1 Spencer Arnould October Case Study October 21, 2013 Distal Esophageal Squamous Cell Carcinoma History of Present

Illness: Patient P is a 65-year old man who has been recently diagnosed with stage IIIB Tumor 3 (T3), Node 1 (N1), Metastasis 0 (M0) distal esophageal squamous cell carcinoma. Patient Ps history began in July where he presented to his primary care provider. He described a prolonged period of mid to lower esophageal dysphagia with solids, but not liquids, and also a right parasternal discomfort when eating daily meals. Patient P was then referred to a gastroenterologist who performed an esophagogastroduodenoscopy (EGD) on July 24, 2013. This examination found a circumferential mass at 28-30 centimeters (cm) from the incisors. The mass was biopsied and confirmed to be basaloid squamous cell carcinoma. On August 21, 2013, Patient P was sent for a computed tomography (CT) scan of the chest, abdomen, and pelvis that demonstrated thickening of the wall of the distal esophagus and a 3-4 millimeter (mm) non-calcified nodule in the left lower lobe that also required a follow-up. After this exam, Patient P was then sent for a barium swallow on September 16, 2013, which revealed a narrowing at 3 cm distal to the carina for approximately 5 to 6 cm in length. After Patient P was fully informed of his diagnosis, he was then referred to both medical and radiation oncology do discuss definitive chemoradiation with the possibility of a surgical transhiatal esophagectomy. Past Medical History: Patient Ps medical history includes hypertension, arthritis, and cataracts. Pateint P also had back surgery that included spinal lumbar fusion, and also bilateral eye surgery. Social History: Patient P was formerly a heavy smoker and moderate drinker. He quit both of these after his diagnosis but still uses smokeless tobacco and drinks on occasion. He also denied using illicit drugs. Medications: Patient P used the following medications: atorvastatin, multivitamin with minerals/lutein, nifedipine, omeprazole, dexamethasone, ondansetron, and prochlorperazine. Diagnostic Imaging: After the initial assessment and consultation with his primary care physician, Patient P was sent for an EGD on July 24, 2013, which showed a circumferential mass at 28-30 cm from the incisors. A biopsy was taken from this exam and the results prompted both a referral to medical oncology and further testing of his distal esophageal squamous cell

2 carcinoma. On August 21, 2013, Patient P was sent for a CT scan of his chest, abdomen, and pelvis that demonstrated both thickening of the wall of the distal esophagus and a 3-4 mm noncalcified nodule in the left lower lobe of the lung. After this examination, Patient P was then sent for a positron-emission tomography (PET) scan on September 12, 2013 which showed uptake in the esophageal wall thickening in the distal esophagus. Most malignant tumors of the esophagus metabolize glucose at a higher rate than normal tissue that in turn causes an increased accumulation of the glucose analog flourodeoxyglucose (FDG) in malignant tissues.1 In addition to these procedures, Patient P also had a barium swallow on September 16, 2013 that revealed narrowing at 3 cm distal to the carina for approximately 5 to 6 cm in length. Radiation Oncologist Recommendation: After review of Patient Ps distal esophageal squamous cell carcinoma, the radiation oncologist discussed treatment options with the medical oncologist. With this type of staging, and the patients overall current condition, the radiation and medical oncologist recommended that he receive definitive preoperative chemoradiation followed by a transhiatel esophagectomy. In patients who are medically and surgically fit, either chemo-irradiation alone or preoperative chemo-irradiation followed by surgery can be considered.2 After a complete discussion about the nature of his squamous cell carcinoma tumor, the radiation oncologist reviewed the logistics, risks, benefits, and also the long and short-term side effects with receiving both radiation and chemotherapy. The radiation oncologist ultimately recommended that Patient T receive 5.5 weeks of daily radiation treatment, or 28 treatment sessions given 5 days a week, in addition to his chemotherapy which was scheduled around normal treatment sessions. The Plan (Prescription): The radiation oncologist treatment recommendation for Patient P was to treat the middle to distal portion of the esophagus to a total dose of 50.4 Gray (Gy) in 1.8 Gy fractions daily. This type of fractionation is the standard dose for esophageal cancer included in all modalities. According to a study by Minsky et al3, they have shown through patient study research that any type of intensification of the radiation dose to higher doses, including 64.8 Gy within the study, does not improve local/regional control or survival, and therein would not be recommended. The use of all three modalities chemotherapy, radiation therapy, and surgery has the potential to increase survival by decreasing distant metastasis and eliminating residual local disease with surgery after chemoradiation.3

