Tumor Apex Research Articles

Outcomes of choroidal melanomas treated with eye physics plaques: A 25-year review

PurposeTo review long-term outcomes of the University of Southern California Plaque Simulator (PS) software and Eye Physics (EP) plaques. We hypothesize that the PS/EP system delivers lower doses to critical ocular structures, resulting in lower rates of radiation toxicity and favorable visual outcomes compared to Collaborative Ocular Melanoma Study plaques, while maintaining adequate local tumor control. Methods and MaterialsRetrospective review of 133 patients treated for choroidal melanoma with 125I brachytherapy, using PS software and EP plaques, from 1990 through 2015. A dose of 85 Gy at a rate of 0.6 Gy/h was prescribed to the tumor apex (with a typical margin of 2 mm) over 7 days. Primary outcomes were local tumor recurrence, globe salvage, and metastasis. Secondary outcomes were changes in visual acuity and radiation complications. ResultsWith median followup of 42 months, 5-year Kaplan–Meier estimated rates for tumor control, globe salvage, and metastatic-free survival were 98.3%, 96.4%, and 88.2%, respectively. Median doses to the macula and optic nerve were 39.9 Gy and 30.0 Gy, respectively. Forty-three percent of patients developed radiation retinopathy, and 20% developed optic neuropathy; 39% lost ≥6 Snellen lines of vision. ConclusionsThe PS/EP system is designed to improve the accuracy and conformality of the radiation dose, creating a steep dose gradient outside the melanoma to decrease radiation to surrounding ocular structures. We report favorable rates of local tumor control, globe salvage, metastases, and radiation complications when compared to the Collaborative Ocular Melanoma Study and other studies. Overall, the PS/EP system results in excellent tumor control and appears to optimize long-term visual and radiation-related outcomes after brachytherapy.

P216] Dosimetric study of several beta-emitting ophthalmic plaques with different plaque materials, by Monte Carlo simulation

Purpose Dosimetric investigation of brachytherapy eye plaques (based on CCB, COB and CIB models) for different coated radionuclides and different plaque materials for the treatment of uveal melanoma. Methods An eye model (including cornea, lens, optic nerve and tumor) and a plaque (with 0.1 mm window, 0.2 mm radionuclide coated foil and 0.7 mm backing), were simulated in a spherical water phantom, using Geant4.10.4. Dose-depth profiles were plotted for Ru-106, Sr-90, Ho-166, Re-188 and Pr-142 plaques. The dose deposited in the tumor and behind the plaque’s backing was calculated for the silver, gold and stainless steel plaques. For validation, dosimetry of CCB, COB and CIB plaques were performed using radiochromic EBT3 film and Plaque Simulator software, and the obtained dose rates were compared with Geant4.10.4 and the manufacturer’s (BEBIG) results. Results The ratio of dose at a point behind the silver backing to the reference point (2 mm depth) was 1.56%, 0.13%, 0.28%, 0.39% and 0.18% for Ru-106, Sr-90, Ho-166, Re-188 and Pr-142 CCB model plaques, respectively. The dose rate at the reference point was 66.4%, 50.7%, 34.8%, 41.87% and 47.1% of the dose rate at a depth of 0.5 mm for the mentioned plaques, respectively. With the same activity, Ho-166 plaque delivered the highest dose to the scleral, while Ru-106 plaque delivered the lowest. The dose per decay at the tumor apex (5 mm depth) was 3.59e−11 Gy, 5.27e−12 Gy, 7.96e−13 Gy, 2.24e−12 Gy and 3.36e-12 Gy for the mentioned plaques, respectively. The deposited dose in the tumor decreased by 50% for gold Ru-106 plaques and increased by 20% for stainless steel ones. Conclusions From the perspective of dose distribution, Ru-106 plaques can be replaced by Sr-90 or Pr-142 plaques for the tumor apex up to 3 mm. The dose fall-off for Ho-166 and Re-188 plaques are more severe, which limits their use only for superficial lesions. Gold plaques show more attenuation and can be made thinner. They may be used in COB and CIB models, due to their vicinity of optic nerve and iris, respectively. For tumor apex up to 5 mm only Ru-106 delivered the sufficient dose.

