Abstract
Introduction
Ultrasound biomicroscopy (UBM) is the only widely used method for the evaluation of anterior uveal melanoma (AUM).
Objective
Documentation of regression of AUM treated with ruthenium-106 (Ru-106) plaque types CCB and CCC using UBM.
Methods
This single institution-based retrospective case series involved 10 Caucasian patients with AUM followed after brachytherapy with UBM from January 2014 until February 2019. The largest prominence of the tumor perpendicular to the sclera or the cornea (including scleral/corneal thickness) (D) and the largest basal dimension (B) were measured in millimeters with UBM for all patients prior to the brachytherapy and at 4-month interval follow-up. Tumor regression was calculated as a percentage of decrease in the initial D and B values.
Results
The study involved 10 patients with a mean age of 64.4 years (yr) (range 46–80 yr). D ranged from 1.82 to 5.5 mm (median 2.99 mm) and B from 2.32 to 12.38 mm (median 4.18 mm). The apical radiation dose in all patients was 100 Gy. The median follow-up was 42.02 months. Regression for D was 21.11 ± 13.66%, 31.09 ± 14.66%, and 34.92 ± 19.86% at 1st, 2nd, and 3rd year of the follow-up, respectively, while for B it was 21.58 ± 16.05%, 28.98 ± 17.71%, and 32.06 ± 18.96%, respectively. Tumor recurrence was documented in 2/10 patients.
Conclusion
The major regression of AUM, treated with Ru-106 plaque types CCB and CCC, was documented in the first 2 years after brachytherapy in our study group. In the following years, only minimal regression was documented that warns of the need for close monitoring and active search for local recurrences.
Keywords: Anterior uveal melanoma, Ultrasound biomicroscopy, Uveal melanoma regression, Brachytherapy, Basal dimension, Tumor prominence
Introduction
Ultrasound biomicroscopy (UBM) is a well-established technique for anterior uveal melanoma (AUM), namely, melanoma of the iris, ciliary body, and anterior choroid, diagnosis and the posttreatment follow-up [1]. Ruthenium-106 (Ru-106) plaques (Eckert & Ziegler BEBIG GmbH, Berlin, Germany) come in 13 different types. The size and shape of the plaques correspond to the size and location of the tumor. Brachytherapy with Ru-106 plaque-type CIA is indicated for AUMs involving ≤6 clock hours with the prominence of ≤5 mm [2]. The tumor regression of 60% at 1 year and 80% at 7 years was documented with this therapy [2]. When AUM is treated with Ru-106 plaque types CCB and CCC, intended for peripheral uveal/choroidal melanoma, the mean regression at 1 year after treatment was only 24.3 ± 9.31% [3]. A retrospective study of the thickness and the base of AUM, treated with Ru-106 CCB and CCC plaques, was set up to evidence the regression of the tumor for minimally 3 and maximally 5 years.
Materials and Methods
This is a single institution-based retrospective case series of 10 Caucasian patients followed after brachytherapy for AUM with UBM using a Lin50 probe (Aviso, Quantel Medical, Paris, France) at the University Eye Clinic, University Hospital “Sveti Duh,” Zagreb, Croatia, from January 2014 until February 2019. In that period, the clinic was the only institution in Croatia performing UBM monitoring of AUM. Brachytherapy with Ru-106 plaque types CCB and CCC (Eckert & Ziegler BEBIG GmbH, Berlin, Germany) was performed in another institution by a single surgeon (N.V.). The tumor measurements before brachytherapy and at 4-month interval follow-up visits were collected from the database of our clinic. AUM encompassed iridociliary (CB + I), anterior ciliary melanoma (CB), and melanoma of the anterior choroid whose anterior border could not be visualized with a 10-MHz probe (CH). UBM was performed with a 50-MHz probe closed with ClearScan® filled with sterile distilled water, in topical anesthesia (tetracaine ophthalmic drops), with the patient sitting, always by the same experienced examiner (B.K.E.) and including 360° of the eye circumference. The largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness) (D) and the largest basal dimension (B) were measured in millimeters. Data on the time, dosage, and duration of brachytherapy and complications were retrieved from the institution of the brachytherapy. Tumor regression was calculated as a percentage of decrease in the initial tumor D and B values recorded with UBM for each patient in a one-year interval of the follow-up for minimally 3 years, with a mean time of 40.8 months and a median of 42.02 months.
