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.

Evaluation of radiation maculopathy after treatment of choroidal melanoma with ruthenium-106 using optical coherence tomography angiography.

BACKGROUND: To assess the impact of brachytherapy on macular microvasculature utilizing optical coherence tomography angiography (OCTA) in treated choroidal melanoma. METHODS: In this retrospective observational case series, we reviewed the recorded data of the patients with unilateral extramacular choroidal melanoma treated with ruthenium - 106 (106Ru) plaque radiotherapy with a follow-up period of more than 6 months. Automatically measured OCTA retinal parameters were analysed after image processing. RESULTS: Thirty-one eyes of 31 patients with the mean age of 51.1 years were recruited. Six eyes had no radiation maculopathy (RM). From 25 eyes with RM, nine eyes (36%) revealed a burnout macular microvasculature with imperceptible vascular details. Twenty-one non-irradiated fellow eyes from the enrolled patients were considered as the control group. Foveal and optic disc radiation dose had the highest value to predict the burnout pattern (ROC, AUC: 0.763, 0.727). Superficial and deep foveal avascular zone (FAZ) were larger in irradiated eyes in comparison to non-irradiated fellow eyes (1629 µm2 vs. 428 µm2, P = 0.005; 1837 µm2 vs 268 µm2, P = 0.021; respectively). Foveal and parafoveal vascular area density (VAD) and vascular skeleton density (VSD) in both superficial and deep capillary plexus (SCP and DCP) were decreased in all irradiated eyes in comparison with non-irradiated fellow eyes (P < 0.001). Compared with non-irradiated fellow eyes, irradiated eyes without RM had significantly lower VAD and VSD at foveal and parafoveal DCP (all P < 0.02). However, these differences at SCP were not statistically significant. CONCLUSION: The OCTA is a valuable tool for evaluating RM. Initial subclinical microvascular insult after 106Ru brachytherapy is more likely to occur in DCP. The deep FAZ area was identified as a more critical biomarker of BCVA than superficial FAZ in these patients.

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.

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.

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.

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.

Evaluation of Hungarian monitoring results and source localization of the 106Ru release in the fall of 2017.

Anthropogenic 106Ru has been detected in the environment from late September to early October 2017 by several European environmental radiological monitoring networks. The paper presents the comprehensive evaluation of Hungarian monitoring results related to the occurrence of 106Ru in various environmental compartments (airborne particulates, deposition, plants, and terrestrial indicators), which was implemented to determine the temporal and spatial variation of the contaminant on a national scale and also to verify the findings based on the data arising from environmental monitoring at a local scale in Budapest. Difficulties in direct comparison of the diverse reported data were also considered; results arising from varied sampling periods were corrected with account taken of the relation between the sampling duration and 4-day-long plume residence (estimation based on the daily monitoring of air and backward trajectory analysis). Integrated analysis of air and deposition measurements and meteorological data was also performed; the deposition processes were investigated by establishing the correlations of activity concentrations measured in the atmosphere and in the deposition samples. In order to study the temporal distribution and spatial localization of the 106Ru contamination and to interpret the measurements at ground level, backward trajectory analysis was performed with HYSPLIT model. The backward trajectory simulations suggested that the release had probably occurred during the last week of September 2017 from the geographical area between Volga and the Urals. In addition, assessment of the doses due to the 106Ru release was implemented considering external exposure from cloudshine and groundshine and internal exposure via inhalation.

Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy: A Growth Curve Model.

PURPOSE: To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns. DESIGN: Modeling of longitudinal observational data. PARTICIPANTS: Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center. METHODS: Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor-node-metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates. MAIN OUTCOME MEASURES: Covariates that independently predict tumor regression. RESULTS: Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression (P < 0.0001). In addition, use of ruthenium isotope as opposed to iodine isotope (P = 0.018) independently contributed to faster regression of tumor thickness. For both isotopes considered alone, initial tumor thickness was the sole clinical predictor of regression (P < 0.0001). CONCLUSIONS: Regression of choroidal melanoma after brachytherapy was associated with several clinical tumor and treatment parameters, most of which were shown to reflect initial tumor size. An independent predictor of regression of tumor thickness was the isotope used. These 2 covariates need to be adjusted for when exploring the associations with the rate of regression of histopathologic or genetic features of the tumor. Our model allows such future analyses efficiently without matching.

