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Dustin Melancon Semester Case Study August 8, 2013 3D CRT for Invasive Ductal Carcinoma of the Left Breast Abstract: Introduction: This study aims to evaluate post-mastectomy radiation therapy (PMRT) using three-dimensional conformal radiation therapy (3D-CRT) with the field-in-field (FIF) technique for invasive ductal carcinoma of the left breast. This treatment technique has been shown in literature to reduce dose to organs at risk (OR), such as the heart, and assists in delivering an even dose distribution to the target. In addition, studies reveal that along with systemic therapy, PMRT with modern techniques can reduce side effects, increase local control, and improve survival.1-4 Case Description: This case study discusses invasive ductal carcinoma in post-mastectomy patients who were treated with chemotherapy then followed by PMRT. The 3 cases include the following: Patient 1 represents a case using tangential photon beams, a supraclavicular field, and an electron boost; Patient 2 represents the left chest wall treated with tangential photon beams and a supraclavicular field; Patient 3 represents a case treated with tangential photon beams and an electron boost. All three 3D-CRT cases featured mixed energy beams with the FIF technique. Conclusion: All plans were evaluated for how well dose objectives and constraints were met using 3D-CRT. Plans were evaluated individually for doses to critical structures based on the dose volume histogram (DVH) and the dose distribution throughout the target. Using 3D-CRT in PMRT cases has been shown in literature to spare critical structures and improve dose homogeneity. Key Words: Post-mastectomy radiation therapy (PMRT), three-dimensional conformal radiation therapy (3D-CRT), post field-in-field (FIF) technique.

Introduction Older PMRT techniques established better local control, but they also had an excessive risk of cardiovascular death. More recent studies show that modern radiotherapy techniques can improve local control and avoid cardiac morbidity, regardless of tumor size, number of positive nodes, or histopathologic grade.1,2 A British Columbia randomized trial with 20 years of followup found that post-mastectomy patients who had chemotherapy and irradiation of all regional lymph nodes and the chest wall areas had significantly reduced rates of breast cancer recurrence, compared with post-mastectomy chemotherapy alone.3 The trial also showed a reduction in overall mortality. With other solid tumors such as lung, esophageal, and rectal cancers, chemotherapy alone cannot always eliminate all residual disease. The microscopic disease may be resistant or become resistant to chemotherapy. Adjuvant PMRT can be delivered to optimize outcome.4 The 3D-CRT technique is commonly used for PMRT, and uses tangential radiation fields to treat the chest wall. The physician may prefer the tangential fields to feature a combination of low and high energy photon beams for better dose homogeneity. The low energy beams allow for adequate dose near the skin surface while higher energy beams can achieve greater depth. Patients without axillary lymphatic involvement are sometimes treated using only tangential fields to the chest wall. The axilla and supraclavicular regions may be treated based on prognostic risk factors, such as involvement of 4 or more positive nodes. An electron boost is usually delivered to the excision site because local tumor recurrence is frequently observed near the site of the tumor bed.3 The protocol at this facility states that patients with reconstructive breast surgery do not receive a boost. A standard course of PMRT consists of 50 to 50.4 Gray (Gy) delivered in 25 to 26 fractions, followed by a 10 to 16 Gy boost to the tumor bed. A typical course of 3D-CRT for any of the 3 cases presented might follow a standard fractionation of 1.8-2.0 Gy per fraction delivered daily in 5 to 7 weeks.3 Several alternative methods of radiation delivery have been developed to shorten the number of treatments. Each technique and fractionation scheme should be individualized to the patients anatomy, tumor characteristics, and institutional resources. Hypofractionation is defined as, The delivery of larger-than-standard doses of radiation over a

