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1 Ashley Pyfferoen March Case Study March 31, 2013 Conformal Treatment for Invasive Ductal Carcinoma of the

Right Breast History of Present Illness: BP is a 74-year-old female who presented for an annual mammogram screening in December of 2012. The mammography results revealed abnormalities in both right and left breast tissue. A diagnostic mammogram was ordered and determined the abnormality detected on the left breast was benign, presumably the result of superimposed breast tissue. Alternatively, the diagnostic mammogram detected a 2.5 centimeter (cm) density located at the 9 oclock position in the right breast that was highly suspicious. A follow-up ultrasound confirmed the results of the diagnostic mammogram and also identified a second site of suspicion. A 3 millimeter (mm) hypoechoic mass was detected in the right 9 oclock position approximately 3 cm from the nipple. Patient BP underwent an ultrasound-guided biopsy of the 2.5 cm site and the pathology report revealed infiltrating mammary carcinoma, no special type, intermediate grade, with ductal carcinoma in situ, intermediate nuclear grade, solid and of the cribiform type. The 3 mm mass was later determined to be a benign cyst after the site was resolved following aspiration. The invasive tumor was estrogen receptor (ER) and progesterone receptor (PR) positive but Human Epidermal Growth Factor Receptor 2 (Her-2) negative. The patient met with a medical oncology surgeon and discussed diagnosis, prognosis, expectations, options for treatment, risks, recovery times and recovery activities. After initial consultation, the patient decided on breast conserving therapy (lumpectomy) with the possibility of post-operative radiation. In January of 2013, the patient underwent a right partial mastectomy with preoperative needle localization and right deep axillary sentinel lymph node biopsy. Post-operatively, the lumpectomy specimen pathology report revealed intraductal papillomas with compact florid hyperplasia and was negative for malignancy. The report also indicated there were 2 benign lymph nodes. The final diagnosis revealed invasive ductal carcinoma, grade 2, 0.4 cm in dimension, located in the lower outer quadrant without peritumoral internal lymphatic tumor emboli, dermal lymphatic involvement or skin/nipple involvement. After surgery, patient BP met with a radiation oncologist to discuss a course of adjuvant radiotherapy to the right breast. After a thorough discussion of the risks, benefits, and

2 alternatives to a course of adjuvant radiotherapy, the patient chose to proceed with radiation treatments. Past Medical History: The patient has several past medical conditions and comorbidities including gastroesophageal reflux disease (GERD), hypertension, hyperlipidemia, bronchospastic airway disease, transient ischemic attacks, gout, obesity, diabetes mellitus type 2, rheumatoid arthritis, osteoporosis, coronary artery disease, peripheral vascular disease, chronic bronchitis, allergies, vertigo, coronary artery stenosis, chronic kidney disease, immunodeficiency due to medications and sleep apnea. Social History: Patient BP is a married saleswoman at a local footwear company. She formerly smoked 0.5 packs of cigarettes daily before quitting in 1995 and rarely uses alcohol. The patient indicated her mother, father, sister and 2 brothers are deceased, 2 from cancer. She also has 4 children, all living and cancer free. The patient did not indicate a history of breast cancer maternally or paternally. Medications: The patient indicated she is taking acetaminophen, Albuterol-ipratoropium, Alendoonate, Allopurinol, Amitriptyline, Amlodipine, asprin, Atorvastatin, Cilostazol, Remicade, Losartan-hydrocholorothiazide, Meclizine, Metoprolol-SL, a multivitamin tablet, Nitroglycerin, Ranitidine, and Tramadol. Diagnostic Images: In early December of 2012, the patient underwent a routine mammogram screening that indicated abnormalities in the right and left breast. A diagnostic mammogram revealed a suspicious lesion located in the lower outer quadrant of the right breast. A subsequent diagnostic mammogram revealed the suspicious site located on the left breast was benign tissue. An ultrasound was performed on the right breast and revealed a 2.5 cm lesion located at the 9 oclock position. An ultrasound-guided biopsy revealed infiltrating mammary carcinoma of the right breast tissue. This region was extradited and the pathology report indicated Grade 2 invasive carcinoma 0.4 cm in size with negative margins. Out of the 2 lymph nodes evaluated, both were benign. Radiation Oncology Recommendations: The radiation oncologist reviewed the information documented by the medical oncologist. After consult with BP, he decided to proceed with external beam radiation therapy to the right breast. The radiation oncologist elected to treat the right breast with photon tangential beams using a 3-Dimensional (3D) conformal treatment plan. Tangential beams have shown to have a decreased effect on cardiac tissue because the beam is

