Plaque Brachytherapy Research Articles

Class 2 Gene Expression Profile of a Hemorrhagic Pigment Epithelial Detachment Misdiagnosed as Melanoma

Abstract Purpose To describe a case of a hemorrhagic pigment epithelial detachment that was initially misdiagnosed as a choroidal melanoma and had a class 2 gene expression profile (GEP) on prognostication fine needle aspiration biopsy (FNAB). Methods Retrospective case report Results A 79-year-old man with a history of atrial fibrillation treated with warfarin presented for guidance regarding systemic surveillance after undergoing prognostic FNAB at the time of episcleral plaque brachytherapy for a presumed cilio-choroidal melanoma. The results of GEP testing were consistent with a class 2 molecular profile. At three month and eight month follow up, the clinical, echographic, and optical coherence tomography (OCT) findings were consistent with a hemorrhagic pigment epithelial detachment (PED) rather than melanoma. By eight months, the lesion had completely resolved. Conclusions This is the first reported case of a GEP class 2 profile obtained from prognostic FNAB of a non-malignant lesion. Given that GEP is not a diagnostic test, it and can lead to erroneous prognostic information in the setting of non-melanoma choroidal lesions.

Real-World Plaque Brachytherapy Clinical Practices among Ocular Oncology Study Consortium Treatment Centers

Real-World Plaque Brachytherapy Clinical Practices among Ocular Oncology Study Consortium Treatment Centers

TCP and Dose Response after Brachytherapy for Choroidal Melanoma

Brachytherapy is a commonly used eye-preserving treatment for choroidal melanomas. We hypothesized that the minimum tumor dose is related to risk of tumor recurrence. We studied consecutive patients with primary choroidal melanomas, treated with Ru-106 plaque brachytherapy from 2005 to 2014 at a single institution to an apical dose of 100 Gy. Plans were retrospectively created using 3D image-guided planning software. Pretreatment retinographies were used to contour the tumor; posttreatment retinographies to determine the accurate plaque position. Dose volume histograms were extracted. Patient and tumor characteristics, treatment details, and clinical outcomes were extracted from patient records. All patients were followed regularly until death or study cut-off (Jan 2018). Biologically effective doses (BED) were calculated using source half times, tissue specific factors (α/β=11.5 Gy, T1/2=1.5h), and a well-established model (Gagne et al, Med Phys, 2012) The relationship between tumor dose and risk of recurrence was examined using multivariate Cox regression modelling. Minimum physical dose to the tumor (D99%), transpupillary thermotherapy (TTT), tumor height, largest base dimension, incident eye, and gender were included in the model. Model robustness was assessed by considering alternative dose metrics, BED, and by taking the competing risk of death and TTT during follow-up into account (Aalen-Johansen estimator for cumulative incidence and Fine & Gray’s model for regression analysis). We included 227 patients (108 females, 110 right eyes), with median treatment time of 120h (IQR: 74-191). Median tumor height and largest base dimension were 4 mm (IQR: 3-6) and 11 mm (IQR: 9-13). Median follow-up time was 4.9 years. The estimated 3-year local control was 80% (95% CI: 75-86). The median D99% was 104 Gy (IQR: 63-138); this was the only significant factor associated with recurrence in multivariate modelling (p=0.0007). Hazard ratio (HR) for 10 Gy increase in D99% was 0.90 (95% CI:0.84-0.96). Estimated 3-year local control for D99%=50 Gy and D99%=100 Gy were 70% (95% CI: 58-85) and 81% (95% CI: 73-91), respectively. The median BED99% was 145 Gy (IQR: 73-196); using BED99% in the multivariate model gave no substantial differences in estimates (HR 0.93 (95% CI: 0.90-0.97, p=0.001). Robustness checks with D1-99% and BED1-99% showed D99% and BED99% to be the most significant dose metrics for recurrence. Competing risk analysis showed cumulative incidences at 3 years for recurrence, death, and TTT of 17% (95% CI: 12-22), 14% (95 % CI: 9-18), and TTT 6% (95% CI: 3-9). Accounting for death and TTT, D99% remained the only significant factor for recurrence (p=0.0004), with HR for 10 Gy increase in D99% of 0.90 (95% CI: 0.85-0.95). The minimum dose to the tumor correlated strongly with risk of tumor recurrence, with 100 Gy needed to ensure at least 80% local control at 3-years.

