Plaque Placement Research Articles

Novel 3D printed universal conical holder for eye plaque quality assurance

For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques. A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after explant. The explant reading was compared with the implant reading adjusted for decay, and the relative error was calculated. The plaque response fraction (PRF) is defined as the fraction of well chamber implant reading over the total seed strength for a plaque. The PRF was aggregated for each individual plaque to confirm the seed lot before implant. The reproducibility test showed the chamber reading's relative standard deviation of 0.40% with the QA holder compared to 0.68% without it. The batch relative assay was performed for 251 plaques. The absolute value of measurement deviation between explant and decay-corrected implant readings is 0.89%±0.86% (mean±standard deviation). The PRFs for individual plaques range from 36.49% to 49.87%, with a maximum standard deviation of 2%. This novel 3D-printed QA holder provides reproducible setup for assaying assembled eye plaques in a well chamber. Batch relative assay can validate the seed batch used and plaque integrity during the implant without assaying individual seeds, saving valuable physicist time and radiation exposure from seed handling.

Apical dose versus volume dose of Ruthenium-106 brachytherapy for uveal melanoma

ObjectiveRuthenium-106 brachytherapy is commonly used to treat uveal melanomas. Most centres prescribe a radiation dose to the tumour apex that is calculated with the tumour located in the centre of the plaque. Recent work suggests that D99%—the minimum radiation dose delivered to 99% of tumour volume—may be a better predictor of tumour control than apex dose. Both dosing regimens may be affected by tumour and treatment variables differently. We explored the effect of differences in these variables on volume and apex dose using a 3-dimensional planning model. MethodsThe time required to deliver 100 Gy to the tumour apices of representative tumours ranging from 2- to 6-mm thickness with central plaque positioning was calculated in Plaque Simulator™. This treatment time was used for further calculations, including D99% with central plaque placement, and apical and tumour volume doses when tumour and plaque characteristics were altered, including eccentric plaque placement, either away from (tilt) or along (offset) scleral surface, tumour shape, and plaque type. ResultsD99% was always greater than the apex dose when plaques were placed centrally, and the difference increased with tumour thickness. Increasing degrees of tumour offset reduced apical dose and D99%, with a greater effect on apical dose for thicker and D99% for thinner tumours, respectively. Differences in tumour shape and plaque type had idiosyncratic effects on apical and volume dosing. ConclusionD99% and apex dose are affected by tumour and treatment characteristics in different ways, highlighting the complexity of radiation delivery to uveal tumours.

Disinsert, retract and rotate technique of plaque brachytherapy.

Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed. The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas. The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration. In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque. https://youtu.be/YMIg3rYyp2o.

Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma

Brachytherapy with episcleral plaques is the most common primary tumor treatment for uveal melanoma. This study aims to compare the risk of tumor recurrence and metastatic death between two frequently used ruthenium-106 plaque designs: CCB (20.2 mm) and CCA (15.3 mm). Data were obtained from 1387 consecutive patients treated at XXX between 1981 and 2022 (439 with CCA and 948 with CCB plaques). During the period, scleral transillumination was performed to delineate tumor margins before plaque insertion, but no minimum scleral dose was used, and accurate plaque positioning was not verified after scleral attachment. Patients treated with CCA plaques had smaller tumors than those treated with CCB plaques (mean diameter 8.6 vs. 10.5 mm, P<0.001). There were no differences in patient sex, age, tumor distance to the optic disc, tumor apex dose, dose rate, or in rates of ciliary body involvement, eccentric plaque placement, or adjunct transpupillary thermotherapy. The average difference between plaque and tumor diameter was greater with the CCB plaque, and a smaller difference was an independent predictor of tumor recurrence. The 15-year incidence of tumor recurrence was 28% and 15% after treatment with CCA and CCB plaques, respectively (competing risk analysis, P<0.001). Multivariate Cox regression analysis revealed a lower risk for tumor recurrence with CCB plaques (HR 0.50). Similarly, patients treated with CCB plaques had a lower risk for uveal melanoma-related mortality (HR 0.77). Adjunct transpupillary thermotherapy did not reduce these risks. Uni- and multivariate time-dependent Cox regressions demonstrated that tumor recurrence was associated with uveal melanoma-related and all-cause mortality. Compared to 20 mm plaques, brachytherapy with 15 mm ruthenium plaques is associated with a higher risk for tumor recurrence and death. These adverse outcomes may be avoided by increasing safety margins and implementing effective methods to verify accurate plaque positioning.

