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Megan Whitley March Case Study March 24, 2013 Clinical Practicum I Medical Dosimetry

Tangential treatment of left breast cancer with neoadjuvant Herpectin-Perjeta History of Present Illness: The patient PK is a 44 year old female with a diagnosis of grade 2 Infiltrating Ductal Cell Carcinoma of the left breast. PK presented with intermittent left breast pain. Upon mammogram and ultrasound she had many areas of abnormalities in the left breast and axilla, and upon palpation, multiple mobile masses were present in the left axilla. Biopsy of one of the breast lesions was positive for grade 2 infiltrating ductal carcinoma which was estrogen and progesterone receptor positive, as well as HER2 positive. Human Epidermal Growth Factor Receptor 2, or human epidermal growth factor receptor 2, is a protein that promotes the growth of cancer cells. Human Epidermal Growth Factor Receptor 2 is associated with other cancer diagnoses, but it is most commonly associated with a diagnosis of breast cancer. It is also not an inherited gene mutation.1 A biopsy of one of her lymph nodes was positive for malignancy. Magnetic Resonance Imaging (MRI) revealed a 5 centimeter (cm) area of enhancement in the left breast with many abnormally appearing lymph nodes. Staging computed tomography (CT) scans were done, as well as a bone scan, a Positron Emission Tomography (PET) scan, and a MRI of the brain. Staging revealed evidence of multiple bone metastases. At this time PK transferred doctors and was prescribed a combination of chemotherapy drugs: Herceptin, Taxotere, and Perjeta. Many chemotherapy drugs have been designed to target the HER2 positive patient. To be selected to use the Perjeta, detection of overexpression of the HER2 protein is required because these are the only patients studied and for whom the research has detected a benefit.2 Herceptin is a more traditional breast cancer chemotherapy drug, and in the case of patient PK, Perjeta and Herceptin were administered, along with Taxotere. After 6 cycles of this chemotherapy regimen, PK had an astounding result. Based on retesting, the multiple bone metastases previously seen on the bone scan, PET scan, and MRI, were resolved. There was one remaining area of concern on the posterior ninth rib, which was not a part of the original results, indicating an association with trauma and not cancer. In her chart her doctors referred to this as an excellent clinical response to treatment. A repeat

bone scan revealed resolution of all the areas of concern. Next, the patient underwent a lumpectomy and axillary lymph node dissection, and there was no evidence of residual malignancy in the breast, with all 15 lymph nodes sampled, registering negative. PK will continue Herceptin and Perjeta adjuvantly and will be starting hormonal therapy. This patient was presented for discussion at tumor boards and chart rounds to determine the proper course of treatment. Past Medical History: Deep vein thrombosis in right arm. Past Surgical History: Mediport placement in the right arm in September 2012. Port removal and relocation to the right superior chest wall in November 2012. Social History: PK works as an art teacher in an elementary school. She is single and lives on her own. She is a nonsmoker and nondrinker. Medications: Coumadin, biotin, multivitamin, Herceptin, Perjeta Family History: PKs paternal grandmother had breast cancer at age 70. Gynecological History: The patient has never been pregnant or bared a child, nor been pregnant. She has been on birth control for 24 years and is interested in genetic counseling. Radiation Oncologists Recommendations: PKs radiation oncologist has decided, after presenting this case for discussion to treat to a total dose of 4256 cGy (centigray). This dose will be broken into 16 treatments that will be administered at 266 cGy/day. Due to the complete response to chemotherapy, the patient will not require a boost prescription or further radiation after the initial 4256 cGy. PK will continue Herceptin and Perjeta adjuvantly and will be starting hormonal therapy. The physician ordered a CT scan for treatment planning purposes. Patient Setup and Immobilization: For the simulation process, the therapist escorted PK to the CT scanner, a GE LightSpeed. Before the complex simulation, the procedure was explained extensively to PK and the consent form was signed. A timeout was taken prior to the beginning of the simulation to verify the patients name, that she knew why she was having a scan, and to verify the breast to be treated. Photos were also taken to be uploaded into the patients electronic chart. The patient was placed on the breast board (see Figure 1). The breast board was placed on the table top with the wingboard, a Vac-Lok, and B headrest on the wingboard (see Figure 2). The patient was placed supine with knee wedge for her knees, both arms extended above her head and holding handles in the B1 position. The radiation oncologist came in to mark the extent of the breast tissue (superior, inferior, medial, lateral), lumpectomy