The study was conducted with the approval of the University Hospital research ethics committee and by complying with the tenets of the Declaration of Helsinki. Descriptive statistics were used for data evaluation.
Results
Our case series included 10 phakic patients, with an equal number of females and males. Descriptive statistics is given in Table 1. The median age for females was 72 years (yr) (average 67.2 ± 13.16 yr, range 46–80 yr) and for males, 62 yr (average 61.6 ± 8.96 yr, range 52–75 yr). All AUMs were melanotic, 3 pertinent only to the ciliary body, 4 were CB + I melanoma, and 3 CH melanoma. CB and CB + I melanomas were found in the lower quadrants. CH melanomas were located in the upper quadrants, 2 in the nasal and 1 in the temporal quadrant. Tumors were evenly distributed by sex (Table 1). According to AJCC 8th edition, 8/10 tumors were classified as pT1b and 2/10 as pT2a and as such were eligible for Ru-106 treatment [4, 5]. The total radiation time was on average 97 ± 67 h (range 29–268 h) (Table 1). The apex dose was 100 Gy in all patients.
Table 1.
Descriptive statistics of the patients
| Patient | Sex | Age, yr | Laterality (R/L) | CH/CB/CB + I | AJCC classification | Duration of BTh, d;h | Dose (Gy) |
|---|---|---|---|---|---|---|---|
| 1 | M | 64 | R | CB + I | pT1b | 3 d; 1 h | 100 |
| 2 | F | 80 | L | CB | pT1b | 6 d; 2 h | 100 |
| 3 | M | 75 | R | CB | pT1b | 11 d; 4 h | 100 |
| 4 | M | 55 | R | CB + I | pT1b | 1 d; 5 h | 100 |
| 5 | M | 62 | L | CB + I | pT1b | 1 d; 15 h | 100 |
| 6 | F | 74 | R | CB + I | pT1b | 3 d; 22 h | 100 |
| 7 | F | 64 | R | CB | pT1b | 2 d; 22 h | 100 |
| Median | 64.00 | 3 d; 1 h | 100.00 | ||||
| Average | 67.71 | 4 d; 7 h | 100.00 | ||||
| SD | 8.15 | 3 d; 4 h | 0.00 | ||||
| 8 | F | 72 | R | CH | pT2b | 3 d; 13 h | 100 |
| 9 | F | 46 | R | CH | pT1b | 3 d; 11 h | 100 |
| 10 | M | 52 | L | CH | pT2b | 3 d; 13 h | 100 |
| Median | 52.00 | 3 d; 13 h | |||||
| Average | 56.67 | 3 d; 12 h | |||||
| SD | 11.12 | 1 h | |||||
| Median (all) | 64.0 | ||||||
| Average (all) | 64.4 | 4 d; 1 h | |||||
| SD (all) | 10.5 | 2 d; 19 h | |||||
R, right eye; L, left eye; BTh, brachytherapy; Dose, dose at the apex of the tumor; CH, melanoma of the anterior choroid whose anterior border could not be visualized with a 10-MHz probe; CB, anterior ciliary melanoma; CB + I, iridociliary melanoma; d, day; h, hour.
The time between the diagnosis and the brachytherapy ranged from 9 to 37 days for 9 patients. In patient No. 9, with CH melanoma, it was 5 months. D prior to brachytherapy was in average 3.20 ± 1.24 mm (range 1.82–5.5 mm, median 2.99 mm) with average regression at the 1st year of 21.11 ± 13.66% (median 27.55%), the 2nd year of 31.09 ± 14.66% (median 33.44%), and the 3rd year of 34.92 ± 19.86% (median 34.33%) (Table 2). The correlation between D prior to brachytherapy and 3 years after brachytherapy is presented in Figure 1 [6]. B prior to brachytherapy was 6.12 ± 3.62 mm (range 2.32–12.38 mm, median 4.18 mm) with average regression at the 1st year of 21.58 ± 16.05% (median 14.55%), the 2nd year of 28.98 ± 17.71% (median 24.08%), and the 3rd year of 32.06 ± 18.96% (median 28.92%) (Table 3).
Table 2.