Neoadjuvant proton beam irradiation vs. adjuvant ruthenium brachytherapy in transscleral resection of uveal melanoma.

BACKGROUND: Uveal melanoma is the most common primary ocular malignancy in adults in the USA and Europe. The optimal treatment of large uveal melanoma is still under debate. Radiation therapy has its limitation due its eye-threatening secondary complications and is therefore often combined with surgical excision of the tumor. METHODS: In a retrospective interventional review, we evaluated in total 242 patients with uveal melanoma that underwent transscleral tumor resection with a predefined protocol, either with adjuvant ruthenium brachytherapy (Ru-106 group, n 136,), or with neoadjuvant proton beam therapy (PBT group, n 106). Kaplan-Meier estimates with log-rank test were used to show survival curves and a multivariable Cox regression model was used to calculate adjusted rate ratios. RESULTS: Local tumor recurrence rates after 3 and 5 years were 4% (95% CI 1.2-17.8%) and 9.1% (95% CI 2.9-27.3%), respectively, in the PBT group and 24.6% (95% CI 15.8-37.1%) and 27.5 (95% CI 17.8-41.1%), respectively, in the Ru-106 group. This leads to an overall recurrence rate almost 4 times higher in the Ru-106 group compared to the PBT group. After adjusting for the a priori confounders and the tumor distance to optic disc and ciliary body infiltration, the adjusted risk of tumor recurrence was 8 times (RR 7.69 (2.22-26.06), p < 0.001) higher in the Ru-106 group as compared to the PBT group. Three- and 5-year metastatic rates were 23.2% (95% CI 5.6-37.1%) and 31.8% (95% CI 20.7-46.8%), respectively, in the PBT group and 13.2% (95% CI 6.8-24.9%) and 30.3% (95% CI 18.3-47.5%), respectively, in the Ru-106 group. There was no statistically significant difference in the overall metastasis rate between the two groups even after adjusting for possible confounders. CONCLUSION: Transscleral resection of large uveal melanomas combined with neoadjuvant proton beam therapy leads to a lower local tumor recurrence rate compared to transscleral tumor resection with adjuvant ruthenium brachytherapy. There was no statistically significant difference in the occurrence of rubeosis iridis, neovascular glaucoma, and in the need for enucleation later on.

RUTHENIUM-106 BRACHYTHERAPY IN THE TREATMENT OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To examine the efficacy and safety of Ruthenium-106 plaque radiotherapy in the treatment of circumscribed choroidal hemangioma. METHODS: Twenty-one eyes of 21 patients diagnosed with symptomatic circumscribed choroidal hemangioma who underwent Ruthenium-106 plaque radiotherapy were included in the study. Clinical response, ancillary tests finding improvement, and major side effects were evaluated. RESULTS: From the initial to the 1-year follow-up visits, vision improved in 12 eyes (57%), was stable in 7 eyes (33%), and became worse in 2 eyes (10%). Based on fluorescein angiography and optical coherence tomography, subretinal fluid and cystoid macular edema resolved in all patients. Changes in logarithm of minimum angle of resolution visual acuity (P = 0.038); tumor thickness (P = 0.0001) and largest diameter (P = 0.007) on ultrasonography; and subfoveal thickness on optical coherence tomography (P < 0.0001), were statistically significant between the initial and the 1-year follow-up visits. Side effects as observed during the follow-up period included: radiation-related retinopathy in 5 (24%) eyes, radiation-related papillopathy in 1 eye (5%), and subretinal fibrosis in 2 eyes (10%). Subretinal fibrosis was the only permanent radiation-related side effect. CONCLUSION: Ruthenium-106 plaque radiotherapy is an effective and safe method of treatment for symptomatic circumscribed choroidal hemangiomas. The incidence of permanent visual loss is low with prompt treatment of complications.

