Absorbed dose distributions from ophthalmic 106 Ru/106 Rh plaques measured in water with radiochromic film.

PURPOSE: Brachytherapy with 106 Ru/106 Rh plaques offers good outcomes for small-to-medium choroidal melanomas and retinoblastomas. The dose measurement of the plaques is challenging, due to the small range of the emitted beta particles and steep dose gradients involved. The scarce publications on film dosimetry of 106 Ru/106 Rh plaques used solid phantoms. This work aims to develop a practical method for measuring the absorbed dose distribution in water produced by 106 Ru/106 Rh plaques using EBT3 radiochromic film. METHODS: Experimental setups were developed to determine the dose distribution at a plane perpendicular to the symmetry axis of the plaque and at a plane containing the symmetry axis. One CCA and two CCX plaques were studied. The dose maps were obtained with the FilmQA Pro 2015 software, using the triple-channel dosimetry method. The measured dose distributions were compared to published Monte Carlo simulation and experimental data. RESULTS: A good agreement was found between measurements and simulations, improving upon published data. Measured reference dose rates agreed within the experimental uncertainty with data obtained by the manufacturer using a scintillation detector, with typical differences below 5%. The attained experimental uncertainty was 4.1% (k = 1) for the perpendicular setup, and 7.9% (k = 1) for the parallel setup. These values are similar or smaller than those obtained by the manufacturer and other authors, without the need of solid phantoms that are not available to most users. CONCLUSIONS: The proposed method may be useful to the users to perform quality assurance preclinical tests of 106 Ru/106 Rh plaques.

Ruthenium-106 Brachytherapy with or without Additional Local Therapy Shows Favorable Outcome for Variable-Sized Choroidal Melanomas in Korean Patients.

PURPOSE: The purpose of this study was to report clinical outcomes of ruthenium-106 (106Ru) brachytherapy with or without additional local therapy for choroidal melanomas in Korean patients. MATERIALS AND METHODS: A total of 88 patients diagnosed with choroidal melanomas were treated with 106Ru brachytherapy between 2006 and 2012. Patients were divided into two groups according to their tumor height: a large group (≥ 6 mm, n=50) and a small group (< 6 mm, n=38). Most patients in the large group received combined therapy with local excision and/or transpupillary thermotherapy. In general, 85-95 Gy was administered to the apex of the tumor, while 100 Gy was administered to the point 2-6 mm from the outer surface of the sclera for patients undergoing combined therapy. RESULTS: The median follow-up duration was 30 months. The 3-year local control rate was significantly higher in the small group than in the large group (94% vs. 70%, p=0.047). The free from distant metastasis (FFDM) rate and the overall survival (OS) rate were also higher in patients in the small group (3-year FFDM, 97% vs. 76%; p=0.031 and 3-year OS, 97% vs. 72%; p=0.036). A total of 13 patients underwent enucleation. The eye-preservation rate was also higher in the small group (3-year eye-preservation rate, 94% vs. 70%; p=0.050), and tumor height was a significant prognostic factor for eye-preservation. CONCLUSION: 106Ru brachytherapy showed favorable outcomes in small choroidal melanomas in Korean patients. Although additional local treatment could improve eye-preservation rate for large tumors, other strategies should be considered for disease control.

Ruthenium-106 brachytherapy for choroidal melanoma without transpupillary thermotherapy: Similar efficacy with improved visual outcome.

