Measurements regarding a combined therapy concept for ophthalmic tumors consisting of brachytherapy and x-rays.

Objective.We present a novel concept to treat ophthalmic tumors which combines brachytherapy and low-energy x-ray therapy. Brachytherapy with106Ru applicators is inadequate for intraocular tumors with a height of 7 mm or more. This results from a steep dose gradient, and it is unfeasible to deliver the required dose at the tumor apex without exceeding the maximum tolerable sclera dose of usually 1000 Gy to 1500 Gy. Other modalities, such as irradiation with charged particles, may be individually contraindicated. A dose boost at the apex provided by a superficial x-ray therapy unit, performed simultaneously with the brachytherapy, results in a more homogeneous dose profile than brachytherapy alone. This avoids damage to organs at risk. The applicator may also serve as a beam stop for x-rays passing through the target volume, which reduces healthy tissue dosage. This study aims to investigate the suitability of the applicator to serve as a beam stop for the x-rays.Approach.A phantom with three detector types comprising a soft x-ray ionization chamber, radiochromic films, and a self-made scintillation detector was constructed to perform dosimetry. Measurements were performed using a conventional x-ray unit for superficial therapy to investigate the uncertainties of the phantom and the ability of the applicator to absorb x-rays. The manufacturer provided a dummy plaque to obtain x-ray dose profiles without noise from106Ru decays.Results.The phantom is generally feasible to obtain dose profiles with three different detector types. The interaction of x-rays with the silver of the applicator leads to an increased dose rate in front of the applicator. The dose rate of the x-rays is reduced by up to 90% behind a106Ru applicator. Therefore, a106Ru applicator can be used as a beam stop in combined x-ray and brachytherapy treatment.

Long-term visual outcomes after ruthenium plaque brachytherapy for posterior choroidal melanoma.

BACKGROUND: To assess the long-term visual outcomes in patients with posteriorly located choroidal melanoma treated with ruthenium plaque brachytherapy between January 2013 and December 2015. METHODS: A retrospective review was conducted on consecutive patients treated with ruthenium plaque brachytherapy for post-equatorial choroidal melanoma with available Snellen visual acuity before and after treatment, and the development and treatment of radiation complications. RESULTS: There were 219 patients with posterior choroidal melanoma treated with ruthenium plaque brachytherapy. Median follow up was 56.5 months, range 12-81 months. Final visual acuity was ≥6/12 in 97 (44.3%) patients, 6/12 to 6/60 in 57 (26.0%), <6/60 in 55 (25.1%) and 10 (4.6%) eyes were enucleated. Radiation maculopathy was the most common radiation complication encountered, occurring in 53 (24.2%) patients. Of these, final visual acuity was 6/12 in 10 patients (18.9%), 6/12 to 6/60 in 26 (49.1%), <6/60 in 16 (30.2%) and 1 eye (1.9%) was enucleated. Twenty-five (47%) with radiation maculopathy were treated with intravitreal anti-angiogenic therapy, 27 (51%) were monitored and one (2%) was treated with scatter photocoagulation. Eyes treated with intravitreal anti-angiogenic therapy had better final vision than those observed or treated with retinal laser (chi-square, p = 0.04). On multivariate analysis, close proximity to the optic nerve and fovea, and large or notched plaque type was associated with final vision worse than 6/12. CONCLUSION: Most patients treated with ruthenium plaque brachytherapy for posterior choroidal melanoma retain 6/60 vision, with almost half retaining 6/12 vision at long term follow up.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters.

PURPOSE: To estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. METHODS AND MATERIALS: Thirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. RESULTS: The radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). CONCLUSIONS: The proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

Ruthenium-106 plaque radiotherapy for uveal melanoma: analysis of tumor dimension and location on anatomical and functional results.

