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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma.

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

I-125 eye-plaque seed economics: To re-use or to not re-use? A single institutional cost savings analysis of re-using I-125 radioactive seeds for eye-Plaque brachytherapy.

INTRODUCTION: Iodine-125 (I-125) seeds, commonly used in low-dose rate brachytherapy for ocular malignancies, are often discarded after a single use. This study examines the potential cost savings at an institution with high ocular melanoma referrals, by re-using I-125 seeds for eye-plaque brachytherapy. METHODS: In this single-institutional retrospective analysis, data was collected from I-125 seed orders from 8/2019 through 10/2022. Information including number of seeds ordered per lot, number of plaques built per lot, and number of seeds used per lot were collected. Cost per lot of seed was assumed to be the current cost from the most recent lot of 35 seeds. RESULTS: During the study, 72 I-125 seed lots were ordered bi-weekly, with a median of 35 seeds per lot (Range: 15-35). Each seed was used on average 2.26 times prior to being discarded. The average duration of each seed lot used was 62.2 days (Range: 21-126). Each seed lot contributed to the construction of an average of 8.4 eye plaques (Range: 2-20). With seed recycling, 2,475 seeds were used to construct 608 eye-plaques. Without re-using practice this would require 5,694 seeds. This resulted in a percentage cost savings of 56.5%, with a total seed cost reduction of $344,884, or $559 per eye-plaque on average. CONCLUSION: This is the first study to evaluate cost savings relative to re-using I-125 seeds for eye plaques. The data demonstrates how an institution can decrease costs associated with I-125 radiation seeds used for eye-plaque brachytherapy by re-using them.

Iris melanoma management with iodine-125 plaque radiotherapy in 144 patients: impact of melanoma-related glaucoma on outcomes.

PURPOSE: To evaluate the outcomes of iris melanoma managed with plaque radiotherapy on the basis of the initial presence or absence of glaucoma. DESIGN: Retrospective, comparative case series. PARTICIPANTS: A total of 144 patients. INTERVENTION: Custom-designed iodine-125 plaque radiotherapy delivering planned 8000 cGy to melanoma apex using transcorneal application. MAIN OUTCOME MEASURES: Tumor control and treatment-related complications. RESULTS: Of 144 patients with iris melanoma, glaucoma was present at the initial visit in 58 (40%). Causes of elevated intraocular pressure included angle infiltration by melanoma in 50 patients (86%), angle neovascularization in 4 patients (7%), and hyphema in 4 patients (7%). At presentation, the eyes displaying iris melanoma with glaucoma (vs. without glaucoma) were statistically more likely to display angle tumor (66% vs. 43%), with minimal thickness (1.9 vs. 2.9 mm), and melanoma seeding in iris stroma (7 vs. 3 clock hours) and angle (5 vs. 2 clock hours). Plaque radiotherapy was performed in all cases. Kaplan-Meier estimates at 7 years post-treatment revealed no statistical differences in outcomes of local recurrence (14% vs. 15%), enucleation (14% vs. 11%), or metastasis (2% vs. 0%) comparing eyes with and without glaucoma. Of the entire group, multivariate analysis for factors predictive of recurrence included partial (vs. complete) anterior segment irradiation and postradiotherapy glaucoma. Factors related to enucleation included diabetes mellitus, poor initial visual acuity, higher radiation dose to tumor apex, and tumor recurrence. There were no factors predictive of metastasis. CONCLUSIONS: Iodine-125 plaque radiotherapy provides adequate tumor control for iris melanoma with a low metastatic potential of 1% at 7 years. Iris melanoma with secondary glaucoma showed a statistically significant greater likelihood of flat tumor with iris and angle seeding and no difference in outcomes compared with eyes without glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Scleral necrosis after plaque radiotherapy of uveal melanoma: a case-control study.

