Large Uveal Melanomas Research Articles

Протонотерапия увеальной меланомы (предварительные результаты)

Purpose. To present preliminary results of treatment of uveal melanoma with proton therapy using the scanning pencil beam technique. Material and methods. In this study we included 7 patients (female) with uveal melanoma aged 23 to 51 years. The tumor was localized in the choroid (4), ciliochoroidal (2) and iridociliary (1) zones. All patients received proton therapy in the hypofractionation mode at a total dose of 49 Gy in 7 fractions (BED0,6=620 Gy; EQD2=143 Gy). The follow-up period for patients ranged from 6 to 33 months. Results. In the early post-radiation period, a radiation reaction was observed in the form of skin erythema (2 patients), exudative retinal detachment (3 patients). Late complications were observed as neovascular glaucoma, which developed 6–11 months after the start of treatment in 4 patients, maculopathy (1 patient), dry eye syndrome with madarosis (3 patients). All treated patients had a slow rate of tumor regression, as a rule, the tumor began to regress after 6–8 months from the start of treatment. Complete regression was observed in 2 patients with T3aN0M0 stages of the process for a period of 24 months, the rest showed partial regression of the tumor. Conclusion. The obtained preliminary results of proton therapy using the scanning pencil beam technique are very encouraging in the treatment of large uveal melanomas and open a new perspective in their successful treatment. The use of photodynamic therapy with chlorin drugs should probably be considered as an adjuvant therapy, the effect of which will accelerate the rate of regression and reduce the incidence of complications. Key words: choroidal melanoma, proton therapy, brachytherapy, uveal melanoma, ophthalmo-oncology, choroidal melanoma treatment

Gene Expression Profile Class Change in a Case of Aggressive, Recurrent Melanoma

Purpose: To report a novel case of a recurrent melanoma that had a change in its genetic expression profile (GEP) class over a 2-year period. Methods: This retrospective case study evaluated a patient with a recurrent uveal melanoma that changed classes from 1A to 1B. Results: A large melanoma was first treated with brachytherapy, and during that time genetic testing revealed a class 1A tumor. Two years later the tumor was noted to be enlarging, and the patient elected for enucleation. Subsequent GEP showed a class 1B tumor. Conclusions: An aggressive and large recurrent uveal melanoma that had changed from a class 1A to a class 1B tumor on subsequent GEP testing has never been reported before to our knowledge. It may imply that a recurrent or aggressive tumor has more mutations over time that could lead to a higher risk for metastasis. The natural course of a tumor’s GEP class should be explored further.

Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma

To report the effective use of neoadjuvant darovasertib and crizotinib in a patient with a large uveal melanoma (UM) in his only functional eye. Case report. One patient with T4b UM. Neoadjuvant darovasertib and crizotinib, followed by plaque brachytherapy. Objective tumor response and conversion from planned enucleation to placement of fovea- and optic nerve-sparing plaque brachytherapy. A patient with a history of left eye blindness from retinal artery occlusion presented with rapidly declining right eye vision due to a primary UM measuring 18 mm in maximal diameter and 16.5 mm in maximal thickness. To salvage vision, neoadjuvant treatment was initiated using darovasertib and crizotinib. After 6 months of neoadjuvant treatment, which included intraocular lens replacement for tumor-associated cataract, the tumor regressed to 14.1 mm in maximal diameter and 2.6 mm in maximal thickness, enabling treatment with plaque brachytherapy rather than enucleation. The combination of darovasertib and crizotinib for UM is an effective neoadjuvant strategy that warrants further investigation as an approach to improve visual outcomes from the treatment of primary UM. The other authors have no proprietary or commercial interest in any materials discussed in this article.

Radiobiological Insights of Staged Brachytherapy Using Eye Plaque for Large Uveal Melanoma