[Late complications of choroidal melanoma brachytherapy and possibility of their prevention]. / Pozdnie oslozhneniia brakhiterapii melanom khorioidei i vozmozhnosti ikh profilaktiki.

Complications and the frequency of their occurrence as the criteria of eye preservation after brachytherapy (BT) are presented in literature with inconsistencies due to the assessment being done after varied follow-up periods (1 month to 5-10 years). The evaluation of complications occurring after applying radioiodine can be found in literature. The complications after BT beta particle emitting ophthalmic applicators are seldom discussed in articles. PURPOSE: to examine the frequency of complications, the characteristics of their development after choroidal melanoma (CM) brachytherapy with ruthenium ophthalmic applicators (OA) during long-term follow-up and determine the possibility of their prevention. MATERIAL AND METHODS: Characteristics of postradiation period after BT were studied in 200 patients with CM (200 eyes). Among them, 127 patients were treated by authors of this study, 73 were provided treatment by other specialized medical facilities in Moscow. The study involved 84 male and 116 female patients aged 56.14±12.8 in average. The follow-up periods spanned 2 to 39 years (mean length 9.84±6.16 years). BT was done only with ruthenium OA (beta radiation) manufactured in Russian. RESULTS: Follow-up period after BT for 83% of patients was 5 years. Complications occurred in 68.5% of patients. Complications were found in 74.63% of patients with CM localized pre-equatorially and in 65.4% of patients with CM localized in the posterior part of the eye. Complications associated with radiation-induced injuries in crystalline lens, retina and choroidal blood vessels were more frequent. CONCLUSION: The frequency of complications depends on the size of CM and its localization. Complications were the least frequent in patients with CM thickness of 5 mm or less.

Complexes of gastrin with In3+, Ru3+ or Ga3+ ions are not recognised by the cholecystokinin 2 receptor.

The peptide hormone gastrin (Gamide) binds trivalent metal ions, including indium (In), ruthenium (Ru) and gallium (Ga), with high affinity. Complexes of gastrin with chelated isotopes of In and Ga have previously been used for the location of tumours expressing the cholecystokinin 2 receptor (CCK2R). The aim of the present study was to purify the complexes of Gamide with radioactive isotopes of In, Ru or Ga and to investigate their ability to bind to the CCK2R. The radioactive Gamide complexes were purified on Sep-Pak C18 cartridges or by anion exchange HPLC. Binding to the CCK2R was assessed with a stably transfected clone of the gastric carcinoma cell line AGS. The 106Ru-Gamide complex could be eluted from the C18 cartridge; the 111In-Gamide and 68Ga-Gamide complexes bound irreversibly. All three complexes were successfully purified by anion exchange HPLC. The failure to detect binding of the 111In-Gamide, 106Ru-Gamide and 68Ga-Gamide complexes to the CCK2R suggests that formation of these complexes will not be useful for the detection of tumours expressing this receptor, but may instead provide alternative ways to block the actions of Gamide as a growth factor or a stimulant of gastric acid secretion. The complexes between the hormone gastrin and radioactive 111In, 106Ru or 68Ga ions were purified by anion exchange HPLC using a NaCl gradient. The failure to detect binding of the complexes to the cholecystokinin 2 receptor suggests that metal ion treatment may provide novel approaches to block the biological actions of gastrin.

WITHDRAWN: Radioisotopes for metastatic bone pain.

BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival. SEARCH METHODS: We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010. SELECTION CRITERIA: Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis. MAIN RESULTS: This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (89Sr) with Samarium-153 (153Sm), Rhenium-186 (186Re) and Phosphorus-32 (32P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of 153Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This update adds new evidence on efficacy of radioisotopes versus placebo, 89Sr compared with other radioisotopes, and dose-comparisons of 153Sm and 188Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

PREDICTORS OF TREATMENT RESPONSE OF VASOPROLIFERATIVE RETINAL TUMORS TO RUTHENIUM-106 BRACHYTHERAPY.

