John T Lucas, Rose McGee, Catherine A Billups, Ibrahim Qaddoumi, Thomas E Merchant, Rachel C Brennan, Jiangrong Wu, Matthew W Wilson
Background/aims Non-irradiative local therapies have shown promise in delaying or supplanting external beam radiotherapy (EBRT) and enucleation in patients with retinoblastoma. We hypothesised that prior focal therapy does not compromise the efficacy of delayed episcleral plaque brachytherapy (epBRT).
Methods We performed an institutional review board-approved medical record review of patients with retinoblastoma who were treated with I-125 epBRT prior to (primary) or following chemoreduction (delayed), alone and in combination with non-irradiative focal therapy. Clinical and treatment characteristics were retrieved. Treatment failure was defined as the need for subsequent EBRT and/or enucleation. Event-free and ocular survival rates were calculated from the date of plaque placement. The cumulative incidences (CIs) of treatment failure and enucleation were compared across strata using Gray’s test.
Results We identified 50 patients with retinoblastoma (54 eyes), who received a total of 56 plaques between January 1986 and December 2010, with a median follow-up of 8.3 years (range, 0.8–21.2 years). The median time from diagnosis to plaque placement was 12.7 months (range, 0.1–128 months). The CI and 95% CI of treatment failure and enucleation following epBRT at 5 years was 37%±7.2% and42.2%±7.3%, respectively. The lack of prior diode or green laser therapy was predictive of increased risk for treatment failure (p=0.02 and 0.03). International Classification group C or D was predictive of decreased time to enucleation (p=0.004). The use of any focal therapy was not predictive of time to treatment failure (p=0.33).
Conclusions The use of non-irradiative focal therapies prior to or following epBRT does not decrease the time to enucleation or treatment failure.
Shah S.N. · Kogachi K. · Correa Z.M. · Schefler A.C. · Aronow M.E. · Callejo S.A. · Cebulla C.M. · Day-Ghafoori S. · Francis J.H. · Lally S. · McCannel T.A. · Paton K.E. · Phan I.T. · Pointdujour-Lim R. · Ramasubramanian A. · Rath P. · Shields C.L. · Skalet A.H. · Wells J.R. · Jennelle R.L. · Berry J.L. · for the Women in Ocular Oncology Consortium
Background: The aim of this study was to determine the known radiation exposure, attitudes, and consequent risk modifications among female ocular oncologists in North America who routinely administer radioactive plaque brachytherapy treatment and are members of the International Society of Ocular Oncology. Methods: Nineteen female ocular oncologists completed an anonymous 17-question radiation exposure survey. Results: Eleven of the participants chose to routinely wear lead protection during surgery; 8 did not. Fifteen of 19 participants reported using an unloaded “nonactive” template to prepare for plaque implantation. During pregnancy, 11 of 13 participants continued to perform plaque brachytherapy. Eight of these 11 undertook measures to decrease radiation exposure self-reported as lead wear and other. The average reported anxiety regarding fertility was 2.1 (SD, 2.2) on a scale from 1 to 10. Conclusion: This study corroborates prior literature that surgeons’ exposure to radiation during plaque brachytherapy is minimal. Nonetheless, there remains some anxiety regarding exposure risk to women, due to potential effects on fertility and fetal health. We found variability in exposure monitoring, required training, and precautions during pregnancy amongst this group of surgeons. Improved education and clearer pregnancy guidelines may equip female ocular oncologists with optimal knowledge regarding risk of radiation exposure.
Abhilasha Maheshwari, Paul T Finger
To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy.
Retrospective interventional case series including 170 consecutive patients treated with 103Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology.
The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2–11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0–7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% (n = 86/170), amelanotic in 10% (n = 17/170), and variably pigmented in 39% (n = 67/170). Tumor pigmentation increased in 64% (n = 106/166), decreased in 18% (n = 30/166), and was unchanged in 18% (n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% (n = 12/120) had decreased tumor-related vascularity and 90% (n = 108/120) showed complete resolution. Subretinal fluid was present in 34% (n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% (n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% (n = 91/149) showed increased reflectivity on regression. We noted a crescendo–decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis.
Findings related to choroidal melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound.
Abhilasha Maheshwari, Paul T Finger, MD
To provide a clinical description of a case of bilateral choroidal melanoma in a patient treated with palladium-103 (103Pd) plaque brachytherapy.
An 81-year-old man presented with choroidal melanoma in both eyes. In consideration of tumor sizes and locations, treatment involved insertion of 103Pd radioactive plaque in the right eye followed by the left at an interval of 2 months.