Effectiveness of brachytherapy in the combination treatment of retinoblastoma

Background: Retinoblastoma is a malignant tumor of the eye retina that occurs mostly in children. In the absence of treatment, the disease leads not only to vision loss, but also to death of the child. At present, combined organ-preserving methods of treatment are preferred. These include polychemotherapy and a local intervention on the tumor, the "golden standard" of which being brachytherapy. Aim: To study the effectiveness of brachytherapy against the background polychemotherapy. Materials and methods : We analyzed retrospectively medical files of 104 children with retinoblastoma aged from 5 months to 5 years (mean age 21 months), who underwent brachytherapy as a local component of management from 2010 to 2015 in the Moscow Helmholtz Research Institute of Eye Diseases. Multifocal lesions were identified in 43 cases and bilateral tumors in 87 children. In 33 cases, the worst eye was removed. Endophytic and mixed forms of tumors growth were most prevalent. Before the brachytherapy, all children received polychemotherapy (2 to 3 courses). The average tumor thickness was 2.74 mm (from 1 to 6.4 mm); its mean maximal transverse dimension was 6.27 mm. Indigenous ophthalmic applicators with isotopes 90 Sr + 90 Y and 106 Ru + 106 Rh were used. The average dose on the tumor apex with the strontium applicator was 142.1 (120–170) Gy, with ruthenic one, 107.4 (69–168) Gy; the scleral doses were 751.3 и 504.4 Gy, respectively. The median follow-up was 51 months. The patients were assessed every 3 to 4 months with ophthalmoscopy and ultrasound examination. The following effectiveness criteria were used: complete resorption, the tumor cannot be identified; partial resorption, a decrease in the initial tumor size by at least 50%; no effect, a decrease in the initial tumor size by less than 50% or an increase in the size of the tumor. Results: Complete resorption of the tumor occurred in 60.6% (n = 63) of the patients at 3 months and in additional 24% (n = 25) at 6 months. During the first year after the radiation, complete resorption of retinoblastoma was achieved 93.3% (n = 97) of the children. All children are alive, no distant metastases have been found. Early complications after brachytherapy were noted in 3 children: hemophthalmia, in 1, retinal detachment, in 1, hemophthalmia with retinal detachment, in 1, when the radiation dose on the sclera exceeded 1000 Gy. Continued tumor growth or relapses were detected in 7 (6.7%) patients. The reason to enucleate two eyes was the tumor invasion into the orbit (1.9%). Visual functions are preserved in 85 (81.7%) children, with a high visual acuity (0.9–1.0) in 21 children, and 0.1–0.8 in 21 children, as well. Conclusion : Brachytherapy is a highly effective method of local destruction of retinoblastoma, which, in the vast majority of cases, allows for complete resorption of the irradiated tumor and for maintenance of high visual acuity in almost half of patients.

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.

Outcomes of I-125 brachytherapy for uveal melanomas depending on irradiation dose applied to the tumor apex - a single institution study.

PurposeThe aim of the study was an evaluation of I-125 brachytherapy patients with uveal melanoma with special consideration for the relationship of the treatment results and the irradiation dose applied to the tumor apex.Material and methodsMedical records of 344 adults with uveal melanoma treated with I-125 brachytherapy in the Department of Ophthalmology and Ocular Oncology of the Jagiellonian University, Medical College in Cracow, Poland were retrospectively analyzed. The study was conducted between 2003 and 2012, and the study group was divided into two subgroups depending on the irradiation dose applied to the top of the tumor: 80 Gy to 100 Gy (n = 177) and 100 Gy to 120 Gy (n = 167).ResultsIt was found that the height of the tumor and the largest diameter of the tumor base decreased with every consecutive follow-up measurement and differed significantly in all comparisons (p < 0.0001). No significant correlation between frequency of complications was found between both study groups (χ2 = 0.27; p = 0.6067). The correlation between survival and the irradiation dose as applied to the tumor top was statistically irrelevant (χ2 = 0.44; p = 0.5084). A logistic regression model showed that patient survival depended on the largest diameter of the base and the height of tumor (p = 0.0216), and the risk of death was larger as these dimensions increased (IR, 1.17). An increase of the largest diameter of the base by 1 mm meant a 17% increase in chances of death. In 13.4% of cases, an enucleation was necessary.ConclusionsThe treatment of choroidal melanomas with I-125 iodine isotope brachytherapy is an efficient and recommended method of treatment and in many cases, an alternative to the enucleation of an eyeball.