BACKGROUND: To report the long-term outcomes of Ru-106 plaque radiotherapy in eyes with uveal melanoma (UM) and to assess the effect of tumor thickness and location on final outcomes. METHODS: Medical records of 234 patients undergoing Ru-106 plaque radiotherapy for UM were reviewed, and the visual outcome, globe preservation, and patient survival were evaluated. The results of 2 groups were compared: 1. between thin (small and medium-sized, thickness < 7 mm, 148 eyes [63.2%]) and thick (thickness ≥ 7 mm, 86 eyes [36.8%]) tumors, and 2. between large (largest basal diameter [LBD] > 12 mm, 109 eyes [46.6%]) and medium/small (LBD ≤ 12 mm, 125 eyes [53.4%]). In addition, a comparison of the juxtapapillary location in 46 eyes (19.7%) versus tumors arising elsewhere and between tumors with and without ciliary involvement in 48 eyes (21.5%) were done. RESULTS: The patients were followed for a median of 54.2 months (range: 6-194.5 months). After adjusting for baseline visual acuity (VA), there was no significant association between final VA and different dimension and tumor location groups. Final globe preservation was 91.9%, and there was no significant difference between different dimension- and ciliary body involvement groups regarding anatomical success rate. The juxtapapillary tumors had lower globe preservation (80.4% vs .94.7%, p = 0.002). The hazard ratio (HR) for enucleation in juxtapapillary tumors was HR = 6.58 (95-CI: 3.84 to 11.21). The overall metastasis rate was 6.8%, with no significant difference in juxtapapillary tumors (4.3% vs.7.4%, p = 0.455). CONCLUSIONS: Ru-106 plaque radiotherapy is an effective treatment for thick and large UM. With this type of treatment, the globe preservation rate is lower in juxtapapillary tumors, but there is no significant difference in the metastasis rate.

No differences in the long-term prognosis of iris and choroidal melanomas when adjusting for tumor thickness and diameter.

OBJECTIVE: To assess the long-term prognosis for patients with iris melanomas and compare it with the prognosis for small choroidal melanomas. DESIGN: Retrospective observational case series. METHODS: All patients treated for iris melanomas at a single referral institution between January 1st 1986 and January 1st 2016 were included. Patients treated for small choroidal melanomas during the same period were included for comparison. The cumulative incidence of melanoma-related mortality was calculated. Patient and tumor characteristics and size-adjusted hazard ratio (HR) for melanoma-related mortality were compared between iris and small choroidal melanomas. RESULTS: Forty-five iris melanomas and 268 small choroidal melanomas were included. Twenty-four iris melanomas (53%) had been treated with local resection, 12 (27%) with Ruthenium-106 brachytherapy, 7 (16%) with enucleation and 2 (4%) with proton beam irradiation. Twenty-one (68%), 7 (16%) and 2 (4%) of the iris melanomas were of the spindle, mixed and epithelioid cell types, respectively. Twenty-three patients had deceased before the end of follow-up. Median follow-up for the 22 survivors was 13.3 years (SD 9.4). Patients with iris melanomas were more often asymptomatic at presentation and had a trend towards significantly lower age (59 versus 63 years, Student's T-tests p = 0.057). Further, iris melanomas had significantly smaller basal diameter (5.8 versus 8.0 mm, p < 0.0001) and tumor volume (79 mm3 versus 93 mm mm3, p < 0.0001) but greater thickness (3.0 versus 2.5 mm, p < 0.0001). The cumulative incidence of iris melanoma-related mortality was 5% at 5 years after diagnosis, and 8% at 10, 15 and 20 years. The incidence was not significantly different to small choroidal melanomas (Wilcoxon p = 0.46). In multivariate Cox regression with tumor diameter and thickness as covariates, patients with choroidal melanomas did not have increased HR for melanoma-related mortality (HR 2.2, 95% CI 0.5-9.6, p = 0.29). Similarly, there were no significant survival differences in matched subgroups (Wilcoxon p = 0.82). CONCLUSIONS: There are no survival differences between iris and choroidal melanomas when adjusting for tumor size. The reason for the relatively favorable prognosis of iris melanomas compared to melanomas of the choroid and ciliary body is likely that they are diagnosed at a smaller size.

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

PURPOSE: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement. METHODS AND MATERIALS: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion. RESULTS: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively. CONCLUSIONS: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.

3D image-guided treatment planning for Ruthenium-106 brachytherapy of choroidal melanomas.

BACKGROUND: Current standard treatment procedures for Ruthenium-106 (Ru-106) brachytherapy for choroidal melanomas do not use 3D image-guided treatment planning. We evaluated the potential impact of introducing 3D treatment planning and quantified the theoretical clinical benefits in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP). MATERIALS AND METHODS: Treatment plans for thirty-two patients were optimized using 3D image-guided treatment planning and compared to the original 2D clinical plans. Optimization of plans was done in an image-based treatment planning system by optimizing the plaque position and treatment time such that the entire tumour received the prescribed dose of 100 Gy. TCP and NTCP for 2D clinical plans and optimized 3D image-guided plans were estimated from published outcome prediction models and compared within patients using Wilcoxon signed-rank test. RESULTS: The median minimum tumour dose (D99% ) for 2D clinical plans was 93 Gy (range: 23-158 Gy), corresponding to 5-year TCP of 75% (IQR 61-86%), while median tumour D99% for optimized 3D image-guided plans was 115 Gy (range 103-141 Gy), corresponding to TCP of 82% (IQR 80-84%). This was a statistically significant increase in estimated TCP (median increase in TCP 8% (IQR: -5-23, p = 0.006). While the dose to normal tissue increased somewhat, there was no significant change in NTCP. CONCLUSION: 3D treatment planning theoretically allows for improved tumour dose delivery for Ru-106 brachytherapy of choroidal melanomas, resulting in a significant increase in expected tumour control compared to traditional approaches using 2D calculations. The deliverability of optimized plans, and potential increased risk of late complications, will have to be confirmed in future clinical studies.