shorter period of time.5 Hypofractionation was originally considered in the 1960s, but was associated with a high rate of late side effects. As technology advanced, hypofractionated treatments regained popularity in the United States. The hypofractionated treatment, also known as Canadian fractionation, is commonly used in the United States has 16 treatments with a higher dose per day. In studies with a median follow-up of 12 years, there were no significant differences in local recurrence between standard fractionation and hypofractionation.5 The cases presented will demonstrate both standard fractionation and hypofractionation regimens. In the case of hypofractionated therapy, there are clinical, logistical, and economic factors that may be considered in the rationale for this therapy. Potential effects of PMRT include skin reactions, lymphedema, brachial plexopathy, radiation pneumonitis, rib fractures, cardiac toxicity, radiation-induced secondary neoplasms, and poor cosmetic results.5,6 The data suggested that the incidence of many of these toxicities will be lower when modern radiotherapy techniques are used; therefore, the cases discussed have been planned and treated using modern techniques. The focused study on delivering a homogenous dose to the target while minimizing dose to critical structures. Danish trials have shown that PMRT with modern techniques did not increase the risk of ischemic heart disease-related morbidity or mortality.3 Several studies have shown benefits of the FIF technique for improving target conformity and reducing dose to OR during tangential irradiation.7,8 The FIF technique also had superior results to most cases that used dynamic or physical wedges.8 The results provided evidence that modern treatment techniques, such as the FIF technique, give patients the benefits of PMRT without toxicity to OR. Even with these improvements, its important that these doses are properly documented in the treatment planning system.9 The 3 cases presented were planned with a FIF technique using a multifractionated approach to PMRT. Plans were evaluated individually based on the cumulative dose volume histogram (DVH), 100% of prescription dose coverage, prescription dose, and maximum and mean doses for OR.

Methods and Materials Patient Selection The patients selected were cases of invasive ductal carcinoma of the left breast who presented to our facility as candidates for PMRT. Each treatment demonstrated the use of the FIF technique. Patient 1, a 65 year-old male, demonstrated that PMRT in men is treated with the same approach as women. The patient had standard fractionation as well as an electron boost to the mastectomy scar. A 3-field monoisocentric technique with beam splitting techniques was used for field matching between the tangential fields and a supraclavicular field. Three separate plans were used for the tangential fields, supraclavicular field, and electron boost. The mixed energy tangential fields featured the FIF technique and allowed for better homogeneity and less dose to critical structures. Patient 2, a 48 year-old female, had reconstructive breast surgery; which included tissue expander and implant placement. Using standard field arrangements, one study demonstrated that adequate dose to the reconstructed breast was feasible in women who had immediate reconstruction after mastectomy, regardless of the reconstruction type of the treatment plan. The results suggested that clinically acceptable doses to the heart and lungs could be achieved in most patients.2 The patients plan was designed using a 3-field monoisocentric technique with beam splitting techniques for matching fields. This case represented a standard fractionation scheme using mixed energy tangential fields with the FIF technique and a supraclavicular field. Patient 2 did not have an electron boost because she had reconstructive surgery. Patient 3, a 60 year-old female, underwent hypofractionated therapy. The radiation oncologist offered to refer the patient somewhere closer to home, but she wanted to have her treatment at the current facility. Because of her long commute, the patient benefited from a short hypofractionated course for PMRT. The treatment consisted of mixed energy tangential fields with the FIF technique to the chest wall and an electron boost to the mastectomy scar. The radiation oncologist elected to not treat the supraclavicular area because the patient did not have axillary lymphatic involvement.

Patient Set-up All patients received computed tomography (CT) scans. They were head first in the supine position on a tilt board immobilization device. Each patient was placed in the supine position on a head support. The head were turned to the right and supported with a tilt board headrest. The left upper arm was extended and positioned above the head while the right arm was positioned akimbo. Each patient had a sponge under their knees for support. The radiation oncologist marked the superior, inferior, medial, and lateral regions of the left chest wall with radiopaque markers. The radiation therapist outlined the mastectomy scar for patients 1 and 3 with radiopaque wire to assist the medical dosimetrist during treatment planning. Target Delineation The Varian Eclipse Treatment Planning System (TPS), version 10.0 was used for all target delineation. A computed tomography (CT) scan was obtained in all cases with each patient in the described treatment position. The radiation oncologist placed the isocenter based on how he wanted to treat the patient. The radiopaque markers were visualized on the TPS and helped the medical dosimetrist determine the target. Any PMRT technique requires irradiation of the entire mastectomy flap, including the entire mastectomy scar, surgical clips, and drain sites.2 The fields for each patient extended from the sternum to at least the mid-axillary line. It was important to provide adequate coverage in the inferior border. This border was placed about 2 centimeter (cm) caudal to the previous location of the inframammary sulcus. The superior border of the chest wall fields abutted the supraclavicular field. To avoid hot spots at the field junction, the radiation oncologist preferred using a monoisocentric technique to create a non-divergent edge. In order to create a nondivergent field edge, asymmetric-jaws beam-split the tangential and supraclavicular fields along the central-axis plane. Critical normal structures near the treatment area included the spinal cord, left lung, right lung, and heart. In addition, the medical dosimetrist used the radiopaque wire on patient 1 and patient 2 that outlined the mastectomy scar to plan the electron boost plan. A 1 cm bolus was added in the TPS for the electron boost plan. The medical dosimetrist added a 2 cm margin in all directions of the surgical scar.

