Optic disc dose reduction in ocular brachytherapy using 125I notched COMS plaques: A simulation study based on current clinical practice

Abstract Purpose Although notched Collaborative Ocular Melanoma Study (COMS) plaques have been widely used, optic disc dose reduction by notched COMS plaques has not been discussed in the literature. Therefore, this study investigated optic disc dose reduction in ocular brachytherapy using 125I notched COMS plaques in comparison with optic disc dose for 125I standard COMS plaques. Methods For this simulation study, an in‐house brachytherapy dose calculation program was developed using MATLAB software by incorporating the American Association of Physicists in Medicine Task Group‐43 Update (AAPM TG‐43U1) dosimetry formalism with a line source approximation in a homogeneous water medium and COMS seed coordinates in the AAPM TG 129. Using this program, optic disc doses for standard COMS plaques (from 12 to 22 mm in diameter in 2 mm increments) and notched COMS plaques with one seed removed (Case #1, from 12 to 22 mm) and with two seeds removed (Case #2, from 14 to 22 mm) were calculated as a function of tumor margin‐to‐optic disc distance (DT) for various tumor basal dimensions (BDs) for prescription depths from 1 to 10 mm in 1 mm intervals. A dose of 85 Gy for an irradiation time of 168 h was prescribed to each prescription depth. Then absolute and relative optic disc dose reduction by notched COMS plaques (Cases #1 and #2) was calculated for all prescription depths. Results Optic disc dose reduction by notched COMS plaques (Cases #1 and #2) had five unique trends related to maximum optic disc dose reduction and corresponding optimal DT for each BD in each plaque. It increased with increasing prescription depth. Conclusions The results presented in this study would enable the clinician to choose an adequate plaque type among standard and notched 125I COMS plaques and a prescription depth to minimize optic disc dose.


| INTRODUCTION
A variety of treatment techniques for juxtapapillary choroidal melanoma (a tumor within 1 mm of the optic disc) 1,2 have been used and such techniques include enucleation, plaque radiotherapy, charged particle (proton or other heavy ions) radiotherapy, stereotactic radiotherapy, and transpupillary thermotherapy. 2,3 Plaque radiotherapy is a preferred modality to enucleation for mediumsized tumors (apical height from 2.5 to 10 mm and maximum tumor basal dimension of ≤16 mm) as it allows for eye and vision retention with equivalent tumor control. 4,5 The Collaborative Ocular Melanoma Study (COMS) randomized trial evaluated 125 I plaque radiotherapy versus enucleation for medium-sized choroidal melanomas but excluded juxtapapillary melanoma from the plaque radiotherapy arm and offered enucleation instead. 3,6 Nevertheless, major institutions have treated juxtapapillary choroidal melanoma using plaque brachytherapy. 1,2,7 One of the major contraindications for plaque brachytherapy is visual change/loss, and its substantial risk factors were found to be proximity of the tumor to the optic disc and radiation dose to the optic disc. 3,8,9 To spare the optic disc and consequently, to reduce the contraindication, notched plaques were devised primarily for juxtapapillary or circumpapillary (overhanging the optic disc) tumors. 3,10 Notched COMS plaques, which have usually one radionuclide seed removed from standard COMS plaques, have been widely used. 11 Customized notched plaques or slotted plaques were also designed and have been used to accommodate the optic disc better than notched COMS plaques. 3,10,12 In the literature, visual outcomes for these notched or slotted plaques were reported. 3,10,12 To the best of our knowledge, however, detailed dosimetry information on radiation dose reduction to the optic disc by the use of notched plaques has not been published before. The purpose of this study, therefore, was to investigate absolute and relative dose reduction to the optic disc in ocular brachytherapy using 125 I notched COMS plaques in comparison with optic disc dose for 125 I standard COMS plaques. This investigation was made based on simulations using our in-house brachytherapy dose calculation program developed in MATLAB software.

