Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement

doi:10.1016/S0002-9394(98)00445-0

American Journal of Ophthalmology

Volume 127, Issue 5, May 1999, Pages 579-589

https://doi.org/10.1016/S0002-9394(98)00445-0 Get rights and content

Abstract

PURPOSE: To determine the outcome of plaque radiotherapy in the treatment of macular choroidal melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, and metastasis.

METHODS: Chart analysis of 630 consecutive patients (630 eyes) with macular choroidal melanoma managed by plaque radiotherapy between July 1976 and June 1992.

RESULTS: The median largest basal tumor diameter was 10 mm, and the median tumor thickness was 4 mm. By means of Kaplan-Meier estimates, visually significant maculopathy developed at 5 years in 40% of the patients, cataract in 32%, papillopathy in 13%, and tumor recurrence in 9%. Vision decrease by 3 or more Snellen lines was found in 40% of the patients at 5 years. Sixty-nine eyes (11%) were enucleated because of radiation complications and recurrence. Twelve percent of the patients developed metastasis by 5 years and 22% by 10 years. Results of multivariate Cox proportional hazards analyses showed that the significant predictors for tumor recurrence were a distance of tumor margin from the optic disk of less than 2 mm (P = .003) and retinal invasion (P = .009). The significant variables that were predictive of metastasis included tumor thickness greater than 4 mm (P = .02) and largest basal tumor diameter greater than 10 mm (P = .03).

CONCLUSIONS: Plaque radiotherapy offers a 91% 5-year local tumor control rate for macular choroidal melanoma. Despite good local tumor control, the risk for metastasis is 12% at 5 years and 22% at 10 years. In 11% of the patients, enucleation eventually became necessary because of radiation complications and tumor recurrence.

Section snippets

Patients and methods

We analyzed the records of all patients who had posterior uveal melanoma with macular involvement treated with plaque radiotherapy on the Ocular Oncology Service, Wills Eye Hospital, between June 1976 and June 1992. A choroidal melanoma with macular involvement was defined as a tumor whose margin extended 3 mm or less from the foveola. Although most patients had more than 5 years of follow-up, those who died, had enucleation, or were lost to follow-up before 5 years were also included in the

Results

Between July 1976 and June 1992, 630 patients (630 eyes) with choroidal macular melanoma received treatment by means of plaque radiotherapy. Of these 630 patients, 317 were women and 313 were men. The median age was 59 years (range, 20 to 91 years). Forty-five patients (7%) had systemic hypertension, 39 (6%) had diabetes mellitus, and 15 (2%) had both of these conditions. The initial visual acuity was better than 20/200 in 91% of the patients and better than 20/40 in 55%. The median intraocular

Discussion

The management of choroidal melanoma with macular involvement is difficult because of the posterior location of the tumor and the potential visual consequences of treatment. Treatment options for macular choroidal melanoma include enucleation, irradiation, laser photocoagulation, and transpupillary thermotherapy. Plaque radiotherapy has been found to offer satisfactory local tumor control and survival for patients with posterior uveal melanoma comparable to charged particle irradiation11 and

