer patient. \200 CHART Continuous Hyperfractionated Accelerated Radiotherapy Trial OHO-08(93-134) 11/16/02 11:19 AM Page 101 EXTERNAL BEAM RADIOTHERAPY 101 External beam radiotherapy Basic principles Treatment with beams of ionizing radiation produced from a source external to the patient is known as external beam radiotherapy. Super \201cial tumors are often tr eated with X-rays of low energy, in the range 80 \200\223300 kV. Electrons, emitted from a heated cathode, are accelerated across an X-ray tube, strike a tungsten anode, and undergo bremsstrahlung interactions. The beam size is selected by using metal cone-shaped applicato rs of different sizes. The main limitations of such beams are: Inherent delivery of high do se to the skin (cid:2) Relatively rapid \200\230fall off \200\231 of dose with depth (cid :2) Higher absorbed dose in bone compared with soft tissue Deeper-seated tumors are mostly treated using megavoltage pho- tons. One option is to use a source of Co-60, emitting gamma rays of average energy 1.25 MeV. Source strengths of about 350 TBq are required to achieve a suf \201ciently high dose rate. (cid:2) It is more common to use megavoltage X-rays produced by linear accelerators, in which elect rons are accelerated to near the speed of light in a waveguide, before striking a thin tran smission target. The resultant X-rays can have energies in the range 4 \200\22320 MV. Such beams offer advantages of higher penetration, higher dose rate, and better collimation than beams of Co-60. Megavoltage photons (cid:2) Maximum dose below skin surface (cid:2) Skin sparing (cid:2) Absorbed dose falls of f exponentially with depth (cid:2) Sharp \200\230fall off \200\231 of dose at beam edge ( penumbra) (cid:2) Whole-body radiation can be used (cid:2) Beam shape modi \201ed by metal shields or multi-leaf collimators (cid:2) Metal \201lters can be used to gradient dose ( cid:2) Treatment from any direction can be used (cid:2) Cross \201re technique with 2 \200 \2234 beams gives higher target dose Some linear accelerators are also con \201gured to pr oduce beams of elec- trons of various energies, usually in the range 4 \200\22320 MeV. Such beams can uniformly treat from skin surface down to a certain depth (related to the energy ), with a fairly rapid fall-off in dose beyond that. For OHO-08(93-134) 11/16/02 11:19 AM Page 102 PRINCIPLES OF RADIATION ONCOLOGY 102 (a) + Max Norm 1 Isodose curves for open beams of 6 MV X-rays. (b) NormNormNorm 1 Isodose curves for 12 MeV electrons. example, 6 MeV electrons will treat to about 1.5 cm deep and 20 MeV to about 5.5 cm. Electr ons offer a good alternative to kilovoltage X-rays for treating super \201cial tumors. The planning process There are six major steps in designing and delivering external beam ra diotherapy treatment: 1. Beam dosimetry The pattern of dose distribution from each linear accelerator has to be m easured prior to clinical use. Due to absorption properties at such high energies, these me asurements can be made using a small ioniza- tion chamber dosimeter in a tank of water. The dosimeter tracks across the beam at preset depths and dose pro \201les are recorded for a range of beam sizes, with and without wedges. It is also essential to OHO-08(93-134) 11/16/02 11:19 AM Page 103 RADIOTHERAPY FRACTIONATION 103 measure calibration factors (known as output factors) which de \201ne irradiation time req uired for a speci \201ed absorbed dose. 2. Planning Computer Simple planning can be carried out using tables or plots of measured b eam data. Mostly, planning is performed using powerful computers with specialized applicati on software. Calculations are based on mea- sured beam data but also depend on algorithms t hat allow for varying attenuation and scatter of X-rays in tissues of different densities. This density information is based on CT scans performed with the patient in the treatment p osition. 3. Target drawing The most important step in planning radiotherapy is de \201ning the targ et i.e. volume of tissue to be irradiated. This includes the gross tumor (e.g. as visualize d clinically or by imaging) together with surrounding tissues that might have microscopic i nvasion of tumor cells or which are known to be at risk of spread of disease. A further mar gin has to be allowed for uncertainties in treatment set-up; these include variations in pa tient positioning, internal organ movement, and tolerances of machine calibration. It is al so essential to de \201ne the position of critical organs i.e. those with a lower toleranc e to radiation such as the spinal cord, eyes, and kidneys. All can be drawn directly into t he planning com- puter on a set of CT images covering the full extent of the involved area. For less sophisticated treatments, the target and critical organs are de \201ned using an terior and lateral radiographs. 