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Ali Fitzpatrick March 3, 2014 Heterogeneity Correction Project

The Comparison of Heterogeneity and Homogeneity in Treatment Planning

Introduction: The human body is comprised of a variety of tissues, including fat, bone, muscle and air. Radiation can interact with these tissues in different ways because they all have different densities.1 In order to create an accurate radiation treatment plan, treatment planning systems are able to account for the different tissue densities that make up the human body. To discover how much of a difference a heterogeneity correction will have upon a patients treatment plan, a test patient computed tomography (CT) series was reconstructed with a tumor in the right lung. One treatment plan was created without correcting for heterogeneity. Then, without changing anything, the same plan was utilized and included a correction for heterogeneity. The goal of this project was to identify the importance of correcting for heterogeneity in order to provide accurate dose coverage of the treatment volume. Methods and Materials: A CT scan was reconstructed from a past patient and labeled a test patient for this project. A CT scan assigns different levels to different attenuation coefficients to represent various structures within the human body.2 A reconstruction algorithm assigns CT numbers which correspond to Hounsfield numbers. These numbers range from -1000 for air, to 1000 for structures comprised of bone. A radiation therapy department typically uses a CT scan to plan from because these Hounsfield units provide quantitative data for tissue heterogeneity corrections. After the CT scan was imported to the Varian Eclipse treatment planning system (TPS), several important structures were contoured including the right and left lung, heart, spinal cord, esophagus, and tumor volume. The main dose constraint was the spinal cord, which has a maximum tolerance dose with a 5 percent (%) risk of occurrence within 5 years (TD 5/5) of 4500 centigray (cGy).3 The heart has a TD 5/5 of 4500 cGy, and the percentage of lung which receives 20 Gy or more of the dose should be restricted to 20% or less in the left lung. Potential complications that could arise from an organ getting a higher dose than these recommended

constraints include infarction or necrosis to the spinal cord, pericarditis or pancarditis to the heart, and acute or chronic pneumonitis to the lung. A plan was created for a tumor that was located slightly midline and towards the posterior volume of the right lung without a correction for heterogeneity. A 0.7 centimeter (cm) margin was placed around the planning tumor volume (PTV) that was created by the radiation oncologist, and a prescription was written for 6600 cGy to be delivered in increments of 200 cGy in 33 fractions. Using the anisotropic analytical algorithm, (AAA) which the Varian Eclipse TPS utilizes when calculating photon treatment plans, a two field plan with beams coming from the anterior (AP) and posterior (PA) directions was created, with both fields using the energy of 23 megavolts (MV). There were no wedges used on the plan, but the weighting was adjusted to compensate for the tumor being located more posterior within the patient. Approximately 58.5% of the dose was delivered from the PA field, while 41.5% of the dose was delivered from the AP field. This plan was then copied, and after making no other changes, a heterogeneity correction was applied to create the second plan. The two plans were then compared with one another. Discussion: There are several studies and resources that are available to evaluate how heterogeneity corrections affect radiation therapy treatment plans. A study conducted by Herman T, Gabrish H, and Herman T, et al4 evaluated heterogeneity corrections in stereotactic body radiation therapy (SBRT) when treating lung tumors in patients. Treatment plans optimized with tissue heterogeneity corrections were prescribed to deliver 6000 cGy in 3 fractions. The same plans were then utilized without heterogeneity corrections. It was discovered that when the plans without heterogeneity corrections were compared to the ones with heterogeneity corrections, the plans without heterogeneity corrections had lower average minimum tumor dose of 13%, a lower average mean tumor dose of 8% and a lower average maximum tumor dose of 6%. These results indicate the importance of using the dosimetric heterogeneity correction while treating with SBRT plans. A study performed by Anneyuko S, Li J and Liu C, et al5 investigated the accuracy of heterogeneity corrections and whether it was necessary to correct for each independent voxel density or if it was sufficient enough to correct for the 5 main densities commonly seen within the human body. These five main densities include air, lung, fat, soft tissue and bone. After comparing the segmented corrections with the full-resolution corrected plans, it was discovered that the segmented corrections were within 3% accuracy of the full-resolution corrected plans.