Early treatment and toxicity outcomes for small posterior uveal melanomas treated using custom loaded eye plaques.

Iodine-125 loaded Collaborative Ocular Melanoma Study plaques can achieve excellent tumor control for patients diagnosed with uveal melanomas. Our ocular cancer team hypothesized that use of novel, partially loaded COMS plaques could ease and improve accurate plaque placement during treatment of small, posterior tumors while providing equivalent tumor control. Records of 25 patients treated with custom plaques were compared to 20 patients treated with fully loaded plaques, who had received treatment prior to our institution's adopting the use of these partial plaques. Tumors were matched with regards to location and dimensions as measured by the ophthalmologist. Retrospective analysis of dosing parameters, tumor control and toxicity outcomes were performed. There were no cancer related deaths, local recurrences or metastases in either cohort at an average follow up of 24 months for patients treated with custom plaques and 60.7 months for patients treated with fully loaded plaques. No statistically significant difference was found in regards to post-operative development of cataracts (χ2 = 0.76) or radiation retinopathy (χ2 = 0.22). Patients treated with custom loaded plaques noted significantly less clinical visual loss (χ2 = 0.006) and were more likely to have vision preserved at ≥20/200 (χ2 = 0.006). Treatment of small, posterior uveal melanomas with partially loaded COMS plaques results in equivalent survival and recurrence outcomes as treatment with fully loaded plaques, while exposing the patient to less radiation. Additionally, treatment with partially loaded plaques reduces the incidence of clinically significant visual loss. These promising early results support the use of partially loaded plaques in well-selected patients.

PO-2163 The effect of eccentric plaque placement on tumour dose in Ruthenium plaque brachytherapy

PO-2163 The effect of eccentric plaque placement on tumour dose in Ruthenium plaque brachytherapy

A Clinical Study of 50 Partially Edentulous Patients with Fixed Partial Denture Restorations to Compare Clinical Parameters and Changes in Gingival Sulcus Width After Displacement with 2 Different Gingival Retraction Cord Materials (Cotton and Polymer).

BACKGROUND The present study aimed to compare the clinical performance and gingival sulcus width changes in partially edentulous patients using cotton and polymer gingival retraction cords. MATERIAL AND METHODS Fifty partially edentulous patients were divided into 2 groups (Gp C and Gp P) and were subjected to single crown/fixed partial denture treatment. Clinical parameters, including plaque index scores, placement time, and hemorrhage control scores, were assessed. Gingival sulcus width changes before and after retraction were evaluated using individual type 4 dental stone dies observed under an optical microscope. Statistical analysis was performed using dependent/independent t tests. RESULTS The mean placement time, hemorrhage control time, and hemorrhagic scores were lower in Gp P than in Gp C, indicating better clinical performance of polymer-based retraction cord. Both groups showed an increase in sulcus width after retraction, but Gp P had a significantly higher sulcus width (690.03±45.37) compared to Gp C (471.38±28.13). The mean difference in sulcus width between baseline and after retraction was also significantly higher in Gp P (525.84 micrometers) than in Gp C (309.11 micrometers). CONCLUSIONS The present study shows that polymer-based cords produce more sulcus width and have better clinical performance compared to cotton-based gingival retraction cords. These results suggest that the use of polymer-based retraction cords can improve the quality of dental impressions in partially edentulous patients.

Ultrasound Verification of Plaque Brachytherapy Placement in Patients Treated for Primary Uveal Melanoma: A Single-Center Experience

Introduction: Proper plaque positioning is essential for effective episcleral plaque brachytherapy and can be verified using ultrasound. In this study, we show our center’s protocol for intraoperative ultrasound verification of plaque placement and present our single-center local recurrence data in patients with primary UM involving the choroid and/or ciliary body. We also indicate our center’s distance metastasis rate for patients presenting with primary UM. Methods: All patients who presented to our institution with UM of the choroid and/or ciliary body between May 2017 and March 2022 and treated with plaque brachytherapy were enrolled. Endpoints include the 24-month local recurrence-free rate (primary) and 24-month metastasis rate (secondary), both estimated using the Kaplan-Meier method (KM). Results: Local Recurrence: 176 patients met the study criteria with median follow-up of 23.2 months. The 24-month recurrence-free probability for this cohort was estimated at 99.1% (95% confidence interval: 0.974–1.00). Metastatic Recurrence: 136 of these patients underwent at least one follow-up surveillance scan. The 24-month metastasis-free survival probability in our cohort was estimated at 87% (95% confidence interval: 81–94%). Conclusions: We show improved local control utilizing ultrasound verification compared to historical controls who received TTT and brachytherapy without intraoperative ultrasound confirmation.