3 directed toward the breast tissue only, thus skimming only the wall of the heart.1 In addition, tangential beams also decrease the chances of developing coronary artery disease and myocardial infarction due to radiation therapy.1 The Plan: The radiation oncologists plan to treat the right breast consisted of a basic 3D conformal plan using photon energy. The plan contained 2 opposite tangential fields to ensure the breast was covered adequately. Segmented fields were included to further improve dose homogeneity. The right breast was prescribed to 4256 centigray (cGy) at 266cGy per fraction for 16 fractions. This hypofractionated treatment has shown to deliver more radiation per fraction with similar results and a shorter treatment regimen (16 days versus 28 days) than with typical fractionation prescriptions for intact breast patients.2 Patient Setup/Immobilization: In late February 2013, the patient presented for a computed tomography (CT) simulation scan in the radiation oncology department. She was placed in the supine position head first into the scanner. A CIVCO wing board was placed under the patient to remove her arms from the fields and maintain immobilization (Figure 1). A head and neck rest was secured to the table for patient comfort. A cushion was placed under her knees for lumbar back support and a rubber band was placed around her feet to ensure immobilization (Figure 2). BBs were placed anteriorly and laterally (left and right) on the patients skin to define a reference point for treatment planning. Radiopaque wires were placed on the patient (medially, laterally, inferiorly and superiorly) to determine field borders and gantry angles. Exac-Trac imaging was used to aid in daily reproducibility and immobilization. Anatomical Contouring: In conclusion of the CT simulation, the axial images were uploaded in the Philips Pinnacle3 8.0 radiation treatment planning system (TPS). The radiation oncologist contoured the lumpectomy cavity and carefully included all of the surgical clips and adequate margin to ensure proper radiation dosage. The medical dosimetrist then contoured organs at risk (OR) including the left lung, right lung and heart. In addition, the dosimetrist also contoured the radiopaque wires to determine the field sizes and gantry angles. The radiation oncologist reviewed these OR structures and the wire contours and made necessary adjustments. The medical dosimetrist was then given the prescription of the plan to proceed. Beam Isocenter/Arrangement: The patient was treated on a Varian Cliniac 21EX machine. The isocenter was placed midline between the superior and inferior wire contours to ensure adequate dose to the breast. It was also placed medially to the breast tissue to ensure the central axis (CA)