4. Dose planning The objective of dose planning is to design a treatment plan such that the target is uniformly irradiated to a high dose whilst ensuring that critical organs do not exceed tolerance doses. Parameters that can be varied include: (cid:2) Beam size (cid:2) Be am direction (cid:2) Number of beams (cid:2) Relative dose per beam (beam weight) (cid:2) W edging (cid:2) Use of compensators 5. Treatment veri \201cation It is essential that beams are correctly positioned and criti cal organs not over-irradiated. Beams are usually veri \201ed by taking radiographs on a r adiotherapy simulator prior to treatment; this can also be done during treatment with radio graphs or Electronic Portal Imaging Devices (EPID). OHO-08(93-134) 11/16/02 11:19 AM Page 104 PRINCIPLES OF RADIATION ONCOLOGY 104 102102102 AAA DVH-VOI 1 DVH-VOI 1 DVH-VOI 1 +++ 105105105 BBB +++ NormNormNorm 102102102 EEE +++ DDD 999999 107107107 CCC ++++++ +++ FFF 575757 DVH-VOI 2 DVH-VOI 2 DVH-VOI 2 MaxMaxMax +++ 333 Three radiotherapy beams converging on CT defined volume of lung cancer. 6. Treatment prescription and delivery The clinical oncologist prescribes the appropriate d ose and frac- tionation schedule. Together with beam con \201guration information, these f orm a data set completely describing the intended treatment. They are entered into a comput er veri \201cation system on the linear accelerator and control set-up and delivery of eac h treatment. Areas of development 3D planning Perhaps the most signi \201cant change in radiotherapy practice in the past 15 years has been the direct use of CT scanning for planning. The advantages of CT planning a re signi \201cant: (cid:2) Tumor and critical structures are more readily de \201ned (cid :2) Dose calculation is more accurate (cid:2) The planning process is truly 3D, offering mo re options for opti- mizing the treatment plan In certain circumstances, adequate coverage of the target whilst avoid- ing critical organs can only be achieved using beams that are non- coplanar; these calculations can only be pe rformed in 3D utilizing the CT information. OHO-08(93-134) 11/16/02 11:19 AM Page 105 RADIOTHERAPY FRACTIONATION 105 Conformal treatment/multi-leaf collimators It has always been the aim of radiotherapy to co nform high dose volume to the target. Normal practice was to use rectangular beams with lim ited use of blocking. Inevitably, some normal tissue was unnecessarily irradiated to high d oses. Improved levels of conforma- tion can be achieved by positioning shaped alloy blocks in the beam and, automatically, with a feature on the accelerator known as multi- leaf coll imators (MLC). Here, the beam can be shaped under com- puter control by sliding a series of 1 cm-wide leaves into the beam. By minimizing the amount of normal tissue irradiated to high dose, it may be possible to de liver higher doses to the target, thereby improving tumor control without increasing morbid ity. Target drawing/image fusion The push toward conformal radiotherapy has highlighted the need to improve tolerances of target drawing. Imaging modalities other than CT (MRI, nuclear me dicine, and PET scanning) may improve target de \201nition and there are bene \201ts in o verlaying or \200\230fusing \200\231 various image sets. Dynamic radiotherapy/intensity modulated radiotherapy With standard techniques it can be di f \201cult to treat an irregularly shaped target in close proximity to a critical organ. T his may be improved by using dynamic therapy, where the machine rotates around the patient, continuously emitting X-rays, and with the beam shape constantly changing. Alternatively, the intensity of radiation across stationary beams may be modulated. Biological planning Radiotherapy prescription is based on absorbed dose even though dif- fe rent tumors and normal tissues are known to react differently to a given radiation dose. Us ing mathematical models to compute a \200\230biological \200\231 dose it would then be pos sible to predict the tumor control probability (TCP) and the normal tissue complication pro b- ability (NTCP) associated with various proposed treatment plans, thus forming a better b asis for selecting the optimal plan. OHO-08(93-134) 11/16/02 11:19 AM Page 106 PRINCIPLES OF RADIATION ONCOLOGY 106 Electron beam therapy Electron beams have been used in treating malignant disease for over three decades. Althoug h electron radiation is radiobiologically equiv- alent to photon radiation, the physical ch aracteristics of electron beams are preferred over photon beams in the treatment of certain anatomical sites. Unlike photons, electrons possess charge and so interact frequently as t hey penetrate tissue; the resulting nearly con- tinuous energy loss leads to a well-de \201ned range in tissue (radiation dose deposited beyond a certain depth in tissue in negli gible). This treats the target volumes lying within a few centimeters of the skin \200\231s surface while sparing any underlying critical structures. The frequent interactions between the penetrating electrons and the tissues have several deleterious effects. Speci \201cally: (cid:2) Large-beam penumbra \200\230Hot \200\231 and \200\230cold \200\231 spots beneath surface discontinuities (cid:2) (cid:2) Signi \201cant changes in dose near inhomogeneities