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

1) To describe the technique of post-operative 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. Retrospective review SUBJECTS: 372 consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from 8/2008-2/2019. Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n=355) underwent intra-operative ultrasound to confirm plaque placement, and additional post-operative ultrasound on day 1-3 post plaque insertion. In cases where intra-tumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to less than 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with need for plaque adjustment. Variables associated with plaque dose needing to be re-calculated, local tumor control, and visual acuity outcomes. In 31 cases (8.3%), post-operative echography showed the tumor apex had shifted outside of 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 (COMS) 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 to those that were not adjusted (median 4.9 mm versus 3.0 mm, p<0.01). Local tumor control was 99% (95% CI: 97-100%) at 5 years and 99% (95% CI: 97-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥3 lines of vision or had less than 20/200 acuity was 14.9% at one year post brachytherapy, 35.3% at three years, and 51.6% at five years. Post-operative ultrasound performed on post-operative day 1-3 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.

Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies.

Quantifying the effect of eccentric ruthenium plaque placement on tumor volume dose.

Ruthenium-106 brachytherapy is a common treatment for small to medium-sized uveal melanomas. In certain clinical contexts, plaques may be placed eccentrically to tumor center. The effect of plaque decentration, a common radiation dose measurement in radiotherapy: D98%, the percentage of the tumor volume receiving at least 98% of the prescribed dose (a commonly used term in radiation oncology), is unknown. We investigated this using two commonly used plaques (CCA and CCB; Eckert & Ziegler, BEBIG GmbH) in silico. Using a Plaque Simulator™ (Eye Physics) plaque modelling software, treatment time required to deliver 100 Gy D98% with central plaque placement was calculated for both plaque models, treating tumors with basal dimensions of 10 mm (CCB plaque only) and 7 mm (CCA and CCB plaques), and a range of thicknesses. D98% was calculated for plaque-tumor edge distances of 0-5 mm. Additionally, we defined minimum plaque-tumor edge distances, at which D98% fell by 10% and 5% (safety margins). D98% decreased as plaque-tumor edge distance decreased, i.e. as plaque eccentricity increased. Minor (< 1 mm) plaque decentration caused minimal D98% changes across tumor thicknesses. Safety margins did not follow a consistent pattern. Eccentric plaque placement reduces the radiation dose delivered to choroidal tumors. Both tumor (thickness, diameter) and plaque (size, location) characteristics are important D98% modulators. Further investigation of the effect of these characteristics and dose to organs at risk is essential.

PHSOR07 Presentation Time: 1:00 PM: Feasibility of Using Dual-Activity Seed Loading When Using Eye Physics Eye Plaques and Plaque Simulator Treatment Planning in Eye Plaque Brachytherapy