Two American Association of Physicists in Medicine (AAPM)
Task Group (TG) reports (TG 129 4 and TG 221 13

2.A | Configurations of notched COMS plaques
Seven different-sized (from 10 to 22 mm in diameter in 2 mm increments) standard COMS plaques 4 and corresponding notched COMS plaques are currently available. The notched COMS plaques were designed to remove one seed 4 but two seeds can be removed to reduce optic disc dose further. As shown in the AAPM TG-129 report, the seed configuration and coordinates of the 10 mm plaque do not allow for seed removal. 4 Also, the seed configuration of the 12 mm plaque does not allow for two seeds removal. 4 Hence, six (from 12 to 22 mm) notched plaques for one seed removal and five (from 14 to 22 mm) notched plaques for two seeds removal are options to reduce optic disc dose. Along the X p axis, one side (+X p direction) of notched COMS plaques has a notch for optic disc accommodation and the other side (−X p direction) has suture lugs for a suture on the surface of the eye [ Figs. 1 Seed(s) in the notch side are removed to reduce optic disc dose. Table 1 shows seed position number(s) removed from standard COMS plaques in Fig. 1 of the AAPM TG-129 report. 4 As an example, seed diagrams for the 14 mm standard COMS plaque and notched COMS plaques with one seed removed and with two seeds removed are shown in Figs. 1(a)-1(c) in order. For one seed removal, seed #4 was removed instead of seed #1. Likewise, for two seeds removal, seed #4 and #9 were removed instead of seeds #1 and #7.

2.B | Eye anatomy
Based on current clinical practice for dose calculation methods in ocular plaque brachytherapy, 13 this study assumed that the spherically shaped eye consisting of water 14 is located in a homogenous water medium. Eye anatomy and coordinates for critical structures in the eye were based on the COMS protocol (Fig. 2). 15 The eye has an outer radius of 12 mm and the inner sclera surface has a radius of 11 mm. The macula (fovea) is located at 11 mm from the eye center in the inner sclera surface. The maximum separation between the macula and the center of the optic disc is 4 mm. Optic disc diameter in a fundus diagram is 1.5 mm.

2.C | Parameters for calculations of optic disc dose
According to the COMS protocol, three parameters are required for calculations of optic disc dose. 15 Basal dimension of tumor at center in the direction from optic disc (BD, parameter #1) and distance from optic disc to tumor margin (DT, parameter #2) are determined in a fundus diagram

2.D | Calculations of optic disc dose for a prescription depth of 5 mm
In our previous study, using our in-house brachytherapy dose calculation program, optic disc dose for seven (from 10 to 22 mm) standard COMS plaques loaded with 125 I seeds (models: IsoAid Advantage IAI-125A, Best Industries 2301 and Bebig I25.S16) was comprehensively investigated as a function of DT for various BDs. 16 The in-house program was developed using MATLAB software (vR2016a, MathWorks, Natick, MA) by incorporating the AAPM TG-43U1 dosimetry formalism with a line source approximation in a homogeneous water medium 17 and COMS seed coordinates from Table 1 in the AAPM TG-129 report. 4 The in-house program was validated for benchmark calculations in the literature, demonstrating similar accuracy to three commercially available treatment planning systems which use the same dose calculation algorithm as our inhouse program. 16 Then optic disc dose calculations were performed for a prescribed dose of 85 Gy normalized to a central-axis depth of 5 mm for an irradiation time of 168 h. 16 In this study, optic disc dose for notched COMS plaques loaded with 125 I seeds was calculated. Of commercially available 125 I seeds, the seed model used in our institution (IsoAid Advantage IAI-125A, IsoAid, LLC, Port Richey, FL) was selected for this study. Using the validated in-house program, dose calculations were performed in the same way as for standard COMS plaques for the following two cases: Case #1) six (from 12 to 22 mm) notched COMS plaques with one seed removed from standard COMS plaques and Case #2) five (from 14 to 22 mm) notched COMS plaques with two seeds removed from standard COMS plaques. As mentioned in the Section 2.A, the 10 mm COMS plaque was not included in Cases #1 and #2, and the 12 mm COMS plaque was not included in Case #2. For each notched COMS plaque, seed position number(s) removed from the corresponding standard COMS plaque are shown in Table 1. Once seed(s) are removed from standard COMS plaques, the prescription depth is not covered by the prescribed dose of 85 Gy.
After seed(s) were removed, therefore, for the same irradiation time of 168 h, air kerma strength (S k ) per seed needed to be increased (i.e., re-normalized 85 Gy to the prescription depth of 5 mm) to ensure full coverage of the prescription depth in both cases.