Tumor regression of the D values
| Patient | Prior to BTh, mm | Regression 1 yr after BTh, % | Regression 2 yr after BTh, % | Regression 3 yr after BTh, % | Regression 4 yr after BTh, % | Regression 5 yr after BTh, % |
|---|---|---|---|---|---|---|
| 1 | 2.16 | 27.78 | 45.37 | 46.30 | 46.76 | |
| 2 | 5.02 | 38.45 | 43.63 | 54.18 | ||
| 3 | 5.5 | 37.82 | 44.00 | 56.00 | ||
| 4 | 3.53 | 14.45 | 23.23 | 15.86 | 8.22 | 11.33 |
| 5 | 2.52 | 0.00 | 10.32 | 12.30 | 12.70 | |
| 6 | 1.82 | 5.49 | 21.43 | 21.43 | ||
| 7 | 3.88 | 2.32 | 6.44 | 6.96 | 10.57 | |
| Median | 3.53 | 14.45 | 23.23 | 21.43 | 11.63 | |
| Average | 3.49 | 18.04 | 27.77 | 30.43 | 19.56 | |
| SD | 1.31 | 15.33 | 15.33 | 19.43 | 15.78 | |
| 8 | 2.25 | 29.33 | 39.56 | 41.33 | ||
| 9 | 1.83 | 27.32 | 27.32 | 27.32 | ||
| 10 | 3.45 | 28.12 | 49.57 | 67.54 | ||
| Median | 2.25 | 28.12 | 39.56 | 41.33 | ||
| Average | 2.51 | 28.26 | 38.81 | 45.40 | ||
| SD | 0.69 | 0.83 | 9.10 | 16.67 | ||
| Median (all) | 2.99 | 27.55 | 33.44 | 34.33 | ||
| Average (all) | 3.20 | 21.11 | 31.09 | 34.92 | ||
| SD (all) | 1.24 | 13.66 | 14.66 | 19.86 | ||
D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness), in mm; Prior to BTh, D of the melanoma prior to brachytherapy, in mm; BTh, brachytherapy.
Fig. 1.
The correlation between the D value prior to brachytherapy and 3 years after brachytherapy. D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness).
Table 3.
Tumor regression of the B values
| Patient | Prior to BTh, mm | Regression 1 yr after BTh, % | Regression 2 yr after BTh, % | Regression 3 yr after BTh, % | Regression 4 yr after BTh, % | Regression 5 yr after BTh, % |
|---|---|---|---|---|---|---|
| 1 | 2.32 | 22.41 | 34.05 | 41.81 | 44.83 | |
| 2 | 3.84 | 34.38 | 38.54 | 42.97 | ||
| 3 | 6.72 | 60.57 | 73.81 | 79.46 | ||
| 4 | 4.49 | 33.63 | 36.30 | 20.49 | 21.38 | 29.84 |
| 5 | 2.79 | 9.68 | 9.68 | 11.11 | 10.04 | |
| 6 | 3.52 | 6.53 | 16.48 | 26.42 | ||
| 7 | 3.87 | 8.79 | 11.37 | 11.63 | 15.76 | |
| Median | 3.84 | 22.41 | 34.05 | 26.42 | 18.57 | |
| Average | 3.94 | 25.14 | 31.46 | 33.41 | 23.00 | |
| SD | 1.32 | 18.02 | 20.62 | 22.27 | 13.22 | |
| 8 | 12.38 | 14.22 | 21.65 | 31.42 | ||
| 9 | 8.92 | 10.76 | 21.41 | 21.64 | ||
| 10 | 12.30 | 14.88 | 26.50 | 33.66 | ||
| Median | 12.30 | 14.22 | 21.65 | 31.42 | ||
| Average | 11.20 | 13.29 | 23.19 | 28.91 | ||
| SD | 1.61 | 1.80 | 2.35 | 5.22 | ||
| Median (all) | 4.18 | 14.55 | 24.08 | 28.92 | 18.57 | |
| Average (all) | 6.12 | 21.58 | 28.98 | 32.06 | 23.00 | |
| SD (all) | 3.62 | 16.05 | 17.71 | 18.96 | 13.22 | |
B, the largest basal dimension, in mm; Prior to BTh, base of the melanoma prior to brachytherapy, in mm; BTh, brachytherapy.