Treatment Planning The dose prescription and key planning parameters are presented for each respective case in Tables 1-3. The plans were generated using forward planning. All tangential fields to the chest wall featured mixed energy photon beams with the FIF technique. The FIF technique attenuates radiation in small areas of the field with customization of the multileaf collimators (MLCs). The most common reason for higher doses at hot spots is a separation size that is too large for 6 megavoltage (MV) beams. Since there is a substantial amount of tissue in the field, a mixture of higher-energy beams can be used to reduce the hot spots. The lower energy remains in the tangential fields to treat the superficial areas of the breast.5 All plans were optimized with heterogeneity corrections on. The goals were to achieve conformal target coverage and preserve as much normal tissue as possible. For Patient 1, the challenge of delivering a prescription dose of 50 Gy in 25 fractions to the tangential fields was complicated by the close proximity of the heart and left lung. The objectives included: maximum spinal cord dose less than 45 Gy, mean heart dose less than 2 Gy, and the left lung dose to be as low as reasonably achievable. The prescription dose for the conventional tangential fields was prescribed to a calculation point placed by the medical dosimetrist at a depth of 12.1 cm within the left breast tissue. The medical dosimetrist placed the calculation point near the mid-plane depth of the medial and lateral tangential beams, in the center of the superior and inferior extents of the left breast volume, and approximately 1.5 cm from the left chest wall. Open tangential fields of 6 and 18 MV beams were utilized for better dose homogeneity. The MLCs helped to block excessive OR doses in the open tangential fields. The FIF portals treated through the same gantry angles of the tangentials fields to reduce high dose regions. The medical dosimetrist accomplished this by converting the 112% isodose level to a structure in the TPS. Next, the medical dosimetrist looked in the beams eye view of the FIF portal and adjusted the MLC to cover the 112% structure. Once calculated, all of the fields were appropriately weighted. The medical dosimetrist then converted the 109% isodose level to a structure to increase dose homogeneity and lower the maximum dose region. In the supraclavicular field, there was a 345 degree gantry rotation to get off of the spinal cord. The MLCs were customized to protect the humeral head and spinal cord. For the mastectomy scar, electrons would deliver dose to the scar and limit the dose to adjacent tissue. The medical

dosimetrist used 9 mega-electron volts (MeV) with a 1 cm bolus at 105 cm source to skin distance (SSD). A block was created in the TPS that was 2 cm around the scar. The medical dosimetrist set the gantry at 35 degrees with the collimator at 10 degrees. A 25x25 cm field size was large enough to cover the entire mastectomy scar. A calculation point was placed at a depth of 2.1 cm, the maximum dose (dmax) of 9 MeV. For Patient 2, the challenge of delivering a prescription dose of 50.4 Gy in 28 fractions to the tangential fields was complicated by the reconstructed breast. Dose constraints kept the maximum spinal cord dose less than 45 Gy for the composite plan. All attempts were made to limit the mean heart dose less than 3 Gy, although no hard constraints were given. The left lung dose was to be as low as reasonably achievable. The prescription dose for the conventional tangential fields was prescribed to a calculation point placed by the medical dosimetrist at a depth of 11.4 cm within the medial tangent field and 14.9 cm within the lateral tangent field. The medical dosimetrist placed the calculation point near the mid-plane depth of the medial and lateral tangential beams, in the center of the superior and inferior extents of the left chest wall volume, and approximately 3 cm from the left chest wall. Open tangential fields of 6 and 18 MV beams were utilized for better dose homogeneity. The MLCs helped to block excessive doses to the heart, lungs, and spinal cord in the open tangential fields. For the FIF technique, the medical dosimetrist converted the 112% isodose level to a structure in the TPS. Next, the medical dosimetrist looked in the beams eye view of the FIF portal and adjusted the MLC to cover the 112% structure. Once calculated, all of the fields were appropriately weighted. The medical dosimetrist then converted the 109% isodose level to a structure to increase dose homogeneity and lower the maximum dose region. The supraclavicular field also featured a 345 degree gantry rotation to get off of the spinal cord. The MLCs were customized to protect the humeral head and spinal cord. A 10 degree enhanced dynamic wedge was added to push dose away from the field junction of the tangent and supraclavicular fields. The chest wall for patient 3 was prescribed to receive 40.5 Gy in 15 fractions at 2.7 Gy per fraction. Objectives included: maximum spinal cord dose less than 45 Gy, the mean heart dose below 2 Gy, and the left lung dose to be as low as reasonably achievable. The prescription dose for the conventional tangential fields was prescribed to a calculation point placed by the medical dosimetrist at a depth of 7.8 cm within the medial tangent field and 11.8 cm within the lateral

