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# Physics of Radiation Therapy • Biological basis • Physical goal • Brachytherapy • Teletherapy • Measurement of dose • Calculation of dose

You might also read: M. Oldham, Radiation physics and applications in therapeutic medicine, Physics Education 460-467 (2001). There are also many texts on the subject - the “classic” is The Physics of Radiology by H. E. Johns and J. R. Cunningham

Biological basis of radiation therapy 1. Cells can be “killed” by ionizing radiation. 2. Most important target appears to be nuclear DNA. 3. Radiation damage to DNA results in non-viable offspring. 4. Rapidly dividing cell populations are the most sensitive to ionizing radiation (e.g. tumors, epithelial cells, hemopoietic cells.

Assessing biological effects Want to quantify the effect of a specific “dose” of ionizing radiation. In this context, dose has a well-defined physical meaning: the energy absorbed per unit mass. The SI unit is Gy = J kg -1. You may still encounter the rad: 1 Gy = 100 rad or 1 rad = 1 cGy. Biological damage can be measured at the level of the cell, the organ, or the complete organism. At the cellular level, the classic endpoint is cell survival.

A “classic” cell survival experiment …

This graph shows typical survival curves for mammalian cells. For x-rays, note the “shoulder” on the survival curve in the low dose region. Radiation is less effective in killing cells at low doses because the cell is capable of repairing some radiation damage. At higher doses the survival is approximately exponential as the survival decreases by a factor of 1/e for each dose increment D0. For mammalian cells D0 is about 1 - 2 Gy. The survival curve depends on the linear energy transfer (LET) of the radiation (see above), local oxygen concentration, temperature, cell cycle, presence of other drugs, dose rate and fractionation.

e. It is believed that this effect is clinically important because many cells in a tumor can be hypoxic. effect of oxygen on survival curves. .g.

assuming that we have to kill every tumor cell in order to achieve a cure….. Clinically. Consider what this would look like for cure.e. change in survival when dose is given in a series of “fractions”. Using a range of doses we can construct a dose-response curve.presumably because malignant cells are repair deficient. tumor regression or growth delay. organ function.g. In vivo assays: Here we might measure animal survival. . it has been found that allowing for repair between fractions gives better results .

At a high enough dose we would have a high probability of curing every tumor. we must also irradiate some normal tissue and its response usually limits the dose that can be used. . Unfortunately.

this ideal dose distribution is not physically achievable. The sources may be implanted permanently or temporarily.” 100% 0% As we will see. but we attempt to satisfy it through two general strategies: brachytherapy and teletherapy. treatment time of days). treatment time of minutes) or low dose rate (LDR. Brachytherapy In brachytherapy radiation sources are placed adjacent to or within the target volume. .The physical goal of radiation therapy Bearing this in mind. Temporary implants may be performed at high dose rate (HDR. from a physics perspective the goal of radiation therapy could be simply stated as “Deliver a high dose to all parts of the tumor while minimizing the dose to surrounding normal tissue.

the Compton effect. Therefore electrons have a finite range in tissue that is proportional to their initial energy. it is actually the electrons that do most of the biological damage. To a good approximation. Because electrons are charged particles. so that there is a small but finite probability that a high energy photon can penetrate a concrete wall two meters thick! It is important to realize that even when photons are used in radiation therapy.tissue interactions Photons (gamma rays or x-rays) interact with matter through the photoelectric effect. . a photon beam is attenuated exponentially with distance. On the other hand. the electron loses energy at a constant rate of about 2 MeV/cm. they interact strongly with atoms in tissue and a single high energy electron can ionize many atoms along its track.Quick refresher on radiation . The relative importance of these three is shown below: All of these produce high energy electrons. or by pair production.

In either case. . from a physics perspective. and I125. Note that if we used an electron (beta particle) source of the correct energy. There are many possible isotopes that could be used but consideration must be given to half-life. multiple sources are usually necessary to achieve a useful dose distribution. These are obtained either as fission products or as the result of neutron capture reactions. cost. The isotopes used most commonly in brachytherapy are Cs137. Although beta emitters are used to treat small malignant deposits. we would be even better off because of the finite range in tissue. so we expect the ratio of doses at Points 1 and 2 to look something like Source P1 r1 r2 P2 D1 D2 α exp (-µr1) exp (-µr2) X r2 2 r1 2 Note: µ is about 0. Ir192. so most brachytherapy is performed with gamma emitters. brachytherapy makes a lot of sense.17 cm -1 for 100 keV photons So.Back to brachytherapy…… For a point gamma ray source the dose will fall off with distance due to the inversesquare law and tissue attenuation. gamma energy. the range of readily available beta emitters is too short. and physical form.

