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Megan Whitley Heterogeneity Project March 5, 2013 Heterogeneity Project When radiation was first used for cancer treatment, the research had not yet been done to determine tissue densities impact on treatment. Once computed tomography (CT) became standard of care the influences of these densities became clear. Nevertheless, the field of radiation oncology developed without the data provided by CTs. Within this timeframe, many charts, concepts, protocols and standards were devised, that are still in place today. Many of our algorithms and treatment planning software (TPS) still utilize these older data sets, and they are also used for performing hand calculations. The problem with the data collected before advent of CT simulation is that it assumes that all tissues within the patient have a uniform density, that they are homogenous.1 Thus, the data on which most treatment decisions are based, depends on dose calculations in which inhomogeneity corrections were not made.2 As we now know, this is inaccurate, and many protocols today are fighting to remedy this by collecting new information and reconstructing these data sets for use in calculations. But, until this time, extra strides are required to ensure that the most accurate treatment regimen is planned. To compensate for the different tissue densities within the body, a correction factor was developed and implemented. This factor, as mentioned earlier from Bentel, is known as an inhomogeneity correction. The reason this correction is vital is because radiation travels through tissues of different densities in different ways. In lung tissue, theres less tissue to attenuate the radiation, therefore less energy is required for penetration. The opposite is true in bone, with the increased density of bone requiring more energy for adequate penetration. And, at the interfaces between lesser and greater densities, for example the interface of the soft tissue of the breast, abutting more dense rib, coupled with the less dense lung, the necessity for a correction factor truly becomes apparent. So, from the CT scan, to compensate for these differences, a number is assigned to the different densities, a Hounsfield Unit (HU). Hounsfield Units assigned to tissue are ranked from +1000, which would represent dense bone, to -1000, for air, while water is 0.3 If there are varying degrees of differentiation within the tissue densities, the area is known as

heterogeneous. If the densities are similar, the tissues are homogenous. So, now knowing what defines these tissue differences, we need to establish what defines their impact. To compensate for the influence of heterogeneity on treatment, the correction factor must be obtained. The correction equates to the dose calculated in a heterogeneous medium being divided by the dose calculated at the same point in a homogeneous medium. Again, the reason that compensating for these differences in densities is due to their influence on radiation. When radiation enters the body, tissues impede its travel. When compensation is not made, the planning process not only becomes easier, but less accurate. If a correction was not used in planning, the beams would simply create boxes of dose, centered within the transection of the beams. As in, a 3 field plan would have a 3 field box, and a 4 field plan, a 4 field box.

Figure 1. Volumetric comparison between two plans, the one on the left has the heterogeneity corrections on, and the one on the right is planned without the corrections. Take Figure 1 for example; in the plan on the right, the dose simply distributes into a shape of relatively uniform dose. The only things shaping the dose are the multileaf collimators (MLCs), the wedges, the weighting, and the sloping of the skin. But, in the plan on the left, the

corrections have been turned on, compensating for the different densities of soft tissue and lung, thus impacting the fluence of the dose, and making the impact of these tissues visible.

Figure 2. Single slice comparison of the isodose lines through the same isocenter within the same plan, except the left plan has the heterogeneity corrections on. As in Figure 2, the plan on the right side depicts a treatment regimen that would be expected from a plan generated for a homogenous attenuation region, and it represents a plan that is not struggling to accomplish goals. On the other hand, the plan on the left accurately portrays

the typical difficulty met when planning a lung. It is very difficult to accurately get radiation to a tumor within the lung, and oftentimes, the anterior and posterior chest walls, and the scapula, receive very high doses. This region of high dose is known as a hot spot, and it represents the buildup region of dose brought on by the lack of attenuation from lung that increases dose within and beyond the lung. As is shown in the upper right hand of the screen shots, the plan without the corrections used is cooler, at 110% hot, and the plan that includes the corrections has a hot area of 114%. Unfortunately, this is both accurate and unavoidable. If these accuracies arent obtained, the true dose distributions are unchecked and unaccounted for, causing great potential for areas of overdose and underdose. The differences are clear as we can see from Figure 2.

