Postoperative Echography for Optimization of Radiation Dosimetry in Patients with Uveal Melanoma Treated with Plaque Brachytherapy.

PURPOSE: (1) To describe the technique of postoperative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy. (2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution. DESIGN: Retrospective review. SUBJECTS: Three hundred seventy-two consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from August 2008 to February 2019. METHODS: Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n = 355) underwent intraoperative ultrasound to confirm plaque placement, and additional postoperative ultrasound on day 1 to 3 postplaque insertion. In cases where intratumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to < 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with the need for plaque adjustment. MAIN OUTCOMES MEASURES: Variables associated with plaque dose needing to be recalculated, local tumor control, and visual acuity outcomes. RESULTS: In 31 (8.3%) cases, postoperative echography showed that the tumor apex had shifted outside the 85 Gy isodose curve, requiring adjustment of the duration of brachytherapy (28 cases) or repositioning of the plaque (3 cases). Collaborative Ocular Melanoma Study tumor size was significantly associated with need to adjust the plaque prescription dose (P = 0.03), with large tumors having the highest rate of adjustment. Tumor thickness was larger in cases requiring plaque adjustment compared with those that were not adjusted (median 4.9 mm vs. 3.0 mm, P < 0.01). Local tumor control was 99% (95% confidence interval, 97%-100%) at 5 years and 99% (95% confidence interval, 97%-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥ 3 lines of vision or had < 20/200 acuity was 14.9% at 1 year after brachytherapy, 35.3% at 3 years, and 51.6% at 5 years. CONCLUSIONS: Postoperative ultrasound performed on postoperative day 1 to 3 after plaque insertion for patients undergoing brachytherapy for uveal melanoma may result in improved local tumor control, particularly in the setting of thicker or larger tumors. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Edge Creep: Increased Pigmentation at the Border of Choroidal Melanomas Treated with Plaque Brachytherapy.

Introduction: There is an increase in pigmentation that occurs in many tumors following plaque brachytherapy for choroidal melanoma. Correctly distinguishing between increased pigment at the tumor border versus true growth is imperative. We performed a retrospective review of patients treated with I-125 brachytherapy for choroidal melanoma at our institution to study this phenomenon. Methods: Records were reviewed for all patients undergoing plaque brachytherapy for uveal melanoma for a 5-year period (N = 195). Patients with iris and anterior tumors were excluded. Tumors treated more than 31 days after presentation were excluded. Fundus images for patients with increased pigmentation at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin were included (N = 20; 8 F, 12 M). Imaging at the last follow-up was reviewed, and it was confirmed that all tumors involuted appropriately with no evidence of local recurrence. The date of initial exam, time to treatment, and follow-up interval were recorded for each included patient. Results: Twenty patients (10%) exhibited increased pigment deposition at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin. Average tumor thickness was 3.2 mm (1.3-5.1); average largest tumor basal diameter was 11.6 mm (7-15.5). Average time from diagnosis to treatment was 25 days (17-31). Average length of follow-up was 35 months (16-68). No patient developed recurrence during the duration of follow-up, and 1 patient had developed metastasis. Conclusion: We describe the phenomenon of increased pigment deposition, "edge creep," at the borders of choroidal melanomas treated with plaque brachytherapy that gave the appearance of initial tumor growth but then subsequently remained stable over time. It is important that treating ocular oncologists be aware of this phenomenon to avoid unnecessary diagnosis of local recurrence.

Predicted vs Observed Metastasis-Free Survival in Individuals With Uveal Melanoma.

Importance: Accuracy of the predicted metastasis-free survival (MFS) by a commercially available gene expression profiling (GEP) test is not known. Objective: To compare the predicted MFS with the observed MFS in patients in this cohort and with those in published studies (published MFS, meta-analysis). Design, Setting, and Participants: This cohort study included consecutive patients from the University of Iowa and Cleveland Clinic who were diagnosed with uveal melanoma who underwent prognostic fine-needle aspiration biopsy at the time of primary treatment. Patients were recruited from December 2012 to December 2020. The predicted MFS for patients was extracted from the GEP report. The observed MFS was defined as time to metastasis. Cox proportional hazards models were fit to identify tumor variables impacting MFS in patients with class 2 tumors. The overall estimate of the published MFS was obtained by performing meta-analysis of data from published series. Analysis took place in August 2021. Main Outcomes and Measures: MFS. Results: There were 92 patients from the University of Iowa and 255 patients from the Cleveland Clinic. The mean (SD) age at diagnosis was 59.4 (13.0) years. The median (IQR) follow-up interval was 38.0 (19.0-57.0) months. The observed MFS for patients with class 2 tumor in this cohort (3 years: 67% [95% CI, 59%-77%]; 5 years: 47% [95% CI, 37%-61%]) and in published studies (3 years: 62% [95% CI, 57%-66%]; 5 years: 40% [95% CI, 34%-46%]) were better than those predicted (50% and 28% for 3 and 5 years, respectively). Within patients with class 2 tumor, those with metastasis had larger tumors compared with nonmetastatic tumors (mean largest basal diameter difference, 1.7 [95% CI, 0.5-3.0] mm; P = .01; mean thickness ratio, 1.3 [95% CI, 1.04-1.5]; P = .01, respectively). An increasing tumor size was significantly associated with increased hazard ratio (1.16 [95% CI, 1.06-1.27]; P < .001) of metastasis. Conclusions and Relevance: These findings suggest the predicted MFS for metastatic tumors (class 2) appears to be worse than that observed here and reported by others. Incorporation of tumor size in the prediction model may enhance its accuracy. Adjuvant therapy trials may not be able to rely on predicted MFS to calculate efficacy with a high degree of confidence.