Efficacy and Safety of Low-Dose Iodine Plaque Brachytherapy for Juxtapapillary Choroidal Melanoma

To evaluate low- vs high-dose plaque brachytherapy for juxtapapillary choroidal melanoma. Retrospective interventional case series. Setting: Single institution. Forty-seven patients with juxtapapillary choroidal melanoma. Iodine-125 plaque brachytherapy. Eyes were divided into apex low-dose (LD) and high-dose (HD) groups (≤ or > median apex dose 84.35 Gy). Main outcome measures were time to distant failure, local failure, death, enucleation, radiation retinopathy, optic neuropathy, and best-corrected visual acuity (BCVA). Freedom from distant failure rates were 96%and 95% in apex LD and HD groups at 5 years and 77% and 95% at 10 years, respectively (P= .84). Freedom from local failure rates were 90% in the apex LD group vs 89% in the HD group at 5 and 10 years (P= .96). Apex LD and HD groups did not differ for time to death or enucleation. Five- and 10-year freedom from radiation retinopathy and optic neuropathy rates were higher in the apex LD than HD group. Loss of ≥3BCVA lines, final BCVA 20/40 or better, and final BCVA 20/200 or worse were more favorable in the 5mm LD compared to HD group. Visual acuity outcomes did not differ between apex LD and HD groups. Low-dose iodine-125 plaque brachytherapy (67.5-81Gy at tumor apex) provides safe and effective tumor control for juxtapapillary choroidal melanoma and may be associated with reduced radiation toxicity. Larger trials are needed to determine the optimaltherapeutic dose for juxtapapillary choroidal melanoma.

Dose Distributions and Treatment Margins in Ocular Brachytherapy with 106Ru Eye Plaques

Brachytherapy with ¹⁰⁶Ru eye plaques is the most common treatment modality for small to medium-sized uveal melanomas in Europe. So far, no standardized or widely accepted dose prescription protocol for the irradiation of intraocular tumors with ¹⁰⁶Ru eye plaques has been defined. For ¹²⁵I plaques, the minimum dose required for tumor control should be at least 85 Gy. Concerning ¹⁰⁶Ru plaques, the dose prescriptions at the University Hospital of Essen foresees minimum doses of 700 Gy to the tumor base and 130 Gy to the tumor apex. These dose prescriptions are expected to ensure sufficient treatment margins. We apply these dose prescriptions to different eye plaque types and tumor sizes and discuss the resulting treatment margins. These investigations are based on Monte Carlo simulations of dose distributions of 3 different eye plaque types. The treatment margin in apical direction has an expansion of at least 0.8 mm for all investigated eye plaques. For symmetrically formed eye plaques, the treatment margin at the base of the tumor goes beyond the visible edge of the plaque. This study focuses on the shape of 85-Gy isodose lines and on treatment margins for different eye plaque types and tumor sizes and shall help exchange knowledge for ocular brachytherapy.

MRI-based treatment planning and dose delivery verification for intraocular melanoma brachytherapy

PurposeEpiscleral plaque brachytherapy (EPB) planning is conventionally based on approximations of the implant geometry with no volumetric imaging following plaque implantation. We have developed an MRI-based technique for EPB treatment planning and dose delivery verification based on the actual patient-specific geometry. Methods and MaterialsMR images of 6 patients, prescribed 85 Gy over 96 hours from Collaborative Ocular Melanoma Study–based EPB, were acquired before and after implantation. Preimplant and postimplant scans were used to generate “preplans” and “postplans”, respectively. In the preplans, a digital plaque model was positioned relative to the tumor, sclera, and nerve. In the postplans, the same plaque model was positioned based on the imaged plaque. Plaque position, point doses, percentage of tumor volume receiving 85 Gy (V100), and dose to 100% of tumor volume (Dmin) were compared between preplans and postplans. All isodose plans were computed using TG-43 formalism with no heterogeneity corrections. ResultsShifts and tilts of the plaque ranged from 1.4 to 8.6 mm and 1.0 to 3.8 mm, respectively. V100 was ≥97% for 4 patients. Dmin for preplans and postplans ranged from 83 to 118 Gy and 45 to 110 Gy, respectively. Point doses for tumor apex and base were all found to decrease from the preimplant to the postimplant plan, with mean differences of 16.7 ± 8.6% and 30.5 ± 11.3%, respectively. ConclusionsBy implementing MRI for EPB, we eliminate reliance on approximations of the eye and tumor shape and the assumption of idealized plaque placement. With MRI, one can perform preimplant as well as postimplant imaging, facilitating EPB treatment planning based on the actual patient-specific geometry and dose-delivery verification based on the imaged plaque position.