Production of electron beams Production of electron beams necessitates the use of electron accelera- tors such as betatrons, microtrons, or linear accelerators. All these accel- erat ors are capable of producing clinically useful beams of X-rays or electrons. With an X-ray beam, a narrow electron beam emerging from an accelerator strikes a thick, high-atomic-numb er target to produce bremsstrahlung photons. An appropriately shaped \202attening \201l ter con- verts the forward-directed bremsstrahlung beam into a clinically useful beam of un iform intensity. In an electron beam, the X-ray target is removed and the emerging electron s are scanned magnetically or scat- tered in foils to produce a uniform broad beam. Most ra diation therapy facilities have high-energy accelerators capable of producing both X-ray an d electron beams. Thus, radiotherapists have both treatment modali- ties at their disposal in the design of an optimal treatment. Since electrons scatter signi \201cantly in air, beam-de \201ning cones or \200\230trimm er \200\231 bars are \201tted to the head of the treatment machine in order to collimate the beam near the skin \200\231s surface. The beam may be shaped further either by \201tt ing a lead or \200\230cerrobend \200\231 aperture at the end of the cone (often called an electron cut-out), or by using lead sheet laid directly on skin. Dosimetric characteristics of electron beams The various dosimetric aspects of electron bea ms in homogeneous tissue are as follows: OHO-08(93-134) 11/16/02 11:19 AM Page 107 ELECTRON BEAM THERAPY 107 Depth dose characteristics Dose builds up slowly to a maximum value and then falls off rapi dly, reaching nearly zero dose at a depth equal to the practical electron range. Beyond the practical range, any radiation dose is due entirely to contamination photons produced in t he head of the linear accelerator and tissues themselves. The magnitude of the contaminatio n dose varies but is usually 1 \200\2235% of maximum dose depending on the energy of the be am and design of accelerator. Effect of \201eld size The shape of a depth dose curve is independent of \201eld size w hen all \201eld dimensions are larger than the practical range. For smaller \201elds, d epth of dose maximum shifts towards shallower depths while dose fall-off becomes less steep . Effect of incident energy The depth of penetration of an electron beam is determined by its incident energy. Practical range (in centimeters) of an electron beam in water is given ap proximately by: E0 2 \211\210 Rp where E0 is incident beam energy expressed in mega electron volts (MeV). Similarly, the clinically useful range \200\224the depth at which the dose falls to 80% of its maximum value \200\224is given by: E0 3 \211\210 d80 The surface dose (commonly de \201ned as dose at 0.5 mm depth) is signi \201cantly higher for an electron beam than for a megavoltage photon beam and ranges from about 85% of dose maximum at low energies (less than 10 MeV) to about 95% at higher energies. The rate at whi ch dose falls off beyond the depth of dose maximum is also energy-dependent, with the rate of dose fall-off decreasing as the beam energy increases. Accelerators that offer an electron beam mode generally allow selec- tion of one of several available electron beam energies. Beam energies may range from as low as 4 MeV up to 50 Me V in some cases. However, energies most commonly used clinically tend to be in the range 6 \200\22315 MeV. Beam pro \201le and penumbra Beam penumbra tend to be larger for electron beams than for p hoton beams. For electron beams, dose falls to 90% of central axis value approximately 1 cm inside the geometric \201eld edge for depths near the dose maximum; a 10 \227 10 cm2 be am, for instance, produces an OHO-08(93-134) 11/16/02 11:19 AM Page 108 PRINCIPLES OF RADIATION ONCOLOGY 108 \200\230effective \200\231 \201eld size of only 8 \227 8 cm2. The corresponding distanc e for a photon beam is only about 0.5 cm. Thus, a larger electron beam is required to cover a given target to a clinically useful dose. This prop- erty of electron beams makes abutti ng of photon and electron beams problematical since a uniform dose across a \201eld junct ion cannot be achieved at all depths. Near-surface irregularities and tissue inhomogeneities Variations in the surface contour an d composition of tissue (i.e. tissue inhomogeneities) strongly in \202uence the shape of t he electron beam dose distribution. Depending on the anatomical site, these effects may be clinically signi \201cant and an estimate of their magnitude may be required. Methods of dose calculation Dose calculations for electron beams are not as accurate as tho se for photon beams. As a result, the use of electron beams may be prevented where the accu racy of the delivered dose distribution is critical. However, accuracy of predicted dose di stributions will improve as better methods of dose calculation evolve. Ray-line method This is the earliest (and simplest) form of dose calculation. Electrons are assumed to trav el along ray-lines