PURPOSE: To evaluate efficacy and toxicity of two different protocols for eye-conserving treatment of patients with small to intermediate-sized choroidal melanomas; the current ruthenium-106 (Ru106) brachytherapy protocol and the preceding protocol of Ru106-brachytherapy with transpupillary thermotherapy (Ru106/TTT). METHODS AND MATERIALS: Long-term outcomes of 449 consecutive patients, of whom 196 (43.6%) treated using Ru106/TTT and 253 (56.3%) treated using Ru106, were compared in terms of local control, survival, eye preservation and visual outcome. RESULTS: Median follow-up was 82.8 months. Patients in the Ru106-group had smaller, less centrally located tumours and better pre-treatment visual acuity (VA). Five-year cumulative incidence of local failure was 11.2% for Ru106/TTT and 5.2% for Ru106, which was not statistically significant after correction for differences in baseline characteristics (hazard ratio for Ru106 = 0.57, p = 0.14). Cumulative incidence of distant metastases was 11.2 versus 6.2%, and cumulative incidence of cause-specific death was 22.4 versus 5.5% for Ru106/TTT and Ru106 respectively. Enucleation was performed in 9.2 versus 4.0% for Ru106/TTT versus Ru106; 5.1 versus 3.2% for local failure and 2.6 versus 0.8% for complications. At one year of follow-up, significantly more patients had lost useful vision (VA < 0.33) in the Ru106/TTT-group than in the Ru106-group (50.0 versus 24.5%). After two and three years, the differences decreased (54.6 versus 34.0% and 61.7 versus 45.8%, respectively) and lost statistical significance. CONCLUSIONS: Both the current Ru106 and the preceding Ru106/TTT-protocols provided excellent tumour control, cosmetic and functional eye preservation and vital prognosis. The Ru106-protocol yielded prolonged preservation of VA and should be regarded the current standard of treatment.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

IMPORTANCE: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. OBJECTIVE: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. MAIN OUTCOMES AND MEASURES: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). RESULTS: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. CONCLUSIONS AND RELEVANCE: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

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.

Ruthenium-106 plaque brachytherapy for uveal melanoma.

BACKGROUND: To report on local tumour control, eye preservation and visual outcome after ruthenium-106 brachytherapy for uveal melanoma. METHODS: Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at one single centre, were included. Primary outcome measures were local tumour control, eye preservation and visual outcome. The influence of patient, tumour and treatment parameters on outcome was analysed by time to event analysis and competing risk regression. RESULTS: The median overall follow-up was 37.9 months. Tumour control: recurrent tumour growth was observed in 17 patients. The estimated local tumour recurrence rate at 12, 24 and 48 months after irradiation was 3%, 8.4% and 14.7%, respectively. The only significant risk factors for tumour recurrence were age (p=0.046) and reduced initial visual acuity (VA, p=0.045). No significant difference could be shown for tumour size or tumour category (T1-T2 vs T3-T4), and for any other tumour or treatment parameters (including combined transpupillary thermo-therapy (TTT)).Eye preservation: The likelihood of keeping the eye 12, 24 and 48 months after irradiation was 97.7%, 94.7% and 91.8%, respectively. Most significant risk factors for secondary enucleation were initial VA (p<0.001), tumour height (p=0.002) and tumour category (p=0.015). VISION: The chances of keeping VA of 20/200 or better at 1, 2 and 5 years after treatment were 86.4%, 80.8% and 61.7%, respectively. Patients receiving sandwich-TTT showed significantly worse visual outcomes. CONCLUSIONS: Ruthenium-106 brachytherapy appears to be a useful treatment regarding tumour control, eye preservation and visual function. Adjunct sandwich therapy resulted in worse visual outcome.

[Risk factors for the recurrence of choroidal melanoma after the Ru-106 brachytherapy]. / Czynniki ryzyka wznowy czerniaka naczyniówki leczonego metoda brachyterapii Ru-106.

PURPOSE: The aim of the study was to determine factors, which are likely to affect local recurrence of choroidal melanoma after ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. MATERIAL AND METHODS: We analysed 355 cases of patients with choroidal melanoma treated ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. These were divided into two groups of patients with confirmed recurrence of choroidal melanoma (97 subjects) and patients without recurrence (control group, 258 subjects). RESULTS: We found a significant relationship between tumour recurrence and the presence of retinal detachment at the time of diagnosis, tumor shape, its large size and location with the marginal adjacency to the optic disc and with the anterior margin located 1-2 optic disc diameters from the macula. Among other risk factors, the use of COB plaque with supplementary transpupillary thermotherapy, dose to the tumor base, visibility of tumor base shade during transillumination, and uncertainty regarding precise plaque placement showed a significant correlation with tumour recurrence, just as the presence of metastases did. CONCLUSION: It seems that large tumour size and its location at the proximity of the optic disc are the key factors to affect the failure of brachytherapy and recurrence in patients with choroidal melanoma.

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.