PURPOSE: To identify predictors of treatment response by evaluating long-term outcomes of vasoproliferative retinal tumors after ruthenium-106 brachytherapy. METHODS: In a retrospective case series, 39 eyes of 38 patients with vasoproliferative retinal tumors received ruthenium-106 brachytherapy between 2001 and 2013. Baseline clinical and morphologic parameters were analyzed regarding posttreatment tumor activity status. RESULTS: Within a median follow-up period of 2.9 ± 2.9 years, overall, a tumor inactivation was achieved in 72% of cases and visual acuity remained stable in 69%. The mean apex dose was 90 ± 23 Gy (range, 51-140 Gy). Mean tumor thickness decreased significantly, from 2.9 ± 0.9 mm to 1.5 ± 1.0 mm (P < 0.001; paired t-test). Persistence or recurrence of tumor activity occurred in 28% of cases, requiring secondary intervention with intravitreal drug injections, vitrectomy, cryotherapy, or repeated brachytherapy. Comparison of inactive and active vasoproliferative retinal tumors revealed significant correlation between both initial basal tumour diameter and area and subsequent tumour activity status. In particular, a diameter >7.5 mm was associated with an 8-fold risk of persistent or recurrent activity, whereas basal area >40 mm demonstrated a 6-fold risk (P = 0.009 and 0.021, respectively; Fisher's exact-test). In contrast, tumor thickness was not found to be of prognostic relevance. CONCLUSION: Ruthenium-106 brachytherapy is an effective and safe therapeutic option for vasoproliferative retinal tumors. Additionally, tumor diameter and area are efficient predictors of persistence or recurrence of tumor activity.

BRACHYTHERAPY ALONE OR WITH NEOADJUVANT PHOTODYNAMIC THERAPY FOR AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control.

PURPOSE: To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy. METHODS: Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable. RESULTS: Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001). CONCLUSION: Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.

Recurrence of choroidal melanoma after Ru- 106 brachytherapy.

AIM: The aim of the study was to analyse the recurrence rates of choroidal melanoma treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy. MATERIAL AND METHODS: We analysed medical records of 97 patients treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy who subsequently presented with recurrence. All patients were treated at the Department of Ophthalmology and Ocular Oncology in Krak6w between 1995 and 2006. RESULTS: The mean time to recurrence was 29.15 months and tended to be shorter in larger melanomas. The 5-year recurrence rate determined using Kaplan-Meier estimator was 28.69%. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc. The recurrence rates were the highest for all types of recurrence after the use of COB plaque with or without adjunctive transpupillary thermotherapy. CONCLUSION: The highest incidence of recurrence was shown in the second year following the Ru-106 brachytherapy and the time to recurrence tended to be shorter in larger melanomas. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc.

Conjunctival squamous cell neoplasia: the Liverpool Ocular Oncology Centre experience.

PURPOSE: To report the outcome of patients with conjunctival squamous cell neoplasia (CSCN)--including conjunctival squamous cell carcinoma (SCC), conjunctival squamous intraepithelial neoplasia (C-SIN) and carcinoma in situ (CIS)-treated at the Liverpool Ocular Oncology Centre (LOOC). METHODS: Patients treated between January 1993 and September 2011 were identified and categorised as having 'primary' or 'salvage' treatment, according to whether they had undergone a surgical procedure before referral to our centre. Invasive SCC was treated by excision with adjunctive ruthenium plaque radiotherapy. C-SIN or CIS was treated with topical 5-fluorouracil (5-FU), and in a few cases, cryotherapy. RESULTS: Primary treatment was administered to 20 patients (16 males, four females). Mean age was 62 years (range, 33-85). Histological examination revealed C-SIN/CIS in ten patients and invasive SCC in nine. Median follow-up was 69 months (range, 34-168). Three patients required further topical chemotherapy for persistent/recurrent C-SIN. Salvage therapy was administered to 21 patients (15 males, six females). Mean age was 63 years (range, 26-82). Histology showed C-SIN/CIS in 11 patients and invasive SCC in ten. Median follow-up was 54.5 months (range, 36-120). At the close of this audit, there was no recurrence of invasive or metastatic disease in either the primary or salvage groups. CONCLUSIONS: Our established protocol for treatment of CSCN has proven successful in local tumour control, and avoids ocular complications. We advocate adjunctive radiotherapy in patients with invasive SCC and chemotherapy in C-SIN/CIS. For improved patient outcome, prompt referral to a specialist centre is encouraged.