<h3>Purpose</h3> Uveal melanoma is a tumor of the eye commonly treated with the application of gold plaques loaded with radioactive I-125 seeds. This study evaluates the dosimetric impact of incorporating dual-activity seed loading in Eye Physics eye plaques under two clinical scenarios that may benefit from this dual-activity approach. <h3>Materials and Methods</h3> Plaque Simulator (Eye Physics, LLC, Los Alamitos, CA) was used to retrospectively re-plan 10 clinical cases for two clinical scenarios: 1) shallow (<5.5 mm) tumors with large base dimensions (16 mm - 19 mm) planned with the largest plaque available from Eye Physics (EP2342 in Fig.1), and 2) tumors very near the optic nerve planned with EP2029N notched plaque (Fig. 1). Five clinical plans were selected for each clinical scenario. The clinical plans chosen were prescribed to at least 2 mm deeper depth than the tumor apex in order to achieve target (base + 2 mm margin) coverage of at least 95%. In the replanning, some of seeds in the plaque were replaced with higher activity seeds. For Scenario 1), EP2342 plaques were planned with the outer ring of sources at twice the activity of the inner sources. For Scenario 2), EP2029N plaques were planned with the 6 seeds closest to the notch at twice the activity of the other sources. Seed loading was kept symmetric for ease of loading, QA, and plaque placement. Plans were based on retinal sketches rather than digitized directly from retinal imaging, so the exact dose to critical structures is an estimate, but the direction and approximate magnitude of the dose change can be analyzed. <h3>Results</h3> In all the cases of large shallow tumors for Scenario 1), the dual-activity plan was able to decrease the prescription depth by 0.8 mm to 1.3 mm. Therefore, doses to all critical structures were consistently lower in dual-activity plans: inner sclera -24.6% ± 1.6%, optic disc -6.5% ± 2.5%, fovea -6.0% ± 3.3% (average ± standard deviation). In 3 out of 5 tumors close to the optic nerve for Scenario 2), the dual-activity plan was able to decrease the prescription depth by 0.5 mm to 0.7 mm. In all 5 of these cases, dose to inner sclera was consistently lower in the re-plans by 20.9%±5.6% and dose to the optic disc and fovea were consistently higher by 19.3%±7% and 21.8%±11.4% respectively. <h3>Conclusions</h3> For large shallow tumors, critical structure dosimetrics were constantly improved due to shallower prescription depth by partially loading with higher activity seeds. The largest dose reduction occurs to the inner sclera since it is close to the plaque, but changes in other critical structures were patient-specific depending the location of the tumor in the eye. It may be beneficial to always plan tumors such as these with dual activities. As this is the largest plaque offered by Eye Physics, this planning approach may allow it to be used for larger tumors while still maintaining reasonable dose to critical structures. For tumors near the optic nerve, the results showed that although scleral dose was decreased, dose to optic disc and fovea were increased. As this difference is due to the location of the tumor relative to the optic nerve and the fovea, it may be beneficial to investigate dual activity plans on a case-by-case basis if scleral dose is a concern for that particular patient.

Relationship between gene expression profile class and tumor thickness regression after plaque brachytherapy for choroidal melanoma

Background and objectiveTo examine the relationship between gene expression profile class and tumor thickness reduction as measured by ultrasonography in response to plaque brachytherapy using a single-center, retrospective cohort study.MethodsA total of 15 patients with choroidal melanoma who underwent biopsy for gene expression profiling and were treated with plaque brachytherapy from a single institution from 12/8/14 through 12/19/19 were retrospectively reviewed for clinical characteristics and rate of tumor regression. Ultrasonographic B-scan tumor height was recorded just prior to plaque placement and following plaque removal in the patient’s chart to assess percent reduction in tumor thickness from baseline.ResultsA total of 15 patients met inclusion criteria and were analyzed in this study. Minimum follow-up was 6 months after plaque removal. The percent regression in tumor thickness from baseline as measured by ultrasonography was greater for class 2 tumors than for class 1 tumors at 12-month follow up after treatment, and this difference was statistically significant (P = 0.012). There was no statistical significance in reduction at 3 months (P = 0.46) and 9 months (P = 0.10) after plaque brachytherapy. Although not statistically significant, class 2 tumors appeared to regress more rapidly than class 1 tumors in response to radiation.ConclusionsIn this study, class 2 choroidal melanoma tumors show a more rapid anatomic response to treatment than class 1 tumors at 12 months post plaque brachytherapy.