Regression of uveal melanoma after ru-106 brachytherapy and thermotherapy based on metabolic activity measured by positron emission tomography/computed tomography.

PURPOSE: To evaluate regression rates of uveal melanoma after combined Ru-106 plaque radiotherapy and thermotherapy according to metabolic activity measured by positron emission tomography/computed tomography imaging. METHODS: A retrospective medical chart review was conducted on 26 patients with uveal melanoma who underwent pretreatment whole-body positron emission tomography/computed tomography and received combined plaque radiotherapy and thermotherapy between 2006 and 2011. Tumors were classified as metabolically active and inactive based on the positron emission tomography/computed tomography imaging and compared with tumor height regression rates after treatment. RESULTS: Before treatment, the median tumor thickness was 8.8 mm for metabolically active tumors (7 eyes) and 5.0 mm for metabolically inactive tumors (19 eyes). The median tumor thicknesses with respect to the original thickness at 3, 6, and 12 months after treatment were 88%, 78%, and 64% for metabolically active tumors and 95%, 89%, and 81% for metabolically inactive tumors, respectively. The monthly tumor regression rates during the first 3 months (4.2% vs. 1.7%, P = 0.022) and the overall monthly tumor regression rates (3.0% vs. 1.5%, P = 0.041) were significantly higher for metabolically active tumors versus inactive tumors. Two patients with positive metabolic activity developed metastatic diseases 2 years after treatment, whereas no patient with negative metabolic activity developed metastatic disease during the study period. CONCLUSION: Positive metabolic activity of uveal melanoma based on the positron emission tomography/computed tomography was significantly associated with rapid initial tumor regression after combined plaque radiotherapy and thermotherapy, suggesting a prognostic value for this diagnostic approach.

Prognosis of choroidal melanoma and the result of ruthenium brachytherapy combined with transpupillary thermotherapy in Korean patients.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of choroidal melanoma in Korean patients and the results of treatment with ruthenium (Ru) 106 plaque brachytherapy. METHODS: The medical charts of 111 patients diagnosed with choroidal melanoma who underwent Ru brachytherapy with trans-pupillary thermotherapy or local resection (61 patients) or who underwent other treatments (26 primary enucleations, 22 γ-knife radiotherapies and two lamellar sclerouvectomies) were reviewed retrospectively. RESULTS: The mean largest basal diameter (LBD) was 11.4±3.2 mm and the mean apical height was 7.8±2.9 mm. Compared with the collaborative ocular melanoma study, mean tumour height was skewed toward higher values (6.2 vs 4.8 in medium tumours, p<0.0001; 10.9 vs 9.5 mm in large tumours, p=0.034) and the LBD in large tumours was skewed toward smaller values (13.6 vs 17.3, p<0.0001). The estimated 5-year metastasis-free rate was 73.9% and the disease-specific survival rate was 84.6%. For the 61 patients that were treated with Ru brachytherapy, the 5-year metastasis-free and disease-specific survival rates were 79.0% and 87.7%, respectively, and the 5-year incidence of enucleation was 25.4%. The mean tumour regression at 6, 12 and 18 months after brachytherapy was 80.2%, 73.1% and 69.2%, respectively. CONCLUSIONS: Choroidal melanomas in Korean patients tend to grow vertically with a relatively large apical height and a small LBD. The prognosis of choroidal melanomas overall as well as prognosis after Ru brachytherapy were similar to those seen in previous studies with Caucasian patients. The enucleation rate after brachytherapy seems to be higher in Korean patients, for which a greater initial tumour height seems to be partly responsible.

Expression of 12 cytokines in aqueous humour of uveal melanoma before and after combined Ruthenium-106 brachytherapy and transpupillary thermotherapy.

