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Amanuel Negussie DOS 423 Heterogeneity Project March 2013 Heterogeneity Correction in Non-Small Cell Lung Cancer Treatment Objective: The objective of this project is to conduct a lung treatment plan with and without heterogeneity correction and evaluate the difference. Purpose: Human anatomy is made of different tissues that have their own unique physical and radiological property. Interaction of tissues with radiation can result in complete absorption, partial absorption, scatter, and transmission. The attenuation of a photon beam in a tissue varies depending on the energy of the photon, the density of the tissue, and the effective atomic number of the tissue.1 In radiation therapy, it is essential to know and understand these factors as they affect the accuracy of the dose delivered to the target. Tissues including lung, oral cavities, teeth, nasal passages, soft tissues, and bones have different radiation absorption factor that can disrupt the amount of dose planned to reach the target. Traditionally, lung tumors were treated assuming the density of all tissues being equivalent to water. Previous radiation oncology task group (RTOG) protocols also supported this technique. This was established due to the limitation of treatment planning systems (TPS); the lack of evidences that supports the need for density correction; and to avoid calculation errors and underdosing of tumors when accounting heterogeneity corrections.2 However, due to the advancement of TPS, the application of heterogeneity correction in dose calculations became more practical. Currently, both RTOGs and American Association of Physics in Medicine (AAPMs) protocols recommend using heterogeneity correction for treatment planning and dose prescriptions.1,3 Since lung is surrounded by ribs, soft tissues, and air cavities, it can greatly be affected by heterogeneity correction. The effect of tissue inhomogeneity is mainly due to the change in absorption of primary or scattered photon beams and the change in secondary electron fluence.4 Consequently, it is difficult to assume accurate dose calculation of lung treatment plans without accounting tissue density variations. Undermining tissue inhomogeneity will create dose buildup at the distal interfaces and dose builddown at the proximal interface of the lung.5 Some studies have shown that heterogeneity corrections in lung treatment plans will increase the dose to

isocenter by 6-18% more than those calculated without correction.6 The dose reaching the target is also lower for high energy photon beams planned without heterogeneity correction.6 In addition, when corrections are applied, the dose to target will be less than prescribed. Therefore, it is necessary to increase the prescribed dose when using heterogeneity corrections in order to maintain the same dose within the planned target volume (PTV).2 Methods and Materials: RL is a 62-year-old man who presented with a stage III-A non-small cell lung cancer (NSCLC) was simulated in a supine position on a wingbord. A Philips large bore 16 slice computed tomography (CT) machine was used for the simulation, and a Pinnacle3 9.0 treatment planning system (TPS) was used to plan the treatment. The treatment was prescribed to 5040 centigray (cGy) at 180cGy per fraction to the 96% isodose line. Gross tumor volume (GTV), PTV, right lung, left lung, heart, and spinal cord were contoured. A two field anterior/posterior (AP) and posterior/anterior (PA) beam arrangement was used. The collimator and table angle were set at 0o for both fields. A 1.5 centimeter (cm) margin around the PTV was used to shape the treatment field with multileaf collimators (MLC). An enhanced dynamic wedge of 15o was used on the AP field to account for the curvature of the thorax and maintain dose uniformity across PTV. A mixed energy of 6 megavolt (MV) and 18 MV was used on both AP and PA fields for a better dose coverage with minimal maximum dose. Although the use of higher energy photon beams in lung treatment planning is controversial, RTOG 617 protocol recommends 6-18 MV energy for NSCLC. A beam weighting of 20% for the 6MV AP field, 12% for the 18 MV AP field, 53% for the 6MV PA field, and 15% for the 18 MV PA field was applied. The primary trial was planned without heterogeneity correction. It was completed with a total monitor unit (MU) of 280, a maximum dose of 5692cGy, and a hot spot of 12% located posteriorly. The dose to each organ at risk (OR) was below the RTOG recommended tolerance limit. The plan met all the guidelines and requirements of RTOG 617 protocol. A first trial was copied and recalculated using heterogeneity correction without any additional change to the plan. The second trial was completed with a total MU of 261, a maximum dose of 6300cGy, and a hot spot of 25% located posteriorly. Results: Figure 1 a, b, and c demonstrate the sagittal, axial, and coronal view of the AP/PA lung plan dose distribution, dose volume histogram (DVH), and MuCheck calculation sheet for the trial calculated without heterogeneity correction. Figure 2 a, b, and c demonstrate the sagittal, axial, and coronal view of the AP/PA lung plan dose distribution, DVH, and MuCheck

calculation sheet for the trial calculated with heterogeneity correction. Figure 3a demonstrates the DVH comparison of the two trials. Figure 1a: The sagittal, axial, and coronal view of dose distribution to the plan without heterogeneity correction