I-125 radioactive seeds embedded in an eye plaque is used to deliver the radiation dose of 85Gy to the apex of the tumor. However, it is challenging to treat a lesion in height (>10 mm) because of a high dose (> 500 Gy) to sclera. A staged radiotherapy (SRT) has been implemented successfully in stereotactic radiosurgery when a single dose is risky for a bigger sized lesion. The hypothesis of this work is that the SRT works for eye plaque brachytherapy of uveal melanoma to break the single fraction into two. To apply the concept of SRT, the following questions need to be answered: What are the two fraction doses? What is the time interval between the two fractions? In this work, the two split fraction doses and time interval are calculated using the "incomplete-repair' model. Equation (1) is the linear-quadratic (LQ) model. f(x) is the cell survival curve (SC). Equation (2) and (3) are radiobiological model developed dealing with the split doses by considering the incomplete repair. Ln(f(x)) = -αx - βx2 (1) Ln(fn(x, Ɵ)) = nLn(f(x))-nβx2hn(Ɵ) (2) hn(Ɵ) = (2/n)[ Ɵ/(1- Ɵ)][n-(1- Ɵn)/(1- Ɵ)] (3) Ɵ = exp(-µΔt) (4) x represents the fraction dose, Ɵx is the initial segment of the survival curve, Ɵ determines the rate at which repair proceeds. n is fraction number and µ represent repair constant which equals to ln2/T1/2. T1/2 is the half-life of I-125. For continuous dose vt delivered at dose rate v for time t, with repair constant µ, the LQ model is modified as Ln (f(vt, µ)) = -α(vt) -β(vt)2g(µt) (5) g(µt) = 2[µt-1+exp(-µt)]/(µt)2 (6) Assuming biological effective dose (BED) is the same for the single fraction and split two fractions, SC when n = 1 should be same as when n = 2. Therefore, the equation (7) is derived. Ɵ = [(α/β)x1 - 2(α/β)(x2)2 + (x1)2]/2(x2)2 - 1 (7) x1 is single fraction dose of 85Gy, x2 is the split dose to two fractions. α/β ratio of 10 Gy is used. By fitting the equation (7), the ranges of doses and time intervals were determined. The fraction doses and time interval to get the same BED as single fraction of 85 Gy are determined from 45 Gy to 50 Gy with time interval of 22 days to 76 days for staged brachytherapy eye plaque (SBEP). Our result is matched the treatment protocol for SBEP reported, e.g., 1st fraction dose of 40Gy and 50 Gy of 2nd fraction with 73 days of time interval are used. The max. dose of scleral dose is 328 Gy compared to the single fraction scleral dose of 543Gy. This work could provide guidelines in SBEP in dosage and time interval. The height of tumor matters the most in the SBEP since the taller the tumor, the higher dose to the sclera is. Reference.

Single-Masked Randomized Phase 2 Study Assessing 2 Forms of Hypofractionated Proton Therapy in Patients With Large Choroidal Melanomas

Patients with large uveal melanomas are at major risk of liver metastases. Some patients are reluctant to undergo the standard treatment (ie, immediate enucleation). Proton therapy yields 5-year local control rates and eyeball retention of >85% and ≈20% in large uveal melanomas. Patients with T3/T4 uveal melanomas refusing enucleation were randomized between standard 4 to 13 Gy-fraction or moderately hypofractionated 8 to 6.5 Gy-fraction proton therapy. The main endpoint was the 2-year local recurrence-free survival without enucleation. A single-masked 1:2 randomized phase 2 trial was conducted between 2015 and 2017 with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse. The 32 patients, with a mean age of 64 years, had T3/4 (N=17/15), M1 (N=2) uveal melanomas, of mean tumor diameter and thickness of 16.5 mm and 9.1 mm, and of posterior location in 56.5%. Median follow-up was 56.7 months. The 2-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval, 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The 2-year-overall survival was 72% (95% confidence interval, 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (P=.39). An 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.

Stereotactic radiosurgery for medium and large uveal melanoma with a non-invasive eye immobilization device, a single institutional case series

To investigate the treatment outcome, visual outcome, and adverse effects of five-fraction stereotactic radiosurgery (SRS) to medium- and large-sized uveal melanoma with a non-invasive eye immobilization device. Medical records of 14 patients with uveal melanoma receiving SRS with a total dose of 50Gy in five fractions from 2008 to 2017 were retrospectively reviewed. A non-invasive eye fixation device was used to achieve and monitor eye immobilization. Local tumor control rates were 85.7% and 75.0% at 2 and 5 years, respectively. The average tumor diameter decreased significantly from 10.0±3.21mm to 8.36±3.71mm (p=0.038) 15 months after SRS, while the average tumor thickness decreased significantly from 5.45±2.21mm to 4.34±2.29 (p=0.036) 21 months after SRS. The 5-year metastasis-free survival was 87.5%. The mean best-corrected visual acuity (BCVA) deteriorated from logMAR 0.296at baseline to logMAR 1.112at the last individual follow-up visits (p<0.001). Adverse effects of SRS were comparable to those reported with proton-beam radiotherapy or Gamma knife therapy. SRS combined with a non-invasive eye immobilization device is an effective and safe alternative eye-preserving treatment for medium- to large-sized uveal melanoma. BCVA at 3 months may be a predictor for BCVA at 1 year.

