1 Dustin Melancon February Case Study February 21, 2013 LDR Brachytherapy for Choroidal Melanoma of the Right

Eye History of Present Illness: Patient PS is a 62-year-old female with choroidal melanoma. Choroidal melanoma is a primary cancer of the eye that arises from the pigmented cells of the choroid.1 On a routine exam by an ophthalmologist, PS was noted to have a pigmented mass posterior to the equator in the inferior nasal retina (Figure 1). The lesion measured 8 x 11 millimeter (mm) with an approximate 3.2 mm thickness (Figure 2). It was 5 mm from the optic disc (Figure 1). A choroidal melanoma is recognized in an eye examination by features such as the degree of pigmentation of the tumor, shape, and location. Choroidal melanoma is visible through the pupil. Most of the time, the ophthalmologist can be nearly certain of the diagnosis from clinical appearance, photographs, and ultrasound pictures; therefore, biopsy is usually avoided.1 On physical examination, the patients pupils were equal and round. They were reactive to light and accommodation. PS did not report any significant changes to her vision. Fundoscopic exam revealed a pigmented lesion in the inferior nasal retina. Fundoscopy allows visibility of the inner eye with the aid of an ophthalmoscope. Photographs taken with an ophthalmoscope and fundus camera are called fundus photographs.2 In January 2013, her ophthalmologist discussed the risks, benefits, and side effects of treatment. PS elected for treatment and the ophthalmologist prescribed an eye plaque procedure. This is a low dose rate (LDR) brachytherapy treatment.2 The ophthalmologist then coordinated with a radiation oncology. Past Medical History: PS has a known history of left-sided glaucoma, which resulted in a loss of peripheral vision due to some nerve damage. On a routine exam by an ophthalmologist, she was noted to have a new lesion in her right inferior nasal retinal area. She denied any previous radiation. She denied pain and any thyroid issues, lumps in the neck, or neck pain. Lastly, PS has no known allergies. Social History: The patient denies use of alcohol, tobacco, and illicit drugs. She is a high school graduate and currently retired. She has one child. She has a family history of cancer in her father, five uncles, and two cousins. Her grandfather had glaucoma.

2 Medications: PS uses the following medications: Vitamin D, aspirin, Simvastatin, and Xalatan. Diagnostic Imaging: On a dilated fundus exam of the right eye, she had a choroidal mass in the inferior nasal retina just posterior to the equator with pigmentation at the base. The normal eye appears orange in the fundus photo, but a gray shadow appears when ocular melanoma is present.2 This measured approximately 8 x 11 mm. Additionally, PS received ultrasound echography of the eye. This modality is a useful tool in determining some dimensions and the location of an eye tumor relative to the critical normal structures (Figure 3, Figure 4).2 The lesion was 3.2 mm thick and demonstrated medium reflectivity by ultrasonography. The location was approximately 5 mm inferonasal from the disc. She proceeded with a metastatic workup. The ophthalmologist agreed to coordinate with a radiation oncologist and her primary care physician for her treatment. Radiation Oncologist Recommendations: The radiation oncologist reviewed the patients records and agreed to participate in the patients care. PS is an excellent candidate for eye plaque therapy (Figure 5). The National Eye Institute launched the Collaborative Ocular Melanoma Study (COMS) to evaluate the efficacy of using iodine-125 (125I) eye plaques in comparison to eye removal for medium size tumors. Eye plaque therapy helps stop tumor growth without causing damage to normal tissue.2 The radiation oncologist discussed the benefits of eye plaque therapy with PS and what she should expect from her treatment. The patient understood the risks, benefits, and side effects. PS signed the informed consent form for eye plaque therapy. The Plan (Prescription): The ophthalmologist, radiation oncologist, and ophthalmic oncologist discussed which radionuclide and source model to use. This decision was based on preoperative comparative treatment planning to determine doses to the tumor.2 The radiation oncologist ordered LDR brachytherapy and the radiation dose was prescribed. They planned to deliver 8,500 cGy over approximately four days to the apex of the tumor, which measured 8 x 11 x 3.2 mm. The apex is defined as the farthest intraocular extent of the tumor, so tissue proximal to that point will receive progressively more than 8,500 cGy. The tumor base typically receives the maximum dose due to source proximity.2 Treatment Planning: When eye plaque treatment is chosen as the treatment modality, the physicist performs the treatment planning, quality assurance of treatment delivery, and radiation safety procedures. Neither anatomical contouring nor dose volume histograms were used in treatment planning. The physicists used Eclipse 10.0 treatment planning software (TPS) with an

