Brachytherapy of Choroidal Melanomas Less Than 10 mm in Largest Basal Diameter: Comparison of 10-mm and 15-mm Ruthenium Plaques.

PURPOSE: To compare tumor control, vision, and complications between patients with a choroidal melanoma of <10 mm in largest basal diameter (LBD) irradiated with 10-mm or 15-mm ruthenium plaques. DESIGN: Retrospective, comparative case series. PARTICIPANTS: One hundred sixty-four consecutive patients with a choroidal melanoma of <10 mm in LBD, 76 and 88 treated with the 10-mm and 15-mm plaque, respectively, from 1998-2014 in a national ocular oncology service. METHODS: Diagnosis was based on growth or high-risk characteristics. The apical dose was 100 to 120 Gy aiming to deliver ≥250 Gy to the sclera. Plaque positioning was modeled retrospectively. An increase of ≥0.3 mm in thickness and ≥0.5 mm in LBD indicated local recurrence. Outcomes were compared with cumulative incidence analysis and Cox regression. Median follow-up time for patients still alive was 8.4 years. MAIN OUTCOME MEASURES: Recurrence rate, low vision, blindness, radiation maculopathy, and optic neuropathy. RESULTS: Melanomas treated with the 10-mm plaque were smaller (median thickness, 1.9 mm vs. 2.6 mm; LBD, 7.1 mm vs. 8.6 mm) and located closer to foveola (median, 2.0 mm vs. 2.8 mm) than those treated with the 15-mm plaque (P < 0.001). The 2 plaques provided a safety margin in 43% versus 40% eyes, provided no safety margin to guard foveola in 17% versus 33%, and did not entirely cover tumor mainly close to the disc in 32% versus 18% of eyes, respectively (P = 0.052). The incidence of a local recurrence was comparable (13% vs. 15% at 10 years; P = 0.31) and associated with plaque positioning (hazard ratio [HR], 2.81 for no safety margin; P = 0.041). At 5 years, the incidence of low vision was 14% versus 24%, and that of blindness was 3% versus 6%. Distance to the foveola was associated with loss of both levels of vision (HR, 0.65 per 1 mm vs. 0.68 per 1 mm; P ≤ 0.001 vs. P = 0.004). The incidence of radiation maculopathy was comparable (19% vs. 18% at 5 years), whereas that of optic neuropathy tended to be higher with the 15-mm plaque (2% vs. 9%; P = 0.054). CONCLUSIONS: The 10-mm ruthenium plaque contributes to better visual preservation, particularly with tumors close to fovea, without increase in local recurrence rate, and may therefore be preferable to the 15-mm plaque.

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.

Effect of calculation method on kidney dosimetry in 177Lu-octreotate treatment.

BACKGROUND: 177Lu-octreotate is an effective treatment modality for patients with metastatic neuroendocrine tumors. The kidney is a critical dose-limiting organ in that modality. We investigated the absorbed doses in the kidney and compared whole kidney volume (WKV) and small (4 cm3) volume of the kidney (SV) methods. We also evaluated a new calculation method that was based on two single photon emission computed tomography/computed tomography (SPECT/CT) scans. METHODS: Absorbed radiation doses in the kidneys were calculated for 24 patients with neuroendocrine tumors. All patients received four cycles of 177Lu-octreotate given at eight-week intervals with a mean activity of 7.1 GBq (range 3.28-8.79 GBq). Absorbed doses and half-lives were calculated by the WKV and SV methods. Dosimetry was determined for the cortex and medulla in the first treatment cycle. RESULTS: The mean absorbed radiation dose was 0.44 ± 0.15 Gy/GBq for the WKV method and, 0.74 ± 0.28 Gy/GBq for the SV method. Three patients had a 20% increase of the absorbed dose over the four treatment cycles for the WKV method compared to eight patients for the SV method. The mean absorbed dose in the medulla was 0.62 ± 0.27 Gy/GBq, whereas the mean absorbed dose in the cortex was 0.41 ± 0.22 Gy/GBq. Both regions had similar half-lives. Patients who received lower activities for medical reasons still had similar absorbed doses to kidneys compared to those who received the full activities. Our study indicates that absorbed doses can be calculated reliably using two SPECT/CT scans, at 24 and 168 hours after each treatment. CONCLUSIONS: Absorbed doses in the kidneys from systemic radionuclide therapy that are measured by the WKV method and SV method cannot be directly compared. There were regional differences within kidneys for the uptake of 177Lu-octreotate. Two SPECT/CTs are sufficient for kidney dosimetry based on our new calculation method.