Incorporating patient-specific CT-based ophthalmic anatomy in modeling iodine-125 eye plaque brachytherapy dose distributions

PurposeTo quantify the dosimetric impact of incorporating patient-specific CT-based models rather than the conventional stylized-standard model for eye plaque brachytherapy planning. Methods and materialsPlaque Simulator was used to plan 16 patients using both CT-based patient-specific eye model and stylized-standard (SS) eye models. Plaque position was initially based on the SS model and compared against their patient-specific model without changing the plaque loading pattern and seed strength. Dosimetric parameters were compared for tumor and healthy ocular structures. ResultsPatient-specific ocular parameters ranged from 0.40 to 1.38 of SS model values. If plaques were placed based on SS model eyelet positions, target volume receiving prescription dose (V100%) is overpredicted by 5.9% on average (max: 27%), and D95% is overpredicted by 17.2 Gy on average (max: 58.1 Gy). If the plaques were recentered, 13 of 16 patients had changes in V100% of less than 2%, whereas half of the patients still had optic disc dose difference greater than 5 Gy (max: 36.2 Gy). The largest differences were observed with a target-to-optic disk distance less than 6 mm. No substantial dose differences were observed for the tumor apex, fovea, lens, and opposing retina. ConclusionsPatient-specific modeling is recommended for clinical planning, especially with target-to-optic disk distances less than 6 mm, due to significant differences compared with SS model.

Scleral Thinning Documented by Ultrasound Biomicroscopy after Plaque Therapy for Anterior Ciliary Melanoma

ABSTRACTPurpose: To evaluate, by ultrasound biomicroscopy (UBM), changes in scleral thickness after ruthenium-106 CCB and CCC plaque (Eckert & Ziegler BE-BIG GmbH, Berlin, Germany) therapy for anterior ciliary melanoma. Methods: Eleven patients with anterior ciliary melanoma underwent ruthenium-106 CCB and CCC plaque radiation with a radiation dose at the tumor apex of 80–100 Gy. UBM measurements performed prior to and after treatment were as follows: the largest prominence of the tumor perpendicular to the sclera and scleral thickness at scleral spur, 1.0 mm, and 2.0 mm posteriorly. Results: The article presents one year follow-up results for each of the 11 patients. The mean regression of the tumor of 24.3±9.31% was observed. The thinning of the sclera was statistically significant at the scleral spur (t=1.80, p ≤ 0.05) and at maximal tumor thickness (t=1.35, P=0.05). Conclusion: UBM documented significant thinning of the sclera at the scleral spur and overlying the maximal tumor thickness after Ru-106 CCB and CCC plaque radiation. Taking into consideration the shortcomings of the study—small sample size, insufficient probe resolution, and subjectively determined anatomic landmarks—observed minimal thickness change of the sclera does not necessarily mean its necrosis. However, thinning of the sclera documented at one year follow-up associated with very slow regression of the tumor indicates the need for the introduction of the CIA plaque treatment in our patients with anterior ciliary melanoma.

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy

Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center's experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary). All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003-December 2013 were retrospectively reviewed. Only patients with ≥18months of follow-up who had lesions contiguous with the optic disc (0mm of separation) were included. The tumor apex prescription dose was 85Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity. Thirty-four patients were included with a median follow-up of 44.1months (range 18.2-129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%-100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up. I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.

Long Term Outcomes of I125 Eye Plaque Brachytherapy in Patients with Choroidal Melanoma

To determine the relationship between MCW prescription parameters and outcomes in patients with choroidal melanoma treated with I125 eye plaque radiotherapy. Background: Choroidal melanoma is a rare condition that impacts vision and survival. Eye plaque therapy is a vision-preserving treatment that has been utilized for many decades; however, further optimization of the treatment parameters is needed to reduce toxicities and improve outcomes. Variations in treatment approaches exist among different institutions. At MCW the prescription dose is typically specified at the tumor apex and the prescription dose and dose rate are slightly lower than used in COMS studies. This retrospective review investigated the relationship between MCW treatment parameters and outcomes.