025 MeV gamma So why not do brachytherapy all the time? 1.g. 2. It is not practical to implant large tumors. 4. Technical aspects Brachytherapy was first performed using radioactive sources (e.66 MeV gamma 0. Radiation protection issues (see below). 5. 6. Time consuming and technically more difficult. This resulted in a significant radiation exposure to the physician and other operating room staff.06 MeV gamma 0.1. 3. .136 .Cesium 137 Iridium 192 Iodine 125 30 yr half life 60 d half life 60 d half life 0. Patient may be a poor surgical risk. May require hospitalization. Access to the tumor may require surgery. radium “needles”) which were implanted during the surgical procedure.

but typically 15 minutes to position the patient and deliver beams from different directions. Teletherapy In teletherapy an external source at a distance of about one meter from the patient is used to irradiate the tumor.. or a radioactive stent can be permanently placed in the vessel. A series of daily fractions. Source r2 D1 r1 D2 α exp (-µd1) exp (-µd2) X r2 2 r1 2 P2 d2 d1 P1 For normal tissue closer to the source. is used. each about 2 Gy. The correct dose of radiation will prevent proliferation of endothelial cells and re-stenosis.. the advantages of using teletherapy are many. both attenuation and the inverse-square law work against achieving an acceptable dose distribution.An interesting recent development is the use of brachytherapy to prevent re-stenosis of coronary arteries after balloon angioplasty. A radioactive source is inserted in the vessel under fluoroscopic guidance. It takes about one minute to deliver the actual treatment. . However.

4. 2. Compton scattered photons. 6. The physical disadvantages can be largely overcome. Treatment is quick and convenient. 5. Electrons have finite range. we need to understand the dose distribution from an external photon beam. 8. No significant radiation dose to staff. Any anatomical site can be treated. 2. 3. Large fields (even the whole body!) can be accommodated. Inverse square law. Can be performed on patients who are not well. etc. 7. 5. Dose is due mainly to electrons.Advantages of teletherapy 1. We need to consider: 1. 4. . Noninvasive. Attenuation of primary photons. 3. Usually done as an outpatient procedure. family members. Dose distribution from a photon beam To understand #8 above.

. If there is no substantial attenuation of the photon fluence over this distance we would expect: D2 = 2D1.Simple model for dose near the surface. D4 = 4D1. 1 2 3 4 5 6 7 8 Electron range Assume each high energy electron is launched in the forward direction and that each has the range shown. .. The dose in each layer of tissue will be proportional to the number of electron tracks per unit volume. D5 = 5D1. but after this layer (in which we reach an equilibrium in electron fluence). D6 = 6D1. But as depth continues to increase the photon fluence will decrease due to the inverse square law and attenuation. the dose would be approximately constant. D3 = 3D1.

but not the quantitative details...From this simple model we expect the dose versus depth curve to look something like. . Approx. Our simple model does predict the general nature of these curves. exponential attenuation Dose Build-up region Depth Here are some examples of real depth-dose curves.

Note that the surface dose is not zero because of backscattering and electron contamination in the beam. The half-life is about 5 years which means that sources must be periodically replaced and adjustments must be made to treatments to account for source decay. A source like this could deliver a lethal whole body dose of gamma rays in a minute. Each beta decay of Co60 results in the emission of two gamma rays . so special handling and shipping procedures are necessary. The only one in wide use now is Cobalt 60. A typical therapy source is about 10 kCi or 370. Photon sources for teletherapy Gamma rays Radioactive isotopes. γ) reactions. we see that a lot can be gained by selecting the photon energy to match the clinical problem.2 MeV.the average energy is about 1.This detailed plot of the build-up region shows the shift of the peak with photon energy. Overall. Cobalt 60 is produced in a nuclear reactor by (n. .000 GBq.

The electrons are stopped in a metal target and a polyenergetic x-ray beam is produced. Note the symbol kV refers to the effective voltage used to accelerate the electrons. For higher energies. A 100 kV x-ray beam would consist of a wide spectrum of energies with 100 keV being the highest. The highest photon energy in the spectrum is equal to the electron energy and the mean photon energy is about one third of this. .X-rays X-rays can be produced by decelerating electrons .300 kV range.this is known as “bremsstrahlung”. an expensive and complicated electron linear accelerator is used. Schematic diagram of an x-ray tube used to produce x-rays in the 50 . At energies below 250 keV this can be accomplished in a relatively simple x-ray tube. The electrons are first accelerated by an electric field.

so how do we get high energy x-rays? Microwave source t E vector Waveguide structure t + 0.333 ns) Wavelength = 10 cm .083 ns t + 0.333 ns Microwave frequency = 3 GHz (period = 0.167 ns t + 0.It is not practical to run x-ray tubes at voltages higher than a few hundred kV.250 ns t + 0.