Management of choroidal melanomas less than 10 mm in largest basal diameter with a 10-mm ruthenium plaque.

PURPOSE: To assess tumor control, complications, and vision after brachytherapy for posterior choroidal melanoma <10 mm in largest basal diameter with the 10-mm ruthenium plaque. METHODS: This was a retrospective cohort study of consecutive choroidal melanomas <10 mm by largest basal diameter in a national ocular oncology service in 1998 to 2010. The median dose was 116 Gy (range, 80-194 Gy) to the apex and 327 Gy (range, 201-824 Gy) to the sclera. The median tumor height and largest basal diameter were 1.9 mm (range, 0.4-5.2 mm) and 7.0 mm (range, 3.3-9.6 mm), respectively. The median distance to disk and foveola was 3.0 mm (range, 0-7.5 mm) and 2.0 mm (range, 0-8.5 mm), respectively. RESULTS: Four recurrences occurred at a median of 1.4 years (range, 0.6-3.1 years) after irradiation. Five-year cumulative incidence of local recurrence was 9% (95% confidence interval [CI], 3-20). Six patients died at a median of 4.2 years (range, 0.28-8.6 years) after treatment, one with evidence of metastases. At 5 years, 57% (95% CI, 31-79), 72% (95% CI, 58-85), and 97% (95% CI, 88-100) of eyes were free of any maculopathy, radiation maculopathy, and optic neuropathy, respectively. Cumulative incidence of developing low vision and blindness were 17% (95% CI, 7-31) and 3% (95% CI, 2-12) at 5 years, respectively. Thickness >3.0 mm, largest basal diameter >7.0 mm, and location ≤ 1.5 mm of foveola were associated with visual loss. CONCLUSION: Local tumor control and vision outcomes support the use of 10-mm ruthenium plaques in managing smallest choroidal melanomas.

Scintigraphy in prediction of the salivary gland function after gland-sparing intensity modulated radiation therapy for head and neck cancer.

BACKGROUND AND PURPOSE: To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. PATIENTS AND METHODS: Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. RESULTS: The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. CONCLUSIONS: Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.

Dosimetry software Hermes Internal Radiation Dosimetry: from quantitative image reconstruction to voxel-level absorbed dose distribution.

OBJECTIVE: The aim of this work is to validate a software package called Hermes Internal Radiation Dosimetry (HIRD) for internal dose assessment tailored for clinical practice. The software includes all the necessary steps to perform voxel-level absorbed dose calculations including quantitative reconstruction, image coregistration and volume of interest tools. METHODS: The basics of voxel-level dosimetry methods and implementations to HIRD software are reviewed. Then, HIRD is validated using simulated SPECT/CT data and data from Lu-DOTATATE-treated patients by comparing absorbed kidney doses with OLINDA/EXM-based dosimetry. In addition, electron and photon dose components are studied separately in an example patient case. RESULTS: The simulation study showed that HIRD can reproduce time-activity curves accurately and produce absorbed doses with less than 10% error for the kidneys, liver and spleen. From the patient data, the absorbed kidney doses calculated using HIRD and using OLINDA/EXM were highly correlated (Pearson's correlation coefficient, r=0.98). From Bland-Altman plot analysis, an average absorbed dose difference of -2% was found between the methods. In addition, we found that in Lu-DOTATATE-treated patients, photons can contribute over 10% of the kidney's total dose and is partly because of cross-irradiation from high-uptake lesions close to the kidneys. CONCLUSION: HIRD is a straightforward voxel-level internal dosimetry software. Its clinical utility was verified with simulated and clinical Lu-DOTATATE-treated patient data. Patient studies also showed that photon contribution towards the total dose can be relatively high and voxel-level dose calculations can be valuable in cases where the target organ is in close proximity to high-uptake organs.