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To associate clinical factors and radiation doses delivered by iodine-125 plaque brachytherapy to visual outcomes and development of radiation-induced ocular complications in patients with uveal melanoma in the era of anti–vascular endothelial growth factor (anti-VEGF) injections.
Retrospective cohort study.
A retrospective chart review was performed for 225 patients treated with iodine-125 brachytherapy for uveal melanoma. The effects of radiation doses (focal doses, average dose to the entire eye, and integral dose) on visual outcomes and development of radiation complications (radiation retinopathy, radiation optic neuropathy, vitreous hemorrhage, and neovascular glaucoma) were analyzed using multivariate Cox regression snalysis.
Median follow-up was 33.6 months (range, 12-105.6 months). Radiation retinopathy was associated with younger age, tumor distance to optic nerve <6 mm, and maximum radiation dose to fovea. Radiation optic neuropathy was associated with White race, tumor distance to optic nerve <6 mm, and integral radiation dose. Vitreous hemorrhage was associated with White race and integral radiation dose. Incidence of neovascular glaucoma was low in our study, with 2 patients (0.9%) developing the complication. Of the 123 patients who developed radiation retinopathy, 82 patients (66.7% of radiation retinopathy patients, 37.3% of total patients) received anti-VEGF injections.
Our study found multiple associations between radiation doses and complications as well as visual outcomes on multivariate analysis. Given that the majority of our patients who developed radiation retinopathy received anti-VEGF injections, our study helps to illustrate the course and progression of radiation-induced complications in the new era of anti-VEGF.
Treatment of radiation maculopathy and radiation-induced macular edema: A systematic review
2021, Survey of Ophthalmology
Radiation maculopathy and radiation-induced macular edema are common, sight-threatening complications after radiotherapy, especially that used for uveal melanoma. While many treatment and preventive strategies have been proposed, management of these conditions is still challenging. Initially, treatments were based on the use of retinal laser, but the outcomes were poor. Subsequently, management has shifted toward injection of intravitreal antivascular endothelial growth factor or corticosteroids. We reviewed current clinical evidence, which mostly relies on small sample-sized and retrospective studies, for the management of radiation maculopathy and, in particular, radiation-induced macular edema. At present, the first-line approach is usually intravitreal antivascular endothelial growth factor. Intravitreal dexamethasone implantation may be an option for those with suboptimal response or contraindications to antivascular endothelial growth factor agents. Possible preventive treatments that require future study are intravitreal bevacizumab and ranibizumab, peripheral laser photocoagulation, and subtenon triamcinolone acetonide.
Local tumour control and radiation side effects for fractionated stereotactic photon beam radiotherapy compared to proton beam radiotherapy in uveal melanoma
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To compare the adverse side effects of fractionated stereotactic photon beam radiotherapy (fSRT) with proton beam radiotherapy (PBR) in patients with uveal melanoma (UM).
A retrospective study investigating 306 UM patients treated with fSRT (N=153) by the Rotterdam Ocular Melanoma Study group (ROMS), The Netherlands, between 1999–2014 or with PBR (N=153) at the Royal Liverpool University Hospital and the Clatterbridge Cancer Centre, Bebington, United Kingdom, between 1993–2014. The tumours treated with fSRT were matched with tumours treated with PBR based on sex, left or right eye, TNM classification, posterior margin ≤ or > 3mm of the fovea and of the optic disc.
The five-year actuarial rates of tumour recurrence were 4.5% for fSRT and 6.1% for PBR. For fSRT and PBR, the five-year actuarial rates of maculopathy were 14.9% and 12.4%, and for vitreous haemorrhage were 29.4% and 4.7%, respectively. Only vitreous haemorrhage (HR: 0.19, 95% CI: 0.07–0.56) was more common after fSRT compared to PBR. Overall, larger tumours were risk factors for maculopathy and secondary enucleation.
Both treatments have excellent local tumour control. In matched groups, vitreous haemorrhage was the only adverse side effect showing a significant difference between groups.
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To evaluate visual and surgical outcomes of cataract surgery in eyes with a history of iodine-125 (I¹²⁵) brachytherapy for ocular melanoma.
Department of Ophthalmology, David Geffen School of Medicine at UCLA and the Stein Eye Institute, Los Angeles, California, USA.
Retrospective case series.
Patients with ocular melanoma treated by I¹²⁵ brachytherapy who subsequently had cataract surgery were evaluated. The recorded data included tumor size, location, preoperative ocular comorbidities, corrected distance visual acuity (CDVA), operative complications, and brachytherapy-related maculopathy before and after surgery.
Thirty-two eyes of 32 patients were included. The mean age at the time of cataract surgery was 66.1 years. The median follow-up was 53.5 months. There were no intraoperative complications. Eighteen eyes (56.3%) had a history of preoperative radiation retinopathy, 10 involving the macula. Between 2 weeks and 4 weeks postoperatively, 22 eyes (68.8%) had an improvement in CDVA (≥2 lines). Seven of 10 eyes that failed to improve had radiation maculopathy. By the last follow-up examination, 13 eyes (40.6%) had improved CDVA, 9 eyes (28.1%) were worse (≥2 lines), and 10 eyes (31.3%) were unchanged (within ±1 line). Of 15 eyes that lost CDVA gains achieved between 2 weeks and 4 weeks postoperatively, 9 eyes had new-onset or worsening maculopathy. Cataract surgery had no effect on local tumor control or distant metastasis.
