The Effects of DIBH on Liver Dose during Right-Breast Treatments: A Case Study Abstract: Introduction: Case Description: Conclusion: Introduction

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1 1 The Effects of DIBH on Liver Dose during Right-Breast Treatments: A Case Study Megan E. Sullivan, B.S., R.T.(T)., Patrick A. Melby, B.S. Ashley Hunzeker, M.S., CMD, Nishele Lenards, M.S., CMD, R.T. (R)(T), FAAMD Medical Dosimetry Program at the University of Wisconsin - La Crosse, WI Abstract: Introduction: Right-sided breast cancer procedures may not incorporate gating techniques because of the extra set-up complications. This study aims to evaluate the effects of deep inspiration breath hold (DIBH) on the dose received by the liver. Case Description: Seven, right-sided breast patients were retrospectively evaluated for dose to the liver. These patients had both DIBH and free-breathing (FB) gated scans taken before treatment. Plans were created for both scans and were evaluated for volume within the field, maximum dose, mean dose, and the volume of liver irradiated at specific dose levels (V n ). Conclusion: The use of a DIBH gated scan reduced the volume of liver being treated during right-sided breast treatments. The average volume in the FB scans was 39.7 cc and the DIBH scans reduced the irradiated volume to 3.9 cc. Deep inspiration breath holds showed benefits to the liver for all patients within this study. This included lower maximum and mean doses along with reducing the amount of liver exposed to 5, 10, 20, and 30 Gy. Introduction Radiation therapy has been used to treat breast cancer for over 40 years. The results have shown to be very beneficial in terms of cancer treatment, along with the total survival rate. During treatments, cancer tissues and normal tissues within the treatment field are irradiated. With increasing technology, techniques have been developed to increase the accuracy of treatments and reduce the exposure to surrounding areas. A relatively new technique includes the use of a four-dimensional computed tomography (4DCT), using a DIBH protocol. The DIBH technique is one method of treatment using a gated scan. Gated scans consist of capturing CT images during specific times of a patient s breathing cycle. This technique creates a consistent breathing interval to conduct a treatment that has far less motion compared to treating without it. Without a method of gating, the chest can fluctuate 0.5 to 0.7 cm laterally

2 2 throughout the treatment. 1 During DIBH treatments, the gate at which the CT scan is acquired is set to when the patient is at full inspiration. Aside from motion reduction during treatment, the DIBH technique offers benefits for the patient anatomically. As the patient holds a deep inspiration, the lung volume is increased. With this increase, the electron density within the lung is decreased, reducing the exposure to the lung while increasing the distance between the treatment fields from organs at risk (OR) within the area. 2 This separation has been shown to be beneficial for left-sided breast treatments because the heart is moved away from the treatment field. This reduces unnecessary exposure to the coronary arteries. Although the heart is usually not a concern during right-sided breast treatments, the right-sided DIBH treatment technique can be advantageous to other organs. Right-sided DIBH treatments are less common. Other gating techniques such as FB or no gating are typically used for right-sided treatments. The reason for using these techniques is because DIBH treatments can be difficult to set-up and execute if the patient has a difficult time holding their breath. The benefit of sparing the heart has been the main focus for DIBH treatments, but the advantage of moving the heart away from the irradiated field does not translate for the treatment of right-sided breast cancer cases. However, if DIBH techniques are used for right-sided breast treatments, other OR, specifically the liver, are moved away from the radiation field. Butler et al 1 reported that during normal respiration, the liver moved 1.5 to 2 cm in the superior-inferior direction and during DIBH the distance was further increased to 3.9 cm. The extra movement in the superior-inferior direction during DIBH may force the liver away from the radiation field to significantly reduce additional radiation being deposited into the liver. The suggested dose tolerances for the liver is a mean dose of less than 30 Gy, which provides a 5% chance of radiation induced liver disease (RILD). 3 The tolerance is intended for healthy livers, which means patients with preexisting liver disease such as hepatitis or poor liver function may have a greater risk of side effects. 4 The concern for treating patients with preexisting liver disease grows as comorbidity becomes increasingly prevalent. It is estimated that 1 in 3 adults and 1 in 10 children in America have nonalcoholic fatty liver disease (NAFLD). 5 This occurrence has increased significantly due to the increase in obesity, type II diabetes mellitus, and physical inactivity. The excess fat within the liver may cause hepatitis, which may then form scar tissue within the liver, causing a decrease in liver function. With a