4 was passing through the most medial portions of the breast tissue (Figures 3-5). The gantry angles were determined when the lateral and medial wires were superimposed. The lateral tangent or right posterior oblique (RPO) field was determined to be 223 degrees () and the gantry angle for the medial tangent or left anterior oblique (LAO) field was measured at 44. This plan did not require a couch or collimator rotation. The field size apertures were based upon the superior and inferior wires placed on the patient during simulation. The superior and inferior field edges were approximately 2 cm above and below the breast tissue, respectively (Figure 6). In addition, 2 cm of flash were administered laterally to account for patient movement (Figure 7). The physician then drew a multi-leaf collimator (MLC) blocked pattern to shield the right lung (Figure 7). After the MLC pattern was drawn, the patient separation was measured along the CA on the CT slice displaying the isocenter. The separation was measured to be 24.105cm. Using department guidelines, the dosimetrist determined the plan would require dual energy to provide adequate dose coverage. In addition to the original tangential beams, the dosimetrist added 2 more beams at the same gantry angles as specified above. The dosimetrist used 6 megavoltage (MV) photon energy on one beam and 10MV photon energy on the other beam containing the same gantry angle. This was also performed on the other tangential set of beams as well. Treatment Planning: Considering the circumstances of the patient, the goal of this radiotherapy treatment was curative. With this information, the dosimetrist attempted to achieve the best dose uniformity to the breast while limiting hot spots. The daily fractionated dose between the RAO 6MV, RAO 10MV, LAO 6MV and LAO 10MV fields were weighted almost equally at 24.5%, 24.5%, 25.5% and 25.5% respectively. After initial calculations, dose distributions to the breast were not sufficient. There were areas receiving both more and less dose then what was prescribed. To improved dose uniformity, a calculation point was added. The dosimetrist placed a calculation point on the same CT slice as the isocenter approximately 1.5cm laterally and 3.8cm posteriorly to ensure dose was delivered in adequate tissue (Figure 6). The beams were altered to deliver the prescription dose to the calculation point as opposed to the isocenter. To decrease hot spots, 3 segmented fields were added to each of the 4 beams. The segmented fields included the original MLC blocks and additional MLC blocks drawn by the medical dosimetrist to reduce the dosage to hot spots near the lateral edge of the breast (Figure 8). These segmented fields, or control points, were weighted accordingly on each beam to ensure the hot spots were

5 minimized to the correct ratio. After the second calculation, the dose homogeneity improved within tolerance. Using the dose volume histogram (DVH), the dosimetrist was able to confirm that the dose to the lumpectomy cavity was within 95% of the prescribed dose and hot spots were minimized to the most anterior, posterior and medial portions of the breast tissue (Figure 9-10). The isodose curves presented a uniform conformal dose to achieve this goal (Figure 10). The physician reviewed this plan and accepted with a normalization of 100% of the prescribed dose for daily treatment. Quality Assurance/Physics Check: The monitor units (MUs) were reviewed for the right breast treatment plan. To verify that the MU calculation was correct, a calculation program was used. All of the MUs for the treatment plan were within tolerance (5%) of the calculations computed by the program. The physicist also verified that the prescription and treatment fields were correct, the digitally reconstructed radiographs (DRRs) were associated properly and the patients treatment schedule was accurate. Conclusion: This treatment plan presented some difficulties for the dosimetrist. The biggest difficulty was eliminating portions of the breast that were overdosed. At times, there was breast tissue receiving 5107cGy, 120% hotter than prescription dose. While it is impossible to eliminate the hot spots medially and laterally due to the beam arrangement, they were minimized within tolerance. The treatment position was easily reproducible and presented little difficulties for the radiation therapists to treat. This plan provided a significant impact on my understanding of how segmentation can be implemented in radiation therapy. It is an invaluable tool that can aid dosimetrists in achieving desired dose uniformity while not giving the patient a severe radiation reaction. This was also a great opportunity to learn about other dosage/fractionation patterns for breast patients. Typically, 5040cGy delivered in 28 fractions is standard in the department so it was nice to incorporate diversity in this treatment plan. Also, this was a great plan to create as an introduction into Intensity Modulated Radiation Therapy (IMRT).

6 Figures

Figure 1. Patient is immobilized on a CIVCO wing board.

Figure 2. A cushion and rubber band were used for patient comfort and immobilization, respectively

Figure 3. Isocenter placement in axial view.

Figure 4. Isocenter placement in sagittal view.

Figure 5. Isocenter placement in coronal view.

Figure 6. Calculation point (blue point) placement in axial view.

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Figure 7. Field size borders and MLC blocks in beams eye view (BEV) window.

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Figure 8. A segmented field for the RPO 10MV beam.

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Lumpectomy Cavity

Total Lungs

Figure 9. Dose Volume Histogram (DVH).

Figure 10. Isodose line distribution in 3 levels (red= 4256cGy).

13 References 1. Harris E, Correa C, Hwang WT, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006:24(25):4100-4106. 2. Whelan T, Pignol J, Levine M, et al. Long-term results of hyporactionated radiation therapy for breast cancer. New Engl J Med. 2010; 362:513-520.