Ultrasonographic and histopathological correlation in choroidal melanoma: survival outcomes from a single-center study in Serbia.

Correlation of fitzpatrick skin type and iris color with tumor size in 823 patients with uveal melanoma

Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

Objectives:To report treatment results and complications of stereotactic radiosurgery in uveal malignant melanoma and to identify risk factors for development of radiation retinopathy.Materials and Methods:This was a retrospective study of 36 patients diagnosed with uveal melanoma between 2014 and 2019. Best corrected visual acuity, funduscopic findings, basal tumor diameter and tumor thickness were recorded at baseline and at follow-up visits at 3-month intervals. The response of tumors to stereotactic radiosurgery and complications were determined.Results:The mean basal diameter of tumor was 10.2 (range: 4.0-19.4, standard deviation [SD]: ±3.3) mm x 9.7 (range: 4.5-18.0, SD: ±3.3), tumor thickness was 5.1 (range: 2.0-11.0, ±2.4) mm at baseline. The mean follow-up period was 17.2 (range: 6-48, SD: ±10.43) months. The mean visual acuity was 0.5 (SD: ±0.3) logMAR before treatment and 0.6 (SD: ±0.3) logMAR after the mean follow-up period. The most common complications after stereotactic radiosurgery were cataract (38.9%) and radiation retinopathy (27.7%). There was a statistically significant relation between radiation retinopathy development and tumor distance from the optic disc (p=0.04). The rate of eye salvage was 83.3% in this study.Conclusion:Our short-term results show stereotactic radiosurgery was an effective and sustained treatment modality among the other eye conservation therapies.

Introduction: It can be challenging to distinguish between choroidal naevi and melanomas in the community setting, particularly without access to ultrasonography (US), required to measure the thickness of melanocytic choroidal tumours. We aimed to determine whether thickness measurement is required for MOLES scoring of melanocytic choroidal tumours. Methods: The dataset of a recent MOLES evaluation was reviewed. Patients were selected for the present study if their MOLES tumour size category was determined by tumour thickness measured with US. The largest basal tumour diameter and tumour thickness were then measured from ultra-widefield fundus images and optical coherence tomography (OCT) images, respectively. Results: The tumour size category was determined by tumour diameter in 203/222 (91.4%) with no influence of tumour thickness. The tumour thickness influenced the MOLES score in 19/222 (8.6%) patients. In 11/19 patients with OCT measurements of tumour thickness, the US measurement exceeded the OCT by more than 25% in 5 patients, more than 50% in 2 patients, and more than 75% in 1 patient. As a result, the revised tumour thickness based on OCT determined the size category in 4/216 (1.8%) patients. The ultra-widefield fundus images measurements increased the diameter score by 1 in 5 patients. As a result, the revised tumour thickness determined the size category in 4/216 (1.8%) patients. If both the revised diameter and thickness scores were considered, the MOLES score reduced in 4 patients. If both the diameter and thickness scores were considered, the MOLES score reduced in 5 and increased in 1. Only 0.94% (2/211) of melanocytic choroidal tumours assessed with MOLES when using Optos ultra-widefield fundus images diameter and OCT to measure tumour diameter and thickness, respectively, required a change in management from a reduction in MOLES score from 1 to 0. Discussion/Conclusion: This study suggests that the MOLES category for size is influenced more by the tumour diameter, if it can be measured accurately, than by the thickness. This study suggests ignoring tumour thickness if this cannot be measured accurately with OCT, unless the tumour has a mushroom shape.