3 3 greater possibility for future patients presenting with decreased liver function, it is of best practice to spare this organ from unnecessary radiation during right-sided breast treatments. Another reason to reduce the excess radiation dose to the liver is because patients are being treated at a younger age. The advances in screening have allowed the detection and treatment of breast cancer earlier. Since patients are being treated at a younger age, there is more time to develop a secondary cancer in areas that received a low dose of radiation. The purpose of this study was to determine if DIBH would decrease the amount of radiation to the liver for right-sided breast cancer patients and thus reducing the risk of radiation induced liver complications. Case Description Patient Selection and Setup Seven, previously treated patients with breast cancer of the right-breast and regional lymph nodes were selected. All of these patients received radiation therapy with the DIBH technique to minimize lung dose. During CT simulation, patients were scanned using both the FB and DIBH techniques separately. Patients were positioned supine on an in-house, inclined breast board with both arms raised and the heads turned towards the unaffected breast. Radioopaque wires were placed by the physician to delineate superior, inferior, medial, and lateral field borders as well as breast tissue and lumpectomy scars. A Philips Brilliance Big Bore CT scanner was used to acquire the FB and DIBH scans with a 3.0 mm slice thickness. The FB scan was acquired first. For the DIBH scans, the patients were gated with Real-time Position Management (RPM) system and were coached with breathing instructions. Before the DIBH scan began, the patients were expected to reproduce a consistent breath hold in order to ensure reproducibility for treatment. The expected time for patients to hold their breath for this scan was about 20 seconds. Upon acquisition of the scans, the CT data sets were transferred to the Eclipse Treatment Planning System (TPS) via the Digital Imaging and Communications in Medicine (DICOM) network. Target Delineation The target volumes including the breast tissue, lumpectomy bed, axillary I, II, and III lymph nodes, supraclavicular (SC) lymph nodes, and in some cases, internal mammary (IM) nodes were contoured by the physician and outlined on both the FB and DIBH scans. The breast

4 4 tissue was cropped 5 mm away from the skin surface. Organs at risk were defined by a certified medical dosimetrist and included the following: right and left lungs, heart, spinal cord, esophagus, and liver. Treatment Planning The prescription was written for 50.4 Gy in 1.8 Gy per fraction to be delivered daily. The target volumes included the breast tissue, lumpectomy bed, axillary I, II, and III lymph nodes, SC lymph nodes, and in some cases, IM nodes. The planning goals for the breast tissue, lumpectomy bed, axillary I, II, and III lymph nodes were to achieve at least 95% of the volume to be covered by at least 95% of the prescribed dose. In cases involving the IM nodes, the goal was to achieve 90% of the volume to be covered with 90% of the prescribed dose. A monoisocentric technique was used for all patients. A Varian 21EX linear accelerator equipped with 6 and 23 MV energies was available to treat DIBH breast plans. Left anterior oblique (LAO) and right posterior oblique (RPO) treatment angles and multi-leaf collimator (MLC) blocks for the SC fields were created based on obtaining coverage of the nodal chains and the need to block the spinal cord, esophagus, and humeral head. An enhanced dynamic wedge was used as needed and when field size limitations allowed. For tangent breast treatment fields, LAO and RPO angles were used. Fields were shaped with MLC blocks based on the borders defined in CT simulation and the ability to block normal structures such as heart and liver without compromising coverage of the breast tissue. When helpful, a field-in-field technique was used to block out unnecessary areas receiving a dose greater than the prescription dose. Physical wedges were used on tangent fields as needed. The most common use was on an RPO breast field with a 30 degree right physical wedge. Figure 1 displays the image registration of the FB and DIBH scans and Figure 2 displays a beam's eye view (BEV) for a patient. The plans used to treat the patients were created on the DIBH scans by certified medical dosimetrists. Plan Analysis & Evaluation For the actual treatments, plans were generated on the DIBH scans by certified medical dosimetrists. For research purposes, retrospective planning was performed on the FB scans and compared against the plans created on the DIBH scans to assess the dose to the liver for each patient. The DIBH plan was copied onto the FB scan and adjustments were made as necessary to generate a plan tailored to the FB scan while simultaneously keeping the plan as similar to the DIBH plan as possible. Plans were normalized appropriately to obtain the same target coverage

5 5 and evaluate comparisons fairly. Dose volume histograms (DVH) were compared and evaluated between the FB and DIBH scans as shown in Figure 3. All planning goals remained consistent for each patient regardless of the structure set. One of the first areas that was analyzed between the FB and DIBH plans was the volume of liver within the target field of treatment. The quantities were determined by contouring the overlap of the field edge with the liver as seen in the axial plane in each plan. The average volume of liver within the treatment field for the FB plans was 39.7 cc, whereas the average for the DIBH plans was 3.9 cc. This comparison shows that DIBH decreased the volume of liver being exposed by primary radiation by 90.2%. For 4 of the patients, DIBH plans completely eliminated any primary radiation delivered to the liver as seen in the Table 1. Visual differences of liver position between a FB scan and a DIBH scan can be seen Figures 1 and 2. Upon determining that DIBH helped to decrease the amount of liver being exposed to radiation, the amount of liver exposed to specific dose levels was then investigated. The dose at each of these volumes decreased from the FB to the DIBH plans. This was expected since the overall volume of liver irradiated was also decreased. The average V 30, V 20, V 10, and V 5 for the FB plans were 37.5 cc, 46.7 cc, 62.6 cc, and cc, respectively (Table 1). The average V 30, V 20, V 10, and V 5 for the DIBH plans were 2.2 cc, 3.9 cc, 7.0 cc, and 18.8 cc, respectively (Table 1). The FB scan had exposed almost twice the amount of liver to 30 Gy than the DIBH plan exposed the liver to 5 Gy. The last aspect evaluated between the two plans was the maximum and mean doses to the liver. The maximum dose for the FB scans had a range between 47.3 Gy and Gy. The DIBH had maximum doses that ranged between 7.33 Gy and 48.8 Gy. The mean dose also followed a similar trend with a range of 1.4 Gy to 5.57 Gy for the FB plans and 0.66 Gy to 2.00 Gy for the DIBH plans. The factors that were evaluated in this study, including the liver volume within the treatment field, dose volumes, mean dose, and maximum dose, were decreased in all of the patients by the DIBH plans. The DIBH plan had a greater effect in some patients than in others. Some variables contributing to the DIBH radiation reduction include target location, liver location, or the effectiveness of the patient s breathing. Conclusion