originating from a single \200\230virtual \200\231 source. An appropria te shift of the percentage depth dose curve along these ray-lines accounts for the effect o f tissue inhomogeneities. Dose distribution calculated in this manner does not re \202ect the lateral scattering of electrons near the edge of inhomogeneities or near-surface irregu larities. Since these effects can lead to considerable dose perturbations, the ray-line met hod has been largely supplanted by the pencil beam method. Pencil beam method This method of dose calculation decomposes a broad electron beam into a set of narrow \200 \230pencil beams \200\231. The dose at any given point in irradiated tissue is the summatio n of the contributions from each of these pencil beams. Individual pencils can be altered a ppropriately to allow for the effects of inhomogeneities. Thus, some account is taken of la teral scattering of the electrons as well as changes along the ray- lines. However, the met hods used for altering the pencils beams are, by necessity, approximate. \200\230Monte Carlo \200\231 A direct computer simulation of individual penetrating electrons is now emerging as a clini cally viable tool for dose calculation. This OHO-08(93-134) 11/16/02 11:19 AM Page 109 ELECTRON BEAM THERAPY 109 calculational technique simulates individual electron trajectories using random numbers to sample theoretical electron-scattering cross-sections; its reliance on random numbers has e arned the technique the name \200\230Monte Carlo \200\231. Clinical applications Breast cancer (cid:2) Treatment of breast or chest wall after surgery (cid:2) Photon beams delivered tang entially or perpendicularly (cid:2) Possible side-effect on underlying lung but rare due to rapid dose fall-off Skin (cid:2) Useful for skin lesions (cid:2) Wire meshes used to increase skin dose (cid:2) Safe over cartilage and bone e.g. ear (cid:2) Lip and eyelid shields used to protect eye and mo uth (cid:2) Total skin irradiation possible e.g. mycosis fungoides Head/neck (cid:2) Useful for positive neck nodes in head/neck cancer (cid:2) Photon beams used to irr adiate entire region including spinal cord (cid:2) Electron beams used additionally, except for spinal cord 110 6 MV photons 100 12 MeV electrons 90 80 m u m i x a m e s o d 70 60 50 40 f o % 30 20 10 0 0 5 10 15 Depth (cm) Tissue penetration of different types of radiotherapy beams. OHO-08(93-134) 11/16/02 11:19 AM Page 110 PRINCIPLES OF RADIATION ONCOLOGY 110 Electron source Scattering foils Photon collimators \200\230Cone \200\231 assembly \200\230Cut-out \200\231 Patient A schematic representation of a typical electron beam collimation system (some components a re not shown). Intra-operative electron therapy Intra-operative radiotherapy using electron beams has also been used clinically. This technique involves exposing the target surgically, thus allowin g a specialized applicator (i.e. collimator) to be used to irradiate the target. In this wa y, any normal tissue overlying the target is spared. The labor and resource intensive natur e of this technique limit its widespread use. OHO-08(93-134) 11/16/02 11:19 AM Page 111 TREATMENT PLANNING 111 Treatment planning The radiation oncologist decides optimum radiation dose distribu- tion for a patient prior to commencing treatment planning. The aim of treatment planning is to model that dose distr ibution as closely as possible using a number of radiation beams of appropriate modality an d energy. The direction and size of each beam has to be determined, together with radiation dose to be given and any modi \201cation that may be required to the inherent dose distri bution of the beam. To achieve this aim, it is necessary to know the precise dose distribut ion that will result from any treatment beam. This is obtained from prior radiation measure ments in unit-density tissue-equivalent material, made available as a set of charts or tabl es (known as the depth dose distribution). These data specify the dose at any point in the beam relative to a reference point (usually the point of maximum dose on the central axis o f the beam). The depth of the reference point increases with increasing beam energy and is in the range 1 \200\2233 cm for commonly available megavoltage (MV) treatment beams. Dose distributions are required for a whole range of clinical settings available on a treat ment machine. The relative dose distribution for the patient is obtained by summing the ind ividual distributions for all beams and is displayed as a map showing lines of constant dos e, known as isodose lines. The radiation oncologist prescribes an absolute dose to an isodo se line and to achieve this dose each individual beam must be calibrated in terms of the nu mber of machine units required to give a speci \201ed dose to its reference point. The machine units control the quantity of radiation given in an individual exposure. This a bsolute calibration is again carried out by prior radiation measurements, provided in tabul ar form as a set of output factors. These also vary with the possible clinical