Purpos. To conduct a comparative analysis of the local tumor control, local and systemic safety of primary endoresection (ER) of «large» choroidal melanoma (CM) compared to brachytherapy (BT) with Ru-106 in statistically homogeneous groups. Material and methods. A total of 35 patients (35 eyes) aged 30 to 75 years (mean — 58 years) with CM were treated with primary ER from 2014 to 2024. Among them, there were 9 (26%) women and 25 (74%) men. According to the international TNM classification (AJCC) (2017), 11 (31%) patients had tumors classified as stage T3, while 24 (69%) had stage T2. No metastases of CM were detected in any patient at the time of treatment. The tumor thickness before treatment ranged from 6.0 to 11.6 mm (mean — 8.2 mm), the largest basal diameter varied from 7.8 to 13.9 mm (mean — 11 mm). A comparative analysis of ER and BT was conducted in two independent groups, which were standardized by the main clinical characteristics: age at the time of treatment, preoperative best-corrected visual acuity, tumor thickness and basal diameter, tumor location, and the follow-up. Results. The comparative analysis of local tumor control did not reveal statistically significant difference (p=0.45). In the ER group, the surgical chorioretinal coloboma without tumor recurrence was observed in 33 patients (94%), tumor recurrence was identified in 2 cases (6%). In the BT group complete tumor regression was observed in 14% of cases, incomplete regression in 75%, and tumor progression in 11%. 23% of patients underwent adjuvant treatment after BT (either repeated BT or transpupillary thermotherapy). The comparative analysis of complication rates (cataract, retino-/maculopathy, neuropathy/partial optic nerve atrophy, retinal detachment, vitreous hemorrhage, secondary glaucoma) after primary ER and BT with Ru-106 did not demonstrate statistically significant difference: complications occurred in 62% of the ER group and in 59% - in the BT group (p=0.93). However, there was a trend towards a statistically significantly lower frequency of all complications except cataract after ER compared to BT (p=0.08). Conclusion. Thus, the comparative analysis in statistically homogeneous groups demonstrated that primary ER of CM is a highly effective approach for the treatment of «large» CM that is comparable to BT in local tumor control and does not increase the risk of enucleation or metastasis in comparable groups. The results suggest that primary ER for CM can be widely used in clinical practice for the treatment of «large» CM.

Adjuvant indocyanine green in transpupillary thermotherapy for choroidal melanoma

To investigate the relationship between choroidal nevus and melanoma thickness measured with or without the sclera included by B-scan ultrasound and to present a simple conversion formula. Medical records were retrospectively reviewed for choroidal nevus or melanoma evaluated at the Mayo Clinic in Rochester, Minnesota, with B-scan ultrasound between February 4, 2004, and April 23, 2020. Charts were retrospectively reviewed for high-quality B-scan images in which the ultrasound transducer was perpendicular to the lesion, measuring the tumor thickness without the sclera included. Measurements were repeated with the sclera included for each patient. Univariate and multiple linear regression analyses were performed to identify factors correlated with scleral thickness. There were 201 tumors included in the study, with a mean patient age ± SD of 61 ± 14 years, largest tumor basal diameter of 11.8 ± 4.8 mm, tumor thickness without the sclera included of 3.72 ± 2.7 mm, and thickness with the sclera included of 4.54 ± SD 2.8 mm. On the univariate analysis, factors associated with perceived scleral thickness by B-scan ultrasound included age (P < .001), tumor thickness (P < .001), and basal diameter (P=.06). On the multivariate analysis, factors associated with perceived scleral thickness included age and tumor thickness (P < .001) for all tumors and for the subset of 141 tumors with a thickness of 2 mm or greater (P < .001). For tumors of 2 mm or greater in thickness, perceived scleral thickness by ultrasound can be estimated by the formula 0.00495(patient age) + 0.02451(tumor thickness without the sclera) + 0.42549. We present a simple formula for converting between B-scan ultrasound measurements of choroidal nevus and melanoma measuring 2 mm or greater in thickness with and without the sclera included.

