A 17-year retrospective study of institutional results for eye plaque brachytherapy of uveal melanoma using 125I, 103Pd, and 131Cs and historical perspective

doi:10.1016/j.brachy.2011.01.006

Brachytherapy

Volume 10, Issue 4, July–August 2011, Pages 331-339

https://doi.org/10.1016/j.brachy.2011.01.006 Get rights and content

Abstract

Purpose

To compare overall survival, local and distant failure rates, ocular toxicity, and vision preservation in patients treated with eye plaque brachytherapy at Tufts Medical Center with those in the published literature.

Methods and Materials

Records were reviewed for 53 patients with the diagnosis of uveal melanoma treated with plaque brachytherapy at Tufts Medical Center over the past 17 years. American Joint Committee on Cancer staging (T1, T2, or T3) were 4, 39, and 10 patients, respectively. All the patients were treated using ¹²⁵I (n = 37), ¹⁰³Pd (n = 5), or ¹³¹Cs (n = 11) to a dose of 85 Gy (documented as 100 Gy before 1996 for the same physical dose).

Results

With a mean followup of 75 months, 38 of 53 patients were still alive. Five patients (all ¹²⁵I) developed liver metastases (9%) with no evidence of local failure. There were 10 definitive local failures and four additional transpupillary thermo-therapy procedures performed to ensure local control for lesions slow to respond. Twelve patients (23%) required enucleation. At most recent followup, 32 patients (71%) maintained 20/200 vision or better in the treated eye. In this first report of ¹³¹Cs plaque therapy with a mean followup of 20 months, there were two transpupillary thermo-therapy procedures and one definitive failure requiring enucleation after 10 months.

Conclusions

Our disease control and ocular results were comparable to those in the literature given the extended followup. We are developing a multi-institutional, prospective clinical protocol for considering radionuclide selection and other prescriptive criteria.

Introduction

When compared with enucleation, eye plaque brachytherapy provides adequate control of primary uveal melanoma tumors, superior vision, and globe preservation [1], [2], [3], [4], [5]. Brachytherapy, when compared to external beam radiotherapy techniques, allows for dose limitation to the retina, optic nerve, lacrimal gland, and eyelids. Since the 2001 publication of the Collaborative Ocular Melanoma Study (COMS) on 657 patients, many institutions have published their experiences. These studies primarily include the use of two radionuclides: iodine-125 (¹²⁵I) [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17] and palladium-103 (¹⁰³Pd) [18], [19], [20], [21]. The literature also contains some reports of cobalt-60 (⁶⁰Co) (22), iridium-192 (¹⁹²Ir) [22], [23], and ruthenium-106 (¹⁰⁶Ru) [20], [24], [25], [26], [27], [28], [29], [30].

In 2003, the American Brachytherapy Society (ABS) published recommendations for the treatment of uveal melanoma using brachytherapy plaques (31). These recommendations covered appropriate patient selection, plaque design, treatment planning, and dose prescription and delivery. Radionuclides available for eye plaque brachytherapy were reviewed, but specific recommendations regarding radionuclide selection were not made. Existing literature contains limited results examining radionuclide choice.

In this article, results from our institutional experience using ¹²⁵I, ¹⁰³Pd, and uniquely cesium-131 (¹³¹Cs) were analyzed, focusing on overall survival, local control, distant metastases, ocular toxicity, and visual acuity (32). Implicit in this analysis, we compared outcomes as a function of radionuclide. Also provided is a comprehensive literature review covering publications spanning the last two decades, and comparison of these results with our observations.

Section snippets

Methods and materials

Records were available for 53 patients treated at Tufts Medical Center (TMC) between January 29, 1992 and July 14, 2009. Patients were included in this retrospective study if they met the following criteria: at least 4 years followup postimplant, followup until the time of enucleation or death, or followup within 6 months of the study end date (March 22, 2010). Table 1 summarizes patient characteristics. American Joint Committee on Cancer (AJCC) staging (T1, T2, or T3) were 4, 39, and 10

Overall survival

At a mean followup of 75 months (range, 2–214 months), 38 of 53 patients were still alive. Cause of death remained unknown in most of the patients who had passed away; however, 4 of 15 patients (27%) were known to have died from metastatic disease to the liver. Median survival was 107 months as illustrated in Fig. 1.

Local control

There were 10 definitive local failures (19%) with a mean time to failure of 30 months (range, 7–150 months). Most of the local failures occurred in men (90%), each of these

Literature review

Review of the literature revealed several COMS reports presenting data from the only randomized multi-institutional prospective trial of eye plaque brachytherapy for the treatment of uveal melanoma [1], [3], [4], [5]. Four reports of a single-center prospective trial using ¹⁰³Pd have been published [18], [19], [20], [21], and a number of retrospective reviews have been published. Table 6 outlines the number of patients, followup, radionuclide selection, local control rates, distant failure

Conclusion

The results of this retrospective study of 53 patients treated with eye plaque brachytherapy for uveal melanoma between 1992 and 2009 at TMC are consistent with those reported in the literature. Uniquely included are patients treated with ¹³¹Cs where results were comparable to those for other radionuclides (i.e., ¹²⁵I and ¹⁰³Pd). This work supports development of a prospective clinical protocol for considering radionuclide selection and other prescriptive criteria.

