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Ashley Pyfferoen Treatment Planning Paper March 24, 2013 Heterogeneity Correction Factor in Treatment Planning The progression and evolution of cancer treatment has allowed significant advancements in the field of radiation therapy. Prior to the introduction of sophisticated treatment planning computers, radiation therapy treatment plans were unreliable and tedious. Patient contours were obtained using inconsistent methods of patient tracing or lead wire measurements.1 Dosimetry required accurate manual manipulation of isodose charts and an extensive knowledge on how to wedge and weight beams properly.1 The inability to account for exact tumor and critical structure locations were among some of the major downfalls of treatment planning before the development of computed tomography (CT) in the 1970s. Together with improved imaging and image based treatment planning, the ability to treat patients safely and accurately dramatically improved. Treatment planning algorithms are now able to deliver sufficient dose to one area while minimizing dose to another. They also have the ability to minimize doses that are higher than prescription using accessory components and compute dosages within seconds. However, one area in need of continued improvement is the ability for the planning computer to account for heterogeneity within the patient. Customary isodose charts show dose distribution with the assumption that all tissues within the patient have an equivalent density of soft tissue.2 Considering the human body is composed of lung tissue, bone and fat in addition to soft tissue can make the treatment of some cancers difficult.3 When a beam of radiation passes through these materials, there can be a pronounced effect on beam attenuation and scatter. These effects are most predominantly seen with bone and lung tissues. The attenuation effects are greatest when the beam traverses bone. Because bone has a greater density then soft tissue, the beam is substantially attenuated making points beyond bone underdosed. If the beam traverses lung tissue before reaching the target, scattering electrons become a concern. While lung tissue is less dense then soft tissue, it is difficult to keep electrons traveling on the central axis to the target through the air cavity. In the early days of treatment computers, it was difficult to account for these effects accurately. Since then, treatment planning developers have established correction factors that aid in patient treatment.

To correct for tissue inhomogeneities, significant information is required including the electron density of the inhomogeneity and the location, size and shape of the inhomogeneity.2 With this information treatment planning physicists developed the tissue-air ratio, the power law tissue-air ratio, the equivalent tissue-air ratio and the isodose shift method.3 Each method has benefits and disadvantages, but all take into account inhomogeneity to some extent. Developers have successfully incorporated this technology into treatment planning computers. To better understand inhomogeneity effects, a demonstration of this principle was conducted on a patient with a lung tumor. This patient presented with a non-small cell lung tumor located on the posterior lung wall of the right lung. To appreciate the differences in patient composition, 2 plans were constructed. In the first plan, the computer was not accounting for inhomogeneity differences. The second plan demonstrated the more realistic approach of inhomogeneity corrections. As an accurate plan comparison; tumor margins, beam arrangements and wedge incorporation were consistent. Figure 1 demonstrates the plan in which inhomogeneities were not corrected for. This plan consisted of 2 beams located anterior/posterior (AP) and posterior/anterior (PA). The red isodose line is representative of 6600 centigray (cGy) or 100% of the dose and covers a majority of the tumor volume. The dose is fairly conformal extending from the outer lung wall to the tumor while sparing dose in the mediastinum. As demonstrated by the green isodose line, there are portions of anterior lung cavity and posterior muscles receiving doses 5% higher than the prescription. To help alleviate some of this dose, a wedge was added.

Figure 1. Axial, sagittal and coronal views depicting isodose line distribution throughout the lung volume without the incorporation of heterogeneity corrections.

Figure 2 demonstrates the plan where heterogeneity corrections were used. While all other factors remained consistent, this plan varies considerably with the homogeneity plan. The tumor volume is considerably underdosed since the red isodose line (100%), does not provide a consistent distribution of adequate dose. While there are still areas receiving 5% higher dose then prescribed, they are only located posteriorly on this plan.

Figure 2. Axial, sagittal and coronal views depicting isodose line distribution throughout the lung volume with the incorporation of heterogeneity corrections. Both Figures 1 and 2 provide an excellent qualitative analysis of how heterogeneity corrections effect the dose distribution. To further the interpretation of these results, a comparison of the dose volume histograms (DVH) associated with each of the plans is helpful. Figures 3 and 4 represent the DVHs for the homogeneity plan and inhomogeneity plan, respectfully. In the homogeneity plan, the mean volume of the PTV is indicated as 6846cGy. In comparison, the PTV only receives a mean volume of 6749cGy in the heterogeneity plan. Data interpolation revealed that on the homogeneity plan, approximately 96% of the PTV was receiving 100% of the dose. Alternatively, the heterogeneity plan was only delivering 100% of the dose to 92% of the PTV. After additional research, a source indicated that for non-small cell lung cancer, 95% should cover the tumor volume.4 This specifies that while accounting for inhomogeneities appropriately, the tumor volume would be underdosed. Figures 3 and 4 also indicate that dosages to all other critical structures decreased when accounting for dose inhomogeneity.