The American Joint Committee on Cancer (AJCC) classification is in its seventh edition. In addition to universal tumor staging (TNM), this classification is very relevant in the field of ocular oncology, which involves iris, ciliary body, and choroidal melanoma. It aimed to separate uveal melanoma into anatomical stages to provide information regarding the prognosis for metastasis and death. The AJCC’s classification of posterior uveal melanoma involves melanoma categorization and staging. Categorization includes measurements of the tumor thickness and tumor base. It defines which of the four previously designated size groups the tumor fits into: T1, T2, T3, or T4 (TABLE 1). The staging process involves the categorization results and information regarding lymph nodes (N) and metastasis (M) to define which of the four anatomical stages the tumor fits into: I, II, III, or IV (TABLE 2). The present article sought to explore the predictive value of the AJCC’s anatomical stage classification system for metastasis and death by posterior uveal melanoma. Based on data from the Ocular Oncology Service at the Wills Eye Hospital, 7731 patients with a diagnosis of ciliary body or choroidal melanoma between 1970 and 2008 were considered. There was adequate tumor information regarding all patients, which enabled retrospective classification of uveal melanoma using AJCC categorization (7 th edition). Basal diameter was estimated using binocular indirect ophthalmoscopy and ultrasonography, and tumor thickness was measured using ultrasonography. Various treatment options were used with these patients, including laser photocoagulation, transpupillary thermotherapy, plaque radiotherapy, local resection, enucleation, and exenteration. Furthermore, systemic monitoring and screening for metastasis were performed. Out of the 7731 patients, 2767 (36%), 3735 (48%), 1220 (16%), and 9 (<1%) were classified as having stage I, II, III, and IV tumors, respectively. Following data analysis, it was estimated that, of the patients with 10 and 20 years of follow-up, the respective probability of metastasis was 12% and 20% for stage I patients, 29% and 44% for stage II patients, 61% and 73% for stage III patients (p < 0.001), and 100% among stage IV patients after 1 year of follow-up. Meanwhile, the respective estimates of melanoma-related death at 10 and 20 years after diagnosis were 6% and 8% for stage I patients, 15% and 24% for stage II patients, 39% and 53% for stage III patients, and 100% among stage IV patients after 1 year of follow-up (p < 0.001). The predictive factors for metastatic disease and death in cases of stage I melanoma include a large tumor base and an increase in tumor thickness. Aging, increase in tumor thickness, a large tumor base, tumor pigmentation, a mushroom configuration, and associated subretinal fluid were predictive factors among stage II patients. Stage III factors included not only the abovementioned factors but also an inferior tumor location. A recent publication by the AJCC Ophthalmic Oncology Task Force mentioned a study using a cohort of 3809 patients from 10 international ocular oncology centers. The estimates of metastasis-free survival 10 years after diagnosis were found to be 94% (stage I), 78% (stage II), and 56% (stage III). Thus, the analysis of 7731 patients with posterior uveal melanoma revealed the AJCC’s clinical classification to be predictive of metastatic disease. Briefly, this classification may be used to select patients at high risk for metastasis for treatment protocols that focus on the prevention of metastatic events. Furthermore, it shows the importance of early detection and disease management.

Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. Progression-free survival (PFS). The secondary outcome was overall survival. The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort. Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.

Metastasis from Uveal Melanoma Associated with Congenital Ocular Melanocytosis: A Matched Study

Clinical Characteristics of UM and Association of Metastasis of Uveal Melanoma with Congenital Oculocutaneous Melanosis in Asian Patients: Analysis of 1151 Consecutive Eyes