tangent field. The medical dosimetrist placed the calculation point near the mid-plane depth of the medial and lateral tangential beams and the center of the superior and inferior extents of the left chest wall. Open tangential fields of 6 and 10 MV beams were utilized for better dose homogeneity. For the FIF technique, the medical dosimetrist converted the 110% isodose level to a structure in the TPS. Next, the medical dosimetrist looked in the beams eye view of the FIF portal and adjusted the MLC to cover the 110% structure. Once calculated, all of the fields were appropriately weighted. The medical dosimetrist then converted the 107% isodose level to a structure to increase dose homogeneity and lower the maximum dose region. For the mastectomy scar, electrons would deliver dose to the scar and limit the dose to adjacent tissue. The medical dosimetrist used 9 MeV with a 1 cm bolus at 110 cm SSD. A block was created in the TPS that was 2 cm around the scar. The medical dosimetrist set the gantry at 28 degrees with the collimator at 25 degrees. A 25x25 cm field size was large enough to cover the entire mastectomy scar. A calculation point was placed at a depth of 2.1 cm, the dmax of 9 MeV. Plan Analysis & Evaluation The objective of radiation therapy in the management of PMRT is to minimize the risk of locoregional recurrence while minimizing the dose to OR. The quality of the plan for PMRT can be assessed by how well the plan covers the chest wall and doses to the left lung and heart. The 3 cases must be looked at individually as to how well dose objectives and normal tissue tolerances were met. A summary of the maximum and mean doses for each case is presented in Table 4. For patient 1, the cumulative plan achieved all of the dose constraints. The cumulative dose objectives and constraints were evaluated. The maximum point dose in the heart was 803.3 centigray (cGy), 123.9 cGy in the spinal cord, 4815.3 cGy in the left lung, and 121.2 cGy in the right lung. Mean doses include 129.9 cGy in the heart, 59.2 cGy in the spinal cord, 857.6 cGy in the left lung and 11.8 cGy in the right lung. The cumulative plan for patient 2 also achieved the dose objectives and obtained prescription dose coverage. The OR on the composite DVH reflected maximum doses of 4460.9 cGy in the heart, 177.5 cGy in the spinal cord, 4986.4 cGy in the left lung, and 831.6 cGy in the right lung. Mean doses include 317.9 cGy in the heart, 64.3 cGy in the spinal cord, 1280.9 cGy in the left lung and 33.5 cGy in the right lung.

The plan for patient 3 also achieved the dose objectives and adequate prescription dose coverage. The OR on the chest wall DVH reflected doses of 3282.5 cGy in the heart, 29.7 cGy in the spinal cord, 3963.8 cGy in the left lung, and 32.1 cGy in the right lung. Mean doses include 174.9 cGy in the heart, 7.4 cGy in the spinal cord, 540.1 cGy in the left lung and 5.4 cGy in the right lung. In analyzing Table 4, the mean and maximum doses for patient 1 and patient 3 were comparable. Patient 2 had higher doses to critical structures than the other patients because this patient had reconstructive breast surgery. Recent studies indicate that implant-based breast reconstruction can create problems in patients receiving PMRT. In patients with left-sided reconstructive breast surgery, the heart and lung were spared at the expense of full chest wall and internal mammary nodes coverage.10 There was a substantial amount of tissue to irradiate within the chest wall. Again, properly weighting the mixed energy beams and using the FIF technique provided an acceptable treatment plan. Although the OR doses were higher for patient 2, the medical dosimetrist established a good compromise between adequate chest wall coverage and kept the OR doses as low as reasonable achievable. All of the 3D-CRT plans presented proceeded through quality assurance (QA) with an independent check for monitor unit (MU) calculation and passed within the tolerance set of +/5%. The precision of this treatment required that the position of the breast be reproduced on a daily basis. Results and Discussion Patients in this study benefited from receiving PMRT because it reduces the risk of recurrence and improves long-term survival.3 Benefits are for patients at the greatest risk of recurrence; these include positive nodes, positive margins, and lymphovascular invasion. Although PMRT can improve local control and survival, this does not diminish the importance of systemic adjuvant therapy. A specialized management plan for patients should be developed to maximize their therapeutic ratio. Radiotherapy can result in long-term morbidity and mortality, so it is vital that PMRT is planned carefully. Principles of radiation biology, radiation physics, mathematics, and anatomy must be understood for treatment planning. Radiation fields used for PMRT are reasonably standard, but each field is individualized according to patient anatomy and the structures at risk. Treatment

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planning demands experience and careful attention to detail for the best patient care. The goal of PMRT is to not only ensure that acceptable dose is delivered to the target, but also minimize dose to the heart, lungs, and spinal cord. This can be achieved with modern radiotherapy methods, such as the FIF technique.