Strontium plaque brachytherapy for exudative age-related macular degeneration: three-year results of a randomized study.

OBJECTIVE: To determine the efficacy of strontium plaque (Sr90) brachytherapy for age-related macular degeneration (AMD) with subfoveal choroidal neovascularization (CNV). DESIGN: Randomized clinical trial. PARTICIPANTS: Eighty-eight eyes of 86 patients with subfoveal CNV secondary to AMD were randomized either to plaque radiotherapy or to observation. INTERVENTION: Radiotherapy was given as episcleral brachytherapy using Sr90 plaques. Two different plaque types were used. Plaque I had a diameter of 8 mm and delivered a dose of 15 Gy at a depth of 1.75 mm in 54 minutes. With plaque II, the corresponding values were 4 mm, 12.6 Gy, and 11 minutes. The control group was observed without any treatment. MAIN OUTCOME MEASURES: The primary outcome measure was visual acuity at 6, 12, 24, and 36 months. Other outcome variables were contrast sensitivity, fluorescein angiographic, and clinically evaluated changes in the macula. RESULTS: Eighty-two patients (84 eyes [95%]) completed the 1-year follow-up, and 80 (93%) and 74 (86%) patients completed the 2- and 3-year follow-ups, respectively. At 6 months, visual loss of > or =3 lines occurred in 20% of treated patients and 42% of control patients (P = 0.031). At 12 months, a visual loss of > or =3 lines occurred in 45% (treated) and 56% (controls) (P = 0.325); at 24 months, in 73% and 71% (P = 0.914); and at 36 months, in 80% and 84% of patients (P = 0.591), respectively. Patients irradiated with plaque I had better results: a visual loss of > or =3 lines occurred in 6% at 6 months (P = 0.008, relative to controls), in 18% at 12 months (P = 0.007), in 59% at 24 months (P = 0.348), and in 71% at 36 months (P = 0.212). In patients treated with plaque II, the corresponding values were 29% (P = 0.032), 65% (P = 0.459), 83% (P = 0.317), and 80% (P = 0.687) at 6, 12, 24, and 36 months, respectively. CONCLUSIONS: The short-term clinical course of exudative AMD is affected by Sr90 brachytherapy, but by 12 months, there was no treatment benefit. This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha.

Tumor Regression After Brachytherapy for Choroidal Melanoma: Reduction of Thickness and Cross-Sectional Area by Shape and Regression Pattern.

PURPOSE: To model regression rate of thickness and cross-sectional area of choroidal melanomas after ruthenium and iodine brachytherapy by shape and regression pattern (RP). METHODS: We enrolled 330 of 388 consecutive uveal melanomas from 2000 to 2008 and analyzed images from I3 System-ABD 10-MHz B-Scan at diagnosis and during a 3-year-long follow-up. We classified tumor shape by Collaborative Ocular Melanoma Study definitions and RP according to an earlier study. We plotted regression over time and compared thickness and cross-sectional area. RESULTS: The observed RP by thickness was classified as decrease (D) in 43%, stable (S) in 5%, increase (I) in 1%, and other in 40% of eyes; main subpatterns were decrease-stable (DS) in 16% and zigzag in 10% of eyes. The corresponding percentages by area were 42%, 3%, 1%, 45%, 16%, and 14%. Regression pattern was discordant in 34% of eyes for thickness versus area. Area reduced faster than thickness when shape was oval to dome or mushroom and if RP was D. Pooled patterns D, DS, decrease-increase (DI), and zigzag corresponded with progressive but increasingly less pronounced regression for 3 years (56% by thickness and 69% by area), 2 years (50% and 52%), 6 months (29% and 33%), and 6 months (19% and 23%), respectively. First-order exponential decay function fitted thickness and area regression for every shape and for patterns D, DS, DI, and zigzag. CONCLUSIONS: Heterogeneity in RP, variation in shape, and tumor cross-sectional area as an alternative measure must be considered when tumor regression rate is used in outcome analysis.