In patients with CB and CB + I melanoma, D prior to brachytherapy was in average 3.49 ± 1.31 mm (range 1.82–5.5 mm, median 3.53 mm) with average regression at the 1st year of 18.04 ± 15.33% (median 14.45%), at the 2nd year of 27.77 ± 15.33% (median 23.23%), and at the 3rd year of 30.43 ± 19.43% (median 21.43%) (Table 2). B prior to brachytherapy was in average 3.94 ± 1.32 mm (range 2.32–6.72, median 3.84 mm) with average regression at the 1st year of 25.14 ± 18.02% (median 22.41%), at the 2nd year of 31.46 ± 20.62% (median 34.05%), and at the 3rd year of 33.41 ± 22.27% (median 26.42%) (Table 3). For patient No. 1, 4, 5, and 7 (Fig. 2), there was a 4-year follow-up with average regression of the D value of 19.56 ± 15.78% (median 11.63%) and the B value of 23.00 ± 13.22% (median 18.57%). Patient No. 4 experienced an increase in the tumor diameter and the base after the 3rd year of follow-up leading to a decrease in the tumor regression (Table 2). The tumor regression continued to decrease throughout the 4th year of the follow-up until the 5th year when it started to increase again (Table 2). The average D of the patients with CH melanoma was 2.51 ± 0.84 mm (median 2.25 mm). The average regression in the 1st year was 28.26 ± 0.83% (median 28.12%), the 2nd year was 38.81 ± 9.10% (median 39.56%), and the 3rd year was 45.40 ± 16.67% (median 41.33%) (Table 2). The average B was 11.20 ± 1.61 mm (median 12.30 mm). The average regression in the 1st year was 13.29 ± 1.80% (median 14.22), the 2nd year was 23.19 ± 2.35% (median 21.65%), and the 3rd year was 28.91 ± 5.22% (median 31.42%) (Table 3). Tumor regression type based on tumor thickness according to Abramson et al. [7] was D in 7/10 patients and S in 3/10 patients.
Fig. 2.
Ultrasound biomicroscopy follow-up of the D and B values for patient No. 7. D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness); B, the largest basal dimension.
Cataract developed in 6/10 patients. No other radiation-related ocular complications were reported. The recurrence was documented in 2/10 patients. All patients were under the regular oncological 6-month interval follow-up managed according to consensus-based guidelines [8]. At the end of the study, all included patients were alive without extraocular extension or distant metastases.
Discussion/Conclusion
UBM is the only widely used method for evaluation of AUM. This paper emphasizes its decisive role in systematic follow-up after Ru-106 plaque types CCB and CCC treatment, both in regression monitoring and recurrence detection. A 360°-UBM examination routine has proven crucial in the detection of noncontiguous recurrence.
The age of initial diagnosis of ciliary body melanoma is between 55 and 62 years [9, 10]. This is in concordance with our results: the median for the patients with CB and CB + I tumors was 64 yr, while for the CH was only 52 yr.
Ciliary body melanoma can be located in any part of the eye circumference [9, 11]. In our study, the exclusive location of CB and CB + I melanomas in the lower quadrants may indicate the connection with UV light exposure [10].
Ru-106 is a beta emitter with low penetrability [4]. Consequently, indications for Ru-106 treatment of AUM are small to medium tumors, although treatment of tumors thicker than 8 mm was reported [2, 12, 13].
For CB melanoma and melanoma close to the iris, CIA- and CIB-type plaques are recommended to protect the cornea and lens [2, 14]. CCB- and CCC-type plaques, as the ones available to our market, were used in our study group. These are disproportionately large plaques for the anterior eye segment, and as such could result in a variety of complications beyond the scope of this study [3]. Consequently, 6/10 of our patients had cataract after the treatment. Although it was taken care that the margin of 2 mm from the tumor to the plaque edge was obliged, that was not an issue as the largest base of the tumor in our study group was 12.38 mm and the diameter of CCB is 20.2 mm and of CCC is 24.8 mm [15]. According to the literature, large uveal melanomas regress faster than smaller ones [16]. Two tumors with the largest diameter (patient No. 2 and 3) had the highest regression in the 1st year as well as in the 3rd year of follow-up (Table 2). However, the tumor with one of the smallest diameters (patient No. 1) had the 3rd highest regression in the 1st year, as well as in the 3rd year of follow-up (Table 2). The finding these 3 patients have in common is the duration of brachytherapy. With the constant dose of 100 Gy at the apex of the tumor, the longer the duration of brachytherapy, the higher regression was documented. Bearing this in mind, patient No. 6 had the smallest tumor in the group, but the 3rd longest duration of brachytherapy and ended up with the 4th highest regression.