Figure 3. Dose volume histogram indicating dosage to each of the critical structures for the homogeneity plan.

Figure 4. Dose volume histogram indicating dosage to each of the critical structures for the inhomogeneity plan. Figures 5-8 represent the monitor unit (MU) calculation page derived for each beam on each of the treatment plans. This documentation includes quantitative measurements used to ensure that each beam is delivering the accurate amount of dose to the appropriate depth. These pages also verify the density correction used for the corresponding treatment trial.

Figure 5. MU calculation document for the AP beam on the homogeneity treatment plan.

Figure 6. MU calculation document for the PA beam on the homogeneity treatment plan.

Figure 7. MU calculation document for AP beam on the heterogeneity treatment plan.

Figure 8. MU calculation document for the PA beam on the heterogeneity treatment plan. This exercise is a principal example of how different radiation treatment plans can look if the appropriate corrections factors are not made. The computer was able to attain a conformal uniform dose in the homogenous plan because the density was assumed to be that of soft tissue consistently. The biggest obstacle to overcome was the patient separation which could easily be taken care of with the appropriate beam weight ratio. The addition of the wedge was also able to even out the dose distribution to obtain a suitable treatment plan. Achieving a uniform dose for the heterogeneous plan proved to be more difficult with the incorporation of the correction factor. As the anterior beam traverses through lung tissue, there is a loss of secondary electron build-up.3 This explains why the anterior portion of the tumor is receiving inadequate dose. The PA beam didnt have difficulty delivering appropriate dose to the tumor considering the placement of the tumor so posterior in the lung. In addition, literature suggests that loss of lateral electronic equilibrium also attributes to the low dosage in the PTV.3 As the beam traverses lung tissue, electrons scatter liberally outside of the beam path.3 Therefore, the beam loses electrons at a faster rate than when traveling through a higher density material such as soft tissue. Because

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the tumor is located so far posteriorly, the AP beam loses significant electrons needed to deliver adequate dose to the anterior part of the PTV. While it is difficult to obtain the same dose uniformity in the heterogeneous plan as the homogenous plan, it is possible to improve the dose received by the tumor. Firstly, by adding more beams at different angles, dose uniformity will improve to the target area. Also, adding wedges on multiple beams can improve dose distribution and decrease areas that are hotter than the prescription dose. Overall, dose uniformity is difficult with the use of 3-dimentional (3D) treatment plans such as the one used in this example. To achieve the best dose uniformity, facilities often use Intensity Modulated Radiation Therapy (IMRT), to achieve good dose coverage while limiting dose to critical structures. While the homogenous plan created a suitable dose distribution around the tumor volume, the conformity is unrealistic because the computer is ignoring the substantial density differences between soft tissue and lung tissue. Regardless if the treatment planning computer ignores the difference in lung density, it is still present. Therefore, it should be accounted for so the plan is an accurate representation of the actual patient contour. Irrespective of how the plan looks on a computer, accuracy is only as good as the ability to implement it.

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References 1. Evans, M. Computerized treatment planning systems for external photon beam radiotherapy. In: Evans, M. Review of Radiation Oncology Physics: A Handbook for Teachers and Students. Vienna, Austria: IAEA; 2005:317-334. 2. Bentel, G. Radiation Therapy Planning. 2nd ed. Columbia: McGraw-Hill; 1996:100-101. 3. Khan, F. The Physics of Radiation Therapy. 4th ed. Baltimore, MD: Lippincott, Williams, and Wilkins; 2010: 220-229. 4. Wang L, Feigenberg S, Fan, J et al. Target repositional accuracy and PTV margin verification using three-dimensional cone-beam computed tomography (CBCT) in stereotactic body radiotherapy (SBRT) of lung cancers. J Appl Clin Med Phys. 2012; 13(2). doi:10.1120/jacmp.v13i2.3708