3 eye phantom template (Figure 6, Figure 7, and Figure 8). The sources were placed onto the template according to the coordinates obtained from the ultrasound exam then compared to the coordinates from Task Group 129 (TG-129). The 125I sources were tested February 1, 2013 with a strength of 7.02 cGy cm2/h. The objective was to maintain the prescribed dose throughout the tumor. The 16 mm eye plaque was selected based on measurements received from the ophthalmologist (Figure 9, Figure 10). It was calculated that the eye plaque needed to stay on the patients eye for four days to obtain desired dose. Quality Assurance/Physics Check: The physicists verified the strength of the sources by placing them in a well-type ionization chamber. Another physicist performed a second check on the brachytherapy plan and the TG-43 based dose distribution was verified by an independent dose calculation method using a spreadsheet calculation. Tolerances of 2% on the central axis of the eye plaque are considered acceptable. Procedure: When using radiation to treat medium choroidal melanoma, the goal is to destroy the tumor and save the eye. High doses of radiation should be given to the tumor and very little to the rest of the eye. Radioactive iodine seeds are glued to one side of the eye plaque and a thin gold sheet is attached to the other (Figure 11, Figure 12). The gold layer acts as a shield to protect the tissues beyond it.2 Radioactive plaque therapy requires two surgical procedures to insert and remove the eye plaque. The patient was under general anesthesia to implant the radioactive plaque. An incision was made in the patients conjunctiva, a thin membrane which covers the outside of the eye.1 The radioactive plaque was stitched to the outside of the eye over the tumor (Figure 13). The conjunctiva was then sewn back over the plaque. The procedure took about two hours. Afterwards, PS was sent home with a lead eye patch to use whenever she was in contact with people. Approximately four days later, surgery was performed again to remove the plaque. This procedure took less than an hour under local anesthesia. The patient was able to go home the same day. The radiation oncologist wanted a follow-up six weeks after the procedure. Conclusion: The most promising, widely available method for irradiating medium choroidal melanoma involves COMS eye plaque. This treatment is an alternative to enucleation, or eye removal. Some of the advantages of eye plaque therapy include the patient keeping their eye and vision under favorable conditions.2

4 Compared to removing the eye, there are disadvantages to COMS eye plaque surgery. There are additional costs because it involves two surgeries, and a radioactive plaque. Radiation can damage healthy parts of the eye, which may cause vision loss. Radiation damage to the lens may cause a cataract.1 After radioactive plaque treatment, many patients experience dryness and irritation of the eye. In some instances, eyelashes may be permanently lost. Occasionally, there may be prolonged redness, irritation, or infection inside the eye. The patient may see double if the muscles are damaged during the procedure to apply or remove the plaque.1 Future dose studies are needed to determine the required base or apex dose for any intraocular tumor. Improved dosimetry methods are also needed to allow more accurate research on the radiation tolerance of normal eye structures and the minimum required dose for tumor control. Research is needed to decrease irradiation of normal ocular structures, to reduce the apex dose, to increase the dose gradient outside the tumor, and to reduce the target volume.2 The medical physicist experienced unique challenges during the brachytherapy treatment planning. The challenges in accurate dosimetry are partly related to the steep dose gradient in the tumor and critical structures that are within millimeters of radioactive sources. Choice of radiation modality and prescribed dose can influence local tumor control, visual acuity, eye retention, and cosmetic results.2 The radioactive seeds provided the physicist with a nice dose distribution and good tumor coverage. I really enjoyed studying eye plaque therapy. This was the first time I heard about brachytherapy treatment for eye malignancies. Two patients have been treated in the past three weeks. The things I see at my clinic site constantly amaze me. Although the COMS procedure might sound unpleasant, the tumor is destroyed in favorable circumstances. When radioactive plaque therapy is successful, the tumor stops growing and may shrink over the course of 6 to 12 months. The patient should be able to keep their vision rather than having their eye removed.2

5 Figures

Figure 1. Transverse diagram of the standard right eye with 22 mm inner diameter.2

Figure 2. Tumor drawing on a fundus diagram, showing an example of tumor base dimensions; (a) right eye, (b) left eye.2

Figure 3. Diagram of an ultrasound A-scan. The A-scan is an amplitude modulation scan that provides data on eye length. A-scans use two signals with different sound speeds. This information is used to determine the distance and thickness of structures. The structural boundaries help localize the tumor. The tumor apex is localized by a display of steeply rising spikes at the apex and at the scleras interior surface. In this way, the apical height, or the tumor thickness, can be determined accurately.2

Figure 4. Schematic diagram for ultrasound B-scan of an eye with ocular melanoma. A B-scan is performed to obtain a complete topographic overview.2

Figure 5. Diagram of a choroidal melanoma in an eye with an eye plaque applied over the tumor base. Other anatomical structures and landmarks are also indicated.2

Figure 6. Phantom in the coronal view.

Figure 7. Phantom in the sagittal view.

Figure 8. Phantom in the transversal view.

Figure 9. There are five standard sizes for COMS eye plaques. From left to right: 20, 18, 16, 14, and 12 mm in diameter. From top to bottom, row 1: gold backings, row 2: silastic seed carrier inserts with seeds loaded, row 3: silastic inserts without seeds, row 4: acrylic pieces to fit in silver rims of dummy plaques.2

Figure 10. 125I seeds, a silastic seed carrier insert, gold backing, and dummy plaque for a 16 mm COMS plaque, from left to right.2

10

Figure 11. Seed arrangement in the silastic seed carrier insert and the gold plaque design. (a) Top view and (b) side view of a 14 mm COMS standard plaque.2

Figure 12. The eye plaque contains radioactive iodine seeds glued to one side and a thin gold sheet attached to the other.1

Figure 13. An incision is made in the conjunctiva, a thin membrane that covers the outside of the eye, and the radioactive plaque is stitched to the outside of the eye over the tumor. The conjunctiva is then sewn back over the plaque.1

11 References 1. About Choroidal Melanoma. COMS Web site. http://www.jhu.edu/wctb/coms/booklet/book2.htm. Accessed February 20, 2013. 2. Chiu-Tsao S. Episcleral eye plaques for treatment of intraocular malignancies and benign diseases. In: Thomadsen BR, Rivard MJ, Butler WM, eds. Brachytherapy Physics. 2nd ed. Madison, WI: Medical Physics Publishing; 2005:673-705. 3. Chiu-Tsao S, Astrahan MA, Finger PT, et al. Dosimetry of 125I and 103Pd COMS eye plaques for intraocular tumors: Report of Task Group 129 by the AAPM and ABS. Med Phys. 2012;39(10):6161-6184.