One-dimensional measurement of the maximal tumor diameter is acceptable for the evaluation of the solid tumor therapy response [7, 17]. However, additional parameters of evaluation have been proposed [16]. We have used a two-dimensional method, monitoring not only the diameter but also the tumor base [18]. There are no recommended values for the tumor regression that would be considered as treatment success. On the contrary, individual regression differs greatly: it may be swift, that is, even linked to higher mortality, there may be no tumor decrease or it can get thicker [19]. In the study of 330 patients with uveal melanoma, only 43% progressively regressed over time [16]. Furthermore, when a two-dimensional method was used, the 1st-year regression of the cross-sectional area was faster than that of thickness [16]. In our study group, patient No. 1–3 with the highest regression of the diameter also had the highest regression of the base.
The most significant average AUM regression in our patients arose during the 1st year after Ru-106 brachytherapy (Fig. 3, 4; Tables 2, 3). In the 2nd year, further regression of approximately 10% for D and 7% for B was documented. However, over the 3rd year, patients experienced only minimal regression, of approximately 3% for D and B. For 2 patients (No. 1 and No. 5), for whom the data over the 4th year were available, only 0.46 and 0.4% of regression, respectively, were recorded.
Fig. 3.
Regression of the D value. D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness); BTh, brachytherapy; CH, melanoma of the anterior choroid whose anterior border could not be visualized with a 10-MHz probe; CB, anterior ciliary melanoma; CB + I, iridociliary melanoma.
Fig. 4.
Regression of the B value. B, the largest basal dimension; BTh, brachytherapy; CH, melanoma of the anterior choroid whose anterior border could not be visualized with a 10-MHz probe; CB, anterior ciliary melanoma; CB + I, iridociliary melanoma.
Local tumor recurrence was diagnosed when a 15% increase in height or 250-μm increase in tumor boundary was documented by UBM on 2 consecutive occasions [4, 20]. Type 1 local recurrence [21] was found in 2/10 patients in our study group. In patient No. 4, 3 years after the brachytherapy, there was an increase in D of 9.6% and in B of 710 μm as compared to the 2nd-year values (Table 4). After the 4th year, D and B increase, as compared to the 2nd year, was 19.6% and 610 μm, respectively. Finally, 5 years after the brachytherapy, the tumor started to shrink again, with the diameter still 15.5% and the base 290 μm higher than the 2nd-year values, respectively. The patient received no additional treatment. The importance of evaluating 360° of eye circumference by UBM at every examination was emphasized in the patient with the second-best 3-year regression (No. 2, Fig. 5) by detecting noncontiguous recurrence following cataract surgery that, in our opinion, played the major role in the pathogenesis of the newfound melanoma, confirmed after enucleation on histopathology [22]. A recurrence of 20% after Ru-106 brachytherapy is on the high side compared to that previously reported [4, 23] (Table 5). A high recurrence of 46.4% was reported in the study of Barker et al. [20], on 28 melanoma cases, 4 having ciliary body melanoma. However, they had no recurrence of ciliary body melanoma as opposed to our case series where both recurrent tumors were CB melanoma.
Table 4.
Recurrence of the ciliary body tumor in patient No. 4 evidenced by increase in the D and B values
| No. 4 | Prior to BTh, mm | 1 yr after BTh, mm | 2 yr after BTh, mm | 3 yr after BTh mm | 4 yr after BTh, mm | 5 yr after BTh, mm |
|---|---|---|---|---|---|---|
| D | 3.53 | 3.02 | 2.71 | 2.97 | 3.24 | 3.13 |
| B | 4.49 | 2.98 | 2.86 | 3.57 | 3.53 | 3.15 |
D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness), in mm; B, the largest basal dimension, in mm; Prior to BTh, D of the melanoma prior to brachytherapy, in mm; BTh, brachytherapy.
