DOS 523 Treatment Planning Heterogeneity factor project Susan Hunt

The process of using radiation to treat cancer has been in use for about 110 years. As our knowledge of radiation physics and radiobiology has evolved, radiation treatment planning has improved immensely. Understanding where we came from will help to understand how things are done today. Many things must be taken into account when planning radiation treatment for any particular patient. The size and shape of the field to be treated, the area of the body and the reproducibility of the setup are all important factors to consider. Since radiation beams are calibrated using a tissue phantom (which has a homogenous density equal to that of water), we must correct for the fact that patients are not made up of water alone. Patients are made of fat, bone, muscle and air. All these different types of tissue scatter and attenuate the beam differently than water does.1 Additionally, all these different types of tissue act differently depending on the energy of the beam. The distribution of energy into the tissue will vary in two important ways. First, the primary beam will be absorbed differently and will scatter differently in different types of tissue. Second, the secondary electron fluence will vary as well.2 As radiation therapy has evolved over the years, increased beam energy has emerged. The higher the energy of the radiation beam, the better its penetrating power, so we can now treat cancers deep inside the body. Whereas x-rays used for imaging are radiation beams in the kilovoltage range, radiation beams used for radiation therapy are in a higher energy range (megavoltage vs kilovoltage). In this higher energy range, the most prevalent interaction of the beam with the irradiated tissue is the Compton interaction. In Compton interactions, the photon (created in the x-ray machine) has enough energy to bump an electron from its orbit around the atoms in the tissue that is being irradiated. This is the primary interaction. During this process, most of the photons energy is transferred to the bumped electron and some is retained by the original photon, which is then scattered into another direction. Then both the electron and the photon can interact with other atoms in the surrounding tissue in secondary reactions.3 The chance of a Compton reaction occurring depends on how many electrons are available to interact with. Obviously, the more electrons are available, the greater the likelihood of an interaction

2 occuring. The number of electrons available in any given tissue is called the electron density of that tissue. This number varies with different tissue types. Since hydrogen has an electron density much higher than other elements (because it contains no neutrons), tissue with high hydrogen levels will have a better chance of Compton interactions occurring when that tissue is radiated. Fat is the tissue within humans that contains the most hydrogen and thus has the highest electron density.3 Physical density is a different matter altogether. We know that hard bone is the human tissue with the highest physical density and as such, hard bone attenuates the radiation beam more than other types of tissue. Air has the lowest density and as such, it attenuates the beam very little. So how do we account for the different tissue types when we are planning a radiation therapy treatment? In the early days of radiation therapy, dose was not actually calculated. When the skin reddened, it was assumed that the necessary dose had been reached. As methods improved, it became possible to calculate the dose the tissue was receiving these calculations were done by hand. Eventually, as computers were developed, the calculations could become more accurate by using mathematical algorithms and by storing large quantities of data to draw from. By the late 1960s, the first computerized treatment planning systems (TPSs) were available. They were crude compared to todays TPSs, but they were a huge leap from the days of hand calculations.4 With the advent of Computed Tomography (CT) scanning, determining the relative electron density of a given tissue has become much easier. CT imaging breaks up the 3 dimensional patient into small, thin slices running in the transverse imaging plane. Each slice is then broken up into hundreds of tiny blocks called pixels. It measures the linear attenuation coefficient of each pixel in the image and assigns it a number, called the Hounsfield Unit (HU). Human tissue ranges from -1000 HU for air to +1000 HU for hard bone. Since the linear attenuation coefficient is a function of both the electron density and the atomic number, we can use the HU assigned to a specific pixel to extrapolate the electron density of that pixel.4 Now that we can determine the electron densities of the various tissues we are irradiating, we can use that information when calculating the dose through a heterogeneous patient. There are different methods used to correct for tissue heterogeneities. One is the tissue-air ratio method, which takes into account the field size and depth but does not account for other factors involved.