Effect of radiation dose on ocular complications after iodine brachytherapy for large uveal melanoma: empirical data and simulation of collimating plaques.

PURPOSE: To calculate radiation doses to intraocular tissues in iodine brachytherapy (IBT) for large uveal melanoma, to study their relationship to ocular complications, and to assess a modified plaque design to reduce doses to the macula and optic nerve. METHODS: Ninety-six patients with a uveal melanoma, classified as large according to the Collaborative Ocular Melanoma Study criteria, underwent primary IBT. Median tumor height and diameter were 10.7 (range, 4.5-16.8) and 16.5 (range, 7.3-25.0) mm, respectively, and median follow-up was 3.5 years (range, 0.3-10.4). Each IBT was retrospectively modeled with a plaque simulator to calculate doses and dose rates to ocular tissues. Cox proportional hazards regression was used to assess their association with time to ocular complications, low vision, and blindness (20/70 or worse and loss of 20/400, respectively). A collimating plaque design was assessed by replacing the actual plaque with the modified one in each model. RESULTS: Median doses to tumor apex and base were 81 (range, 40-158 Gy) and 384 (range, 188-1143) Gy, respectively, and the median dose rates at these points were 53 (range, 11-204) and 289 (range, 84-1213) cGy/h, respectively. Median doses to the lens, macula, and optic disc were 69 (range, 20-141), 79 (range, 12-632), and 83 (range, 10-377) Gy, respectively. Dose to the lens was associated with cataract (hazard ratio [HR] 1.15 for each 10-Gy increase, P = 0.002), and dose to the optic disc with optic neuropathy (HR 1.08, P = 0.001). Dose to the macula predicted low vision (HR 1.06, P = 0.025) and blindness (HR 1.10, P < 0.001). A collimating design provided a median reduction of 36 (range, +19 to -198) and 30 (range, +9 to -160) Gy in modeled doses to the macula and optic disc, respectively. CONCLUSIONS: Simulated dose distribution together with tumor height predicts major complications and vision loss after IBT. Simulation suggests that clinically meaningful dose reduction to normal tissues is feasible with a redesigned brachytherapy protocol, which may help to reduce complications and vision loss after IBT of large uveal melanoma.

Ocular complications after iodine brachytherapy for large uveal melanomas.