Dosimetric and radiobiologic comparison of 103Pd COMS plaque brachytherapy and Gamma Knife radiosurgery for choroidal melanoma

PurposePlaque brachytherapy (BT) and Gamma Knife radiosurgery (GKRS) are highly conformal treatment options for choroidal melanoma. This study objectively compares physical dose and biologically effective dose (BED) distributions for these two modalities. Methods and MaterialsTumor and organ-at-risk (OAR) dose distributions from a CT-defined reference right eye were compared between 103Pd COMS (Collaborative Ocular Melanoma Study Group) plaques delivering 70 Gy (plaque heterogeneity corrected) over 120 h to the tumor apex and GKRS plans delivering 22 Gy to the 40% isodose line for a representative sample of clinically relevant choroidal melanoma locations and sizes. Tumor and OAR biologically effective dose-volume histograms were generated using consensus radiobiologic parameters and modality-specific BED equations. ResultsPublished institutional prescriptive practices generally lead to larger tumor and OAR physical doses from COMS BT vs. GKRS. Radiobiologic dose conversions, however, revealed variable BEDs. Medium and large tumors receive >1.3 times higher BEDs with COMS BT vs. GKRS. OAR BEDs have even greater dependence on tumor size, location, and treatment modality. For example, COMS BT maximum BEDs to the optic nerve are lower than from GKRS for large anterior and all posterior tumors but are higher for anterior small and medium tumors. ConclusionsBT and GKRS for choroidal melanoma have different physical dose and BED distributions with potentially unique clinical consequences. Using published institutional prescriptive practices, neither modality is uniformly favored, although COMS BT delivers higher physical doses and BEDs to tumors. These results suggest that lowering the physical prescription dose for COMS BT to more closely match the BED of GKRS might maintain equivalent tumor control with less potential morbidity.

Nomogram for predicting radiation maculopathy in patients treated with Ruthenium-106 plaque brachytherapy for uveal melanoma.

PurposeTo develop a predictive model and nomogram for maculopathy occurrence at 3 years after 106Ru/106Rh plaque brachytherapy in uveal melanoma.Material and methodsClinical records of patients affected by choroidal melanoma and treated with 106Ru/106Rh plaque from December 2006 to December 2014 were retrospectively reviewed. Inclusion criteria were: dome-shaped melanoma, distance to the fovea > 1.5 mm, tumor thickness > 2 mm, and follow-up > 4 months. The delivered dose to the tumor apex was 100 Gy. Primary endpoint of this investigation was the occurrence of radiation maculopathy at 3 years. Analyzed factors were as follows: gender, age, diabetes, tumor size (volume, area, largest basal diameter and apical height), type of plaque, distance to the fovea, presence of exudative detachment, drusen, orange pigment, radiation dose to the fovea and sclera. Univariate and multivariate Cox proportional hazards analyses were used to define the impact of baseline patient factors on the occurrence of maculopathy. Kaplan-Meier curves were used to estimate freedom from the occurrence of the maculopathy. The model performance was evaluated through internal validation using area under the ROC curve (AUC), and calibration with Gronnesby and Borgan tests.ResultsOne hundred ninety-seven patients were considered for the final analysis. Radiation-related maculopathy at 3 years was observed in 41 patients. The proposed nomogram can predict maculopathy at 3 years with an AUC of 0.75. Distance to fovea appeared to be the main prognostic factor of the predictive model (hazard ratio of 0.83 [0.76-0.90], p < 0.01). Diabetes (hazard radio of 2.92 [1.38-6.20], p < 0.01), and tumor volume (hazard radio of 21.6 [1.66-281.14], p = 0.02) were significantly predictive for maculopathy occurrence. The calibration showed no statistical difference between actual and predicted maculopathy (p = 1).ConclusionsOur predictive model, together with its nomogram, could be a useful tool to predict the occurrence of radiation maculopathy at 3 years after the treatment.