3 Patient Immobilization: On September 27, 2013, Patient P underwent a CT simulation scan for radiation therapy. He was placed on Civco thorax board (Figures 1, 2, and 3), which included his arms above his head, resting within adjustable arm cups for support. An egg crate cushion and knee cushion were placed underneath his back and knees for additional support. While the CT scanning parameters were being set, the radiation therapist gave Patient P barium solvent (in liquid shake form) before scanning the thorax region. This barium solution was enhanced on the CT scan and highlighted the entire esophageal passage and entrance into the stomach, making the localization much easier. After the scan was complete, the radiation therapist placed reference tegaderms on the patient in order to help with alignment on the first day. One tegaderm was placed 12 cm below the superior sternal notch (SSN) (Figure 1) and two different tegaderms were placed on either side of the patient for side levels (Figure 2). The radiation therapist also placed straightener marks on the patient (one superior of the CT reference mark) to make sure that he would line up straight on the first day. Anatomical Contour: After the scan was completed, the images were sent to the Digital Imaging Communications of Medicine (DICOM) conquest server, which can import and export images to the necessary treatment planning stations. The images from Patient Ps scan were transferred to the Eclipse contouring station for the physicians and residents to contour tumor volumes. Both the physicians and residents contoured the gross tumor volume (GTV), and the clinical target volume (CTV), while also contouring the necessary anatomic structures that needed to be avoided. After this process, the physician and resident decided on an adequate expansion volume known as the planning target volume (PTV). In this specific case, the physician decided that he wanted to expand the GTV by 1 cm circumferentially and radially in order to delineate a suitable PTV for planning margin. After the physicians completed the contouring, a planning directive was dictated for the medical dosimetrists to follow. This form allows the physicians to communicate, suggest, and recommend planning guidelines for the medical dosimetrist to follow while planning the case. Once the physicians were completely done with contouring the areas of interest, the medical dosimetrist contoured normal structures based on the anatomical area of concern. In this case, the external body, heart, spinal cord, lungs, and liver were contoured due to the extent of the PTV extending throughout the area. Beam Isocenter/Arrangement: After the contours had been drawn and the volumes expanded, the CT scan was then exported to the conquest server, and re-imported into UMPlan treatment

4 planning software. After the scan was imported into the treatment planning system, the medical dosimetrist obtained the treatment-planning directive in order to the follow both the physician and departmental guidelines on adequate dosing for thoracic patients. The medical dosimetrist began by designing a four-field box technique that essentially gave dose through four different angled beams allowing for acceptable coverage around the PTV. These beam angles for a fourfield box include 0, 90, 180, and 270. Although this type of design works in many esophageal cases, this specific case did not allow for this exact treatment planning due to the extent and length of the PTV within the thoracic region. The medical dosimetrist tailored this four-field box technique by adding an additional segment beam with an angle of 160, in order to gain adequate coverage around the entire PTV (Figures 4, 5, and 6). Treatment Plan: The planning system used to calculate the treatment plan was UMPlan. While initially looking at these types of cases, one of the issues that often arise is the comparison of intensity modulated radiation therapy (IMRT) versus standard 3 dimensional conformal radiation therapy (3DCRT). Although the department usually stays with 3DCRT esophageal planning, an IMRT plan for this specific case would be helpful in bringing the overall dose down on critical structures. Ultimately the 3DCRT plan was the choice by the physician due to the unnecessary IMRT treatment planning complexity for this specific case. When starting to plan this 3DCRT case, the medical dosimetrist usually starts out with 6 MV beam energy, and evaluates the necessity for higher energies. In this specific distal esophageal case, the PTV extended from the upper middle to distal portion of the GE junction, giving rise to a more elongated target volume that extended the distance of the thorax (Figure 5, 6). Although most dosimetrist like to utilize 6 MV beam energies, especially when treating through lung tissue, the separation of the patient and length of the PTV did not allow for enough coverage margin. The medical dosimetrist used 16 MV beam energy for all angles within the plan. As figures 7 through 8 demonstrate, all of the fields for this plan, including the segmented field, had a 0.7 cm blocking margin around the PTV. Although the medical dosimetrist only used 5 total fields within the treatment plan, this technique allowed for adequate coverage to conform and evenly distribute dose around the target volume. The medical dosimetrist also weighted the fields based on the dose to the spinal cord, lung tissue, and heart. Since the anterior posterior (AP) and posterior anterior (PA) fields did not encompass very much lung tissue, a higher weight was used in comparison to the two oblique lateral fields. The AP and PA fields in this treatment plan were weighted higher than both