scar marker, and a nipple marker. Then the laser origin was marked with 3 bbs. The scan then began and was taken in 2.5 millimeter (mm) slices. After the scan was complete, the radiation oncologist came in and set the isocenter, the table was shifted, and the treatment isocenter was marked on the patient. The doctor also setup the medial tangent field. Photographs were taken of the setup with the isocenter demarcated. The CT images were then transferred to the picture archiving and communication system (PACS) software and then to the Eclipse treatment planning software (TPS). Patient Contouring: After the patient was pulled in to Eclipse for planning, contouring was done of both the lungs separately, and then a combination structure called total lung volume, as well as the heart, the spinal cord, the carina, the body, the scar and all of the field delineating wires, and the thyroid gland. All of the radiopaque marks that are used to indicate regions of interest are made of a substance with higher atomic number than that of human tissue. This allows them to be seen on the scan. These marks and/or wires have to have their density forced to the Hounsfield value of 1. This is so the plan does not compensate for the change in homogeneity, causing an associated decrease in transmission. Next, the radiation oncologist was called to contour the clinical target volume (CTV), which is the cavity, or balloon. A 1 cm expansion was placed around the CTV. A plan was generated based upon the expansion and the CTV receiving the prescribed dose of radiation. Treatment Planning: First, since the medial beam was placed at the time of simulation, it was opposed to produce the lateral tangent beam. With both of the beams created, a non-coplanar technique was used to provide non-divergent posterior borders and to decrease the radiation received in the lung and heart. The energy was set to 6 megavoltage (MV) for both beams. The separation of the patient was not large so this energy provided adequate penetration and achieved proper dose distribution. Both the separation and the dose distribution can be seen in Figure 3. An initial calculation was done at this time and it was decided that electronic compensators (ECs) were required. Due to the use of ECs, the weighting was left as equally divided in half. At this facility the weighting is left alone when using ECs. With ECs you have the ability to edit the fluence or the dose cloud. Once the changes are made, the EC determines how the MLCs (multi-leaf collimators) move to create the chosen fluence. This can be seen in Figure 4. By choreographed movements that increase or decrease the transmission, MLCs influence the dose to the CTV. After the plan has the V20 per lung less than 30%, the mean lung dose less than 20

Gy, the heart V20 dose less than 10%, and the mean dose to the liver less than 28 Gy, the dosimetrist works with the plan until the hot spot is decreased as far a possible without effecting the coverage to the CTV. These doses are registered on a dose volume histogram (DVH) and reported to the physician (Figure 5). Once these were achieved, the radiation oncologist approved the plan. Then the approved plan was exported to Mosaiq and the beam data was provided by dosimetry for comparison by the therapist at the treatment console (Figure 6). Finally a quality assurance (QA) plan was developed, digitally reconstructed radiographs were provided for the first day of treatment, and a backup calculation was performed in RadCalc (see Figure 7). Physics: Once the plan was approved, the secondary calculation verified (see Figure 7), and ready for treatment, the final step was to run a trial fraction of the plan to make sure that the information accurately transferred to the record and verify software, and that the plan would behave in the manner in which it was meant. Blocked or open tangential breast fields would not require a quality assurance check, but this plan uses ECs, and verification must be obtained to prove that the MLCs are performing as designed. A QA plan was created by the physicist to run on the Delta4. The fluence that registered within the Delta4 was compared to the approved treatment plan fluence. For the plan to pass QA, 95% of all the points tested within the phantom must have a 3% more or less deviation from the predetermined dose. This plan passed QA. First Day of Treatment: Before the first day of treatment, a beam verification simulation (BVS) is performed to verify patient positioning, beam arrangement, beam modification, and accuracy. The on-site physician authorizes the beginning of treatment after approving the port films. The port films are taken with an on board imager (OBI) in real-time, so that changes can be made and recorded for the treatment regimen to begin. This process prepares both the patient and the therapists to begin treatment. Conclusion/Impact: PK is a 44 year old female that presented with triple-positive infiltrating ductal carcinoma of the left breast with metastatic bone disease. When I first heard this diagnosis, I was heartbroken for this young woman. But, as I was introduced to the details of PKs diagnosis, I became so intrigued. PKs pre radiation status is one of complete pathologic response in the breast and nodes, and complete radiographic response in the bones. This startled and delighted me, fueling my interest to learn more about this special patient. As I searched the facility for more data, a radiation oncologist at Central Dupage Hospital (CDH) stated that PK is

the second breast cancer patient with bone metastasis that she has seen with this response. Due to the age of PK, 44 years old, and the comparable age of the other patient, the responses to this regimen are remarkable, and well worth further research. I think I will always remember this patient and the inspiration that I feel. Oftentimes we are met with poor outcomes, horrible stories of the irreversible damage of cancer treatment, and the horrible loss of life cancer has cost. This case fits none of those classifications, and redefines the answer to the question Are we making any progress in the fight against cancer. This story and these patients are an inspiration to the fight against cancer. This is the outcome to wearing the pink, for walking the walks, of relaying for life, and running for cures. This is the defense for the donations. Everyone needs these stories of hope, and that is what PK has given to mehope.

Figures

Figure 1. This is a picture of the immobilization used for PK. On the table is a wing board, a Vac-lok, and a knee wedge.

Figure 2. This illustrates the wing board and the Vac-lok separately, as the Vac-lok must be stacked on to both the headrest and the wing board for proper immobilization and accurate treatment.

Figure 3. This is a visual representation of the even dose distribution obtained with the ECs.

Figure 4. This illustrates the dose distribution at the level of the isocenter. The tumor bed and the expansion are also represented, along with the ECs used to appropriately shape the dose distribution.

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Figure 5. This is a dose volume histogram (DVH) that depicts the radiation received by the tumor and the organs at risk.

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Figure 6. This is the beam data sheet generated for documentation and comparison for daily treatment and chart checks.

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Figure 7. This is a secondary calculation performed to verify the accuracy of the initial calculation. This is a backup for quality assurance purposes.

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References 1. Mayo Clinic Foundation. HER2-positive breast cancer: What is it? http://www.mayoclinic.com/health/breast-cancer/AN00495. Updated April 11, 2012. Accessed March 26, 2013. 2. Genentech Inc. Strengthen her defense. http://www.perjeta.com/?cid=per_pa_F001184_P000517&c=MBPTUA1001&gclid=CO To2uLCm7YCFdE-MgodzUAAVQ. 2013. Accessed March 26, 2013.