6 6 For right-sided breast patients with compromised liver function, it may be beneficial to take additional measures like DIBH to avoid treating the liver with unnecessary radiation. The additional setup difficulties should be considered when deciding whether to use DIBH or not. By evaluating the amount of liver being treated, along with the doses at specific volumes of the liver, the effects of DIBH compared to FB were able to be evaluated. The results of the current study demonstrate that DIBH techniques can reduce the amount of radiation received by the liver. This is one of the first studies that has taken an indepth look at liver dose using DIBH techniques for multiple patients. Rice et al 4 reported on an evaluation of a single case study that calculated the dose received by the liver for both the DIBH and FB plans and yielded similar results. For a single case, the DIBH technique reduced the mean and maximum dose by 46 and 3.5%, respectively. The V 10, V 20, and V 30 were all decreased by over 50% to show an overall benefit to DIBH. The reduction of unnecessary dose to the liver may help to prevent cases of RILD. One case of RILD has been documented to be caused by a treatment of the right chest wall. 6 The RILD may progress to liver fibrosis and liver failure. This shows that a reduction of liver dose may be of importance in certain patients. The limitations of this study are primarily found in the patient sample size as it is reflective of one institution within a one year time span. The scans that were available for this retrospective study were from patients treated with the DIBH technique in efforts to reduce dose to the lung. As reduction in lung dose was the original motive for the implementation of the DIBH technique, only patients with nodal involvement were treated using DIBH. For this reason, two-field breast plans were not evaluated in this study. Another limitation of this study that should be noted is in reference to the resources needed to implement DIBH. The DIBH technique is a more labor intensive process than the FB technique for both the patient and the institution. When compared to a FB technique, DIBH plans require an additional CT scan, some form of gating system, trained staff, ability of patients to hold breath for at least twenty seconds at a time, and additional time on the treatment machine. Additional research should be conducted on the extent of damage done to unhealthy livers by radiation. Overall, there was an improvement in liver dose reduction with the DIBH technique, however, it was evident that some patients benefited from the DIBH technique more than others. For this reason, the labor intensive

7 7 process may not offer a significant improvement in liver dose metrics for every scenario and thus should be evaluated case by case.

8 8 References 1. Butler LE, Forster KM, Stevens CW, et al. Dosimetric benefits of respiratory gating: a preliminary study. J Appl Clin Med Phys. 2004;5(1): Bruzzaniti V, Abate A, Pinnarò P, et al. Dosimetric and clinical advantages of deep inspiration breath-hold (DIBH) during radiotherapy of breast cancer. J Exp Clin Cancer Res. 2013;32(1): Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Rad Oncol Biol Phys. 1991;21(1): Rice L, Harris S, Green M, Price P. Deep inspiration breath-hold (DIBH) technique applied in right breast radiotherapy to minimize liver radiation. BJRcase reports. 2015;1(2): López-Velázquez JA, Silva-Vidal KV, Ponciano-Rodríguez G, et al. The prevalence of nonalcoholic fatty liver disease in the Americas. Ann Hepatol. 2014;13(2): alcoholic.pdf 6. Khozouz R, Huq S, Perry M. Radiation-Induced Liver Disease. J Clin Oncol. 2008;26(29):

9 9 Figures Figure 1. Image registration of FB and DIBH scans with treatment fields displayed on a patient in the coronal plane (left) and in the sagittal plane (right).

10 Figure 2. Beams eye view of medial tangent field on FB scan (left) and DIBH scan (right) for a patient. The breast contour is shown in green and liver contour is shown in brown. 10

11 11 FB DIBH Figure 3. Dose volume histogram in absolute dose and absolute volume for a patient. Breast coverage is shown in magenta and liver coverage shown in brown.

12 12 Table 1. Liver dose metrics comparing FB and DIBH techniques for all patients (Pt). Volume in field (cc) Mean Dose (Gy) Max Dose (Gy) V30 (cc) V20 (cc) V10(cc) V5 (cc) FB DIBH FB DIBH FB DIBH FB DIBH FB DIBH FB DIBH FB DIBH Pt Pt Pt Pt Pt Pt Pt AVG