Abstract 1967: Potential of aqueous humor as a liquid biopsy for uveal melanoma

Abstract Introduction: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and arises from the uvea (iris, ciliary body and choroid). Although there are prognostic biomarkers available, identifying them requires intraocular tumor biopsy. Blood biopsy has emerged as a significantly less invasive alternative that also offers the ability to longitudinally track disease. However, blood biopsy has been unsuccessful for clinical use in identifying prognostic biomarkers in UM due to low detection rates. Thus, eye-specific aqueous humor (AH) biopsy may be a better alternative. Methods: This case series includes 20 primary UM patients with 13 (65%) choroid and 7 (35%) ciliary body (CB) tumors. AH samples were collected prior to brachytherapy plaque placement (n = 17), after brachytherapy (n = 19) and at enucleation (n = 1). A tumor wash sample (n = 1) was collected after routine fine needle aspiration biopsy. Nucleic acids ([NA], dsDNA, RNA, ssDNA and miRNA) were quantitated by Qubit Assay Kits. All AH samples and cells from tumor washing underwent DNA isolation and was followed by shallow whole-genome sequencing for copy-number profiling. Results: Comparison of pre- and post-radiation samples revealed significantly higher concentration of ssDNA (n = 10 pairs, P = 0.039) and miRNA (n = 10 pairs, P = 0.008) in choroid post- samples and significantly higher concentration of dsDNA (n = 7 pairs, P = 0.031) and miRNA (n = 7 pairs, P = 0.016) in CB post- samples. Between choroid (n = 12) and CB (n = 7) post- samples, there was a significantly higher concentration of dsDNA (P = 0.022) and RNA (P = 0.009) in post- CB samples, suggesting NA content is released from the disturbance of tumor cells by radiation and due to the proximity of the tumor to the AH in CB. Highly recurrent UM somatic copy number alterations (SCNAs) of monosomy 3, 6p gain, 6q loss and 8q gain were identified in post- AH samples. There was a significant difference between altered SCNA profiles in CB and choroid (P= 0.038). Altered SCNA profiles were found in 1/12 (8.3%) and 4/7 (57.1%) post-radiation AH samples of choroid and CB, respectively. No SCNAs were found in the same eyes’ pre-radiation sample. A high concordance of DNA profiles between a tumor wash and post- AH sample was identified (r = 0.978) and UM mutations GNAQ and BAP1 were detected in 3/6 (50%) post- AH with 2/5 (40%) matching tumor samples, demonstrating AH dsDNA’s tumor-origin. Conclusions: The AH is a source of cfDNA, with a higher yield of NAs after radiation in UM. Given the significant increase in NA concentration after radiation and in CB compared to choroid tumors, we hypothesize that all detected NAs post-radiation are tumor-derived due to apoptosis of tumor cells and subsequent release of cfDNA and due to the proximity of the CB tumor to AH. These results represent the first time that UM SCNAs and mutations were identified in cfDNA isolated from the AH, and this suggests that the AH can serve as a liquid biopsy for UM, especially in CB tumors. Citation Format: Deborah H. Im, Chen-Ching Peng, Liya Xu, Mary E. Kim, Dejerianne Ostrow, Venkata Yellapantula, Moiz Bootwalla, Jaclyn A. Biegel, Xiaowu Gai, Peter Kuhn, James Hicks, Jesse L. Berry. Potential of aqueous humor as a liquid biopsy for uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1967.

Monte Carlo simulation of tilted contact plaque brachytherapy placement for juxtapapillary retinoblastoma

BackgroundThe 106-Ruthenium contact plaque applicator is utilized for the treatment of intraocular tumor within a thickness of less than 6 mm. If anything obstructs the placement of the plaque applicator, the treatment is generally difficult because the applicator has to be temporarily located just on the opposite side of the retinal tumor. Furthermore, the plaque applicator edge of approximately 1 mm does not contain 106Ru, estimating the delivered radiation dose for eccentric tumor is challenging because the lateral dose profile is inadequately provided by the manufacture’s certification. This study aims to simulate tumor coverage of the tilted applicator placement for treating an infant with juxtapapillary retinoblastoma and to achieve the effective treatment.Case presentationWe present an infant with retinoblastoma whose tumor involved macular and was invading just temporal side of the optic disc. Additionally, posterior staphyloma was induced by a series of previous treatments, making it more difficult to treat the standard plaque placement. Thus, the applicator type of CCA was intentionally tilted to the eyeball and the distance between the posterior edge of the applicator and the eyeball had to be then equal to or more than 2 mm based on the dose distribution of the applicator calculated using Monte Carlo simulation to minimize damage to surrounding tissues while covering the tumor. It was then comparable to the certification and previous reports. Based on the acquired dose distribution, the optimal placement of the applicator was derived from varying the distance between the applicator’s edge and the eyeball, and the distance was then determined to be 2 mm. In this case, the minimum dose rate in the tumor was 25.5 mGy/min, and the time required to deliver the prescribed dose was 26.2 h. Therefore, the tilted 106Ru plaque applicator placement could deliver the required dose for the treatment. The physical examination revealed no active tumor as a result of the treatment.ConclusionsOptimizing the placement of the 106Ru plaque applicator, it was possible to guarantee that the prescribed dose will be delivered to the tumor even if the standard placement is not possible for the juxtapapillary tumor.