Effect of plaque brachytherapy dose and dose rate on risk for disease-related mortality in 1238 patients with choroidal melanoma.

BACKGROUND: Episcleral brachytherapy is the most common treatment for medium-sized choroidal melanomas. Although controversial, inadequate brachytherapy dose and dose rates have at least a hypothetical implication on patient survival. METHODS: All patients who received ruthenium-106 or iodine-125 brachytherapy for choroidal melanoma at St. Erik Eye Hospital 1996 to 2016 were included (n=1238). Cox regression hazard ratios for melanoma-related mortality across deciles, quartiles and individual integers of apex radiation doses (Gy) and dose rates (Gy/hour) were calculated, adjusted for tumour size and location. RESULTS: The average radiation dose at the tumour apex ranged from 73.0 Gy in the first decile to 108.6 Gy in the tenth. Decreasing apex dose by 1 Gy increments or by decile or quartile group was not associated with melanoma-related mortality (p>0.2) The average radiation dose rate at the tumour apex ranged from 0.5 Gy/hour in the first decile to 2.8 Gy/hour in the tenth. Similarly, decreasing apex dose rate by 1 Gy/hour increments or by decile or quartile groups was not associated with melanoma-related mortality (p>0.5). CONCLUSION: There are no increased hazards for choroidal melanoma-related mortality after brachytherapy with decreasing doses between 108.6 and 73.0 Gy, or with decreasing dose rates between 2.8 and 0.5 Gy/hour.

OCT changes in peri-tumour normal retina following ruthenium-106 and proton beam radiotherapy for uveal melanoma.

INTRODUCTION: Uveal melanoma is most commonly treated with radiotherapy, destroying the tumour cells with adequate safety margins and limiting collateral damage to surrounding structures to preserve maximal vision. We used optical coherence tomography (OCT) to study the effects of radiotherapy on the retina. METHODS: Patients with posteriorly located choroidal melanoma treated with proton beam radiotherapy (PBR) and ruthenium-106 brachytherapy between January 2010 and June 2014 underwent spectral domain OCT. RESULTS: Images of 32 patients following ruthenium-106 brachytherapy and 44 patients following proton beam teletherapy were analysed. Following plaque brachytherapy, an early marked disruption of the outer retinal layers could be observed in 30 cases (94%) with retinal atrophy evident in 26 cases (81%). In contrast, the images from patients who underwent PBR showed subtle outer retinal layer change with 16 cases (36%) showing some inner-outer segment junction disruption by 6 months and 63%  by 24 months with minimal atrophy. In cases with tumours <2 mm from the fovea, the visual loss was significantly less at 6 and 12 months in the proton beam group. CONCLUSION: In comparison to ruthenium-106 plaque brachytherapy, PBR leads to more subtle and slower changes in the outer retinal layers enabling retention of visual function for longer. The difference in dosing regime and dose distribution across the tumour is likely to be causative for this structural differential.

Ru-106 plaque radiotherapy for vasoproliferative tumors of retina: a 15-year single-center experience.

PURPOSE: This study evaluates the outcomes of ruthenium-106 (Ru-106) plaque brachytherapy for vasoproliferative tumors (VPTs) of the ocular fundus in a single referral ocular oncology center. METHODS: The clinical charts of all patients diagnosed with VPT who underwent plaque radiotherapy from 2002 to 2017 were reviewed. Clinical features, types of treatment, outcomes and complications were evaluated. RESULTS: Of 46 patients with VPT diagnosis in our ocular oncology clinic, 25 (54.34%) cases were treated with Ru-106 plaque brachytherapy. Eleven patients (44%) were male, and the mean age at the time of diagnosis was 40.92 ± 13.11 years. The mean follow-up time was 47.56 ± 36.87 months. Inferotemporal quadrant was the most common site of the tumor (64.00%). The mean delivered apex and scleral dose was 101.56 ± 6.51 and 412.26 ± 113.66 Gray (Gy), respectively. Initial tumor length, width and thickness were 10.26 ± 3.42, 8.05 ± 2.83 and 4.27 ± 1.10 mm, respectively. The mean tumor thickness decreased to 2.60 ± 0.63 mm, postoperatively. Complete resolution of subretinal fluid around the tumor was achieved in 81.80% of cases. Visual acuity was more than 20/400 in 64% of patients before treatment and 60% of patients at last follow-up. CONCLUSION: Our study showed that Ru-106 plaque radiotherapy is an effective and safe method of treatment in VPTs.