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

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

Delivered dose uncertainty analysis at the tumor apex for ocular brachytherapy.

To estimate the total dosimetric uncertainty at the tumor apex for ocular brachytherapy treatments delivered using 16 mm Collaborative Ocular Melanoma Study (COMS) and Super9 plaques loaded with (125)I seeds in order to determine the size of the apex margin that would be required to ensure adequate dosimetric coverage of the tumor. The total dosimetric uncertainty was assessed for three reference tumor heights: 3, 5, and 10 mm, using the Guide to the expression of Uncertainty in Measurement/National Institute of Standards and Technology approach. Uncertainties pertaining to seed construction, source strength, plaque assembly, treatment planning calculations, tumor height measurement, plaque placement, and plaque tilt for a simple dome-shaped tumor were investigated and quantified to estimate the total dosimetric uncertainty at the tumor apex. Uncertainties in seed construction were determined using EBT3 Gafchromic film measurements around single seeds, plaque assembly uncertainties were determined using high resolution microCT scanning of loaded plaques to measure seed positions in the plaques, and all other uncertainties were determined from the previously published studies and recommended values. All dose calculations were performed using plaque simulator v5.7.6 ophthalmic treatment planning system with the inclusion of plaque heterogeneity corrections. The total dosimetric uncertainties at 3, 5, and 10 mm tumor heights for the 16 mm COMS plaque were 17.3%, 16.1%, and 14.2%, respectively, and for the Super9 plaque were 18.2%, 14.4%, and 13.1%, respectively (all values with coverage factor k = 2). The apex margins at 3, 5, and 10 mm tumor heights required to adequately account for these uncertainties were 1.3, 1.3, and 1.4 mm, respectively, for the 16 mm COMS plaque, and 1.8, 1.4, and 1.2 mm, respectively, for the Super9 plaque. These uncertainties and associated margins are dependent on the dose gradient at the given prescription depth, thus resulting in the changing uncertainties and margins with depth. The margins determined in this work can be used as a guide for determining an appropriate apex margin for a given treatment, which can be chosen based on the tumor height. The required margin may need to be increased for more complex scenarios (mushroom shaped tumors, tumors close to the optic nerve, oblique muscle related tilt, etc.) than the simple dome-shaped tumor examined and should be chosen on a case-by-case basis. The sources of uncertainty contributing most significantly to the total dosimetric uncertainty are seed placement within the plaques, treatment planning calculations, tumor height measurement, and plaque tilt. This work presents an uncertainty-based, rational approach to estimating an appropriate apex margin.

Эффективность брахитерапии при ретинобластоме

Purpose. To assess the tumor control and complications of ruthenium 106 (Ru-106) and strontium 90 (Sr-90) plaques radiotherapy for retinoblastoma. Material and methods. The study included 60 children with retinoblastoma who were treated in the Ocular Oncology and Radiology Service at the S. Fyodorov Eye Microsurgery Federal State Institution with plague radiotherapy between 2006 and 2015. The mean patient age at the plaque treatment was 22 months (from 5 to 74 months). Prior this treatment the management of the retinoblastoma was carried out in one hundred tumors (92% of cases) and included various combinations of treatments such as systemic and/or local chemotherapy, external beam radiotherapy, laser coagulation, thermotherapy and cryotherapy. Five retinoblastomas (8%) were managed by plaque radiotherapy without any previous treatment. The Ru-106 plaques were used in 68.5% of cases (72 tumor foci) and the Sr-90 plaques – in 31.5% of cases (33 tumors). The mean doses to the tumor apex were 89 Gy for Ru-106 and 190 Gy for Sr-90 plaques, and to the tumor base were 348 Gy for Ru-106 and 757 Gy for Sr-90 plaques. Results. A complete tumor control was achieved in 87% of cases during a mean follow-up of 3.5 months. The failures after the plaque radiotherapy in 11% of cases were controlled with the thermotherapy and in 6% of cases with the repeated plaque radiotherapy. Radiation complications included nonproliferative retinopathy in 19% of cases, proliferative retinopathy – 4%, papillopathy – 11%, retinal detachment – 2%, vitreous hemorrhage – 18%, cataract – 3%, glaucoma and scleral necrosis – 0%. The mean follow-up period was 27 months (from 2 to 72 months). Conclusion. Plaque radiotherapy should be considered as an important and effective option for retinoblastoma, especially in resistant and recurrent tumors after a failure of other methods to achieve the tumor control. Complications such as radiation retinopathy and papillopathy, vitreous hemorrhage and retinal detachment should be anticipated, depending on the location, size of the tumor and previous treatment.