PURPOSE: To evaluate anterior and posterior segment complications and their management after iodine 125 plaque brachytherapy (IBT) for large uveal melanoma. DESIGN: Retrospective nonrandomized interventional study. PARTICIPANTS: Ninety-six patients with a large uveal melanoma according to the Collaborative Ocular Melanoma Study criteria. METHODS: The patients underwent primary IBT (median dose to tumor apex, 87 Gy). The median tumor height and diameter were 10.7 mm (range, 4.5-16.8) and 16.5 mm (range, 7.3-25.0), respectively, and the median follow-up time was 3.5 years (range, 0.3-10.4). Cumulative incidence analysis and competing risks regression were used to analyze the time to individual complications and to identify risk factors. Death and secondary enucleation were analyzed as competing risks. MAIN OUTCOME MEASURES: Cataract, iris neovascularization, glaucoma, maculopathy, optic neuropathy, vitreous hemorrhage, and persistent exudative retinal detachment (RD). RESULTS: The 5-year cumulative incidences of cataract, iris neovascularization, and glaucoma were 69% (95% confidence interval [CI], 57%-78%), 62% (95% CI, 50%-71%), and 60% (95% CI, 48%-70%), respectively. Posterior segment complications were less common. The 5-year incidences of maculopathy and optic neuropathy were 52% (95% CI, 35%-65%) and 46% (95% CI, 30%-61%), and those of vitreous hemorrhage and persistent RD were 36% (95% CI, 23%-48%) and 25% (95% CI, 15%-36%), respectively. More than 80% of complications were diagnosed within 3 years. Cataract was the earliest complication to appear. Except for cataract, the cumulative incidence of dying without developing a particular complication was 0.24 to 0.62 times that of first developing the complication. Increasing tumor height, which correlates to increasing doses to adjacent tissues, was associated with time to cataract (P = 0.017), iris neovascularization (P = 0.087), and RD (P = 0.046). Maculopathy and optic neuropathy were associated primarily with distance to the fovea (P = 0.015) and optic disc (P = 0.015), respectively. Of 57 patients with cataract, 47% underwent cataract extraction, and 12% of 51 patients with glaucoma were treated with cyclophotocoagulation. The prevalences of cataract, elevated intraocular pressure, and RD were 43%, 39%, and 13%, respectively, at 5 years. CONCLUSIONS: The frequency with which ocular complications develop after IBT is notably influenced by competing risks. Cumulative incidence and prevalence analysis provide realistic estimates for patient counseling.

First-day iodine kinetics is useful for individualizing radiation safety precautions for thyroid carcinoma patients.

OBJECTIVE: There is considerable variation in the national regulations of different countries for the release of patients from hospitals after radioiodine therapy. Individual variations make these practices, when based on the worst case scenarios, too restrictive for the majority of patients. However, there are cases in which strict rules are needed to comply with the dose limits to other individuals, especially children. We have developed a method to individualize radiation safety precautions. MATERIALS AND METHODS: Twenty-three patients with differentiated thyroid carcinoma were included in the study. Four weeks after thyroidectomy, 1.1-3.7 GBq of radioiodine was administered and iodine kinetics were followed with external measurements until hospital discharge. The absorbed dose at the wrist holder was measured with thermoluminescence dosimetry (TLD) during hospital stay and after hospital discharge for up to 1 week. The TLD results were compared with the iodine kinetics. The dose to other individuals was estimated with extra TLDs located both on the patient's bed and given to family members. The kinetics data were fitted in both monoexponential and biexponential models and both for the full measurement period (down to the residual activity level<400 MBq) and for the first 24 h after radioiodine administration. RESULTS: The biexponential model was capable of predicting the cumulated dose up to 1 week for both the longer and the shorter measured data set. The occupancy factors both for a person sleeping on the same bed and for a person living in the same apartment with the patient were in agreement with the recommended occupancy factor values of the American Thyroid Association. From these findings it is possible to individualize radiation safety precautions by taking into account the iodine pharmacokinetics and living conditions of a patient. CONCLUSION: By measuring the activity content within the body for the first 24 h after radioiodine administration it is possible to individualize radiation safety precautions for thyroid carcinoma patients.

Accuracy requirements for head and neck intensity-modulated radiation therapy based on observed dose response of the major salivary glands.

BACKGROUND AND PURPOSE: We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model. MATERIALS AND METHODS: Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D(mean)) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS). RESULTS: The maximal slope and D(50) values of the dose response model were -0.0411/Gy and 30.4Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of +/-10%, if actual D(mean) of the gland is within +/-2.4Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0mm for the parotid glands and 2.7mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7+/-1.3mm (mean+/-SD) while that of systematic 3D errors was 3.4+/-1.6mm. The SD of random set-up errors was 1.5mm. The magnitude of D(mean) shifts due to set-up errors was 1.5+/-1.4Gy. The steepness of dose gradients within the glands was 0.8+/-0.5Gy/mm in the most critical direction (toward the glands). CONCLUSIONS: When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow dosimetric and positional tolerances should be adopted for the major salivary glands due to steep dose response curve obtained for the glands.

Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study.