2.E | Generation of dose conversion factors for different prescription depths
A prescription depth is not always 5 mm and it is determined based on the tumor apex. According to the COMS protocol, 14 a prescription depth is 5 mm for the tumor apex <5 mm and the apex for the tumor apex ≥5 mm. In the recent American Brachytherapy Society consensus guidelines, 18 a prescription F I G . 1. Seed diagrams for (a) 14 mm standard Collaborative Ocular Melanoma Study (COMS) plaque, (b) 14 mm notched COMS plaque with one seed (seed #4) removed and (c) 14 mm notched COMS plaque with two seeds (seeds #4 and #9) removed. The dotted rectangle(s) in (b) and (c) represent removed seed(s).
T A B L E 1 Seed position number(s) removed from standard Collaborative Ocular Melanoma Study (COMS) plaques. Detailed information on seed positions and configurations for each COMS plaque is found in Fig. 1   The following unique trends for D Abs reduction ðGyÞ are observed.
1. D Abs reduction ðGyÞ increases with DT, reaches the maximum value (MaxD Abs reduction ) and then decreases with DT. For the largest 2-3 BDs, however, dose reduction continuously decreases with DT.
Examples include those for BDs of 7 and 9 mm in the 12 mm notched plaque [ Fig. 4(a)] and those for BDs of 15, 17, and 19 mm in the 22 mm notched plaque [ Fig. 4(f)].

2.
Maximum absolute optic disc dose reduction (MaxD Abs reduction ) is usually larger with smaller plaques but does not continuously decrease with plaque size.
3. The magnitude of MaxD Abs reduction does not vary with BD in each plaque except for those for the largest 2-3 BDs.

3.B | Dose conversion factors for different prescription depths
Dose conversion factors are presented in Table 2 for six standard COMS plaques, six notched COMS plaques with one seed removed    (Table 3). Of these, Scenario #1 (standard COMS plaque and prescription depth of 5 mm) and Scenario #6 (notched COMS plaque with two seeds removed and prescription depth of 3 mm) give the highest (197.6 Gy) and the lowest (65.0 Gy) optic disc doses, respectively. The optic disc dose difference between these two scenarios is 132.6 Gy. When 85 Gy is prescribed at 5 mm, dose reduction from optic disc dose (197.6 Gy) for the standard plaque is 56.9 Gy for one seed removal (Scenario #2) and 92.7 Gy for two seeds removal (Scenario #3). At a depth of 3 mm, dose reduction from optic disc dose (124.5 Gy) for the standard plaque is 37.3 Gy for one seed removal (Scenario #5) and 59.5 Gy for two seeds removal (Scenario #6). Although absolute dose reduction is larger for a depth of 5 mm, relative dose reduction is similar between the two depths [i.e., approximately 29% for one seed removal (Scenarios #2 and #5) and 47% for two seeds removal (Scenarios #3 and #6)].

