Search

Purpose: I 125 Eye Plaque brachytherapy is the standard treatment for medium-sized uveal melanomas (UM). Patients develop radiation toxicities (RTT), including radiation maculopathy (RM), radiation neovascular glaucoma/iris neovascularization (RNGI) and radiation optic neuropathy (RON). We aim to investigate demographics, pretreatment tumor characteristics and posttreatment complications as predictors of RTT., Methods and Materials: An IRB-approved single-institution retrospective chart review was performed from 2011 to 2019 for patients with posterior UM treated with brachytherapy. We collected demographics, pretreatment tumor characteristics and posttreatment complications. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using logistic regression model. Hazard ratios (HR) and corresponding p-values were reported. All tests were two-sided; statistical significance was considered when p<0.05., Results: Two hundred and fifty eight patients were evaluated. Median follow-up was 33.50 months (range 3.02-97.31). 178 patients (69.0%) had RTT. 131 patients (50.8%) developed RM. Fifty-six patients (21.7%) developed RON. Nineteen patients (7.4%) developed RNGI. UVA found shorter distance to fovea (DF) (p = 0.04), posttreatment exudative retinal detachment (PERD) (p = 0.001) and posttreatment vitreous hemorrhage (PVH) (p = 0.001) are associated with RTT. MVA found shorter DF (HR=1.03, p = 0.04), PERD (HR=2.52, p = 0.01) and PVH (HR=3.34, p = 0.006) are associated with RTT. MVA found female sex (HR=1.731, p = 0.031) and tumor height (HR=1.13, p = 0.013) are associated with RM and pretreatment retinal detachment (HR=3.41, p<0.001) is associated with RON., Conclusions: Shorter DF, PERD and PVH are associated with RTT; female sex and tumor height are associated with RM and tumor height is associated with RON. These findings serve as prognostic tools to counsel patients and promote early intervention in management of RTT., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Tilting of the posterior plaque margin during eye plaque brachytherapy can lead to tumor underdosing and increased risk of local recurrence. We performed a quantitative analysis of the dosimetric effects of plaque tilt as a function of tumor position, basal dimension, height and plaque type using 3D treatment planning software., Materials and Methods: Posterior and anterior tumors with largest basal dimensions of 6, 12 and 18 mm and heights of 4, 7 and 10 mm were modeled. Both Eye Physics and COMS plaques were simulated and uniformly loaded. Plans were normalized to 85 Gy at the tumor apex. Posterior plaque tilts of 1, 2, 3 and 4 mm were simulated., Results: Volumetric coverage is more sensitive to tilt than the area coverage. Wide, flat tumors are more susceptible to tilt. Apical dose changed significantly as a function of tumor height and diameter. No other parameter exhibited significant differences. Posterior tumors are slightly more susceptible to tilt due to the use of notched plaques. Plaque type does not significantly alter the effect of plaque tilt., Conclusions: Wide, flat tumors are the most susceptible to plaque tilt. Tumor location or plaque type does not have a significant effect on dosimetry changes from plaque tilt. Robust clinical procedures such as the use of mattress sutures, pre- and post-implant ultrasound and post-implant dosimetry can all mitigate the risk associated with plaque tilt., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: A common treatment planning technique for eye plaque brachytherapy is to model the tumor as an ellipse. For posterior tumors near the optic disc and fovea, this approach may lead to overlap between tumor and the organ at risk (OAR). We hypothesized that a superior plan can be generated by modeling the actual tumor shape., Materials and Methods: Forty eye plaque patients with tumors <1 cm from the optic disc and fovea were selected. Two treatment plans were generated for each patient: an elliptical tumor model plan and a true tumor model plan. Dosimetric data were collected for each plan, and Wilcoxon signed-rank tests were used to asses any statistically significant differences., Results: Equivalent tumor coverage was confirmed between the elliptical and true tumor plans for all patients. Qualitative analysis showed greater dosimetric differences between plans as the distance from the OARs increased from 0 to 2 mm but the largest differences were observed between 2 and 4 mm. Minimal differences between models were seen beyond 4 mm. Statistically significant dosimetric improvements were found for tumors <4 mm from the fovea and <2 mm from the optic disc., Conclusions: Intuitively, accurate modeling of the tumor accounting for irregularities in the shape should result in a more conformal plan and an overall reduction in OAR dose. However, this technique is only beneficial for tumors that are within 4 mm of the fovea or optic disc. An elliptical tumor model allows for an acceptable plan unless the tumor is located posteriorly and has an irregular shape., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To describe the presentation and the authors' evolving management strategy for intraocular dissemination of uveal melanoma cells following radiotherapy during the past decade., Patients and Methods: Patients with uveal melanoma who developed intraocular dissemination of pigmented cells following radiotherapy. Histopathology was available in two cases., Results: Four patients underwent treatment for progressive intraocular dissemination of uveal melanoma cells at 9 to 41 months following I-125 plaque radiotherapy (three patients) or proton beam radiotherapy (one patient). Treatments included primary enucleation (one patient), vitrectomy followed later by enucleation (one patient), and vitrectomy followed by intravitreal chemotherapy (two patients). Enucleated eyes demonstrated diffuse invasion of intraocular tissues by viable melanoma cells. No patient has developed systemic metastasis to date., Conclusions: Intraocular dissemination of pigmented cells following radiotherapy for uveal melanoma should raise suspicion for viable invasive melanoma cells. Prompt vitrectomy with intravitreal chemotherapy can be effective in avoiding enucleation in selected cases. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:573-579.]., (Copyright 2019, SLACK Incorporated.)