Low-dose brachytherapy strategies to treat uveal melanoma: is less more?

The Collaborative Ocular Melanoma Study (COMS) has established equivalency of globe salvaging brachytherapy compared with enucleation in terms of survival for medium-sized choroidal melanoma. The radiation dose protocol followed by the COMS was 85 Gray to a prescription point of the tumor apex or 5 mm inner sclera; whichever was greater. While the COMS realized appropriate local and distant tumor control rates, ocular morbidity due to radiation complications remains a significant clinical challenge. Recent studies challenge the COMS radiation dose paradigm by demonstrating similar tumor control by utilizing lower radiation doses that are associated with reduced radiation toxicity. Improved operative techniques including intraoperative ultrasound can aid to obtain adequate radiation delivery to the tumor by ensuring optimal plaque position. Adjuvant transpupillary thermotherapy, intravitreal anti-VEGF and posterior sub-Tenon steroids may further enhance outcome by providing additional tumor control and/or facilitating visual recovery.

Ruthenium-106 brachytherapy for thick uveal melanoma: reappraisal of apex and base dose radiation and dose rate.

PurposeTo evaluate the outcomes of ruthenium-106 (106Ru) brachytherapy in terms of radiation parameters in patients with thick uveal melanomas.Material and methodsMedical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm) uveal melanoma treated with 106Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA), and treatment-related complications were assessed.ResultsFifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD). Mean radiation dose to tumor apex and to sclera were 71 (± 19.2) Gy and 1269 (± 168.2) Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14) Gy/h and 6.44 (± 1.50) Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9) mm decreased to 4.5 (± 1.6) mm, 3.4 (± 1.4) mm, and 3.0 (± 1.46) mm at 12, 24, and 48 months after brachytherapy (p = 0.03). Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8%) patients. Mean Log MAR (magnification requirement) visual acuity declined from 0.75 (± 0.63) to 0.94 (± 0.5) (p = 0.04). Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04). Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes.ConclusionsThick uveal melanomas are amenable to 106Ru brachytherapy with less than recommended apex radiation dose and dose rates.

Multidimensional dosimetry of ¹⁰⁶Ru eye plaques using EBT3 films and its impact on treatment planning.

The purpose of this study was to establish a method to perform multidimensional radiochromic film measurements of (106)Ru plaques and to benchmark the resulting dose distributions against Monte Carlo simulations (MC), microdiamond, and diode measurements. Absolute dose rates and relative dose distributions in multiple planes were determined for three different plaque models (CCB, CCA, and COB), and three different plaques per model, using EBT3 films in an in-house developed polystyrene phantom and the mcnp6 MC code. Dose difference maps were generated to analyze interplaque variations for a specific type, and for comparing measurements against MC simulations. Furthermore, dose distributions were validated against values specified by the manufacturer (BEBIG) and microdiamond and diode measurements in a water scanning phantom. Radial profiles were assessed and used to estimate dosimetric margins for a given combination of representative tumor geometry and plaque size. Absolute dose rates at a reference depth of 2 mm on the central axis of the plaque show an agreement better than 5% (10%) when comparing film measurements (mcnp6) to the manufacturer's data. The reproducibility of depth-dose profile measurements was <7% (2 SD) for all investigated detectors and plaque types. Dose difference maps revealed minor interplaque deviations for a specific plaque type due to inhomogeneities of the active layer. The evaluation of dosimetric margins showed that for a majority of the investigated cases, the tumor was not completely covered by the 100% isodose prescribed to the tumor apex if the difference between geometrical plaque size and tumor base ≤4 mm. EBT3 film dosimetry in an in-house developed phantom was successfully used to characterize the dosimetric properties of different (106)Ru plaque models. The film measurements were validated against MC calculations and other experimental methods and showed a good agreement with data from BEBIG well within published tolerances. The dosimetric information as well as interplaque comparison can be used for comprehensive quality assurance and for considerations in the treatment planning of ophthalmic brachytherapy.