Ophthalmic applicator displacement as a method of treating large diffuse uveal melanomas.

The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas. This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023). To achieve appropriate radiation dose distribution for large tumors with a base greater than 18 mm, brachytherapy (106Ru in 7 patients and 125I in 2 patients) with applicator displacement was used as primary treatment. Median follow-up was 2.9 years, and for patients with positive primary treatment results, it was 1.7 months. Median time to local relapse was 2.3 years. In 5 patients, a positive result of local treatment was obtained, out of whom, one patient underwent enucleation due to complications. In the next 4 cases, local recurrence developed. In all tumors, the use of applicator displacement method caused that planning target volume (PTV) was effectively covered with treatment isodose. Brachytherapy with ocular applicator displacement allows for the treatment of tumors with base measurements larger than 18 mm. The application of this method may be considered as an alternative for eye enucleation in particular cases of large diffuse tumors, such as a neoplasm of the eye with vison, or when a patient does not consent to enucleation.

Ruthenium-106 plaque radiotherapy for uveal melanoma: analysis of tumor dimension and location on anatomical and functional results

BackgroundTo report the long-term outcomes of Ru-106 plaque radiotherapy in eyes with uveal melanoma (UM) and to assess the effect of tumor thickness and location on final outcomes.MethodsMedical records of 234 patients undergoing Ru-106 plaque radiotherapy for UM were reviewed, and the visual outcome, globe preservation, and patient survival were evaluated. The results of 2 groups were compared: 1. between thin (small and medium-sized, thickness < 7 mm, 148 eyes [63.2%]) and thick (thickness ≥ 7 mm, 86 eyes [36.8%]) tumors, and 2. between large (largest basal diameter [LBD] > 12 mm, 109 eyes [46.6%]) and medium/small (LBD ≤ 12 mm, 125 eyes [53.4%]). In addition, a comparison of the juxtapapillary location in 46 eyes (19.7%) versus tumors arising elsewhere and between tumors with and without ciliary involvement in 48 eyes (21.5%) were done.ResultsThe patients were followed for a median of 54.2 months (range: 6–194.5 months). After adjusting for baseline visual acuity (VA), there was no significant association between final VA and different dimension and tumor location groups. Final globe preservation was 91.9%, and there was no significant difference between different dimension- and ciliary body involvement groups regarding anatomical success rate. The juxtapapillary tumors had lower globe preservation (80.4% vs .94.7%, p = 0.002). The hazard ratio (HR) for enucleation in juxtapapillary tumors was HR = 6.58 (95-CI: 3.84 to 11.21). The overall metastasis rate was 6.8%, with no significant difference in juxtapapillary tumors (4.3% vs.7.4%, p = 0.455).ConclusionsRu-106 plaque radiotherapy is an effective treatment for thick and large UM. With this type of treatment, the globe preservation rate is lower in juxtapapillary tumors, but there is no significant difference in the metastasis rate.

Photon-based High-dose Single-fraction Radiosurgery, an Effective Treatment Modality for Large and Posterior Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor. This malignancy is frequently treated using brachytherapy, stereotactic radiotherapy, or proton therapy. The objective of this study was to assess the role of stereotactic radiosurgery in the treatment of large and posterior UM. From January 2014 to July 2021, we treated 65 patients (median age=71 years; range=31-89 years) affected by UM. Inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, life expectancy >6 months, tumor thickness >10 mm, diameter >16 mm or posterior UM. The treatment was delivered with a True Beam™ LINAC with arc modulation technique. All patients received 27 Gy in one fraction (biological effective dose ≈100 Gy, assuming an α/β of 10). The median follow-up was 36 (range=3-90) months. Acute toxicities were reported in 14 patients, whereas late toxicity occurred in 45 (69.2%). Fifteen patients (23.0%) underwent enucleation: eight (12.3%) for failure of local control and seven (10.7%) for late treatment co-morbidities. The 5-year local control, and progression-free, metastasis-free, enucleation-free, and overall survival rates were 80%, 43%, 62%, 65% and 56%, respectively. In multivariate analysis, tumor dimensions significantly influenced survival [larger basal diameter: progression-free [hazard ratio (HR)=2.42] and overall (HR=2.61) survival; greater thickness: overall survival (HR=2.36)]. In multivariate analysis, patients without local control had a higher risk of distant metastasis (HR=3.25). Stereotactic radiosurgery offers an effective and safe approach for selected cases of UM due to the satisfactory results in terms of local control, eye conservation and survival.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PurposeEye‐dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed.Material/MethodsThe HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye‐dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in‐house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)‐398 Code of Practice for absolute dose measurement, and the IAEA TRS‐398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread‐out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor‐specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated.ResultsA pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall‐offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2, and 0.80 mm, respectively. Average distal fall‐offs of the HollandPTC eyeline were 0.20 g/cm2, and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source‐to‐axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165–350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%.ConclusionsHollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation‐related toxicities. This interinstitutional comparison could support further research on ocular post‐PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Impact of uveal melanoma thickness on post-plaque radiotherapy outcomes in the prophylactic anti-vascular endothelial growth factor era in 1131 patients.

The impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti-vascular endothelial growth factor (VEGF) era remains unknown. To evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness. This was a retrospective, interventional case series. Patients with uveal melanoma were included in this study. A review of medical records was conducted of patients with uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab from 7 July 2000 to 2 November 2018. Radiation-related outcomes of cystoid macular oedema (CME), radiation maculopathy, papillopathy, retinopathy, iris neovascularization (NVI) and neovascular glaucoma (NVG) were compared based on tumour thickness (small [<3.0 mm] vs medium [3.1-8.0 mm] vs large [>8.0 mm]). Of 1131 eyes, 341 (30%) had small, 633 (56%) medium and 157 (14%) large melanoma. Comparison (small vs medium vs large) at 4 years following radiotherapy revealed large melanoma with greater Kaplan-Meier estimated risk of CME (37% vs 37% vs 63%, P < .001), earlier onset of CME (33 vs 26 vs 19 months, P < .001) and greater development of NVI (<1% vs 2% vs 13%, P < .001) and NVG (1% vs 2% vs 12%, P < .001). Radiation-induced maculopathy, papillopathy and retinopathy were not associated with tumour thickness. Compared with small and medium uveal melanoma, large uveal melanoma demonstrated greater 48-month risk for CME, shorter time to CME onset and greater development of NVI and NVG following plaque radiotherapy and prophylactic intravitreal bevacizumab.

DNA alteration-based classification of uveal melanoma gives better prognostic stratification than immune infiltration, which has a neutral effect in high-risk group.

BackgroundIn uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra‐tumor immune population, compare it to other established biomarkers and to patients' outcome.MethodsPrimary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed using: transcriptomic profiling (n = 15), RT‐qPCR (n = 36), immunohistochemistry (n = 89), Multiplex Ligation‐dependent Probe Amplification (MLPA) for copy number alterations (CNA) analysis (n = 89), array‐CGH (n = 17), and survival statistics (n = 86).ResultsGene expression analysis divided uveal melanomas into two groups, according to the IFNγ/STAT1‐IRF1 pathway activation. Tumors with IFNγ‐signature had poorer prognosis and showed increased infiltration of CD8+ T lymphocytes and macrophages. Cox multivariate analyses of immune cell infiltration with MLPA data delineated better prognostic value for three prognostic groups (three‐tier stratification) than two (two‐tier stratification). CNA‐based model comprising monosomy 3, 8q amplification, and LZTS1and NBL1 deletions emerged as the best predictor for disease‐free survival. It outperformed immune cell infiltration in receiver operating characteristic curves. The model that combined CNA and immune infiltration defined risk‐groups according to the number of DNA alterations. Immune cell infiltration was increased in the high‐risk group (73.7%), where it did not correlate with patient survival, while it was associated with poorer outcome in the intermediate risk‐group.ConclusionsHigh degree of immune cell infiltration occurs in a subset of uveal melanomas, is interferon‐gamma‐related, and associated with poor survival. It allows for two‐tier stratification, which is prognostically less efficient than a three‐tier one. The best prognostic stratification is by CNA model with three risk‐groups where immune cell infiltration impacts only some subgroups.

Secondary glaucoma in small versus large uveal melanoma patients treated with stereotactic radiosurgery on linear accelerator.