Purpose: We sought to formally compare Collaborative Ocular Melanoma Study (COMS) and similar-shaped (circular) eye physics (EP) plaques dosimetrically by examining both tumor coverage and critical structure doses., Methods and Materials: The plans of patients with uveal melanoma treated consecutively with eye plaque brachytherapy at a single institution from January 2016 to December 2017 were reviewed. Both a COMS plan and an EP plan using plaques of the same shape were generated for each patient using the Isoaid Plaque Simulator software such that >90% of the tumor + 2 mm margin received 85 Gy over 72 hours from iodine-125 sources. Dose statistics were recorded and analyzed using standard statistical methods., Results: Plans from a total of 62 patients were analyzed. The mean tumor volume was 0.46 cm 3 (range: 0.02-2.02), and tumors were located on average 5.89 mm (range: 0-15.0) from the macula and 6.25 mm (range: 0-16.0) from the optic disc. All plans met the treatment planning criteria for tumor coverage and were optimized to reduce dose to the adjacent organs at risk. There were no significant differences in the mean doses to the fovea (mean difference [MD] = -0.87 Gy; 95% confidence interval [CI]: -4.90 to 3.16; p = 0.80), macula (MD = -1.02 Gy; 95% CI: -4.15 to 2.11; p = 0.65), or optic disc (MD = 1.07 Gy; 95% CI: -0.77 to 2.91; p = 0.34) between the COMS and circular EP plaques., Conclusions: Overall, neither the COMS plaques nor the circular EP plaques provided consistently superior dosimetry for the treatment of uveal melanoma. The choice of plaque may be based on other considerations such as cost and surgeon preference., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Uveal melanoma is the most common primary intraocular cancer; however, the molecular features that predict response to therapy are poorly understood. Our objective was to determine whether gene expression profiling (GEP) is associated with rate of tumor regression after I-125 plaque brachytherapy for uveal melanoma., Patients and Methods: Retrospective review of 138 patients with posterior uveal melanoma treated with I-125 plaque brachytherapy in which GEP class and 3-month post-radiation ultrasonographic tumor thickness data were available. Statistical analysis was performed using t test and Fisher's exact test., Results: GEP class assignment was class 1 in 83 (60.1%) and class 2 in 55 (39.9%) patients. Mean patient age was 60.9 years for class 1 and 68.1 years for class 2 tumors (P = .002). Mean initial tumor diameter was 13.0 mm for class 1 and 14.1 mm for class 2 tumors (P = .02). Mean initial tumor thickness was 5.2 mm for class 1 and 6.1 mm for class 2 tumors (P = .047). Three months after I-125 plaque radiotherapy, mean reduction in tumor thickness was 26.5% for class 1 and 16.7% for class 2 tumors (P = .03)., Conclusion: Class 1 uveal melanoma tumors exhibit more rapid early tumor regression than class 2 tumors after I-125 plaque radiotherapy., (Copyright 2015, SLACK Incorporated.)