so a metal “flattening filter” is used to produce a more uniform beam. the electron beam is focused onto a metal target (usually tungsten). At high energies the bremsstrahlung beam is forward peaked.25 MeV range.An electron linear accelerator uses microwaves propagating in a special waveguide to accelerate the electrons. but medical accelerators operate in the 4 . An ionization chamber (more on these later) measures the radiation output in real time and is the means by which the dose to the patient is controlled. As shown below. . A set of moveable collimators allow the user to define rectangular beams of dimensions from 4 to 40 cm. The largest linac accelerates electrons to 2 GeV.

This aids in patient setup. Note that rotation of the entire accelerator assembly allows a photon beam to be directed at the patient at any angle without moving the patient. such as wall-mounted lasers are used in conjunction with marks on the patient. This is called an isocentric setup.Typical clinical linear accelerator… Axis of rotation When the beam is not on. Other devices. a light field is projected onto the patient which is coincident with the radiation field. .

Cut-away view of modern linear accelerator .

In a typical bunker for a high energy accelerator the primary radiation barriers (see above) are about 2 m thick! These rooms are fairly expensive to build. .4 million dollar range.. only the patient can be present during the actual irradiation. Primary barrier Because even the scattered and leakage radiation dose rates are quite high in the room.Typical teletherapy installation. Total cost of room and accelerator is in the 2 .. A specially designed shielded room (or bunker) is needed to protect staff and often the general public.

Image guidance: high energy or low energy x-ray imaging systems .Recent Technology Innovations Multi-leaf collimators: up to 120 independent leaves.

Plotting the dose along the central axis of this opposing pair of fields we get something that looks like.. The resulting dose distribution will be the sum of the contributions from the two fields.We have seen how the correct selection of photon energy can mitigate the physical disadvantages of brachytherapy. . However a single beam of photons still produces a dose distribution that is far from ideal... Consider what happens if you use two beams entering the patient from opposite directions..

These examples show that even with this simple arrangement we can get more dose in a deep-seated tumor than in the overlying normal tissue. This idea can be extended to more complex arrangements ranging from standard 3. 4 or more field geometries to quite complex individualized plans that incorporate beam modifiers. .

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Split Absolute 7500 cGy 7200cGy 6996 cGy 6500 cGy 6000 cGy 5940 cGy 5500 cGy 5000 cGy 4500 cGy 4000 cGy 3500 cGy 3200 cGy 3000 cGy 2500 cGy Dose distribution superimposed on CT scan of patient anatomy .

Intensity Modulated Radiation Therapy (IMRT) PTV (tumor) .

Therefor we might expect a broad electron beam to produce a depth-dose curve that is constant up to the range of the electron and then falls off rapidly.. . Recall that electrons have a finite range in tissue and that dose is deposited in roughly equal amounts per unit pathlength. Real depth-dose curves show roughly these features…. reasonably flat field.With a linear accelerator it may also be possible to extract the electron beam before it hits the thick target. This beam is usually scattered by a thin metal foil to produce a large.

Electron scattering is responsible for “blurring” of the sharp fall-off and also results in a relatively fuzzy edge to the beam. These isodose plots show that the distribution tends to deteriorate with depth. . electron beams are very useful in treating targets relatively close to the surface. especially when sensitive normal tissues (such as the spinal cord) lie directly beneath the target volume. Nonetheless.

such as protons. these installations are an order of magnitude more expensive than photon facilities and it is questionable whether they are justified when modern conformal photon techniques can produce competitive results. can produce excellent dose distributions with a single field. However. Depth-dose curve for a single beam of 187 MeV protons. .Other types of radiation. The so-called Bragg peak near the end of the range occurs because the proton energy loss per unit pathlength is a strong function of energy.

.) Probability of control Dose Recall the theoretical dose-response curve constructed from cell-survival data. Complete dose-response curves do not exist for human tumors but there is some clinical trial data and anecdotal data that suggest the curve is very steep in the region of typical clinical operation. In Canada. A change of only 5% in the dose delivered can result in a detectable difference in clinical response.The need for accurate dosimetry (or why cancer centres should employ medical physicists…. This dose measurement should be traceable to a national standard so that the results of clinical trials in one centre are comparable to those in another centre in the same country or a different one. Thus it is common to state that the absolute dose at any point in the patient should be known to 5% or better. national standards for dose are the responsibility of the National Research Council.