Correcting for heterogeneity is important in creating accurate treatment plans, even if every tissue for every Hounsfield number is not accounted for. Allowing for a heterogeneity correction factor to be applied for the five major densities can make a big difference in treatment planning and the dose that the treatment volume receives. Results: When observing the treatment plan without a heterogeneity correction, the isodose lines differ greatly from the plan with the correction (Figures 1 and 2). It is important to mention again that all treatment planning factors were kept exactly the same when moving from the plan without the heterogeneity correction to the one with the correction. Looking at the plan without the correction, the isodose lines are only affected by the outer contour of the patient. As the radiation travels through the different tissues of the thorax, it is not affected specifically by the density of the material it transverses, as the plan is assuming that all tissue has a Hounsfield number of zero. The maximum dose to the PTV is 6866 cGy, which is smaller than that of the corrected plan in which the PTV receives a maximum dose of 7143 cGy (Figures 3 and 4). Tissues that have a higher density attenuate the beam more, and because the uncorrected plan assumes that there is no difference in lung tissue from its surrounding tissues, this result is expected. Looking at the monitor units (MU) that are coming from each field also show that the plan without the heterogeneity correction delivers 109 MU from the AP direction, while the plan with the correction only needs to deliver 101 MU (Figures 5 and 6). Differences in densities of tissues will shift isodose lines.6 Air will attenuate the radiation beam less so that there will be a higher dose at the distal end of the lung where tissue resumes. In situations where bone is included in the field, there is more attenuation of the beam. Looking at the plan that does correct for heterogeneity, one can observe that the isodose lines are shifted more laterally, because the radiation beams transverse lung. The lung tissue does not attenuate the beam as much as soft tissue would. Medially one can see that the isodose lines dont change as much, because tissue from the heart will attenuate some of the radiation. In order to make the uncorrected plan look similar to the corrected plan, the use of wedges would be necessary. The heels of the wedges would need to be medial, to pull dose towards the lateral portion of the right lung. Although this would not create the most ideal plan, it would mimic what is shown in the plan which exhibits the heterogeneity correction. Conversely, if one wanted to make the corrected plan look more like the uncorrected plan, the

heels of the wedges would need to be placed laterally, towards the right of the patient. This would draw the isodose lines more medially to provide better coverage to the PTV. Conclusion: Upon the completion of this project, it can be seen that correcting for heterogeneity for a radiation treatment plan can have a large impact on the dose that the treatment volume receives. In the case of this lung example, it is important to correct for the amount of air that the radiation will travel though. In different cases where the radiation beam will transverse through a higher density material like bone, it is also important to correct for the amount of attenuation that will take place. Although one may be able to create a plan that theoretically looks good without correcting for heterogeneity, it is important to realize that an accurate dose description may not be attainable. A few exceptions to the benefits of heterogeneity apply if a patient has a metal prosthesis or other artificial densities in the treatment field. In this example, it is necessary to turn heterogeneity off in a plan so the planning system does not mistake artifact for air. Planning without a heterogeneity correction could be beneficial because there is no way of knowing what the density of the metal is. CT values are dependent on individual CT scanners, but CT values used may vary for different treatment planning systems or dose calculation algorithms.7 One limitation of the AAA that Varian Eclipse uses is that the Hounsfield units only extend from 1000 to approximately 3070. However, the density of a metal prosthesis could possibly extend to a greater density than 3070. The TPS will create a plan that is as accurate as possible, but there is no way of knowing what dose the patient will actually receive. Excluding the few exceptions, correcting for heterogeneity can create a more accurate dose distribution in radiation therapy planning. The human body consists of a variety of tissues that the radiation travels through and it is important to realize how the material will attenuate or scatter the radiation as it enters the medium. Overall, density changes within the radiation field will affect the isodose lines of a treatment plan, and creating the most optimal plan for a patient to receive the intended therapeutic benefit requires corrections for these densities.

Figures

Figure 1: Isodose lines in plan without heterogeneity correction.

Figure 2: Isodose lines in plan with heterogeneity correction.

PTV

GTV

Right Lung

Heart

Cord

Left Lung

Figure 3: Dose Volume Histogram for plan without heterogeneity correction.

PTV

GTV

Right Lung

Heart

Cord

Left Lung

Figure 4: Dose Volume Histogram for plan with heterogeneity correction.

Figure 5: Monitor unit calculation for plan without heterogeneity.

Figure 6: Monitor unit calculation for plan with heterogeneity.

References 1. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 3rd ed. Mosby, Inc; 2010. 2. Khan FM. The Physics of Radiation Therapy. 4th ed. Philadelphia Lippencott Williams & Wilkins; 2010. 3. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Journal of Radiation Oncology Biophysics. 1991(21);109-122. 4. Herman T, Gabrish H, Herman t, Vlachaki M, Ahmad S. Impact of tissue heterogeneity corrections in stereotactic body radiation therapy treatment plans for lung cancer. Journal of Medical Physics. July 2010;35(3):170-173. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936187/. 5. Saito AI, Li JG, Liu C, Olivier KR, Dempsey JF. Accurate heterogeneous dose calculation for lung cancer patients without high-resolution CT densities. Journal of Applied Clinical Medical Physics.2009; 10(2). Retrieved from http://www.jacmp.org/index.php/jacmp/article/view/2847/1586. 6. Bentel C. Radiation Therapy Planning. 2nd ed. The McGraw-Hill Companies; 1996. 7. Saw C, Loper A, Komanduri K, Combine T, Huq S, Scicutella C. Determinitation of CTto-density conversion relationship for image-based treatment planning systems. Medical Dosimetry. 2005; 30(3):125-128. Retrieved from http://bscw.rediris.es/pub/bscw.cgi/d864947/Determination_of_CT-todensity_conversion_relationship_for_image-based_treatment_planning_systems.pdf.