PURPOSE: To determine the aqueous humour levels of 12 cytokines in eyes with uveal melanoma and whether their expression changes after combined Ru-106 brachytherapy and transpupillary thermotherapy (TTT). METHODS: Aqueous humour samples were collected from 20 patients with previously untreated uveal melanoma undergoing combined Ru-106 brachytherapy and TTT, both at the time of plaque placement and removal. Using multiplex biochip array technology, 12 different cytokines were measured, including interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF) and monocyte chemoattractant protein (MCP)-1. Aqueous humour from 20 patients undergoing cataract surgery was used as control. RESULTS: IL-6, IL-8, IFN-γ and MCP-1 were highly expressed in uveal melanoma, whereas IL-2, IL-10 and TNF- α were low in expression. There was a positive correlation between tumour height and IL-8 level (p = 0.020). Vascular endothelial growth factor tends to be highly expressed in melanoma-containing eyes (p = 0.056). Levels of IL-6, IL-8 and IL-1ß increased after the mean 117 ± 38 hrs of brachytherapy and adjunctive TTT with a tumour apex dose of 61 ± 28 Gy and a scleral contact dose of 786 ± 226 Gy. Increase in levels of IL-6 (p = 0.003) and IL-8 (p = 0.046) positively correlated with scleral contact dose. CONCLUSIONS: Cytokines such as IL-6, IL-8, IFN-γ and MCP-1 may be implicated in the progression of uveal melanoma. Ocular irradiation from a Ru-106 plaque promoted an increase in the levels of IL-6, IL-8 and IL-1ß, modulation of which could be useful in managing radiation-related side effects.

One-day session LINAC-based stereotactic radiosurgery of posterior uveal melanoma.

PURPOSE: LINAC-based stereotactic radiosurgery (SRS) of posterior uveal melanoma is a conservative method to treat uveal melanoma. METHODS: This was a retrospective clinic-based study of patients with posterior uveal melanoma in stage T2/T3 who underwent 1-day session SRS at LINAC accelerator or SRS plus combined methods from 2001 to 2008. RESULTS: Thirty-nine patients with posterior uveal melanoma were treated with SRS (age 25-80 years, median 54 years). Median tumor volume at baseline was 0.6 cm3 (range 0.2-1.3 cm3). The therapeutic dose (TD) was 35.0 Gy, median of maximal dose applied was 49.0 Gy (range 37.0-60.0 Gy). Patient data were analyzed in groups: group 1, single SRS irradiation; group 2, SRS with subsequent endoresection or cyclectomy or additional transpupillary thermotherapy (TTT) or brachytherapy by Ru106 plaques; group 3a, enucleation after single SRS; group 3b, enucleation after SRS and endoresection/cyclectomy or TTT or brachytherapy Ru106. In patients with visual acuity of 20/40 or better, the median rate of best-corrected visual acuity (BCVA) decline was higher than that of the total and significantly higher than the rate of decline in the complementary group of patients with BCVA less than 20/40 (p=0.0077; Mann-Whitney U test). CONCLUSIONS: One-step LINAC-based SRS with a single dose 35.0 Gy is a method to treat middle-stage posterior uveal melanoma and to preserve the eye globe or as the first step of combined methods: irradiation before endoresection or cyclectomy.

The comparison of ruthenium brachytherapy and simultaneous transpupillary thermotherapy of choroidal melanoma with brachytherapy alone.

PURPOSE: To compare the outcomes of combined treatment of choroidal melanoma with ruthenium brachytherapy (BT) simultaneously with transpupillary thermotherapy (TTT) and treatment with BT alone. METHODS AND MATERIALS: Two matched groups of patients, one treated with BT and simultaneous TTT (Group BT+TTT, n=63), the other treated with BT alone (Group BT, n=70) were analyzed retrospectively. The main outcome measures were rate of tumor regression, recurrences, enucleations, metastases, recurrence-free and overall survival rate, and visual acuity, assessed by Kaplan-Meier analysis. RESULTS: Patients were matched according to mean age (p=0.22), mean tumor thickness (6.4 vs. 6.25mm, range 2.5-10.8mm, p=0.59), and mean length of followup (42 vs. 34.4 months, range 3-109, p=0.052). Tumor largest basal diameter (13.0 vs. 12.9mm), tumor location, and mean radiation dose (apical 135 vs. 136Gy and scleral 1294 vs. 1438Gy) were also similar in both groups (p>0.1). Treatment with BT+TTT resulted in higher rate of tumor regression (63% vs. 49%, respectively, p=0.036), lower 5-year tumor recurrence rate (96% vs. 83%, p<0.034), and higher eye-globe preservation (98% vs. 87%, p<0.024) and recurrence-free survival rates (89% vs. 67%, p<0.017) than treatment with BT alone. There was no difference in complications (p>0.5), metastasis-free (93% vs. 81%, p>0.22) and overall survival rates (91% vs. 81%, p>0.39), or in visual outcomes. CONCLUSION: Combined treatment of choroidal melanoma with ruthenium BT and simultaneous TTT seems to provide higher local control, eye-globe preservation, and recurrence-free survival rates than treatment with BT alone and results in similar rates of metastases and overall survival.