. In general there are two ways we could tackle this problem. stating the dose at an arbitrary point P to within 5% is actually a very challenging problem.So how hard can it be? Source Arbitrary distance Polyenergetic photon beam Beam modifier Electron contamination P Electrons Irregular shape Inhomogeneous medium Scattered photons Considering all of the variables in the problem (some of which are illustrated above for a typical teletherapy setup). ..

(Hamilton 4000 pts. (This last constraint is on the verge of disappearing as computing power gets cheaper and cheaper. g. spatial distribution of the electron density).g. photon spectrum and fluence rate everywhere in the beam) and the characteristics of the patient (e. in principle. In practice. Use these data along with a reasonable physical model to calculate the dose under the sort of arbitrary conditions illustrated on the previous page.g. . In vivo measurements are possible in some circumstances.) Strategy #2 We could measure the dose directly using a suitable instrument.Strategy #1 If we knew the radiation beam properties (e. we could. One could think about manufacturing a simulated patient from tissue substitutes and measuring the dose within it. calculate the dose at every point. per year) A hybrid solution Measure the dose delivered to a tissue-like material under a finite number of standard conditions. but it is hard to imagine this as a practical solution when thousands of patients are treated per year at a large centre. a Monte Carlo simulation) is too slow. but it is not possible to do this in most cases. not all the information is readily available and the calculation (e.

. Source 100 cm Square field 10 cm X 10 cm Flat surface Water or polystyrene P ( 10 cm depth) How do we measure the dose at P under these standard conditions? .An example of standard conditions..

A physicist’s view of the perfect patient … .

4. Convenient. In the clinical environment an ionization chamber is the best choice because: 1. Cannot measure dose rate. Detector is small enough to provide adequate spatial resolution under most circumstances. This can be detected and related to dose. Real time (rate or integrated dose).24 mK in water) Thermoluminescence: Absorbed radiation raises electrons to long-lived traps. 5. Can be shipped to standards lab for calibration. 3. These are collected by a high voltage resulting in a small current (typically nA). Heating removes electrons from traps and their return to the valence band is accompanied by light emission. Fricke dosimetry: Radiation induced chemical changes in a solution can be detected by absorption spectroscopy. Ionization chamber: Radiation ionizes gas molecules. 2.Measurement of Dose Possible Methods Calorimetry: Temperature increase (1 Gy -> 0. Sufficiently sensitive. .

Dair . we have Stopping power for plastic Dplastic = Dair X Stopping power for air .7 eV to ionize one molecule. Putting this together. is equal to this total energy divided by the mass of the air in the cavity. The dose to the air. it will not cause a significant perturbation of the radiation field in the medium. the dose that would be delivered to the volume of plastic that would replace the air. If the cavity is a true Bragg-gray cavity. To calculate this we need to know the “stopping powers” for air and plastic.Calculating dose from ionization charge Air Plastic If the air cavity is small enough. there is a simple relationship between the Dair and Dplastic. in this case a plastic tissue “phantom”. The stopping power is a measure of electron energy loss per unit pathlength. This assumption is the basis of Bragg-Gray cavity theory. In air it takes an average of 33. The total energy deposited in the air cavity is equal to the product of the charge and the energy required to produce a unit charge. It is a weak function of electron energy so we need to know something about the energy spectrum of electrons in the medium.

the goal of 5% for any point in any patient is tough to meet. 4. Perturbation of the radiation field. 3. Incomplete collection of charge produced. When all these factor and their uncertainties (as well as uncertainties associated with calibration and charge measurement) are taken in to account. Given this. Changes in density of the air. 5. . 2. Effects of the chamber wall.In practice a real ionization chamber (see above.3%. the overall uncertainty in a measurement of absolute dose under standard conditions may be as high as 2 . for example) is not an ideal Bragg-Gray cavity and corrections must be made for: 1. Differences in the electron energy spectrum compared to calibration conditions.

For example: A P If we measure the dose at P for the smaller field and then increase the field size. We could then calculate the contribution from the segment marked S.Calculation of the dose under non-standard conditions Approach #1 Source r r' P dV Dose ( r ) = Dp ( r ) + ∫ V Ds ( r . the increment in dose to P is due to the annular region marked A in the diagram. r’ ) “Easy” “Difficult” The functions Dp and Ds are derived from dose measurements in phantoms. S .

Any other beam can be considered a summation or superposition of elemental pencil beams. . Approach # 2 Measure or calculate the three dimensional dose distribution due to a “pencil” beam in water.. Each of these pencil beams is weighted to reflect their contribution to the total dose.This allows us to do the integral shown on the previous page. a wedge shaped beam modifier would affect the weight of each pencil beam that passes through it. For example..

Weighted pencil beams We then add all of these appropriately weighted pencil beams together to get the final dose distribution. This process is equivalent to a convolution integral. .