3 Another method is the power law tissue-air ratio, which does a slightly better job of accounting for all the factors involved, but which still has its limitations. Another factor to consider is the fact that dose builds up or down in the regions where low density tissue (such as lung) interfaces with more dense tissue such as muscle.5 All modern treatment planning systems have some sort of algorithm designed to compensate for tissue heterogeneities. Some of these algorithms are correction-based and others are modelbased, but both types recognize that in certain areas of the body (like the lung), differences in dose of up to 30 percent may occur in the tissue surrounding these areas.4 For this project, I created two treatment plans on Geisingers Pinnacle Treatment Planning System. Both plans treat a tumor centrally located in the right lung. I used the Hot Script created by the medical physicist to contour the heart, each lung, spinal cord, body and the Gross Tumor Volume (GTV). I then added a 1.5 cm margin around the GTV to obtain the Planned Target Volume (PTV). Both plans should deliver 200 cGy per fraction to the GTV. Plan 1 used the heterogeneity factor to calculate the dose distribution and Plan 2 assumed the tissue being irradiated was homogeneous. In Figure 1, you can see the dose distribution for Plan 1, using the heterogeneity factor. The GTV is contoured in pale green and the blue contour shows a 1.5 cm margin around the tumor. The GTV is completely encased in the 98% isodose line and the 100% isodose line just skims the lateral edge. A very small volume of the heart is within the 20% isodose line. Additionally, the hottest areas in the tissue anterior and posterior to the lungs is receiving 105% of the prescribed dose. In Plan 2, the 100% isodose line cuts right through the center of the GTV and the 98% isodose line skims just inside the medial edge of the PTV. Additionally, the hot spots anterior and posterior to the lungs are now at 109% of the prescribed dose. In fact, the entire plan is hotter. Figure 3 shows the isodose curves for both plans side-byside for comparison. If you look at the Dose Volume Histograms (DVHs) for both plans (Figures 4 and 5), you will see that the GTV receives more dose in Plan 1 (using the heterogeneity factor algorithm to account for heterogeneity) than in Plan 2, while the dose to the critical structures (like the heart) is slightly less in Plan 1. Since the goal of Radiation Therapy is to deliver the highest possible dose to the tumor while keeping dose to the surrounding healthy tissue as low as possible, Plan 1

4 could be considered the better plan. Similarly, comparing the Monitor Unit (MU) Calculation sheets for both plans (Figures 6 and 7) shows that the isodose (and, in turn, the actual dose) at the calculation point is higher for Plan 1 than for Plan 2. The dose per monitor unit in Plan 1 is also higher than for Plan 2 so Plan 1 gives you more bang for your buck. Since the actual MUs are less for Plan 1 than for Plan 2, it will take less time to deliver the treatment using Plan 1. Deducing from all this data, using the heterogeneity correction factor when planning in certain tissue (especially the lung) can result in a more homogeneous dose.

Figure 1 Plan 1 isodose lines

Figure 2 Plan 2 isodose lines

Figure 3 side-by-side comparison of Plan 1 and Plan 2 isodose lines

Figure 4 Dose-Volume Histogram for Plan 1

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Figure 5 Dose- Volume Histogram for Plan 2

Figure 6 MU Calculations for Plan 1

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Figure 6 page 2

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Figure 7 MU Calculations for Plan 2

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Figure 7 page 2

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References: 1. Washington CM and Leaver D. Principles and Practices of Radiation Therapy 3rd edition. St. Louis, MO: Mosby Elsevier; 2010. 2. Khan FM. The Physics of Radiation Therapy 4th edition. Philadelphia, PA: Lippencott Williams & Wilkins; 2010. 3. Hendee WR, Ibbott, GS and Hendee, EG. Radiation Therapy Physics 3rd edition. Hoboken, NJ: John Wiley & Sons, Inc; 2005. 4. Khan FM and Gerbi BJ. Treatment Planning in Radiation Oncology 3rd edition. Philadelphia, PA: Lippencott Williams & Wilkins; 2012. 5. Bentel GC. Radiation Therapy Planning 2nd edition. New York, NY: McGraw-Hill; 1996.