Figure 1b: DVH of the plan without heterogeneity correction

Figure 1c: MU dose calculation for the plan without heterogeneity

Figure 2a: The sagittal, axial, and coronal view of dose distribution to the plan with heterogeneity correction

Figure 2b: DVH of the plan with heterogeneity correction

Figure 2c: MU dose calculation for the plan with heterogeneity correction

Figure 3a: DVH comparison of the plans with and without heterogeneity correction. The solid lines represent the plan with heterogeneity correction, and the dashed lines represent the plan without heterogeneity correction.

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Discussion: The two trials have evident differences in their MU, PTV coverage, and maximum dose. When calculated with heterogeneity correction, the second trials maximum dose increased by 648cGy. Although the location remained the same, the hotspot increased by 13%. On the other hand, the MU of the AP field with the homogeneity plan increased by 15% for the 6MV and 10% for the 18 MV photon beam. The MU calculation demonstrated a -5.5% difference for the 6MV and 6.32% difference for the 18 MV AP fields (Figure 1c and 2c). This is over my clinical sites tolerance limit, which is +/- 3% difference. In addition, the PTV coverage by the 100% isodose line appeared more adequate in the plan calculated without heterogeneity correction (Figure 1a and 1c). Whereas, dose uniformity in the lung appeared worse when the distributions were corrected for inhomogeneity (Figure 2a and 2c). The dose to OR were also lower in the plan with heterogeneity correction than without (Figure 3a).This is due to the differences in absorption and scatter of the photon beam as it passes through different tissues. Since the target is located at the posterior edge of the lung, the AP beam has to penetrate more tissues than the PA beam. When heterogeneity correction is applied, the MU increased for the AP fields so that the same desired dose can be delivered to the target. Heterogeneity correction increases with lower energy beams.1 This was demonstrated in the two trials as the MU increased by 20% for the 6MV and 13% for the 18 MV AP field (Figure 1c and 2c). Lower energy beams cannot travel far into tissues compared to high-energy beams. Accordingly, the AP 6MV beam will lose more energy than the 18MV beam as it passes through tissues to reach the target. As a result, when calculated with heterogeneity correction, the change in MU for the 6MV will be higher than the 18 MV. Conclusion: Dose determination using heterogeneity correction is an essential component of dose optimization which allows us develop a reliable treatment plan. The two plans calculated with and without heterogeneity correction demonstrated that different density tissues that lie in the path of a photon beam affect dose distribution to target volumes. Heterogeneity correction simply accounts the density differences between air spaces, lung tissues, bone minerals, and soft tissues. Generally, tissue heterogeneity in a lung depends on the lung density, the lung length traversed, beam energy, and beam field size. When a correction is applied, the dose distribution will be distorted due to tissue inhomogeneity. This will not just affect the dose to the PTV but also to OR.

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References 1. AAPM Report No. 85. Tissue Inhomogeneity Corrections for Megavoltage Photon Beams. College Park, MD. 2004. 2. Frank SJ, Forster KM, Stevens CW, et al. Treatment planning for lung cancer: traditional heterogeneous point-dose prescription compared with heterogeneity-corrected dosevolume prescription. Int J Radiation Oncology Biol Phys.2003; 56(5): 1308-1318. 3. RTOG 0617. A Randomized Phase III Comparison of Standard dose (60Gy) Versus Highdose (74 Gy) Conformal Radiotherapy with Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients with Stage IIIA/IIIB Non-Small Cell Lung Cancer. 2012. 4. Khan F. The Physics of Radiation Therapy. 4th ed. Baltimore, MD: Lippincott, Williams, and Wilkins; 2010: 220-229. 5. Bentel GC. Radiation Therapy Planning. 2nd ed. New York, NY: McGraw-Hill; 1996:100-101. 6. Orton CG, Chungbin S, Klein E, et al. Study of lung density corrections in a clinical trial (RTOG 88-08). Int J Radiation Oncology Biol Phys.1998; 41(4): 787-794.