Novel Eye Plaque Designs for Brachytherapy of Iris and Ciliary Body Melanoma and the First Clinical Application

Background: While traditional eye plaque brachytherapy can be used for the treatment of iris melanoma, it faces challenges of poor patient tolerability due to cornea-plaque touch caused by radius of curvature mismatch and potential dosimetric inaccuracy from incomplete coverage. We present novel plaque designs and the first clinical application of the plaques for iris melanoma. Methods: Two dome-shaped plaques (EP2132 and EP1930) were designed to vault above the cornea to treat tumors of the iris and ciliary body. Image-based treatment planning of the first 2 clinical cases using the EP2132 plaque covered the tumor base plus a 2 mm margin and the involved ciliary body with at least 75 Gy to the tumor apex. Results: The tumors decreased in size following treatment. The patients tolerated the treatment well. There was no adverse event associated with the traditional iris plaques, such as decreased vision, pain, corneal edema, glaucoma, or cataract. Conclusion: The novel dome-shaped plaques for the treatment of iris melanoma provide effective dose distribution, improved surgical maneuverability, and increased tolerability for the patient. This plaque model can be used to treat iris melanoma of various sizes, configurations, and locations, including the ciliary body. The need for a customized plaque platform for each patient is minimized.

99mTc-3PRGD2 single-photon emission computed tomography/computed tomography for the diagnosis of choroidal melanoma: A preliminary STROBE-compliant observational study.

Recent successes in monitoring and diagnosing a variety of tumors using 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) imaging encouraged us to expand the use of this tracer. This case-control study aimed to evaluate the feasibility of 99mTc-3PRGD2 imaging for detecting choroidal melanoma (CM) and for monitoring tumor response to plaque brachytherapy (PB). Ten consecutive patients with CM who underwent 99mTc-3PRGD2 imaging before and 3 months after PB were reviewed. The tumor-to-occipital bone (T/O) and mirrored contralateral normal tissue-to-occipital bone (N/O) ratios were calculated by region of interest analysis at baseline and 3 months post-PB. T/O values were compared between patients with CM with comorbid secondary retinal detachment (RD) and those without RD. The relationship between T/O value and tumor volume was also investigated. 99mTc-3PRGD2 SPECT/CT showed focal uptake in CM. The mean T/O ratio before PB was 1.90 ± 1.26 and the mean N/O ratio was 0.80 ± 0.21 (P = .02). The 99mTc-3PRGD2 concentrations in 5 patients with CM with RD were higher (T/O = 2.69 ± 1.39) than in those without secondary RD (T/O = 1.10 ± 0.18) (P = .008). T/O ratios at 3 months post-PB were significantly lower than that at baseline (1.23 ± 0.59, P = .03). There was a linear relationship between T/O and tumor volume (y-hat = 0.028 + 0.003x, R2 = 0.768, P = .001). The 95% confidence interval for the (T/O)/volume ratio was 0.002 to 0.005. 99mTc-3PRGD2 imaging is a feasible modality for the diagnosis of CM. Furthermore, follow-up for at least 20 months after PB indicated that coanalysis of 99mTc-3PRGD2 imaging and tumor volume may provide a promising prognostic predictor in patients with CM.

Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling. A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor. The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively. Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

Purpose: To describe our early experience with gene expression profiling (GEP) assessment for juxtafoveal, subfoveal, and peripapillary indeterminate high-risk melanocytic lesions to assist in making early treatment decisions in patients who did not feel comfortable with either close observation or definitive treatment. Methods: A prospective cohort of patients with indeterminate lesions who underwent GEP were enrolled. Nonparametric statistical analysis was utilized given the small sample size. Results: Fifteen patients were included in this series. Six (40%) were class 1A and 9 (60%) class 1B. Class 1A and 1B lesions had a median of three and four clinical risk factors, respectively (p = 0.27). There was no statistically significant difference for the largest basal diameter between the classes (p = 0.31); however, class 1B lesions were thicker than class 1A lesions (p = 0.03). None of the class 1A lesions showed definite growth or metastasis over a mean follow-up period of 17.1 ± 1.8 months from fine needle aspiration biopsy. All class 1B patients opted for plaque brachytherapy, and to date none of these patients have developed metastasis, with a mean follow-up of 18.7 ± 8.4 months. Conclusion: There may be a role for GEP assessment in high-risk, indeterminate, posteriorly located choroidal lesions to assist in treatment planning.

Prior non-irradiative focal therapies do not compromise the efficacy of delayed episcleral plaque brachytherapy in retinoblastoma

Background/aims Non-irradiative local therapies have shown promise in delaying or supplanting external beam radiotherapy (EBRT) and enucleation in patients with retinoblastoma. We hypothesised that prior focal therapy does not compromise...