Tumour control probability after Ruthenium-106 brachytherapy for choroidal melanomas.

Purpose: Ruthenium-106 (Ru-106) brachytherapy is a common eye-preserving treatment for choroidal melanomas. However, a dose-response model describing the relationship between the actual delivered tumour dose and tumour control has, to the best of our knowledge, not previously been quantified for Ru-106 brachytherapy; we aimed to rectify this.Material and methods: We considered consecutive patients with primary choroidal melanomas, treated with Ru-106 brachytherapy (2005-2014). Dosimetric plans were retrospectively recreated using 3D image-guided planning software. Pre-treatment fundus photographies were used to contour the tumour; post-treatment photographies to determine the accurate plaque position. Patient and tumour characteristics, treatment details, dose volume histograms, and clinical outcomes were extracted. Median follow-up was 5.0 years. The relationship between tumour dose and risk of local recurrence was examined using multivariate Cox regression modelling, with minimum physical tumour dose (D99%) as primary dose metric.Results: We included 227 patients with median tumour height and largest base dimension of 4 mm (range 1-12, IQR 3-6) and 11 mm (range 4-23, IQR 9-13). The estimated 3 year local control was 82% (95% CI 77-88). Median D99% was 105 Gy (range 6-783, IQR 65-138); this was the most significant factor associated with recurrence (p < .0001), although tumour height, combined TTT and Ru-106 brachytherapy, and sex were also significant. The hazard ratio (HR) for a 10 Gy increase in D99% was 0.87 (95% CI 0.82-0.93). Using biological effective dose in the model resulted in no substantial difference in dose dependence estimates. Robustness cheques with D1-99% showed D99% to be the most significant dose metric for local recurrence.Conclusion: The minimum tumour dose correlated strongly with risk of tumour recurrence, with 100 Gy needed to ensure at least 84% local control at 3 years.

Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

PURPOSE: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement. METHODS: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods. RESULTS: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation. CONCLUSIONS: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.

Blue-Light Fundus Autofluorescence Imaging following Ruthenium-106 Brachytherapy for Choroidal Melanoma.

PURPOSE: To describe changes in blue-light fundus autofluorescence (FAF) and corresponding alterations in optical coherence tomography (OCT) within the irradiation field after ruthenium-106 brachytherapy (RBT) for choroidal melanoma. METHODS: Consecutive patients with choroidal melanoma were included in a retrospective case series. Patients were treated with RBT at a single institution. As part of their routine examination patients underwent multimodal imaging including ultrasonography, fundus photography, OCT, and FAF imaging (excitation = 488 nm). FAF images were analysed for changes within the irradiation field. RESULTS: 31 patients (mean age 65.7 years) were treated with RBT for unilateral choroidal melanoma. Mean tumour height before therapy was 2.7 mm (SD 1.0). Mean follow-up time was 23.3 months (SD 13.3). Main FAF characteristics attributable to RBT emerged as increased FAF with speckled decreased FAF (FAF mottling) within the irradiation field and a rim of increased FAF at its border. OCT scans demonstrated loss of the ellipsoid zone and the external limiting membrane, thinning of the neurosensory retina, and alterations of the retinal pigment epithelium like clumping, migration, and atrophy. CONCLUSIONS: FAF changes in the irradiation field after RBT of choroidal melanomas follow a characteristic pattern that correlates with distinct OCT alterations. FAF and OCT imaging give additional information to monitor effects of RBT and, therefore, complement multimodal imaging techniques after plaque therapy.

AVATAR: Analysis for Visual Acuity Prediction After Eye Interventional Radiotherapy.

AIM: The aim of this study was to detect clinical factors predictive of loss of visual acuity after treatment in order to develop a predictive model to help identify patients at risk of visual loss. PATIENTS AND METHODS: This was a retrospective review of patients who underwent interventional radiotherapy (brachytherapy) with 106Ru plaque for primary uveal melanoma. A predictive nomogram for visual acuity loss at 3 years from treatment was developed. RESULTS: A total of 152 patients were selected for the study. The actuarial probability of conservation of 20/40 vision or better was 0.74 at 1 year, 0.59 at 3 years, and 0.54 at 5 years after treatment. Factors positively correlated with loss of visual acuity included: age at start of treatment (p=0.004) and longitudinal basal diameter (p=0.057), while distance of the posterior margin of the tumor from the foveola was inversely correlated (p=0.0007). CONCLUSION: We identified risk factors affecting visual function and developed a predictive model and decision support tool (AVATAR nomogram).