machine set- tings and must be measured over the complete range to be used. Types of radiotherapy There are two types of radiotherapy: (cid:2) Palliative, where the ai m is the relief of symptoms. (cid:2) Radical, where the aim is to achieve a cure. Palliative radiotherapy Treatment planning for palliative radiotherapy is a simple procedur e as treatment usually consists of a single or parallel opposed treatment beams, where the patient is considered to be unit-density tissue- equivalent material of uniform thickness. OHO-08(93-134) 11/16/02 11:19 AM Page 112 PRINCIPLES OF RADIATION ONCOLOGY 112 For single beams the dose is usually prescribed to the reference point, which is the point of maximum absorbed dose in the central axis of the beam (or occasionally to a point at dep th). Parallel, opposed pairs of beams are normally prescribed to mid-separation of the pati ent, again in the central axis of the beam. In all cases, treatment planning can be performed manually from the set of depth dose and o utput tables for the treatment beams as already described. Prescribed doses for palliative irradiation are usually low, so doses to vulnerable organs close to or within the treated v olume are not a problem. Radical radiotherapy Treatment planning for radical radiotherapy provides a more compli- ca ted problem and is carried out with computerized treatment plan- ning systems. The main aim is to provide a high and uniform dose to the target volume while ensuring that the dose to any vulnerable organs is kept as low as possible and within speci \201ed constraints. It is important to determine carefully the anatomy of the patient in the region to be treated and the location of the target volume within this region, so that the dose distribution can be calculated accurately. Methods used depend on whether the dose calculations are to be p er- formed on a single two-dimensional plane through the patient or over the full three-dim ensional treatment volume. The simplest method is to determine the external contour by a mechanical or optical device and the target position from AP and lateral radiographs. Use of a treatment simulator can a lso provide the information required for two-dimensional planning especially if it is equip ped with a computerized tomography (CT) option. Full CT scanning is essential for three-dimensional planning and is by far the best techniq ue, as it provides all the necessary information as well as a density map of the patient th at can be used for dose calculation. Magnetic resonance (MR) scanning can provide better diagnostic information than CT but prod uces geometrical distortions in the image that must be corrected. MR scanning is therefore only used in conjunction with CT planning. In all cases it is essential during the treatment planning process that patients consistent ly remain in the treatment position; immobiliza- tion devices can assist in this. The correct determination of the planning target volume (PTV) is obviously essential to the success of radiotherapy. The gross tumor volume (GTV) is that which is palpable or radiolo gically demonstra- ble, but must be surrounded by a margin to allow for microscopic spread, giving a clinical target volume (CTV). A further margin must be applied to the CTV to allow for geometri- cal inaccuracies in the treatment set-up and patient/organ movement OHO-08(93-134) 11/16/02 11:19 AM Page 113 TREATMENT PLANNING 113 during treatment, and this de \201nes the planning target volume. Progression from the GTV to the PTV is straightforward in two- dimensional planning. However, enlarging the CTV to the PTV, slice by slice on CT may not give correct margins in three dimensions when there i s a signi \201cant difference in the size of the CTV on adjoining slices. Further problems exist in de \201ning margins at the superior and inferior limits of the CTV due to the wi dth of the CT slice. Problems can be overcome by the use of three-dimensional volume-growin g algorithms that are available on computerized planning systems. Beam arrangements Optimum beam arrangements required to treat a particular site have been w idely investigated and adopted into protocols in each radio- therapy center, with little va riation from one center to another. However, some sites in the head and neck and the chest may require individualized beam arrangements. In general, co-planar beam arrangements are used, but the avail- ability of fully three-dim ensional treatment planning systems allows the placement of non-coplanar \201elds. The nu mber of beams required is less with a high-beam energy and a small depth to the center of t he target. In the pelvis, three or four beams are used at the highest avail- able energy, p referably 12 \200\22316 MV. Three beams are suf \201cient in the chest, using an energy of 6 \200\2238 MV, as at higher energies the range of the secondary electrons in lung tissue makes the calculation of the dose distribution uncertain. In the head and neck region, two \201elds are generally suf \201cient, using an energy 4 \200\2236 MV, as it may be