Abstract 554: Aqueous humor as a liquid biopsy for uveal melanoma

Abstract Purpose: Metastatic Uveal Melanoma (UM) is usually fatal within one year of symptom onset. There are a variety of biomarkers that can stratify patients' metastatic risk, but identifying them requires intraocular tumor biopsy. Liquid biopsy offers a less invasive alterative without the risks of retinal detachment and intraocular hemorrhage. We investigated whether the aqueous humor (AH) has sufficient tumor-derived cell-free DNA (cfDNA) to function as a liquid biopsy for UM. Methods: This case series includes 12 AH samples from 7 eyes of 7 UM patients from whom AH was sampled during routine brachytherapy plaque placement and/or removal. Double stranded DNA (dsDNA), single stranded DNA (ssDNA), RNA, and microRNA (miRNA) were quantified with respective Qubit High Sensitivity Assay Kits (Thermo Fischer) for each sample. The lower limit of detection was 0.01 ng/µL for dsDNA, 0.05 ng/µL for ssDNA, 0.25 ng/µL for RNA, and 0.05 ng/µL for miRNA. CfDNA was then isolated and sequenced on an Illumina platform to assess genome-wide somatic copy number alterations (SCNAs). Results: Aqueous humor derived cfDNA was detected in all samples, ranging from 0.085-28.8 ng/µL (mean = 2.7 ng/µL). RNA was detected in 2 of 12 samples (mean = 1.6 ng/µL, range = 0.7-2.5 ng/µL), and miRNA was detected in 11 of 12 samples (mean = 1.7 ng/µL, range = 0.094-16.2 ng/µL). There was a significantly higher cfDNA concentration in post-radiation samples than pre-radiation samples, (median = 0.082 ng/µL in pre-radiation, 0.21 ng/µL in post-radiation, W = 1, z = -2.55, p &amp;lt; 0.05, Wilcoxon Signed-rank test). This finding was similar when comparing all nucleic acid concentrations (dsDNA, ssDNA, RNA, and miRNA) between pre- and post-radiation (median = 0.085 ng/µL in pre-radiation, 0.333 ng/µL in post-radiation, W = 1, z = -3.46, p = 0.00027). Confirmed UM genomic alterations of 6p gain, 6q loss, and 8q gain were identified in one post-radiation AH sample from an eye with an iridociliary body tumor. These SCNAs are characteristic of UM. No SCNAs were found in the AH from the pre-radiation sample in the same eye, or any of the other AH samples sequenced to date. Conclusions: The AH is a source of cfDNA in eyes with UM, with a higher yield of all nucleic acids detected after brachytherapy radiation treatment. UM associated SCNAs were identified in the AH of one eye with an iridociliary tumor after radiation only. We hypothesize this may be due to intratumoral necrosis from the radiation as well as the proximity of the primary tumor to the AH in the case where SCNAs were identified. These results represent the first time that UM SCNAs have been identified in cfDNA isolated from the AH, and this provides preliminary evidence that the AH can serve as a liquid biopsy for UM. Citation Format: Mary E. Kim, Liya Xu, Chen-Ching Peng, Peter Kuhn, James Hicks, Jesse L. Berry. Aqueous humor as a liquid biopsy for uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 554.

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy

PurposeBrachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement. Methods and MaterialsSix patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion. ResultsPlaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0–5.2], 5.10 mm ± 0.26 [4.9–5.4], and 5.33 mm ± 0.45 [4.9–5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5–5.1], 4.13 mm ± 1.42 [2.5–5.1], and 4.2 mm ± 1.21 [2.8–5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0–0.5] and 0.63 mm ± 0.60 [0.7–1.2] for posterior and anterior lesions, respectively. ConclusionsFusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.

Histologic Findings of Choroidal Vasculopathy in Eyes Enucleated following Radiation Therapy for Uveal Melanoma: Radiation Choroidopathy.