Fig. 5.
Ultrasound biomicroscopy follow-up of the D and B values for patient No. 2. D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness); B, the largest basal dimension.
Table 5.
Previously reported studies of patients treated with Ru-106 brachytherapy for uveal melanoma
| Study | Eyes treated, n | Tumor location | Mean/median age of patients, yr | Median of D value, mm | Median of B value, mm | Median apical dose, Gy | Median follow-up, months | Local tumor recurrence, n (%) | Location of recurrent tumor |
|---|---|---|---|---|---|---|---|---|---|
| Rospond-Kubiak et al. [4] | 126 | Anterior to equator 40%, posterior to equator 60% | 60.04/– | 4.80 | 10.67 | 100 | 66.5 | 19 (15) | Not specified |
| Damato et al. [23] | 458 | Choroidal melanoma | 61/– | 3.20 | 10.60 | 100–115 | 46.8 | 9 (2) | Choroid |
| Barker et al. [20] | 28 | Uveal melanoma | −/60 | 2.6 | 9.40 | 75.5 | 71.0 | 13 (46.4) | Choroid |
| Present study | 10 | Choroidal melanoma 30%, ciliary body 30%, ciliary body + iris 40% | 64.4/64 | 2.99 | 4.18 | 100 | 42.02 | 2 (20) | Ciliary body |
D, the largest prominence of the tumor perpendicular to the sclera or the cornea (including the scleral/corneal thickness); B, the largest basal dimension.
According to COMS, only the tumor size was taken into consideration in assessing the treatment and the outcome [24]. Nowadays, the measures of prognosis are multifactorial [25, 26]. However, when brachytherapy is used without histopathological confirmation, only anatomic predictors are available [1, 24]. Those are provided by UBM, whose role has been recognized in dealing with AUM [1]. Being aware of the variable interobserver and high intraobserver reproducibility of UBM [27], all the measurements in this study were performed by the same examiner (B.K.E.).
The study aims to present the single-institution experience in follow-up of regression after Ru-106 plaque treatment by UBM. Usage of CCB and CCC Ru-106 plaques for the anterior ciliary tumors, low regression rate with a high percentage of complications, and high recurrence raise the concern of the treatment efficacy. The drawbacks of the study are a rather small number of patients and the short period of follow-up.
As evidenced by this study, the most significant regression of AUM arose during the first 2 years after brachytherapy with Ru-106 plaque types CCB and CCC. Regression in the 1st year of follow-up was 21.11 ± 13.66% for D and 21.58 ± 16.05% for B. In the 2nd year, further regression of approximately 10% for D and 7% for B was documented. However, over the 3rd year patients experienced only minimal regression of approximately 3%, suggesting further close follow-up and search for local recurrences. Measuring therapeutic response is a key step toward highly needed tumor regression grading system establishment that will enable prediction of recurrence-free and overall survival. The importance of examining 360° of eye circumference by UBM in follow-up is mandatory not to miss noncontiguous recurrence.
Statement of Ethics
This study was conducted with the approval of the Ethics Committee of the University Hospital “Sveti Duh” under Approval No. 01-4212/9. The Ethics Committee approved the use and analysis of previously collected patient data for this retrospective study, and which, according to the committee, did not require written informed consent of the patients. The paper does not report on the use of experimental or new protocols, and all data analyzed were collected as part of routine diagnosis and treatment. All procedures performed in this study were under the ethical standards of the institutional research committee and in accordance with the 1964 Helsinki declaration and its later amendments. The personal data collected are confidential and have not been used to publish this work.
Conflict of Interest Statement
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.
Funding Sources
No funding was received for this research.
Author Contributions
All authors on the list meet the ICMJE criteria for authorship. Concept: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Design: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Definition of intellectual content: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Literature search: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Data acquisition: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, and Nenad Vukojević. Data analysis: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Statistical analysis: Biljana Kuzmanović Elabjer and Andrej Pleše. Manuscript preparation: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Manuscript editing: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Manuscript review: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević. Guarantor: Biljana Kuzmanović Elabjer, Mladen Bušić, Andrej Pleše, Mirjana Bjeloš, Daliborka Miletić, and Nenad Vukojević.