The inhomogeneity correction factor was introduced at a time when many radiation oncologists had a great deal of practice, and they were not used to seeing these new areas of concern and the increased complications within the plans. As is logical, this new correction was not received well. So, for a while, doctors chose not to use this factor. In the lung for example, areas can be seen where the isodose lines fall apart and regions of both under and overdose occur. Also, to obtain proper penetration, a decrease in monitor units (MU) can be seen, and optimal outcomes in treatment planning are much more difficult to achieve. For this, they blamed the factor. Although some physicians still make the choice not to use it today, now physicians are taught to use the inhomogeneity correction while in school, and come into the field with experience viewing plans with these characteristics. Such differences in MU can be seen in Figures 3 and 4.

Figure 3. This is the beam data report generated from the plan with the inhomogeneity correction factor.

Figure 4. This is the beam data report generated from the plan without the inhomogeneity correction factor. Heterogeneity correction is evident when viewing differences in the monitor units required in each plan. The MLCs for both plans were designed from a margin of 1.5 centimeters around the tumor volume. There are two fields, both an anterior-posterior (AP) and a posterior-

anterior (PA). The weighting was placed as 60% on the AP field and 40% on the PA field. The same wedge was used on each field, a 15 wedge with the heel placed superiorly. The beam data in Figure 3, for the plan with corrections on, demonstrates the MU for field A at 186, and for field B at 146. The beam data in Figure 4, for the plan with corrections off, demonstrates the MU for field A at 200, and for field B at 174. These differences reflect that lung tissue provides less attenuation than bone or soft tissue. Without the corrections, the algorithm assumed the lung was actually soft tissue. This difference in tissue requires less MU for accurate penetration, rendering the homogenous plan with concerns for overdose. Herein resides the need for both remedying the outdated data sets and tables, and furthering implementation of the inhomogeneity correction factor. This figure comparison demonstrates the differences in the plans with and without the corrections, in regards to their impacts on the target and organs at risk. A dose volume histogram, or DVH, is the ideal mechanism in which to illustrate these differences. This DVH has two lines. The one with squares illustrates the plan that utilizes the inhomogeneity correction factor, and the line with triangles illustrates the plan without the correction. If the line on the DVH illustrated with squares is analyzed, it shows that the target is not covered as well as the triangle line. The healthy structures are also receiving more dose with the corrections on. As stated before, corrections may not make a task easier, but, the plan is more accurate. And, after all, accuracy is the back bone and mainstay of cancer treatment.

Figure 5. This is a comparative DVH that represents the dosages to both the target and the organs at risk in both plans, and allows for a simple, visual comparison. The last 2 figures show the more complete overviews of the difference in the final products of the plans. Figure 6 demonstrates the dose at isocenter in a coronal, sagittal, and axial view. It also includes a DVH with only the plan with corrections. Then, for comparison, the same illustration is used for the plan without corrections in Figure 7.

Figure 6. Multi plane views of a plan created with the inhomogeneity corrections.

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Figure 7. Multi plane views of a plan created without the inhomogeneity corrections. These treatment plans were generated using Varians Eclipse TPS with the convolution/superposition algorithm. Convolution/superposition is one of the semiempirical algorithms used today, collectively named correction-based algorithms.4 The name correctionbased algorithms reflects the impact that the inhomogeneity correction factor has had on

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treatment planning and radiation oncology. In fact, within Eclipse there are means to turn the correction factor off, but no one in the department knew how, exemplifying how stringently the factor is used in modern day treatment planning. Without this factor, both under and over dosing may occur, leaving some areas too damaged, and some with a higher incidence of recurrence. With continued use of the factor, and the research to recreate widely used data sets, the future of both dosimetry and cancer treatment look to be more accurate, beneficial, and complete.

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References 1. Hendee WR, Ibbott GS, Hendee EG. Radiation Therapy Physics. 3rd ed. Hoboken, NJ: John Wiley & Sons; 2005:250. 2. Bentel GC. Radiation therapy planning. 2nd ed. Colombia: Macmillan Publishing Company; 1992:99. 3. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis, MO: Mosby-Elsevier; 2010: 435. 4. Khan F, Gibbons J, Mihailidis D, Alkhatib H. Khans Lectures: Handbook of the Physics of Radiation Therapy. Baltimore, MD: Lippincott Williams & Wilkins; 2011: 184.