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Figures

Transverse view of chest wall plan. The green isodose line represents the 100% prescription line. The transverse view of the supraclavicular plan. The green isodose line represents the 100% prescription line.

Transverse view of the electron boost plan. The green isodose line represents the 100% prescription line. One centimeter of bolus applied daily.

Figure 1. Patient 1: Dose Distribution for chest wall, supraclavicular, and electron boost plans.

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Figure 2. Patient 1: Cumulative DVH.

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Transverse view of chest wall plan. The green isodose line represents the 100% prescription line.

The transverse view of the supraclavicular plan. The green isodose line represents the 100% prescription line.

Figure 3. Patient 2: Dose Distribution for chest wall and supraclavicular plans, cumulative DVH.

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Transverse view of chest wall plan. The green isodose line represents the 100% prescription line.

The transverse view of the boost plan. The green isodose line represents the 100% prescription line. One centimeter of bolus applied daily.

Figure 4. Patient 3: Dose Distribution for chest wall and electron boost, cumulative DVH.

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Tables Table 1. Chest Wall Prescription and Treatment Planning Parameters Prescription and Treatment Planning Parameters Case Site Patient 1 Left chest wall Patient 2 Left chest wall Patient 3 Left chest wall

Prescription Beam Energy Fractionation Prescription Dose 6 MV and 18 MV Standard Fractionation 50 Gy in 25 fx 6 MV and 18 MV Standard Fractionation 50.4 Gy in 28 fx 6 MV and 10 MV Hypofractionation 40.5 Gy in 15 fx

Treatment Planning Parameters Beam Arrangement Gantry Angles Collimator Planning Technique (2) Co-planar beams 130,310 0 3D-CRT/ FIF (2) Co-planar beams 129, 309 0 3D-CRT/ FIF (2) Co-planar beams 125, 305 14, 346 3D-CRT/ FIF

Note: The couch angles are set to 0 for all beams.

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Table 2. Supraclavicular Field Prescription and Treatment Planning Parameters Prescription and Treatment Planning Parameters Case Site Patient 1 Supraclavicular region Prescription Beam Energy Fractionation Prescription Dose 6 MV Standard Fractionation 50 Gy in 25 fx 6 MV Standard Fractionation 50.4 Gy in 28 fx N/A N/A N/A Patient 2 Supraclavicular region Patient 3 N/A

Treatment Planning Parameters Beam Arrangement Gantry Angles Collimator Planning Technique (1) Beam 345 0 3D-CRT (1) Beam 345 0 3D-CRT N/A N/A N/A N/A

Note: The couch angles are set to 0 for all beams.

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Table 3. Boost Prescription and Treatment Planning Parameters Prescription and Treatment Planning Parameters Case Site Patient 1 Mastectomy scar Prescription Beam Energy Fractionation Prescription Dose 9 MeV Standard Fractionation 10 Gy in 5 fx N/A N/A N/A 9 MeV Standard Fractionation 9 Gy in 3 fx Patient 2 N/A Patient 3 Mastectomy scar

Treatment Planning Parameters Beam Arrangement Source-to-Skin Distance (SSD) Gantry Angles Collimator Planning Technique (1) Electron beam 105 SSD 35 10 3D-CRT N/A N/A N/A N/A N/A (1) Electron beam 110 SSD 28 25 3D-CRT

Note: The couch angles are set to 0 for all beams.

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Table 4. Plan Analysis and Evaluation Plan Analysis and Evaluation Organs at Risk Patient 1 (cGy) Dmean Dmax 129. 9 857. 6 11.8 59.2 803.3 4815. 3 121.2 123.9 Patient 2 (cGy) Dmean Dmax 317.9 1280. 9 33.5 64.3 4460. 9 4986. 4 831.6 177.5 Patient 3 (cGy) Dmean Dmax 174. 9 540. 1 5.4 7.4 3282.5 3963.8 32.1 29.7

Heart Left lung Right lung Spinal cord

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