At 1-year follow-up, bilateral local control has been associated with apical tumor height regression, and visual acuity has been preserved (20/20 in the right eye and 20/25 in the left). Exudative subretinal fluid has resolved. There has been no metastasis.
Bilateral choroidal melanomas are rare, reported to be either simultaneous or sequential as well as treatable. In this case, we were able to achieve tumor regression and preserve visual acuity in both eyes after plaque brachytherapy.
Alexander Böker, Daniel Pilger, Dino Cordini, Ira Seibel, Aline I. Riechardt, Antonia M. Joussen, Nikolaos E. Bechrakis
Uveal melanoma is the most common primary ocular malignancy in adults in the USA and Europe. The optimal treatment of large uveal melanoma is still under debate. Radiation therapy has its limitation due its eye-threatening secondary complications and is therefore often combined with surgical excision of the tumor.
In a retrospective interventional review, we evaluated in total 242 patients with uveal melanoma that underwent transscleral tumor resection with a predefined protocol, either with adjuvant ruthenium brachytherapy (Ru-106 group, n 136,), or with neoadjuvant proton beam therapy (PBT group, n 106). Kaplan-Meier estimates with log-rank test were used to show survival curves and a multivariable Cox regression model was used to calculate adjusted rate ratios.
Local tumor recurrence rates after 3 and 5 years were 4% (95% CI 1.2–17.8%) and 9.1% (95% CI 2.9–27.3%), respectively, in the PBT group and 24.6% (95% CI 15.8–37.1%) and 27.5 (95% CI 17.8–41.1%), respectively, in the Ru-106 group. This leads to an overall recurrence rate almost 4 times higher in the Ru-106 group compared to the PBT group. After adjusting for the a priori confounders and the tumor distance to optic disc and ciliary body infiltration, the adjusted risk of tumor recurrence was 8 times (RR 7.69 (2.22–26.06), p < 0.001) higher in the Ru-106 group as compared to the PBT group. Three- and 5-year metastatic rates were 23.2% (95% CI 5.6–37.1%) and 31.8% (95% CI 20.7–46.8%), respectively, in the PBT group and 13.2% (95% CI 6.8–24.9%) and 30.3% (95% CI 18.3–47.5%), respectively, in the Ru-106 group. There was no statistically significant difference in the overall metastasis rate between the two groups even after adjusting for possible confounders.
Transscleral resection of large uveal melanomas combined with neoadjuvant proton beam therapy leads to a lower local tumor recurrence rate compared to transscleral tumor resection with adjuvant ruthenium brachytherapy. There was no statistically significant difference in the occurrence of rubeosis iridis, neovascular glaucoma, and in the need for enucleation later on.
Marina Marinkovic, Nanda Horeweg, Mirjam S Laman, Jaco C Bleeker, Martijn Ketelaars, Femke P Peters, Gre P M Luyten, Carien L Creutzberg
Background and purpose To evaluate ruthenium-106 (Ru106) brachytherapy as eye-conserving treatment of iris melanomas (IMs) and iridociliary melanomas (ICMs).
Materials and methods Eighty-eight patients received Ru106 brachytherapy between 2006 and 2016. Primary outcome was local control, and secondary outcomes were metastasis, survival, eye preservation, complications and visual acuity (VA).
Results Overall median follow-up was 36 months. Of 88 patients, 58 (65.9%) had IM and 30 (34.1%) had ICM. ICM were on average larger and more advanced than IM. Local failure-free survival at 3years was 98.9% (SE 1.2%). Metastasis-free survival was 98.2% (SE 1.8%) at 3years; no deaths due to melanoma occurred during follow-up. Eye preservation rate was 97.7%. Treatment-related toxicities were mostly mild and observed in 80.7% of the patients. Common toxicities were worsening of pre-existing or new cataract (51.1%), dry eyes (29.5%) and glaucoma (20.5%). VA was not affected by Ru106 brachytherapy, with only 2.3% having VA <0.33 (low vision) at follow-up.
Conclusions Ru106 for IM and ICM yielded excellent local control (98.9%) and eye preservation (97.7%). Toxicities were common, but mostly mild and transient. Moreover, Ru106 did not affect visual acuity.
Imad Jaradat, Ahmed Zewar, Ibrahim AlNawaiseh, Khaleel AlRawashdeh, Samer Khurma, Mustafa Mehyar, Ghadeer Abdeen, Yacoub A. Yousef
To evaluate King Hussein Cancer Center experience in using Iodine-125 COMS radioactive plaque for treatment of Uveal Melanoma in Jordan.
Retrospective case series of eyes with uveal melanoma treated by Iodine-125 COMS radioactive plaque therapy. Data collection required access to medical, radiology, Labs and pathology reports. Main outcomes studied includes: Demographics, tumor features, eye salvage, visual outcome, metastasis, and mortality.