Retinal Capillary Hemangioma Leading to a Diagnosis of von Hippel-Lindau Disease in a Patient with Retinopathy of Prematurity.

Von Hippel-Lindau (VHL) disease is a rare inherited cancer syndrome that results in the development of tumor formation in multiple systems. In the eye, retinal capillary hemangioma (RCH) can lead to severe vision loss. Retinopathy of prematurity (ROP) is likewise a rare disease in which abnormal retinal vasculature develops in premature infants. Hallmarks of this disease include temporal dragging of the macula and retinal vessels. Here, we describe a 36-year-old myopic woman with a known history of ROP who presented with a vitreous hemorrhage in the right eye. As the vitreous hemorrhage cleared, she was found to have not only a retinal tear but also a juxtapapillary RCH that lead to a diagnosis of VHL disease in the patient, her mother, and her aunt. This is the first reported case of an individual with concomitant ROP and RCH from VHL. Her vision was remarkably well preserved over 25 years of follow-up despite having a moderate-sized laser scar temporal to the disc from treating the juxtapapillary RCH, likely due to the temporal macular dragging from her underlying ROP. This case highlights the importance of being aware that rare diagnoses can co-exist, and one must be aware of the protean manifestations of VHL.

Gene Expression Profiling Prognostication of Posterior Uveal Melanoma: Does Size Matter?

PURPOSE: Investigate the influence of tumor size by American Joint Committee on Cancer (AJCC) stage, Collaborative Ocular Melanoma Study (COMS) size, tumor largest basal diameter (LBD), and tumor thickness on prognostication by gene expression profiling (GEP) class. DESIGN: Two-center retrospective study. PARTICIPANTS: Two hundred fifteen consecutive patients diagnosed with posterior uveal melanoma over a 5-year period who were evaluated with prognostic fine-needle aspiration biopsy at the time of primary treatment. METHODS: Patient demographics, tumor clinical size, AJCC stage, COMS size, GEP class, presence of metastasis, and mortality data were collected. Metastasis-free-survival (MFS) was defined as time to metastasis or death from any cause. Comparisons were made using Pearson chi-square tests or Fisher exact tests for categorical factors, and t tests or Kruskal-Wallis tests for continuous measures. Cox proportional hazards models were fit to identify whether size measurements increased the prognostic discrimination index (C-statistic). MAIN OUTCOME MEASURES: Metastasis-free-survival. RESULTS: The average follow-up interval was 22.0 months (range, 12.0-37.0 months). Eighty-nine tumors were class 1A, 48 class 1B, and 78 class 2. Twenty-one patients developed metastatic disease detected by surveillance and confirmed by liver biopsy. Three-year MFS was 96% for class 1 and 63% for class 2. Five-year MFS was 96% for class 1 and 49% for class 2. All size measures significantly improved prognostic discrimination index by GEP class, as shown by increase in the C-statistic with addition of size variables (C-statistic 0.750 GEP alone, 0.830 GEP with AJCC [P = 0.016], 0.822 GEP with COMS [P < 0.001], 0.842 GEP with LBD [P <0.001], and 0.847 GEP with tumor thickness [P < 0.001]). Class 2 patients with metastasis had larger tumors compared with nonmetastatic class 2 tumors (AJCC class, P = 0.004; COMS class, P = 0.024; with metastasis mean thickness 6.5 mm [interquartile range (IQR), 3.8-9.5 mm]; without metastasis, 3.9 mm [SD, 3.1-6.0 mm]; P = 0.008), with metastasis mean LBD 14.9±2.8 mm, without metastasis, 12.3±2.7 mm (P < 0.001). All class 1 tumors with metastasis were large and required enucleation. CONCLUSIONS: Incorporation of tumor size enhances the prognostic discrimination index of the GEP test in patients with posterior uveal melanoma. All size tumor parameters are equivalent in their ability to enhance GEP prognostication.