5 lateral fields in order to spare lateral lung dose through the thoracic region. Although this treatment plan encompasses expansions and blocking margins for each field, the physician and medical dosimetrist also need to consider the dose conformity, tissue sparing, and possible setup error or daily variability during treatment. In a study by Chen et al4, image-guided radiation therapy (IGRT) using MV x-rays can effectively detect set-up errors and thereby reduce PTV margins. This technique will also reduce the radiation dose to critical organs and lead to the possibility of dose escalation. This practice not only allows for better accuracy and target delineation, but also prevents from radiation toxicity to critical organs at risk. The overall normal tissue complication probability (NTCP) for this case was 14.13%, which falls within our clinics tolerance levels of 15%. The overall maximum dose to the PTV treatment volume was 54.4 Gy, with the spinal cord receiving a maximum dose of 45.6 Gy, and the heart receiving a mean dose of 32.4 Gy (Figure 9). Quality Assurance: The monitor unit calculation and monitor unit check were completed in both the download (through UMPlan) as well as the second check through a medical physicist. A medical physicist not only calculates the plan through another software program, but also sometimes hand checks both the monitor units and back-up time to make sure the plan agrees with the tolerance that was set. The monitor units on this 5-field esophagus technique were within tolerance and within the back-up time associated with the department tolerance guidelines. Conclusion: Although this distal esophageal case fell within the standards of planning with a four-field box technique, with the addition of a segmented field, not all cases would be this forward. Many cases can include special circumstances that do not allow for this method of treatment, which can make treatment planning much more difficult. One of the things most enjoyable about this case was the ability to learn about target coverage. Since the PTV extended from the middle to distal portion of the esophagus, it covered a non-uniform elongated path throughout the chest. The treatment planning process for this case allowed me to understand not only where to insert beams, but also what the beams should cover. Although I learned more about esophageal treatment planning throughout this entire process, I did struggle with gaining adequate coverage around the PTV. While it took some time trying to utilize different beam angles and beam weights, I felt that I completed the plan with excellent coverage to the tumor volume and minor dose to the critical structures. Overall, this case was a great learning

6 opportunity for me to use some critical problem solving skills, and come up with something that agrees with the planning directive targets. I felt that I did a great job with this plan and look forward to learning from future distal esophageal cases.

7 Figures

Figure 1. Patient P on a Civco thorax board with Tegaderm reference mark and straighteners.

Figure 2. Patient P on a Civco thorax board with Tegaderm side levels.

Figure 3. Set-up picture of Patient P on a Civco thorax board, egg crate cushion, and knee rest.

Figure 4. Axial view of isocenter on Patient T. The pink color indicates the 50.4 Gy or 100% isodose line, and the orange color indicates the 47.8 Gy or 95% isodose line.

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Figure 5. Sagittal view of Patient T. The pink color indicates the 50.4 Gy or 100% isodose line, and the oange color indicates the 47.8 Gy or 95% isodose line.

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Figure 6. Coronal view of Patient T. The pink color indicates the 50.4 Gy or 100% isodose line, and the oange color indicates the 47.8 Gy or 95% isodose line.

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Figure 7. Upper Left: AP Beams Eye View (BEV). Upper Right: Left Posterior Oblique (LPO) Segment BEV. Lower Left: PA BEV. Lower Right: Left Lateral BEV.

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Figure 8. Right Lateral BEV.

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Figure 9. Dose Volume Histogram (DVH) showing the various structures that were contoured in the plan.

15 References 1. Chao K, Perez C, Brady L. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011:357-371. 2. Heath E, Heitmiller R, Forastiere A. Esophageal Cancer. In: Hall L, ed. Clinical Oncology. Atlanta, GA: American Cancer Society; 2001:331-343. 3. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (RTOG 94-05) Phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J of Clin Onc. 2001;20(5):1167-1174. doi:10.1200/jco.20.5.1167. 4. Chen YJ, Han C, Schultheiss T, et al. Setup variations in radiotherapy of esophageal cancer: evaluation by daily megavoltage computed tomographic localization. Int J Rad Onc. 2007;68(5):1537-1545.