neces sary to provide a high dose close to the entrance surface while minimizing the exit skin do se. The central axis of the beams pass through one point (known as the isocentre) which is plac ed at the center of the PTV, with the directions of the treatment beams chosen to avoid the irradiation of sensitive structures. Placing the beams uniformly around the patient is adv an- tageous in obtaining a uniform dose distribution over the target, and the selection of beam directions where the depth of the target is kept small reduces the overall dose to the patient. Beam size Beam sizes should be chosen so that the resulting high-dose volume encompasses th e PTV with a minimum dose not <95% of the iso- center dose. To achieve this, \201eld dime nsions must be larger than the PTV due to the fall off in dose towards the edge of the beam . The margins required are typically in the region of 6 \200\22310 mm and depend on how man y beams contribute to the fall off in dose. A development arising from three-dimensional treatment planning that assists greatly in the determination of beam size is the beam \200\231s eye OHO-08(93-134) 11/16/02 11:19 AM Page 114 PRINCIPLES OF RADIATION ONCOLOGY 114 view (BEV) approach. Here the observer is placed at the radiation source and the projection of any structure that has been outlined on a CT image set is displayed on a plane normal t o the central axis of the beam. A projection of the beam portal is superimposed and its siz e can be determined according to the projection of the PTV. The approach also assists in th e selection of the optimal beam direc- tions with respect to the separation of the target a nd vulnerable organs. The technique of conformal radiotherapy is increasingly used in which the beam shape is mat ched more closely to the PTV. This is achieved by the use of customized blocks or multi-lea f collimators (MLC) on individual beams, and in both cases the use of BEV is essential. Beam weight The relative contribution of a beam to the treatment plan is known as the beam weight. The de \201nition varies between centers and is de \201ned either as the relative contribution of the dose to the isocentre or to the reference point. The adjustment of bea m weights is a method of achieving uniformity of dose over the PTV and giving approxi- mate ly the same dose to the isocentre from each beam will give good uniformity. Care should be taken to ensure that the entrance dose under the beam portals is not excessive. The inherent dose distribution of a beam can be altered by the insertion of a wedge-shaped \201lter that produces a dose gradient in one dimension across the beam. Wedges can be us ed to com- pensate for obliquity at the skin surface or to assist in obtaining dose uniform ity in the PTV when the beams are not uniformly spaced around the patient. Wedges are chara cterized by the angle through which the isodose lines are tilted and normally a selection a re available (or can otherwise be achieved), producing tilts of up to 60 . Selection of the optimum beam weights and wedges is assessed by the closeness of the result ing dose distribution to that required by the radiation oncologist. Modi \201cation of the inherent dose distribution over the beam in two dimensions is possible by the use of physi cal compensators or, more recently, by the dynamic movement of the leaves of an MLC. The use of the treatment simulator depends on the patient data used for planning. In three- dimensional CT planning, the radiation oncologist usually outlines the CTV on the relevant CT slices together with the outline of any vulnerable organs. The CT data represent the pat ient with computer graphics used to simulate the treatment beams. This can be thought of as virtual simulation and the patient only visits the treatment simulator at the end of the t reatment planning process to have the treatment veri \201ed. OHO-08(93-134) 11/16/02 11:19 AM Page 115 TREATMENT PLANNING 115 Treatment sheet The \201nal action of the treatment planning process is to produce a trea tment sheet that provides a set of instructions to allow the treat- ment radiographer to se t up the patient as planned and to deliver the correct dose distribution, including the num ber of monitor units to be applied to each beam. Accuracy has to be assured by a set of che cks at all stages of the planning process, and these should form part of a quality assuranc e system, such as ISO 9002, with fully documented procedures and work instructions. OHO-08(93-134) 11/16/02 11:19 AM Page 116 PRINCIPLES OF RADIATION ONCOLOGY 116 Total body irradiation (TBI) Treatment intensi \201cation with high doses of chemotherapy and/or radiotherapy is used t o try to improve cure rates for sensitive tumors. In some benign diseases such as aplastic anemia and thalassaemia, myelo-ablative therapy, usually with chemotherapy alone, precedes engraftment of normal donor marrow to overcome the underlying host problem. Aims (cid:2) To eliminate any residual malignant disease. (cid:2) To ablate residual marrow to p ermit engraftment of peripheral