Treatment of poorly-pigmented tumors of small sizes can be carried out using photodynamic therapy (PDT). The material for the analysis was data on 112 patients. We used data from the Belarusian Cancer Registry, medical records of patients with clinically diagnosed choroid melanoma (C69.3 according to ICD-10) for the period 2013–2021. The size and level of blood flow in the tumors were assessed using an ultrasound machine with a doppler attachment. PDT was carried out using a «UPL PDT» semiconductor laser (Lemt, Republic of Belarus, λ=661 nm) with a light spot diameter of 1 to 3 mm for 60 s per field with a light dose of 50 J/cm2. The entire surface of the tumor was exposed to the action, with the fields “tiled”, from the periphery to the top of the tumor, with overlapping fields. Tumor pigmentation was assessed visually. To evaluate the treatment outcome, the general group of patients was divided into three subgroups according to thickness and basal diameter. Group I – 40 (35.7%) patients, with an average tumor thickness of 1.4±0.2 mm, basal diameter – 5.8±1.5 mm. II – 51 (45.5%) patients, with an average tumor thickness of 2.3 ± 0.3 mm, basal diameter – 7.9 ± 1.5 mm. III – 21 (18.8%) patients. The mean value of the tumor thickness was 3.8±0.4 mm, the basal diameter was 9.8±1.4 mm. After PDT in the general group (n=112), 29 (25.9%) patients had complete tumor resorption, and 83 (74.1%) patients had stabilization. The eyeball was saved in 107 (95.5%) patients. Continued growth and relapse were recorded in 34 patients: 25 (22.3%) and 9 (8.0%), respectively. In 29 (85.3%) patients, the eyeball was preserved after treatment of relapse and continued growth. 5 (4.5%) enucleations were performed. Adjusted one-year cumulative survival was 100%, 3-year and 5-year 95.8±2.4%, 93.7±3.1%, respectively

Independent Prognostic Significance of Gene Expression Profile Class and Largest Basal Diameter of Posterior Uveal Melanomas

Purpose: To assess the expression of molecular markers of peripheral blood lymphocyte activation (СD7+, CD54+, CD95+) before and after eye-preserving treatment for Т1 to Т3 choroidal melanoma (CM). Material and Methods: Expression of molecular markers of peripheral blood lymphocyte activation (СD7+, CD54+, CD95+) was examined before and after eye-preserving treatment for Т1 to Т3 CM. The major study group (group 1) consisted of 25 patients (14 (56.0%) women and 11 (44.0%) men; mean age (standard deviation (SD)), 51.7 (16.6) years) who received the eye-preserving treatment (transpupillary thermotherapy (TTT (delivered using the developed methodology) combined with strontium-90/yttrium-90 (90Sr/90Y) brachytherapy (BT)) for moderate to large (T1-T3) CM (tumor base, 3.1 to 15 mm; tumor thickness, 3.1 to 9.0 mm). The control group (group 2) consisted of 16 patients (12 (75.0%) women and 4 (25.0%) men; mean age (SD), 55.4 (11.2) years) who received TTT only for small (T1) CM (tumor base, ≤ 12 mm; tumor thickness, ≤ 3 mm). Results: The expression of markers CD7+, СD54+, and CD95+ before treatment for Т1-Т3 CM was higher than before treatment for small Т1 CM, but the difference was significant only for the absolute expression of CD7+ (р = 0.0008). After TTT for small Т1 CM, a statistically significant increase was observed only in the absolute and percentage expression of CD7+ (р = 0.04 and р = 0.0000, respectively) and the absolute expression of FAS-ligand CD95+ (р = 0.05). Additionally, the level of СD54+ increased after treatment, but not significantly. Absolute expression levels of these molecular markers decreased after TTT plus BT, but not significantly. Additionally, the percentage expression of СD7+ decreased statistically significantly (р = 0.02), and the percentage expression of СD95+ decreased statistically insignificantly (р = 0.06). After eye-preserving treatment for CM, there were significant differences between the two groups in the absolute and percentage expression of FAS-ligand CD95+ (р = 0.003 and р = 0.000, respectively) and CD54+ (р = 0.03 and р = 0.000 respectively), with these levels being lower in group 1. Conclusion: Expression of molecular markers of peripheral blood lymphocyte activation (СD7+, CD54+, CD95+) increased with tumor progression in patients with CM. The expression of the markers increased after TTT only for small Т1 CM, and decreased after TTT plus BT (90Sr/90Y) for Т1-Т3 CM, likely due to the effect of radiotherapy.

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