Ruthenium-106 brachytherapy.

Brachytherapy is the most common method for treating uveal melanoma, and currently the ruthenium-106 (Ru-106) and iodine-125 (I-125) applicators are the most frequently used. Ru-106 applicators were introduced by Prof. Peter Lommatzsch in the 1960s, and since then have been used widely by many ocular oncologists, mainly in Europe. The Ru-106 isotope is a beta ray (electron) emitter, and as such it has a limited depth of penetration. This is the reason why many experts use Ru-106 applicators for tumors with a maximal thickness of up to 7.0 mm, although others use it successfully for thicker tumors. The Ru-106 applicators are manufactured commercially and have a half-life of about 1 year. Ru-106 brachytherapy for uveal melanoma provides excellent local control rates and eye preservation with a relatively low recurrence rate. The main advantage of Ru-106 over other isotopes is the better preservation of vision in the treated eye, and less damage to the healthy parts of the eye due to its limited range of radiation. This can also be achieved by positioning the Ru-106 plaque eccentrically, away from the macula and optic nerve head. Ru-106 brachytherapy can be used in combination with other methods of treatment of uveal melanoma, such as local resection or transpupillary thermotherapy, and is sporadically combined with other isotopes, such as gamma-emitting cobalt-60 and I-125.

[Results of 10-year use of complex treatment of choroidal melanoma stage T2 with brachytherapy and transpupillary thermotherapy].

We studied the results of complex treatment of choroidal melanoma (CM) using Ru-106+Rh- 106 brachytherapy (BT) combined with transpupillary thermotherapy (TTT). 70 patients (70 eyes) with CM prominence ranged from 2.5 till 10.8 mm (mean 6.5+0.24 mm) were enrolled into the study. Follow-up was 6-120 months, median 47 months. TTT (810 microm) was carried out 24-48 hours later ophthalmic applicator suturing. Absolute or partial regression was achieved in 69 patients (99%) from 6.4+0.24 mm till 2.4+1.9 mm. In 1 case treatment was not effective. In 1 patient enucleation was performed due to secondary glaucoma. Dissemination with liver metastases was observed in 3 patients. Kaplan-Meier analysis showed 5 year eye preservation as high as 99%, absence of metastases--94%, survival rate without recurrence--91%, total efficacy (patients without negative results)--89%. Thus complex treatment (BT + TTT) of CM compared with monotherapy BT showed to have better local outcomes (including eye preservation) and it does not reduce survival rate even in patients with stage T2 (less than 10 mm).

Predicting local control of choroidal melanomas following ¹°6Ru plaque brachytherapy.

BACKGROUND: We evaluated the control rate of choroidal melanomas treated with ¹°6Ru plaque brachytherapy to identify the risk factors associated with local recurrence and lack of response. METHODS: A retrospective review of ¹°6Ru plaque brachytherapy for patients with choroidal melanoma treated at St Bartholomew's Hospital, London. Survival analysis was used to assess associations between evaluated age, sex, location, foveal proximity, tumour base and height, presence of lipofuscin and subretinal fluid, apex dose, radiation rate and type of plaque with time to local recurrence. Logistic regression analysis was used to assess to evaluate the association between the same set of variables and lack of tumour response. RESULTS: From January 2002 to December 2006 189 patients were treated. The follow-up ranged from 12 to 78 (median 33) months. None of the patients received adjuvant diode laser thermotherapy. The control rate was 85.7% (14 recurred while 13 did not respond). Of the patients who had local recurrence, univariate survival analysis demonstrated an association with younger patients, foveal proximity, preoperative subfoveal fluid and tumour base >11 mm. Age and foveal proximity remained significant in a Cox multiple variable model (p=0.03). Of the patients who did not respond, logistic regression analysis showed that lack of response was associated with a tumour height >5 mm, confirmed through multiple variable analysis (p=0.027). CONCLUSIONS: Tumours that are close to the fovea in young patients appear more likely to show local recurrence. Tumour height >5 mm was the only prognostic factor that determined lack of response. These results may be used to select which tumours require adjuvant therapy.