Ultra-widefield fundus photography for radiation therapy planning of ocular tumours.

PURPOSE: The use of planar ultra-widefield fundus photography (UWF) may result in distortions and inaccurate measurement. The aim of the study was to evaluate the accuracy of UWF instead of the standard narrow field (SF) for the treatment planning phase of ocular tumours. METHODS: Distortions between conformal SF and UWF were assessed in 43 patients with choroidal melanoma treated with either proton therapy or brachytherapy. imagej software was used to measure distortion. RESULTS: The median interquartile range ([IQR]) distortion for all cases was 3.7% [1.7-10.8]. For cases with tumours within 6 mm of the optic disc, distortions appeared clinically nonsignificant. For peripheral and/or large tumours, significantly larger distortions were observed on UWF (median 4.4% [2.7-22.6] for tumours ≥6 mm from the optic disc versus 3.3% [1.6-9.9] for those <6 mm, p = 0.04). Images can be subdivided into three groups: minimal distortion (79.1% of eyes), similar level of major distortion for both measured distances (11.6%) and distortion with unequal level of distortion between the measured distances (9.3%). CONCLUSION: Distortions with UWF appeared minimal in posterior regions of the fundus and increased with the distance from the posterior pole. UWF could therefore be used for treatment planning of ocular tumours as the planned radiation dose to the macula and optic disc are not impacted.

Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm.

BACKGROUND: Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and ß-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope. METHODS: All patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups. RESULTS: 317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5-7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%). CONCLUSIONS: Rates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.

Dosimetry of ruthenium-106 ophthalmic applicators with thin layer thermoluminescence dosimeters - Clinical quality control.

Ruthenium-106 ophthalmic applicators have proven to be effective when using beta emitters in brachytherapy. For dose calculations , typically, the dosimetric reference data given by the manufacturer are used. An additional check of the applicators is usually not provided. However, the medical physicist is responsible for correct dosimetry in the clinic; therefore dosimetric verification is desirable. Despite the fact that the use of beta-ray emitting sealed brachytherapy sources is a safe treatment method, errors can occur (Kaulich et al., 2004). Hence, a method for absolute dose measurements based on the use of thin layer MCP-N-thermoluminescence detectors (TLD Poland, Krakow, Poland) is described in this study. A custom-made polymethyl methacrylate (PMMA)- based phantom was developed for this study. The surface of the phantom was designed to fit with spherical shells of ruthenium-106 ophthalmic applicators (e.g. applicator type CCA, CCB and CIA by Eckert & Ziegler BEBIG GmbH, Berlin, Germany) studied in this work. To verify the reference data from the source certificates, absolute point dose values were measured at different phantom depths with the thermoluminescence detectors and compared to the certificate values. Calibrations of the thermoluminescence detectors were performed in a water phantom with a 6 MV CLINAC (Artiste, Siemens Medical, Erlangen, Germany) before. A comparison with scintillator measurement results given by the manufacturer in the applicator certificate shows the measurement series of absolute dose using MCP-N thin layer detectors being in good accordance with the values of the applicator certificate. The dose values calculated with the source certificate can be confirmed with a maximum deviation of 6.5%. Further, it can be shown that compared to TLD-100, the use of MCP-N thermoluminescence detectors is an advantage, when calibrating with 6 MV photons. The phantom measuring procedure presented in this study provides a practice-oriented realization for quality control of ruthenium-106 ophthalmic applicators in clinical routine The phantom seems capable of performing periodic system tests, as well as controlling the introduction of new applicators delivered by the manufacturer.

Optical coherence tomography angiography-based analysis of intrinsic vasculature in juxtapapillary melanoma after ruthenium-106 plaque brachytherapy.

In this case report, we demonstrate the use of optical coherence tomography angiography (OCTA) as a tool to evaluate intrinsic vasculature in a case of juxtapapillary melanoma which underwent ruthinium.106 plaque brachytherapy. In this case, OCTA could demonstrate a decrease in caliber and density of the intrinsic vasculature of the tumor post brachytherapy.

Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma.

PURPOSE: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma. METHODS: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan's grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded. RESULTS: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 µm at baseline to 223 ± 34 µm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded. CONCLUSION: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.