Secondary radiation-related side effects like secondary glaucoma (SG) of different modalities of treatment in uveal melanoma patients can appear in certain interval after therapy. This study describes the incidence of SG in patients after stereotactic radiosurgery (SRS). The data of 230 patients treated by SRS were reviewed for SG. Group of 83 patients who were observed 5 years after treatment in one center with follow-up regularly at least 4 times per year were analyzed. In group of 83 patients with the median age 59 years, the median tumor volume at baseline was 0.41cm3. The survival without SG after single dose SRS was 94 % in 1.5 year, 77 % in 2 years, 57 % in 3 years, 43 % in 3.5 years, and 18 % in 4.5 year after irradiation. In 6 patients (7.2 %) secondary enucleation was necessary due to SG. Both predictors (tumor volume and age of patient) at the time of SRS were not statistically significant by Cox proportional-hazards regression. Complications like SG in 5 year interval after irradiation can lead to secondary enucleation of the eye globe (Fig. 3, Ref. 44).

23-mm iodine-125 plaque for uveal melanoma: benefit of vitrectomy and silicone oil on visual acuity.

To review outcomes in mostly large uveal melanoma treated with a 23-mm-diameter iodine-125 plaque, the largest size available at our center, and the influence of vitrectomy and silicone oil 1000 centistokes for radiation attenuation. A one-to-one matched case-control comparison was performed. Case patients were treated with a 23-mm-diameter iodine-125 plaque and vitrectomy with silicone oil 1000-cSt placement. Control cases, treated with 23-mm plaque alone, were matched to cases with respect to tumor size and distance from tumor apex to optic nerve and fovea. Postoperative complications, visual acuity and metastasis were reviewed. Twenty case patients with uveal melanoma treated with a 23-mm plaque were identified. The final logMAR vision was 0.83 in case patients and 2.06 in control patients (P = 0.0064); the change from pre-treatment to last follow-up logMAR vision was 0.70 in cases and 1.62 in controls (P = 0.019). Of good vision outcomes, 65% of cases and 25% of controls achieved vision ≥20/200 (P = 0.025). Of poor vision outcomes, 35% of cases and 80% of controls achieved vision <20/200 (P = 0.0053), and 5% of cases and 35% of controls achieved "light perception" or "no light perception" vision (P = 0.044). Thirty-nine of the 40 eyes (98%) achieved local tumor control. Metastasis occurred in 15% of cases and 45% of controls (P = 0.082). Iodine-125 brachytherapy for mostly large uveal melanoma is effective in achieving local tumor control. Furthermore, combining brachytherapy with vitrectomy and silicone oil 1000-cSt for radiation attenuation significantly improves vision over the use of plaque alone.

Endoresection or not?

SummaryEye salvaging treatment of large uveal melanomas by primary irradiation bear the risk of severe secondary complications due to tumour regression. The so called „toxic tumour syndrome’ comprises a multitude of such problems such as retinal detachment, ocular ischemia, melanomalytic reactions, secondary glaucoma either by neovascularization or by tumour debris deposition or both. Surgical resection of tumours addresses these issues. Surgical resection can be performed either as an endoresection or as by means of transscleral resection. Both surgical procedures are challenging and pose by themselves some risks, which need to be addressed appropriately.

T2 Fluid-Attenuated Inversion Recovery Imaging of Uveal Melanomas and Other Ocular Pathology

Background/Aims: This study describes patterns of intraocular lesions on T2 fluid-attenuated inversion recovery (FLAIR) imaging, exploring a prospective role of FLAIR imaging sequence in diagnosis and treatment. Methods: A retrospective study of orbital magnetic resonance imaging (MRI) studies from the years 2000 to 2015 was performed. MRI sequences included: pre-contrast T1-weighted, T2-weighted, T2 FLAIR, and postcontrast T1 and T2 imaging gadolinium, which were evaluated by a neuroradiologist. Two cases of melanoma were correlated to their pathology. Results: Twenty-four patients with intraocular pathology were evaluated. All lesions, regardless of pigmentation, revealed previously described melanotic patterns on T1- and T2-weighted images; 80% of 10 melanomas localized were hyperintense on T2 FLAIR, which better delineated lesion margins. All of the four inflammatory pathologies on T2 FLAIR were hyperintense, as were 80% of the amelanotic neoplasms. Pathology of two large uveal melanomas paralleled the findings seen on T2 FLAIR. Conclusions: T2 FLAIR appears beneficial in the demarcation of pigmented ocular lesions and may aid in determining protein content or previous treatment. Data also promote previous assertions that blood flow impacts intensity of lesions on T2 FLAIR. Further research is warranted.