Purpose: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB)., Methods and Materials: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method., Results: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02)., Conclusions: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate plaque movement as a potential factor in local failure using intraoperative ultrasonography at plaque insertion and removal., Methods: Prospective study of 162 patients with uveal melanoma undergoing intraoperative B-scan ultrasonography at insertion and removal of iodine 125 plaques., Results: Tilting of the posterior plaque edge more than 1.0 mm away from the sclera was detected in 15 patients (9%) at plaque insertion and in 85 patients (53%) at plaque removal (P < .001). Factors associated with tilt at plaque removal included male sex (P = .009), decreased tumor distance to the fovea and optic disc (P < .001 for both), notched plaque (P = .001), and episcleral hematoma (P = .009). Plaque tilt caused a reduction greater than 10% in actual radiation dose to the tumor apex in 37 patients (23%). Local failure occurred in only 3 patients (2%), all of whom had tilt of 1.95 mm or greater at plaque removal., Conclusions: Plaque tilt after initial accurate placement occurs frequently during brachytherapy for uveal melanomas and may represent an important cause of local treatment failure. Recognizing and counteracting the effects of plaque tilt may reduce the risk of local failure., Trial Registration: clinicaltrials.gov Identifier: NCT00459849.

Purpose: To investigate factors associated with lipid exudation after plaque radiotherapy for uveal melanoma., Design: Retrospective interventional case series., Methods: Records of 139 consecutive uveal melanoma patients treated with I-125 plaque radiotherapy were reviewed. Lipid exudation was the major outcome measured., Results: Lipid exudation was detected in 19 patients (13.7%). Mean time from plaque therapy to lipid exudation was 10 months (range, 3-23 months). Lipid exudation was associated with younger patient age (P = .0002), increased low-density lipoprotein (P = .004), decreased high-density lipoprotein (P = .026), increased tumor thickness (P = .024), and exudative retinal detachment (P = .016). Patients with lipid exudation had worse visual outcome (P < .0001) and increased neovascular glaucoma (P = .01)., Conclusions: Lipid exudation after plaque radiotherapy for uveal melanoma is associated with poor ocular outcome. Factors associated with this lipid exudation are distinct from those associated with radiation retinopathy, and they may suggest interventions to combat this complication.

Purpose: To examine the outcomes and complications of transpupillary thermotherapy for treatment of small choroidal melanomas., Design: Retrospective case-matched comparative study and retrospective observational study., Participants: The case-matched study consisted of 36 patients treated with either transpupillary thermotherapy or plaque radiotherapy (18 patients per group). The observational study consisted of 21 patients treated with transpupillary thermotherapy alone (primary transpupillary thermotherapy) and 9 patients treated with transpupillary thermotherapy plus plaque radiotherapy (adjuvant transpupillary thermotherapy)., Main Outcome Measures: Visual acuity, local tumor control, and metastasis., Results: The case-matched groups did not differ significantly with respect to age, gender, initial visual acuity, tumor location, or length of follow-up (mean, 33 months for transpupillary thermotherapy vs. 40 months for plaque radiotherapy). There was no significant difference in final visual acuity (P = 0.810) or postoperative visual acuity change (P = 0.919) between the 2 groups. In the observational study, the mean follow-up was 32 months (range, 4-58 months). Indications for primary transpupillary thermotherapy included documented growth (10 patients) and the presence of >/=3 risk factors for growth (11 patients). Retinal complications occurred in 16 patients (76%). The mean posttreatment visual acuity change was minus 2 lines (range, minus 9 to plus 7 lines). Local failure occurred in 6 patients (29%). Local failure was associated with an increased number of transpupillary thermotherapy spots per session (P = 0.023) and decreased tumor pigmentation (P = 0.001). Indications for adjuvant transpupillary thermotherapy included tumor radioresistance (6 patients) and the presence of risk factors for local failure (3 patients). All 9 tumors that received adjuvant transpupillary thermotherapy regressed rapidly, with no local failures. The mean postoperative visual acuity change was -1.9 lines (range, -9 to +5 lines). No patient in either study developed metastasis., Conclusions: The recent interest in transpupillary thermotherapy as primary therapy for choroidal melanoma is based largely on the assumption that transpupillary thermotherapy may provide better visual outcomes than plaque radiotherapy. However, this study found no significant difference in visual outcomes between transpupillary thermotherapy and plaque radiotherapy. Further, the local failure rate with transpupillary thermotherapy was substantially higher than with plaque radiotherapy. The most promising role for transpupillary thermotherapy seems to be as an adjunct to plaque radiotherapy. The appropriate indications for transpupillary thermotherapy in the management of choroidal melanoma need to be re-evaluated.