First Clinical Application of a Novel Eye Plaque -EP2132- Designed for Iris Tumor Treatment

Eye plaque brachytherapy has been one of the most common and effective treatment approaches for intraocular tumors. When treating iris melanoma, it requires the plaque be placed onto the cornea and ensure a 2- to 3-mm margin around the tumor. Because the curvature of a plaque is normally designed to conform onto the sclera, it can be difficult to fit and suture onto a large area of the cornea. The patients often feel painful with a metal plaque on cornea. A dome shaped plaque (model EP2132) has been designed to arc above the cornea to treat tumors of the iris. We present the first clinical case using this plaque with image-based treatment planning.

Episcleral Plaque Brachytherapy for Diffuse Choroidal Hemangioma: Case Report, the Utility of MRI, and Review of the Literature

Episcleral Plaque Brachytherapy for Diffuse Choroidal Hemangioma: Case Report, the Utility of MRI, and Review of the Literature

Fast Verification of Eye Plaque Assembly and Seed Strength Using a Novel Device

Eye plaque brachytherapy is commonly performed by mounting high-strength seeds onto gold plaques, which are then sterilized and temporarily applied to the patient’s eye. The plaques are either assembled in-house, or ordered pre-assembled. The QA of eye plaque construction is usually performed visually, and is therefore susceptible to difficulty in visualization of the seeds. Moreover, incorrect mixing of different seed activities cannot be detected. We recently introduced in our clinic a novel device designed within a multi-center collaboration. We report preliminary results in the fast and accurate verification of both the construction and seed loading pattern. The method is applicable to all types of eye plaques and seed models.

Gamma Knife radiosurgery for locally recurrent choroidal melanoma following plaque radiotherapy

BackgroundFor the majority of eyes with choroidal melanoma, radiation therapy is the treatment of choice. Local recurrence after radiation therapy can occur, however, and when it does, salvaging the globe with useful vision is atypical.Case presentationWe report a case of late, local failure 7 years following previous brachytherapy successfully managed with Gamma Knife radiosurgery (GKR). With 3 years of follow up after GKR, the visual acuity is 20/20 and there is no evidence of systemic metastases.ConclusionTo our knowledge, this is the first report of successful salvage GKR therapy after brachytherapy failure in an eye with choroidal melanoma. GKR is an option for select cases of local recurrence after radiation plaque brachytherapy.

Trends in Radiation Practices for Female Ocular Oncologists in North America: A Collaborative Study of the International Society of Ocular Oncology

Background: The aim of this study was to determine the known radiation exposure, attitudes, and consequent risk modifications among female ocular oncologists in North America who routinely administer radioactive plaque brachytherapy treatment and are members of the International Society of Ocular Oncology. Methods: Nineteen female ocular oncologists completed an anonymous 17-question radiation exposure survey. Results: Eleven of the participants chose to routinely wear lead protection during surgery; 8 did not. Fifteen of 19 participants reported using an unloaded “nonactive” template to prepare for plaque implantation. During pregnancy, 11 of 13 participants continued to perform plaque brachytherapy. Eight of these 11 undertook measures to decrease radiation exposure self-reported as lead wear and other. The average reported anxiety regarding fertility was 2.1 (SD, 2.2) on a scale from 1 to 10. Conclusion: This study corroborates prior literature that surgeons’ exposure to radiation during plaque brachytherapy is minimal. Nonetheless, there remains some anxiety regarding exposure risk to women, due to potential effects on fertility and fetal health. We found variability in exposure monitoring, required training, and precautions during pregnancy amongst this group of surgeons. Improved education and clearer pregnancy guidelines may equip female ocular oncologists with optimal knowledge regarding risk of radiation exposure.

The Use of Intravitreal Anti-VEGF and Triamcinolone in the Treatment of Radiation Papillopathy

Background/Aims: To evaluate a treatment regimen for radiation papillopathy. Methods: This is a prospective noncomparative interventional case series of patients who developed radiation papillopathy after plaque brachytherapy for uveal melanoma. Treatment consisted of intravitreal bevacizumab (IVB) (1.25 mg in 0.05 mL) at the time of diagnosis, and 1 week later, intravitreal triamcinolone (IVK) (2.00 mg in 0.05 mL). One month later, patients again received both IVB and IVK. Patients were then switched to monotherapy with monthly IVB until the papillopathy resolved. Results: Eleven patients developed radiation papillopathy, with 9 receiving treatment. On multivariate analysis, total radiation dose to the optic nerve was the only significant predictor of papillopathy (p = 0.005). Four of nine patients presented with a significant decline in visual acuity (VA) at the time of diagnosis of papillopathy. In all 4, significant improvement was documented following treatment. Five patients did not present with a decrease in VA, and in this group, 80% remained stable with treatment. Conclusions: In this series, patients who had a precipitous drop in VA at the time of diagnosis of radiation papillopathy returned to baseline VA following this treatment algorithm. This protocol was effective at maintaining stability of VA in 80% of those who developed papillopathy but did not present with an acute drop in VA.