References
- 1.Simpson ER, Gallie B, Laperrierre N, Beiki-Ardakani A, Kivelä T, Raivio V, et al. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014;13((1)):1–14. doi: 10.1016/j.brachy.2013.11.008. [DOI] [PubMed] [Google Scholar]
- 2.Razzaq L, Keunen JE, Schalij-Delfos NE, Creutzberg CL, Ketelaars M, De Keizer RJ. Ruthenium plaque radiation therapy for iris and iridociliary melanomas. Acta Ophthalmol. 2012 May;90((3)):291–6. doi: 10.1111/j.1755-3768.2010.01967.x. [DOI] [PubMed] [Google Scholar]
- 3.Kuzmanović Elabjer B, Bušić M, Miletić D, Bjeloš M, Vukojević N, Bosnar D. Scleral thinning documented by ultrasound biomicroscopy after plaque therapy for anterior ciliary melanoma. Semin Ophthalmol. 2018 May;33((4)):571–5. doi: 10.1080/08820538.2017.1346131. [DOI] [PubMed] [Google Scholar]
- 4.Rospond-Kubiak I, Wróblewska-Zierhoffer M, Twardosz-Pawlik H, Kocięcki J. Ruthenium brachytherapy for uveal melanoma: single institution experience. J Contemp Brachytherapy. 2017;9((6)):548–52. doi: 10.5114/jcb.2017.72606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Hyrcza M. Uvea: pathologic TNM staging of uveal melanoma, AJCC 8th edition [Internet] PatahologyOutlines.com website. [cited 2020 May 11]. Available from: http://www.pathologyoutlines.com/topic/eyeuveatnmuvealmelanoma.html.
- 6.Kaiserman I, Anteby I, Chowers I, Blumenthal EZ, Kliers I, Pe'er J. Changes in ultrasound findings in posterior uveal melanoma after ruthenium 106 brachytherapy. Ophthalmology. 2002 Jun;109((6)):1137–41. doi: 10.1016/s0161-6420(02)01054-0. [DOI] [PubMed] [Google Scholar]
- 7.Abramson DH, Servodidio CA, McCormick B, Fass D, Zang E. Changes in height of choroidal melanomas after plaque therapy. Br J Ophthalmol. 1990 Jun;74((6)):359–62. doi: 10.1136/bjo.74.6.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Weis E, Salopek TG, McKinnon JG, Larocque MP, Temple-Oberle C, Cheng T, et al. Management of uveal melanoma: a consensus-based provincial clinical practice guideline. Curr Oncol. 2016;23((1)):e57–64. doi: 10.3747/co.23.2859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Shields CL, Kaliki S, Furuta M, Mashayekhi A, Shields JA. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina. 2012 Jul;32((7)):1363–72. doi: 10.1097/IAE.0b013e31824d09a8. [DOI] [PubMed] [Google Scholar]
- 10.Costache M, Patrascu OM, Adrian D, Costache D, Sajin M, Ungureanu E, et al. Ciliary body melanoma: a particularly rare type of ocular tumor. Case report and general considerations. Maedica. 2013 Sep;8((4)):360–4. [PMC free article] [PubMed] [Google Scholar]
- 11.Marigo FA, Finger PT. Anterior segment tumors: current concepts and innovations. Surv Ophthalmol. 2003;48((6)):569–93. doi: 10.1016/j.survophthal.2003.08.001. [DOI] [PubMed] [Google Scholar]
- 12.Brewington BY, Shao YF, Davidorf FH, Cebulla CM. Brachytherapy for patients with uveal melanoma: historical perspectives and future treatment directions. Clin Ophthalmol. 2018 May;12:925–34. doi: 10.2147/OPTH.S129645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Naseripour M, Jaberi R, Sedaghat A, Azma Z, Nojomi M, Falavarjani KG, et al. Ruthenium-106 brachytherapy for thick uveal melanoma: reappraisal of apex and base dose radiation and dose rate. J Contemp Brachytherapy. 2016;8((1)):66–73. doi: 10.5114/jcb.2016.57818. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Eckert & Ziegler BEBIG Ru-106 eye applicators and I-125 ophthalmic seeds [Internet] Eckert & Ziegler BEBIG. [cited 2020 May 11]. Available from: https://www.bebig.com/fileadmin/bebig_neu/user_uploads/Products/Ophthalmic_Brachytherapy/Ophthalmic_Brochure__Rev._06__English.pdf.