BACKGROUND: Radioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Adult subjects (n = 160) diagnosed with papillary or follicular thyroid carcinoma were randomly allocated to receive either 1100 MBq (30 mCi) or 3700 MBq (100 mCi) activity of radioiodine ((131)I) following thyroidectomy. The study participants were prepared for ablation using thyroid hormone withdrawal. Ablation was considered successful when serum thyroglobulin concentration was less than 1 ng/mL and no uptake was present in (131)I scan. Ablation was successful following one administration of radioiodine in 42 (52%; 95% CI, 41% to 63%) of the 81 evaluable study participants who received 1100 MBq, and in 43 (56%, 45% to 67%) of the 77 subjects who received 3700 MBq activity (P = .61). There was no difference between the groups in the numbers of repeat radioiodine treatments needed to complete ablation (P = .27). The higher activity was associated with more nausea and taste disturbances, and a longer stay in a radioprotected isolation unit. None of the participants died from thyroid cancer during a median follow up of 51 months; three subjects in the 3700 MBq group and none in the 1100 MBq group were diagnosed with distant metastases during follow-up. In a meta-analysis of four randomized studies that compared the 1100 and 3700 MBq activities, the 1100 MBq activity tended to be associated with a higher risk of unsuccessful ablation (relative risk 1.148, 95% CI 0.974 to 1.353, P = .10). CONCLUSIONS/SIGNIFICANCE: The results provide no conclusive evidence that 3700 MBq activity is more effective for ablation of the thyroid remnant than 1100 MBq activity. The 3700 MBq activity is associated with more adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00115895.

Iodine brachytherapy as an alternative to enucleation for large uveal melanomas.

PURPOSE: To evaluate the safety and efficacy of iodine 125 plaque brachytherapy (IBT) for large uveal melanomas. DESIGN: Retrospective, nonrandomized comparative trial (historical control). PARTICIPANTS: One hundred twenty-one consecutive patients with a large uveal melanoma according to the Collaborative Ocular Melanoma Study (COMS) criteria who attended a national ocular oncology service. METHODS: Ninety-seven patients (80%) underwent primary IBT (mean dose to tumor apex, 87 Gy) with noncollimated 20- to 25-mm plaques. Assessment of metastatic disease at death and visual outcome followed COMS guidelines. Time to low vision (20/70 or worse) and blindness (loss of 20/400 vision) in the study eye were modeled by Cox proportional hazards regression, based on both single- and repeated-failure data sets. Person-years of retained vision were calculated. MAIN OUTCOME MEASURES: All-cause and melanoma-specific survival, local and distant recurrence, and preservation of vision and cosmesis. RESULTS: Median tumor height was 10.7 mm (range, 4.5-16.8 mm), and largest basal tumor diameter was 16.1 mm (range, 7.3-25.0 mm). The Kaplan-Meier estimate for all-cause and melanoma-specific survival was 62% (95% confidence interval [CI], 49%-72%) and 65% (95% CI, 52%-75%) at 5 years. The corresponding estimate for local tumor recurrence was 6% (95% CI, 2%-14%) and for major cosmetic abnormality was 38% (95% CI, 26%-52%). The median visual acuity in the study eye was 20/100 at baseline and 20/1600 at 2 years after treatment. The Kaplan-Meier estimate for avoiding low vision and blindness was 11% (95% CI, 4%-24%) and 26% (95% CI, 16%-37%) at 2 years, respectively. Tumor height and location entirely posterior to the ora serrata were the most robust predictors of visual loss. In this series, 49 person-years without low vision (median, 0.6 years; range, 0.04-8.2 years) and 111 person-years without blindness (median, 1.0 years; range, 0.03-8.6 years) in the treated eye were conserved. CONCLUSIONS: Iodine 125 plaque brachytherapy seems to be a safe and effective alternative to enucleation with regard to survival and local tumor control. It provides a fair chance of preserving the eye with acceptable cosmesis and a reasonable chance of conserving useful vision for 1 to 2 years.