Endoresection of large uveal melanomas: clinical results in a consecutive series of 200 cases

BackgroundTo report eye salvaging rate, visual acuity (VA), local recurrences, complications and the potential benefit of adjuvant brachytherapy after endoresection of large uveal melanomas.Methods200 patients were included in this retrospective...

Selecting uveal melanoma for PRAME‐TCR T cell immunotherapy

PurposeTo determine which uveal melanoma may be candidates for PRAME‐directed immunotherapy using TCR‐modified autologous T cells.MethodsExpression of PRAME was determined in uveal melanoma by an Illumina array. HLA polymorphisms were determined on peripheral blood leukocytes. Clinical and histological characteristics of UM were derived from clinical charts and pathology reports.ResultsPRAME expression was highly variable; tumor size, thickness, and the presence of an inflammatory phenotype were associated with PRAME expression. 20/37 monosomy 3 cases expressed PRAME, and 8/20 disomy 3 tumors. 10‐year survival data on 60 UM showed worse survival of UM with high PRAME compared to those with a low PRAME. However, six of the eight PRAME‐positive disomy 3 cases died from metastases. With this information, all cases with PRAME‐positive primary tumors who carry the HLA‐A2 antigen should be followed closely for the development of metastases, as they can be candidates for PRAME‐TCR autologous T cell therapy.ConclusionsUveal melanoma may be good candidates for treatment with autologous T cells that have been modified so that they carry PRAME‐specific T cell receptors. Large uveal melanoma with a high PRAME expression (independent of chromosome 3 status) in HLA‐A2 positive patients are potential candidates for PRAME‐TCR autologous T cell therapy. A high PRAME expression, also in disomy 3 tumors, was associated with an inflammatory phenotype and with death due to metastases.

Monosomy 3 by chromogenic in situ hybridization (CISH) in Iranian patients with uveal melanoma

PurposeThe aim of this study was to investigate the rate of monosomy 3 by CISH technique in Iranian patients with uveal melanoma (UM) and its correlation with clinical and histopathological features. MethodArchival formalin fixed, paraffin-embedded material from 50 patients who had undergone enucleation for large uveal melanomas was obtained. Monosomy of chromosome 3 alteration by chromogenic in situ hybridization (CISH) was investigated. Clinical and histopathological features of tumors were collected. ResultsThe patients had a mean age of 56.6±7.6 years. Mean basal diameter and thickness of tumors were 14.1 mm and 10.2 mm, respectively. Four patients (8%) were identified to harbor monosomy of chromosome 3. In the mean follow-up of 5.3 years (range, 3.2–9.5 y), only one case with monosomy 3 died of UM metastasis. The most common type of cellularity was mixed cell (86%).There was not any statistically significant correlation between monosomy of chromosome 3 and type of cellularity, ciliary body involvement, and largest basal diameter. ConclusionThe low rate of monosomy chromosome 3 and the consequent low rate of mortality may be indicative of good prognosis in Iranian patients with uveal melanoma.

Eviscerated eyes unexpectedly containing uveal melanoma

AbstractPurpose To present two cases with eviscerated eyes containing uveal melanoma and review the literatureMethods All the evisceration specimens from a 15 year period were analyzed for malignancies. A literature search on the accidental finding of intraocular malignancy after evisceration was performedResults We found an incidence of intraocular malignant melanoma of 0.7% (2/315). In these 2 cases, a standard evisceration procedure with implantation of an acrylic ball had been performed for pain in a longstanding blind eye with opaque media. Both patients had a history of glaucoma and massive intraocular hemorrhage, confirmed by repetitive ocular ultrasound (US) and orbital CT. Histopathology showed a large intraocular uveal melanoma with substantial necrosis and haemorrhage After negative screening for metastases, one week following the evisceration an enucleation of the scleral shell and implant was performed, with implantation of a new acrylic ball with donor sclera. External beam radiation of 5,000 cGy was given to the orbital socket. The first patient died from liver metastases 3 years after the diagnosis, without evidence of local recurrence. The second patient has a too short follow‐up The literature is scarce on this subject, with only 9 published cases. US is the mainstay in the screening for intraocular tumors in opaque eyes. There are no guidelines on the management after accidental evisceration of uveal melanomaConclusion Ultrasound can not always distinguish primary choroidal hemorrhage from secondary hemorrhage due to uveal melanoma with necrosis. An atypical clinical history of a blind painful opaque eye with prolonged massive intraocular hemorrhage and ocular hypertension may be suspect for malignant melanoma, in which case evisceration should be avoided