Little has been published about the choroidal vascular changes that occur years after radiation exposure. The aim of this study was to review the histological changes observed in the choroidal vasculature following radiotherapy for uveal melanoma. Records from a single institution were retrospectively reviewed from June 7, 2007 to June 7, 2017; 101 patients with a diagnosis of uveal melanoma that underwent enucleation had their records reviewed. Out of these, a total of 26 eyes had undergone plaque brachytherapy prior to enucleation, which had been performed at a mean time of 7.2 years (range from 0 years to 30 years) after the initial plaque placement. A histopathologic analysis was conducted on all 26 eyes with special emphasis on the choroidal changes. Of these 26 eyes, 18 demonstrated evidence of radiation-induced vasculopathy. Of the 18 eyes, 10/18 (55%) had radiation retinopathy and 16/18 (89%) had radiation choroidal vasculopathy. One patient had a phthisical eye, and the choroid could not be evaluated because the characteristics of the vasculature could not be determined. Nine cases had vitreous hemorrhage (50%), all cases had radiation retinopathy, and 8/9 (89%) had radiation choroidopathy. Of the 16 cases with radiation choroidal vasculopathy, 3/16 (19%) had only intratumoral radiation choroidal vasculopathy, 3/16 (19%) had only extratumoral radiation choroidal vasculopathy, and, thus, 10/16 (32%) had both intratumoral and extratumoral radiation choroidal vasculopathy. In patients with radiation choroidal vasculopathy, 2/16 (13%) had hyalinization of the choroidal vessels. Another 3/16 (19%) cases with radiation choroidal vasculopathy had ectatic vessels. The other 11/16 (68%) had evidence of both hyalinization of the choroidal vessels as well as ectatic vessels in the choroid. Histological evidence of radiation retinopathy and choroidopathy were seen in 69% of eyes enucleated after receiving radiation therapy, which, in some cases, also had vitreous hemorrhage. Polypoidal choroidal vasculopathy, choroidal neovascularization, and retinal choroidal anastomoses (RAP-type lesions) were seen in 12 of the 16 eyes (75%). Irradiation of malignant tumors of the eye causes not only radiation retinopathy but also radiation choroidopathy. The role of radiation choroidopathy in the subsequent visual loss following radiotherapy and the role of anti-VEGF therapy needs to be recognized and distinguished from radiation retinopathy. Our data adds to the prior limited knowledge that radiation affects the choroid and can induce specific phenotypes similar to the clinical spectrum of CNV, PCV, and RAP.

Choroidal melanoma treatment in times of coronavirus disease 2019.

Choroidal melanoma treatment in times of coronavirus disease 2019.

Intra-operative ocular ultrasonography of iodine-125 brachytherapy plaques in patients with uveal melanoma.

PurposeBrachytherapy with iodine-125 (125I) has been extensively used as a conservative treatment for uveal melanoma (UM). Surgical technique for correct placement of episcleral radioactive plaques (ERP) in UM cases with posterior choroidal location and/or small size can be difficult and inaccurate. In this study, the correct positioning of plaques was assessed by intra-operative ultrasound control.Material and methodsThis was a longitudinal, retrospective study of consecutive 20 patients with UM (small-medium size and/or posterior location) who received 125I brachytherapy. Location of plaques was adjusted by intra-operative ocular ultrasonography control. To perform ocular intra-operative ultrasonography, a 10 MHz probe was used to longitudinal and transverse bases in corresponding dummy plaques.ResultsThe study included 8 males and 12 females, with a mean age of 66.3 years (SD = 14.53), 5 right eyes (RE) and 15 left eyes (LE). In ultrasound examination, 4 UMs were of mushroom morphology and the rest nodular. Means of the size of UM by ultrasound were (mm): Lb: 10.60 (SD = 2.24) × Tb: 9.88 (SD = 1.54) × H: 4.02 (SD = 1.44) (3 cases corresponding to small size of collaborative ocular melanoma study (COMS), and 17 cases to medium). The plaques used were between 14 and 20 mm in diameter, with an average distance between the edge of greater base of the tumor and the edge of plate of 2.44 mm (SD = 0.34). It was necessary to surgically reposition the plaque in 4 cases (20%).ConclusionsIntra-operative ultrasound control improves the accuracy of radioactive plaque placement for the treatment of medium-small UMs in posterior location. Probably, this technique should be applied in all cases of brachytherapy, regardless of the isotope chosen and the location of tumor mass, in order to perfectly adjust therapeutic position.