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Analysis of dose to the macula, optic disc, and lens in relation to vision toxicities – A retrospective study using COMS eye plaques
2022, Physica Medica
Citation Excerpt :
Based on eligibility, affordability, cosmetic appeal, and favorable treatment outcome, plaque brachytherapy is currently the primary treatment method for medium-size uveal melanoma (3.1–8.0 mm thickness), as opposed to external beam therapy [12]. A wide range of reported toxicity and incidence rates for plaque brachytherapy exist across institutional studies with radiation retinopathy rates extending from 20 to 74 %, and cataract rates varying from 15 to 68 % [6,10,13–15]. Multivariate models have indicated that patient age, smoking status, and preexisting medical conditions as well as tumor apex height, tumor basal diameter, have a statistically significant impact on patient outcome and toxicities [2,4,9].
The aim of this study was to relate common toxicity endpoints with dose to the macula, optic disc, and lens for uveal melanoma patients treated with Iodine-125 Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy.
A cohort of 52 patients treated at a single institution between 2005 and 2019 were retrospectively reviewed. Demographics, dosimetry, and clinical outcomes were recorded. Univariate, relative risk, and Kaplan-Meier analyses were performed to relate dose to toxicity endpoints including retinopathy, vision decline, and cataracts.
By the end of follow up (Median = 3.6 years, Range = 0.4 – 13.5 years), 65 % of eyes sustained radiation retinopathy, 40 % demonstrated moderate vision decline (>5 Snellen lines lost), and 56 % developed cataracts. Significant (p < 0.05) risk estimates exist for retinopathy and VA decline for doses >52 Gy to the macula and >42 Gy to the optic disc. Moreover, dose to the lens > 16 Gy showed a significant risk for cataract formation. Kaplan-Meier analysis demonstrated significantly different incidence of radiation retinopathy for > 52 Gy to the macula and > 42 Gy to the optic disc. In addition, the Kaplan-Meier analysis showed significantly different incidence of cataract formation for patients with lens dose > 16 Gy.
Dose-effect relationships exist for the macula and optic disc with respect to the loss of visual acuity and the development of retinopathy. To better preserve vision after treatment, further research is needed to reduce macula, optic disc, and lens doses while maintaining tumor control.
Preliminary Results of Uveal Melanoma Treated With Iodine-125 Plaques: Analysis of Disease Control and Visual Outcomes With 63 Gy to the Target Volume
2022, Advances in Radiation Oncology
Our purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach.
This was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis.
Sixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse.
In patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes.
Local tumor control and treatment related toxicity after plaque brachytherapy for uveal melanoma: A systematic review and a data pooled analysis
2022, Radiotherapy and Oncology
Citation Excerpt :
A reference list of 662 records was identified from the initial PubMed search. After screening and after applying the exclusion criteria (Supplementary Fig. S1), the two reviewers agreed to include 103 studies [1,8,9,11–16,29–122] for data collection and modelling of outcomes. Full details of the included studies are reported in Supplementary Materials Table 1.
Uveal melanoma (UM) represents the most common primary intraocular tumor, and nowadays eye plaque brachytherapy (EPB) is the most frequently used visual acuity preservation treatment option for small to medium sized UMs. The excellent local tumor control (LTC) rate achieved by EPB may be associated with severe complications and adverse events. Several dosimetric and clinical risk factors for the development of EPB-related ocular morbidity can be identified. However, morbidity predictive models specifically developed for EPB are still scarce.
PRISMA methodology was used for the present systematic review of articles indexed in PubMed in the last sixteen years on EPB treatment of UM which aims at determining the major factors affecting local tumor control and ocular morbidities. To our knowledge, for the first time in EPB field, local tumor control probability (TCP) and normal tissue complication probability (NTCP) modelling on pooled clinical outcomes were performed.
The analyzed literature (103 studies including 21,263 UM patients) pointed out that Ru-106 EPB provided high local control outcomes while minimizing radiation induced complications. The use of treatment planning systems (TPS) was the most influencing factor for EPB outcomes such as metastasis occurrence, enucleation, and disease specific survival, irrespective of radioactive implant type. TCP and NTCP parameters were successfully extracted for 5-year LTC, cataract and optic neuropathy. In future studies, more consistent recordings of ocular morbidities along with accurate estimation of doses through routine use of TPS are needed to expand and improve the robustness of toxicity risk prediction in EPB.
Management of uveal melanomas, guidelines for oncologists
2018, Bulletin du Cancer