Cataract surgery after I¹²⁵ brachytherapy for ocular melanoma improved CDVA in most eyes during the immediate postoperative period. Gains were often lost with further follow-up. Progression of radiation maculopathy was primarily responsible for subsequent visual decline.
Ocular malignancies treated with iodine-125 low dose rate (LDR) brachytherapy at a single high-volume institution: A retrospective review
2022, Medical Dosimetry
Citation Excerpt :
A large retrospective study performed by Gunduz et al. of 1300 patients treated for uveal melanoma with plaque therapy from 1976 to 1992 looked at the 5-year incidences of retinopathy.8 Further analysis by Gunduz et al. also looked at 630 patients treated for uveal melanoma with plaque therapy from 1976 to 1992 and analyzed various long term side effects of eye plaque treatment including maculopathy, cataract, papillopathy, and vitreous hemorrhage.16 Gunduz et al showed a 5-year incidence of 43.1% for retinal retinopathy, 40% for radiation maculopathy, 13% for radiation papillopathy, 32% of cataract formation, and 12% of vitreous hemorrhage.16
The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds. The seeds activities were chosen to deliver 85 Gy to the tumor apex or to a prescription point (if the apex < 5 mm). The plaque sizes used were 10, 12, 14, 16, 18, 20, and 22 mm including notched or deep notched. The plaques were modeled in Varian BrachyVision version 11.6 (Varian Medical Systems) with seed coordinates from the AAPM Task Group 129. The Task Group 43 from AAPM was used for brachytherapy dose planning. Dose data were extracted for the apex, prescription point, sclera, retina opposite to the implant, lens, macula, and optic disc. The radiobiological dosimetry were calculated using appropriate α/β ratios found in the literature and then correlated to clinical side effects. Average biologically effective dose for associated organs at risk were calculated in cases where toxicity occurred. These included: radiation cataract (70.66 Gy), disc atrophy (475.49 Gy), foveal atrophy (263.07 Gy), radiation papillopathy (373.45 Gy), radiation maculopathy (213.62 Gy), vitreous hemorrhage (1437.68 Gy), vascular occlusion (1080.93 Gy), nonproliferative retinopathy (1066.89 Gy), proliferative retinopathy (1590.71 Gy), exudative retinal detachment (1364.32 Gy), and rhegmatogenous retinal detachment (2265.54 Gy). Average biologically effective dose was higher in patients who developed radiation induced long term side effects than in the whole patient population except for radiation maculopathy. In spite of the small patient population and short-term follow-up, it is of interest to correlate the radiation induced effects and create a guideline for the improvement of the treatment of patients treated with LDR brachytherapy.
Delivered dose changes in COMS plaque-based ocular brachytherapy arising from vitrectomy with silicone oil replacement
2019, Brachytherapy
Citation Excerpt :
Although local tumor control rates have been found to be excellent with ocular brachytherapy, typically >90%, radiation toxicity and vision loss continues to be a major issue (4, 5). The primary radiation side effects that can affect visual function include active radiation retinopathy affecting the macula and optic nerve, atrophy of the retina and optic nerve, and neovascular glaucoma (6–12). Several studies have demonstrated increased radiation dose to the fovea and optic nerve, increased tumor size, and dose to healthy retina as the primary predictors of radiation-related loss of visual acuity (4, 5, 13–16).
The purpose of the study was to determine dosimetric effects of performing concurrent I-125 Collaborative Ocular Melanoma Study plaque brachytherapy and vitrectomy with replacement using silicone oil, previously shown to be a means of shielding uninvolved parts of the eye.
Monte Carlo simulations using MCNP6 were performed to compare the dosimetry with all eye materials assigned as water, and for the vitreous (excluding the tumor), composed of polydimethylsiloxane oil for three generic, one large tumor, and two patient geometry scenarios. Dose was scored at the tumor apex, along the sclera, and within a 3D grid encompassing the eye. The assessed patient cases included vitrectomies to treat intraocular pathologies; not to enhance attenuation/shielding.
The doses along the sclera and for the entire eye were decreased when the silicone oil replaced the vitreal fluid, with a maximum decrease at the opposite sclera of 63%. Yet, absolute changes in dose to critical structures were often small and likely not clinically significant. The dose at the tumor apex was decreased by 3.1–9.4%. Dose was also decreased at the edges of the tumor because of decreased backscatter at the tumor-oil interface.
Concurrent silicone vitrectomy was found to reduce total radiation dose to the eye. Based on current radiation retinopathy predictive models, the evaluation of the absolute doses revealed only a subset of patients in which a clinically significant difference in outcomes is expected. Furthermore, the presence of the silicone oil decreased dose to the tumor edges, indicating that the tumor could be underdosed if the oil is unaccounted for.

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^☆: Supported by TUBITAK (Dr Gündüz), the Macula Foundation, New York, New York (Drs Gündüz and C. Shields), the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (Dr J. Shields), the Eye Tumor Research Foundation (Dr C. Shields), and the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Philadelphia, Pennsylvania (Drs Gündüz, C. Shields, and J. Shields).

¹: Biostatistical consultation was provided by J. Cater, PhD.

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Original ArticlesRadiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement 1☆,

Abstract

Section snippets

Patients and methods

Results

Discussion

Surv Ophthalmol

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Int J Radiat Oncol Biol Phys

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Original Articles
Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement 1☆,