Microcirculation patterns in indocyanine green angiography and the results of plaque therapy in choroidal melanoma.

PURPOSE: To determine the effect of radioactive plaque therapy on blood vessel behaviour in choroidal melanomas using indocyanine green (ICG) angiography. MATERIAL AND METHODS: Fifty-five patients with choroidal melanoma were studied. Ruthenium-106 plaques were used in 30 eyes, in 11 the "sandwich method" (Ruthenium-106 plaque with transpupillary thermotherapy), was applied and 14 tumours were treated with Iodine-125. In all cases ICG angiography was performed prior to treatment and 12 months after, and at different time afterwards. Baseline tumour microcirculation patterns (MCPs) were studied prior to treatment and post-treatment blood vessels changes were evaluated. Total follow-up period ranged from 14-22 months (mean: 16 months). RESULTS: Pre-treatment ICG angiography revealed complex MCPs, combining parallel with cross-linking, arcs with branching, loops and networks patterns in 23 (41.8%) and non-complex MCPs, including straight, parallel without cross-linking and arcs without branching patterns in 32 (58.2%) melanomas. Twelve months after treatment, 38 tumours (69.1%) showed a significant changes in their MCPs. The mean ultrasonographic regression rate in tumours with complex MCPs was 57.4% as opposed to 36.2% in the group with non-complex MCPs (p = 0.01). No statistically significant correlation in the height regression rate was found among the various methods of therapy, however a significant difference between the type of therapy and MCPs changes was observed (p < 0.001). Melanomas treated with Ruthenium-106 and TTT demonstrated slight or no MCPs changes, while tumours treated with Ruthenium-106 and Iodine-125 plaques alone showed a significant MCPs changes (p < 0.001). The statistical analysis showed the correlation between the type of baseline MCPs and the degree of their changes after treatment (p < 0.001). Tumours with networks, loops, arcs with branching and parallel with crossing showed an increased regression as compared to other MCPs. Twelve patients whose tumours contained complex MCPs developed metastatic disease. CONCLUSIONS: This study suggests that the response of choroidal melanoma to irradiation is related to MCPs as identified by ICG angiography; the presence of complex MCPs is associated with a high regression rate after plaque therapy and a high risk of development of systemic metastatic disease.

Ruthenium-106 plaque radiotherapy alone or in combination with transpupillary thermotherapy in the management of choroidal melanoma.

PURPOSE: To evaluate the results of ruthenium-106 (Ru-106) plaque radiotherapy alone (group A) or in combination with transpupillary thermotherapy (TTT) (group B) in the management of choroidal melanoma with tumor thickness (height) <8 mm. The tumors in each group were subclassified as those with thickness 5 and <8 mm. METHODS: In this retrospective review, the main outcome measures were globe conservation rate, the rate of a reduction of at least 50% in tumor thickness, treatment complications, visual acuity (VA) change, and metastasis. Kaplan-Meier curves for prediction of decrease in tumor thickness of at least 50% over time were constructed. RESULTS: A total of 54 patients (24 in group A and 30 in group B) were included in this study. The groups were matched with respect to patient age, tumor base diameter, tumor thickness, tumor distance to optic disc, tumor distance to foveola, and baseline visual acuity (VA). The mean follow-up was 24.6 months in group A and 44.9 months in group B. Globe conservation was achieved in 21 (87.5%) eyes in group A and in 26 (86.7%) eyes in group B. The globe conservation rates did not differ significantly between groups A and B or between tumors 5 to <8 mm in thickness in each group (P > 0.05). There was no statistical difference between groups A and B in the rate of tumor thickness reduction of at least 50% (P> 0.05). There was a significant decrease in final VA compared to baseline VA in group B (P = 0.007) but not in group A. Radiation complications were similar in groups A and B. Liver metastasis occurred in two patients in group A and in one patient in group B. Statistical analysis could not be carried out for the latter two variables because of the small number of affected patients. CONCLUSIONS: Compared to Ru-106 plaque radiotherapy alone, Ru-106 plaque radiotherapy combined with TTT did not result in a significant change in the globe conservation rate or the rate of at least 50% reduction in tumor thickness in choroidal melanomas <8 mm in thickness. Although Ru-106 plaque radiotherapy is mainly used for choroidal melanomas >or=5 mm thick, it can also be considered in selected tumors with thickness between 5 and 8 mm with comparable tumor control.