Objectives: To determine the clinical relevance of exudative retinal detachment (ERD) and the rate of ERD resolution after plaque radiotherapy of posterior uveal melanomas., Methods: Retrospective, nonrandomized study of 135 consecutive patients with posterior uveal melanoma treated by iodine 125 plaque radiotherapy. Extent of ERD and tumor thickness were assessed before radiotherapy and at postoperative follow-up visits. Local tumor control was assessed at each follow-up visit., Results: An ERD was present in 71 patients (53%) and was a risk factor for local treatment failure (P =.03). The ERD resolved after radiotherapy in 59 (83%) of the 71 patients. The ERD resolved within 1 year in 64 patients (90%) (mean time to resolution, 5.6 months). The rate of ERD resolution correlated with the rate of decrease in tumor thickness (P =.004). The ERD did not resolve and the tumor thickness continued to increase in 5 patients, who required further intervention. A recurrent retinal detachment developed in 5 patients, who were diagnosed as having rhegmatogenous retinal detachment (3 patients) and lipid exudation secondary to tumor vasculopathy (2 patients). Two patients with local tumor recurrence did not develop a recurrent ERD. Local tumor control was achieved in 130 patients (96%)., Conclusions: An ERD may be a risk factor for local failure after plaque radiotherapy for uveal melanoma. If an ERD does not resolve within 9 to 12 months of radiotherapy and the tumor is not regressing, treatment failure should be suspected. A recurrent ERD does not necessarily represent local tumor recurrence.

Purpose: To examine the expression of proteins in the Rb and p53 tumor suppressor pathways in uveal melanomas following plaque radiotherapy., Methods: Immunohistochemistry and cell culture studies. Immunohistochemistry for Rb, p16, cyclin D1, p53, HDM2, and Bcl-2 was performed on twelve eyes containing posterior uveal melanomas that were enucleated following plaque radiotherapy. Cell culture studies were performed in three cases., Results: The irradiated eyes were enucleated for radiation complications (five cases), local tumor recurrence (three cases), and other reasons (four cases). On histopathologic examination, all cases showed evidence of tumor cell loss. However, residual tumor cells were present in all cases, including those that were clinically regressed. Residual cells from three of the clinically regressed cases were cultured and demonstrated minimal cell division, marked cell death, and extensive chromosomal damage. Strong p53 staining was observed in six cases (50%) and was significantly associated with recent radiotherapy (P = .04). Abnormal cytoplasmic staining for Rb was observed in four cases (33%)., Conclusions: Plaque radiotherapy of uveal melanomas induces DNA damage, inhibits cell division, and promotes cell death. These changes may be due, at least in part, to induction of p53, which activates genes involved in both cell cycle arrest and apoptosis. Plaque radiotherapy can also cause alterations in the expression of Rb, but the significance of this finding will require further study.

Objective: The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma., Design: The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used., Participants: Seven hundred sixty-six posterior uveal melanoma patients were studied., Intervention: Either iodine-125 plaque or helium ion radiation therapy was performed., Main Outcome Measures: Local tumor recurrence and systemic metastasis were measured., Results: Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence., Conclusions: Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.

Purpose: Plaque radiotherapy has been reported to have a higher relapse rate than charged-particle radiotherapy for posteriorly located uveal melanomas, which also are more technically difficult to localize accurately. The authors used intraoperative echography in patients with posterior uveal melanoma to determine the rate of inaccurate localization of iodine 125(125I) episcleral plaques using standard localization techniques., Methods: The authors reviewed the records of 29 consecutive patients with medium-sized posterior uveal melanomas who underwent 125I episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement., Results: After careful plaque placement using standard localization techniques, 4 of 29 plaques (14%) did not cover at least one tumor margin. All four of these plaques were associated with posterior tumors with at least one margin posterior to the temporal arcades. Two (7%) additional juxtapapillary plaques were displaced away from the sclera by the optic nerve. In all six cases, it was possible to immediately reposition the plaque to achieve coverage of all tumor margins., Conclusions: Placement of 125I episcleral radioactive plaques for posteriorly located uveal melanomas using standard localization techniques occasionally results in suboptimal plaque positioning. Intraoperative echography can identify plaques that are localized poorly and allows immediate adjustment to achieve optimal plaque positioning.