- 15.Eckert & Ziegler BEBIG Ru-106 eye applicators [Internet] Eckert & Ziegler BEBIG. [cited 2020 May 11]. Available from: https://www.bebig.com/fileadmin/bebig_neu/user_uploads/Products/Ophthalmic_Brachytherapy/Fact_sheet_Ru-106_Eye_Applicators__Rev.06__English.pdf.
- 16.Rashid M, Heikkonen J, Kivelä T. Tumor regression after brachytherapy for choroidal melanoma: reduction of thickness and cross-sectional area by shape and regression pattern. Invest Ophthalmol Vis Sci. 2015 Apr;56((4)):2612–23. doi: 10.1167/iovs.14-16322. [DOI] [PubMed] [Google Scholar]
- 17.Novak-Andrejčič K, Jančar B, Hawlina M. Echographic follow-up of malignant melanoma of the choroid after brachytherapy with 106Ru. Klin Monbl Augenheilkd. 2003;220((12)):853–60. doi: 10.1055/s-2003-812561. [DOI] [PubMed] [Google Scholar]
- 18.James K, Eisenhauer E, Christian M, Terenziani M, Vena D, Muldal A, et al. Measuring response in solid tumors: unidimensional versus bidimensional measurement. J Natl Cancer Inst. 1999;91((6)):523–8. doi: 10.1093/jnci/91.6.523. [DOI] [PubMed] [Google Scholar]
- 19.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92((3)):205–16. doi: 10.1093/jnci/92.3.205. [DOI] [PubMed] [Google Scholar]
- 20.Barker CA, Francis JH, Cohen GN, Marr BP, Wolden SL, McCormick B, et al. 106Ru plaque brachytherapy for uveal melanoma: factors associated with local tumor recurrence. Brachytherapy. 2014 Nov;13((6)):584–90. doi: 10.1016/j.brachy.2014.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Rouberol F, Roy P, Kodjikian L, Gérard JP, Jean-Louis B, Grange JD. Survival, anatomic, and functional long-term results in choroidal and ciliary body melanoma after ruthenium brachytherapy (15 years' experience with beta-rays) Am J Ophthalmol. 2004 May;137((5)):893–900. doi: 10.1016/j.ajo.2003.12.032. [DOI] [PubMed] [Google Scholar]
- 22.Kuzmanović Elabjer B, Bušić M, Bjeloš M, Miletić D, Vukojević N. A non-contiguous recurrence of the ciliary body melanoma-is cataract surgery a risk factor? Int J Ophthalmol. 2020 Apr;13((4)):681–3. doi: 10.18240/ijo.2020.04.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Damato B, Patel I, Campbell IR, Mayles HM, Errington RD. Local tumor control after 106Ru brachytherapy of choroidal melanoma. Int J Radiat Oncol Biol Phys. 2005 Oct;63((2)):385–91. doi: 10.1016/j.ijrobp.2005.02.017. [DOI] [PubMed] [Google Scholar]
- 24.Margo CE. The collaborative ocular melanoma study: an overview. Cancer Control. 2004 Sep-Oct;11((5)):304–9. doi: 10.1177/107327480401100504. [DOI] [PubMed] [Google Scholar]
- 25.Honavar SG. Is Collaborative Ocular Melanoma Study (COMS) still relevant? Indian J Ophthalmol. 2018 Oct;66((10)):1385. doi: 10.4103/ijo.IJO_1588_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Salvi SM, Aziz HA, Dar S, Singh N, Hayden-Loreck B, Singh AD. Uveal melanoma regression after Brachytherapy: relationship with chromosome 3 monosomy status. Ocul Oncol Pathol. 2017 Jul;3((2)):87–94. doi: 10.1159/000451001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Urbak SF, Pedersen JK, Thorsen TT. Ultrasound biomicroscopy. II. Intraobserver and interobserver reproducibility of measurements. Acta Ophthalmol Scand. 1998;76((5)):546–9. doi: 10.1034/j.1600-0420.1998.760507.x. [DOI] [PubMed] [Google Scholar]