| DISCUSSION
This study demonstrated that optic disc dose reduction by notched COMS plaques has its own trends (Figs. 4 and 7), and corresponding reasons for the five trends mentioned in the Results are as follows: T A B L E 2 Dose conversion factors (ratios of total reference air kerma per seed) for various prescription depths (1-10 mm in 1 mm intervals) for 125 I (model IAI-125A) standard Collaborative Ocular Melanoma Study (COMS) plaques, notched COMS plaques with one seed removed (Case #1) and notched COMS plaques with two seeds removed (Case #2). The data were normalized to those for a prescription depth of 5 mm   In this study, optic disc dose reduction for Case #1 and Case #2 was investigated. As more seeds near the optic disc are removed, dose contribution to the direction of the optic disc decreases. As a T A B L E 3 Six possible scenarios for a clinical example [BD = 3 mm, DT = 3 mm, and apical height = 3 mm in 14 Fig. 3(b) and Table 2 5 Notched (one seed removed) 3 0.62 87.2 37.3 30.0 Fig. 3(b) and Table 2 6 Notched (two seeds removed) 3 0.62 65.0 59.5 47.8 Fig. 6(a) and Table 2 F I G . 9. result, more optic disc dose reduction occurs for Case #2 (Fig. 9).
However, differences in dose reduction between Case #1 and Case #2 do not continuously decrease with plaque size because the number of seeds and seed configurations depend on the plaque size.
Due to more dose reduction to the optic disc in Case #2, DT maxD becomes shallower (i.e., DT maxD moves toward 0 mm) in Case #2 than in Case #1 for the same BD. However, the difference in DT maxD between the two cases for the same BD is consistent (0.7-0.8 mm for 14, 16, 18, and 22 mm plaques and 0.5-0.6 mm for 20 mm plaque) because in each plaque, seed configurations are the same and the only difference is dose contribution per seed to the optic disc. Figure 10 shows the comparison of optic disc dose reduction between Case #1 and Case #2 for 14 mm COMS plaques.
DT maxD is shallower in Case #2 and its difference between the two cases is 0.7 mm. The 20 mm plaque has the largest number of seeds (24 seeds in total) and thus, the lowest TRAK per seed, resulting in the smallest differences in MaxD reduction and in DT maxD between the two cases. In both cases, after seed removal, the prescribed dose of 85 Gy was re-normalized to each prescription depth but the irradiation time of 168 h was kept. As a result, S k per seed was higher for notched COMS plaques than for corresponding standard COMS plaques and S k per seed was higher for Case #2 than for Case #1 in the same COMS plaque.
MaxD Abs reduction has dependence on the prescription depth.
MaxD Abs reduction increases with increasing prescription depth because a deeper prescription depth requires higher TRAK per seed for both standard and notched COMS plaques and thus, dose reduction is larger at a deeper depth. From the results of this study, it is concluded that tumor size (i.e., BD and apical height (determining prescription depth)) has effects on optic disc dose reduction. For the same DT, as BD increases, D Abs reduction ðGyÞ decreases (Figs. 4 and 7). As apical height increases, D Abs reduction ðGyÞ increases (Table 2). Juxtapapillary tumors as well as tumors close to the optic disc can benefit from notched COMS plaques in reducing dose to the optic disc. As shown in the Results, DT maxD is 0 mm only for tumors with the largest 2-3 BDs and there exists optimal DT maxD (nonzero mm) for tumors with small BDs. Therefore, notched COMS plaques would be the most beneficial to juxtapapillary tumors or circumpapillary tumors when their BDs are large and to peripapillary tumors (tumor <3.5 mm from the optic disc) or extrapapillary tumors (tumor ≥3.5 mm from the disc margin) when their BDs are small. 1 The clinical example discussed in the Results showed that there are various scenarios in selecting COMS plaque type and prescription depth, and this example would help the clinician choose the best scenario to minimize radiation dose to the optic disc without treatment planning. As shown in Table 3, for tumors with apical height <5 mm, prescribing to the tumor apex gives lower optic disc dose than prescribing to a depth of 5 mm for both standard and notched COMS plaques. Depending on the prescription depth, however, a standard COMS plaque can reduce optic disc dose more than a notched COMS plaque. For example, Scenario #4 (standard COMS plaque and prescription depth of 3 mm) gives lower dose to the optic disc than Scenario #2 (notched COMS plaque and prescription depth of 5 mm) (124.5 vs 140.7 Gy). For tumors with apical height ≥5 mm, a prescription depth is always the tumor apex and notched COMS plaques would be always more beneficial.

| CONCLUSION
This simulation study has comprehensively investigated dose reduction to the optic disc in ocular brachytherapy using 125 I notched COMS plaques based on current clinical practice. Optic disc dose reduction by the use of notched COMS plaques has its own trends.
The results (figures and tables) presented in this study would enable the clinicians (both ophthalmologist and radiation oncologist) to choose an adequate plaque type among standard 125 I COMS plaques and notched 125 I COMS plaques (with one seed removed and two seeds removed), and a prescription depth to minimize optic disc dose for a given clinical case.