Long-term outcomes of eye-conserving treatment with Ruthenium(106) brachytherapy for choroidal melanoma.

PURPOSE: To evaluate long-term outcomes of eye-conserving treatment using Ruthenium-106 plaque brachytherapy with or without transpupillary thermotherapy (TTT) for small to intermediate size choroidal melanomas. METHODS: Outcomes of 425 consecutive patients were analysed. The median basal tumour diameter was 10.9 mm (range 4.8-15.9 mm), and the median apical height 4.2 mm (range 1.2-9.3 mm). Brachytherapy doses ranged from 400 to 600Gy with TTT (86%), or from 600 to 800Gy without TTT (14%), specified at the scleral surface. Kaplan-Meier survival curves, log-rank tests and Cox regression analysis were used for analysis. RESULTS: Median follow-up was 50 months. Five-year actuarial local control was 96%. Five-year overall and metastases-free survival rates were 79.6% and 76.5%. Prognostic factors for metastasis-free survival were peripheral location (p=0.02) and smaller basal diameter (p<0.001). No dose effect relationships were found. Radiation side effects were frequent, with 2- and 5-year rates free of radiation complications of 60% and 35%. Five-year enucleation rate was 4.4% (10 for local recurrence, 7 for complications). Cosmetic and functional (visual acuity >0.10) eye preservation rates were 96% and 52% at 5 years. CONCLUSIONS: Ruthenium-106 brachytherapy for choroidal melanoma provides excellent rates of local control and eye preservation.

Braquiterapia com rutênio-106 em melanomas uveais - resultados preliminares: experiência uni-institucional / Ruthenium-106 brachytherapy for uveal melanomas - preliminary results: a single institutional experience

OBJETIVO: Analisar os resultados preliminares da braquiterapia com rutênio-106 em pacientes portadores de melanomas uveais. MATERIAIS E MÉTODOS: No período de abril de 2002 a julho de 2003, 20 pacientes com diagnóstico de melanoma uveal foram tratados com braquiterapia com rutênio-106. A dose calculada no ápice tumoral variou de 55 Gy a 100 Gy. Pacientes com lesões com altura maior que 5 mm foram submetidos a termoterapia transpupilar concomitante à colocação da placa oftálmica. RESULTADOS: Quanto à localização da lesão, esta se encontrava na coróide em 75 por cento dos casos, na íris em 15 por cento e no corpo ciliar em 10 por cento dos pacientes. Com seguimento mediano de 19 meses, a sobrevida livre de progressão para a braquiterapia e para a associação com a termoterapia transpupilar foi de 69 por cento e 87 por cento, respectivamente. Observou-se redução significante da altura tumoral após o tratamento. Nenhum dos pacientes foi submetido a enucleação. CONCLUSÃO: Nossos resultados preliminares mostram que a braquiterapia com rutênio-106 é uma opção adequada para o tratamento conservador de melanomas uveais em termos de controle local, manutenção do globo ocular e visão útil, com índice aceitável de complicações.

OBJECTIVE: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. MATERIALS AND METHODS: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. RESULTS: As regards the lesions site, 75 percent of the lesions were located in the choroid, 15 percent in the iris, and the remainder 10 percent in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69 percent, and 87 percent for associated brachytherapy and transpupillary thermotherapy. A significant tumor height reduction was observed after treatment. No patient was submitted to enucleation. CONCLUSION: Our preliminary results show that ruthenium-106 brachytherapy is an appropriate method for conservative treatment of patients with uveal melanomas in terms of local management, ocular and visual acuity preservation with an acceptable complications incidence rate.