Les mélanomes de l’uvée sont les tumeurs oculaires malignes primitives les plus fréquentes de l’adulte. L’énucléation a été longtemps le traitement de référence. Depuis, plusieurs études ont montré que des traitements conservateurs n’affectaient pas le risque de métastases, ni la survie. Les mélanomes choroïdiens sont à la fois radiorésistants et localisés près de structures visuelles (nerf optique et macula) de l’œil qui peuvent être parfois préservées sans compromettre le contrôle tumoral. Les traitements conservateurs utilisent des applicateurs par plaque de curiethérapie et les particules chargées telles que les protons. Si le pronostic fonctionnel visuel est lié au traitement local, le pronostic vital est lié au risque métastatique, avec un risque d’évolution hépatique chez 20 à 50 % des patients, selon la taille et la génomique tumorale notamment. Cette évolution est souvent létale pour le patient dans les 15 mois. La prise en charge de ces patients est complexe de par la rareté de la maladie. Les traitements systémiques (chimiothérapie, traitements ciblés, immunothérapie etc.) sont d’efficacité limitée, et bien que les techniques de traitement local des métastases soient prometteuses, elles ne sont possibles que pour des patients sélectionnés. Le réseau national MELACHONAT a pour mission d’améliorer la prise en charge des patients quel que soit le stade de leur maladie. L’association de patients ANPACO est un réel soutien pour les patients en termes de parcours de soins et d’accès à la connaissance. Cette revue est une mise au point sur les traitements locaux des mélanomes uvéaux et de leur évolution métastatique.
Uveal melanomas are the most frequent primary malignant eye tumor. Enucleation was historically the gold standard. Since then, several studies showed that conservative treatments did not increase the risk of metastasis or survival. Choroidal melanomas are both radioresistant and located close to visual structures (the optic nerve and macula) of the eye, which may be preserved in some settings without compromising tumor control, as this is the first priority. Different types of radiation therapy may be used for such tumors: brachytherapy and charged particles, including proton beam therapy. If visual prognosis is dependent to the local treatment, the vital prognosis is dependent on the metastatic risk, with a risk of liver involvement in 20 to 50% of patients, depending on tumor size and genomics. Median survival after the discovery of liver metastases is about 15 months. The management of these patients is often complex. Systemic therapies (chemotherapy, targeted therapies, immunotherapy, etc.) yield limited response rates and although local treatments of liver metastases are promising, they are only feasible in selected patients. The mission of the MELACHONAT national network is to improve the management of patients regardless of the stage of the disease. The patient association ANPACO is dedicated to help uveal melanoma patients in their health care path and to promote knowledge dissemination within the patient community. The aim of this review is to focus on the local treatments of uveal melanomas as well as the management of their metastatic evolution.
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In choroidal melanoma the radiation threshold dose for local control remains largely unknown. The present study examined a group of patients that received a wide range of minimum tumor dose in order to investigate a dose-response relationship. A literature review is performed to compare our results with available evidence in brachytherapy and charged particle external beam radiotherapy.
A retrospective study was conducted on all choroidal melanomas treated with Strontium-90 (Sr-90) at the University Hospital of Leuven between 1983 and 2012. Local failure was defined as primary endpoint and was estimated according to the competing risk method.
In 135 patients, the minimum tumor dose (Dmin) ranged from 0 Gy to 287 Gy (median: 27.6 Gy). Multivariable analysis revealed Dmin ≥ 65 Gy (p = 0.04; HR = 0.09) and tumor distant from the optic disc (p < 0.001, HR = 0.09) to be independent variables favoring local control. The scleral dose, the tumor diameter and tumor height did not significantly affect local failure in multivariate analysis.
This is the first study to examine a group of patients treated with a Dmin ranging from 0 Gy to >250 Gy. Treatment with a Dmin of 65 Gy is necessary to achieve durable tumor response. The dose-response data provided by our study could be used for the design of future trials examining the ideal dose for the treatment of choroidal melanoma with brachytherapy or charged particle external beam radiotherapy.
Evaluating Retinal Sequelae of Radioactive Episcleral Plaque Brachytherapy for Medium-Sized Choroidal Melanomas Using Optical Coherence Tomography Angiography
2017, Advances in Ophthalmology and Optometry
Citation Excerpt :
Despite radical surgical excision, there remained a 45% mortality rate from metastasis by 15 years [5]. Radiation therapy, in the form of brachytherapy, was first pioneered in Europe in the 1930s as a potential globe-salvaging treatment option for uveal melanoma [6]. Brachytherapy thus became an alternative therapy with less morbidity than enucleation, but was not performed routinely in the United States until the National Eye Institute introduced a prospective study to evaluate this treatment option.

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: This work was presented in part at the 52nd annual meeting of the American Society for Radiation Therapy on 1 November 2010 in San Diego, CA.

: Conflicts of interest: Drs. Leonard, Gagne, Mignano, Duker, and Bannon have no conflicts of interest. Dr. Rivard is a consultant to GE HealthCare, Inc. and IsoRay Medical, Inc.

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