Regression patterns of choroidal melanoma: After palladium-103 (103Pd) plaque brachytherapy.

Purpose:To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy.Methods:Retrospective interventional case series including 170 consecutive patients treated with 103Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology.Results:The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2–11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0–7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% (n = 86/170), amelanotic in 10% (n = 17/170), and variably pigmented in 39% (n = 67/170). Tumor pigmentation increased in 64% (n = 106/166), decreased in 18% (n = 30/166), and was unchanged in 18% (n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% (n = 12/120) had decreased tumor-related vascularity and 90% (n = 108/120) showed complete resolution. Subretinal fluid was present in 34% (n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% (n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% (n = 91/149) showed increased reflectivity on regression. We noted a crescendo–decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis.Conclusion:Findings related to choroidal melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound.

Early ultrasonographic tumor regression after linear accelerator stereotactic fractionated photon radiotherapy of choroidal melanoma as a predictor for metastatic spread

Background and purposeDuring extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. Material and methods256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. ResultsNAC for tumor thickness at months 3, 6, and 12 had a statistically significant (p < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. ConclusionsOur results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk.

Plaque brachytherapy for posterior uveal melanoma in 2018: improved techniques and expanded indications.

Plaque brachytherapy remains the dominant globe-sparing therapy of uveal melanoma. This report highlights recent advances, which have expanded plaque brachytherapy's uses as well as improved the surgical technique. Plaque brachytherapy is effective for tumors that may previously have demanded enucleation. Plaque brachytherapy can be used to control large melanomas as well as melanomas touching the optic nerve. Improvements in planning and design have made plaque therapy simpler for the surgical operator and may reduce collateral radiation damage to normal ocular structures. The COMS implies a required dose of 85 Gy to the tumor apex for treatment of uveal melanoma. However, multiple reports indicate that lower doses may be equally effective for tumor control while reducing radiation dose to uninvolved structures. Vitreoretinal surgeons can be called upon safely to treat long-term side effects of radiation or tumor death such as intractable vitreous hemorrhage or inflammation. Further, vitreoretinal surgeons have employed tumor endoresection as primary local tumor control or in combination with plaque brachytherapy. Plaque brachytherapy for uveal melanoma remains highly effective for local tumor control and prevention of metastasis. Indications for plaque brachytherapy have expanded, and the technique has improved.

Recent advancements in the management of retinoblastoma and uveal melanoma.

Retinoblastoma and uveal melanoma are the most common intraocular malignancies observed in pediatric and adult populations, respectively. For retinoblastoma, intra-arterial chemotherapy has dramatically improved treatment outcomes and eye salvage rates compared with traditional salvage rates of systemic chemotherapy and external beam radiation therapy. Intravitreal injections of chemotherapy have also demonstrated excellent efficacy for vitreous seeds. Uveal melanoma, on the other hand, is treated predominantly with iodine-125 plaque brachytherapy or with proton beam therapy. Major strides in uveal melanoma genomics have been made since the early 2000s, allowing ocular oncologists to better understand the metastatic risks of the tumor on the basis of specific genetic signatures. Loss-of-function mutations of the BAP1 gene are associated with the highest metastatic risk, whereas gain-of-function mutations of SF3B1 and EIF1AX often confer a better prognosis. Expression of a cancer-testis antigen called PRAME (preferentially expressed antigen in melanoma) has been shown to increase metastatic risks in both low-risk and high-risk melanomas. New therapeutic approaches, including molecular therapies and nanoparticle phototherapy, are currently being investigated as alternative treatment modalities for uveal melanoma.

EP-2250: Salvage second treatment of posterior uveal melanomas with episcleral plaque brachytherapy

EP-2250: Salvage second treatment of posterior uveal melanomas with episcleral plaque brachytherapy

DEXAMETHASONE INTRAVITREAL IMPLANT VS RANIBIZUMAB IN THE TREATMENT OF MACULAR EDEMA SECONDARY TO BRACHYTHERAPY FOR CHOROIDAL MELANOMA.

To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 μm to 243 ± 58 μm and from 437 ± 71 μm to 254 ± 44 μm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.