Management of diffuse choroidal hemangioma in Sturge-Weber syndrome with Ruthenium-106 plaque radiotherapy.

PURPOSE: To evaluate Ruthenium-106 plaque radiotherapy in the treatment of diffuse choroidal hemangioma (DCH) associated with serous retinal detachment. METHODS: A retrospective analysis was performed in five patients treated for DCH associated with Sturge-Weber syndrome (SWS). In all cases, Ruthenium-106 plaque therapy with a target apex dose of 30.98-47.36 Gy (mean:38.9 Gy) was performed. The outcomes of treatment were regression of DCH, assessed by B-scan ultrasonography; resolution of serous retinal detachment, measured by B-scan ultrasonography and optical coherence tomography (OCT); changes in best corrected visual acuity (BCVA) and the development of radiation-related complications. All investigations were repeated 3 months after treatment and then at six monthly intervals within 22-122 months (mean: 62 months) of follow-up. RESULTS: The initial BCVA of the affected eyes ranged from counting fingers at 1 m to 0.1 by the Snellen chart. Mean tumor basal diameter was 16.7 mm (range: 13.8 to 18.5 mm) and mean tumor thickness was 4.4 mm (range: 2.4 to 5.8 mm). Tumor regression was found in all cases with the prompt resolution of subretinal fluid. In three patients, BCVA improved and in two it remained stable. During the follow-up period, in one case secondary glaucoma was treated with transscleral cyclophotocoagulation, and in another case, recurrence of the hemangioma was treated with repeated Ruthenium-106 plaque irradiation and transpupillary therapy. CONCLUSION: Ruthenium-106 plaque radiotherapy is an effective and safe treatment option for DCH associated with SWS. Brachytherapy led to tumor regression and resolution of serous retinal detachments, and visual stabilization was achieved in most cases.

Endoresection technique with/without brachytherapy for management of high posterior choroidal melanoma: extended follow-up results.

PURPOSE: To evaluate the long-term efficacy and safety of endoresection for high posterior choroidal melanoma. METHODS: Retrospective nonrandomized interventional case series. Forty-one patients had endoresection as primary treatment for posterior choroidal melanoma. Of these, 21 patients had adjuvant brachytherapy. The inclusion criteria were tumor thickness ≥8 mm, base diameter <15 mm, and posterior tumors not extending anterior to the equator. Main outcomes measures were enucleation rate, visual outcome, surgical complications, local recurrence, metastasis, and mortality. RESULTS: Mean follow-up time was 102.5 months. Mean preoperative best-corrected visual acuity was 20/100. Mean tumor thickness was 9.8 mm (range, 7.7-13.5 mm; standard deviation, 1.7 mm), mean base diameter was 9.9 mm (range, 5-15 mm; standard deviation, 2.8 mm). At the latest visit, 36 patients (87.8%) still retained the eye. Mean postoperative best-corrected visual acuity was 20/1,625. Retinal detachment was the main postoperative complication (28.9%). At completion of follow-up, 12% of patients had phthisis bulbi, and 3 developed chronic hypotony. Five patients (12.2%) had local tumor recurrence; none of them had received brachytherapy as initial treatment. At 5 years of follow-up, 3 patients (7.3%) had liver metastasis. On Kaplan-Meier analysis at 10 years, all-cause mortality was 7.3% and specific mortality because of melanoma was 2.4%. CONCLUSION: Endoresection of high posterior melanomas was not associated with a higher risk of metastasis, death, or local recurrence than other reported techniques used to treat similar melanomas.