Between September 2008 and March 2015, 28 eyes for 28 patients had intraocular uveal melanoma and treated by Iodine-125 radioactive plaque therapy. The mean age at diagnosis was 48 years and 16(57%) were males. The mean tumor thickness was 8 mm (range: 4–13 mm), and 27(96%) patients had medium or large size tumor. The radioactive plaques used had a median size of 16 mm (range: 12–20 mm). The mean apical dose was 83.5 Gy (range 81–87 Gy), and the median radiation rate was 7.25 (range: 4.5–13). At median follow up of 2 years (range 0.5–7 years), eye salvage rate was 93%. Four (15%) patients had distance metastasis, and 3(11%) were dead. Fifty percent of patient had visual acuity better than 20/200 at the last date of follow up.
Our preliminary results are encouraging and are comparable to another countries worldwide. The use of Iodine-125 COMs plaque therapy at the inspection of implementation of plaque therapy in the developing countries can lead to eye salvage in more than 90% of cases, and reserves functional vision in more than 50% of cases.
Tahra AlMahmoud, Sean Quinlan-Davidson, Gregory R Pond, Jean Deschênes
No abstract available
Reichstein, David; Karan, Kayla
Purpose of review Plaque brachytherapy remains the dominant globe-sparing therapy of uveal melanoma. This report highlights recent advances, which have expanded plaque brachytherapy’s uses as well as improved the surgical technique.
Recent findings Plaque brachytherapy is effective for tumors that may previously have demanded enucleation. Plaque brachytherapy can be used to control large melanomas as well as melanomas touching the optic nerve. Improvements in planning and design have made plaque therapy simpler for the surgical operator and may reduce collateral radiation damage to normal ocular structures. The COMS implies a required dose of 85 Gy to the tumor apex for treatment of uveal melanoma. However, multiple reports indicate that lower doses may be equally effective for tumor control while reducing radiation dose to uninvolved structures. Vitreoretinal surgeons can be called upon safely to treat long-term side effects of radiation or tumor death such as intractable vitreous hemorrhage or inflammation. Further, vitreoretinal surgeons have employed tumor endoresection as primary local tumor control or in combination with plaque brachytherapy.
Summary Plaque brachytherapy for uveal melanoma remains highly effective for local tumor control and prevention of metastasis. Indications for plaque brachytherapy have expanded, and the technique has improved.
Ryan Sangwoo Kim, BA; Patricia Chevez-Barrios, MD; Mukul Divatia, MD; et al.
Importance Intraoperative adequacy check of biopsy samples can lead to a higher biopsy yield rate, and subsequent genomic analysis can provide patients with valuable prognostic information.
Objectives To examine the yield rates for transscleral and transvitreal fine-needle aspiration biopsies of small uveal melanoma less than 3.6 mm in apical height and to discuss techniques that would maximize yield rates and minimize complications.
Design, Setting, and Participants A retrospective, consecutive observational case series was conducted from January 29, 2013, to May 23, 2017, at Retina Consultants of Houston and Houston Methodist Hospital among 44 patients with uveal melanoma of the ciliary body or choroid.
Interventions or Exposures Fine-needle aspiration biopsy and intraoperative histopathologic analysis prior to iodine 125 brachytherapy.
Main Outcomes and Measures Tumor locations and dimensions were identified by histopathologic analysis and B-scan ultrasonography. Either transscleral or transvitreal biopsy was performed for tumors anterior to the equator and posterior to the equator, respectively. Biopsy specimens were checked for adequacy intraoperatively. Specimens were examined using hematoxylin-eosin, double immunostain with human melanoma black 45 and Ki67, and gene expression profile.
Results A total of 44 patients were included in the study, with a mean (SD) age of 63.3 (12.7) years (21 men [47.7%]; 23 women [52.3%]). Median tumor height was 2.7 mm (interquartile range, 2.3- 2.9 mm). Forty of 44 biopsy samples (90.9%; 95% CI, 82.4%-99.4%) yielded adequate cells for gene expression profile analysis. Transscleral and transvitreal yield rates were 11 of 11 (100%) and 29 of 33 (87.9%), respectively. Most localized vitreous hemorrhages were resolved by 3 months. There was a moderate association between localized vitreous hemorrhage and transvitreal biopsy method, for which the phi value was −0.526 (95% CI, −0.712 to −0.157; P < .001).
Conclusions and Relevance These findings suggest intraoperative adequacy evaluation of fine-needle aspiration biopsy specimens leads to high yield and is more informative for patients.