PURPOSE: To identify risk factors and outcome of scleral necrosis after plaque radiotherapy of uveal melanoma. DESIGN: Case-control study. PARTICIPANTS: A total of 73 cases with scleral necrosis and 73 controls without necrosis after plaque radiotherapy. Controls were matched for anteroposterior tumor epicenter and follow-up duration. INTERVENTION: Plaque radiotherapy with iodine-125, cobalt-60, iridium-192, or ruthenium-106. MAIN OUTCOME MEASURES: Scleral necrosis. RESULTS: Of 5057 patients treated with plaque radiotherapy for uveal melanoma, 73 (1%) developed radiotherapy-induced scleral necrosis. Scleral necrosis occurred in <1% of patients (3/1140) when plaque radiotherapy was used for tumors <3 mm in thickness, 1% of patients (33/3155) with 3- to 8-mm tumor thickness, and 5% of patients (37/762) with >8-mm-thick tumors. On the basis of tumor location, scleral necrosis was detected after plaque radiotherapy of iris melanoma in 0% of patients (0/91), ciliary body melanoma in 29% of patients (67/235), and choroid melanoma in <1% of patients (6/4731). The mean time interval between plaque radiotherapy and scleral necrosis was 32 months (median, 23 months; range, 4-126 months). The mean basal dimension of scleral necrosis was 4 mm (median, 3 mm; range, 1-15 mm), equivalent to 29% of mean tumor base (median, 24%; range, 6%-100%) and 22% of mean plaque size (median, 19%; range, 5%-75%). Multivariate analysis of factors that predicted clinically evident scleral necrosis included ciliary body (P = 0.0001) and pars plana to ora serrata (P < 0.0001) locations of anterior tumor margin, tumor thickness ≥ 6 mm (P = 0.0001), and radiation dose ≥ 400 Gy to the outer sclera (P = 0.0455). Scleral necrosis remained stable in 48% of patients (35/73), increased in size/severity in 48% of patients (35/73), or progressed to scleral perforation in 4% of patients (3/73) over a mean follow-up of 79 months (median, 54 months; range, 5-351 months). Treatment of scleral necrosis included observation in 81% of patients (59/73), scleral patch graft in 14% of patients (10/73), and enucleation in 5% of patients (4/73). CONCLUSIONS: Scleral necrosis after plaque radiotherapy of uveal melanoma was detected in 1% of cases. Factors predictive of scleral necrosis included increasing tumor thickness, ciliary body and peripheral choroidal location, and higher radiation dose to sclera. Most patients (81%) did not require treatment, and 4% evolved to full-thickness perforation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Plaque radiotherapy for residual or recurrent iris melanoma after surgical resection in 32 cases.

PURPOSE: To evaluate plaque radiotherapy for management of residual or recurrent iris melanoma after surgical resection. DESIGN: Retrospective, nonrandomized interventional case series. PARTICIPANTS: We included 32 patients with residual or recurrent iris melanoma after surgical resection. INTERVENTION: Custom designed iodine-125 plaque radiotherapy. MAIN OUTCOME MEASURES: Tumor control, recurrence, poor visual acuity, enucleation, metastasis, and radiation complications. RESULTS: There were 32 eyes with residual (n = 12) or recurrent (n = 20) iris melanoma after surgical resection that were treated with iodine-125 plaque radiotherapy. The residual melanoma was evident clinically in 3 cases and histopathologically in 9; plaque radiotherapy was delivered at a mean interval of 2 months after resection. For the recurrent cases, the mean interval from initial tumor resection to detection of recurrence was 58 months, at which time plaque radiotherapy was applied. For all cases, the mean tumor basal diameter was 6 mm (range, 1-13) and thickness was 2 mm (range, 0.8-4.0) at the time of radiotherapy. Anterior chamber seeding was present in 26 (81%) eyes and glaucoma in 11 (34%) eyes. Visual acuity at presentation was good (20/20-20/50) in 27 (84%), intermediate (20/60-20/150) in 3 (9%), and poor (≤20/200) in 2 eyes (6%). At 6 years after plaque radiotherapy, outcomes included complete tumor control in 87%, poor visual acuity in 9%, enucleation in 13% (for reasons of tumor recurrence [n = 3] and severe glaucoma [n = 1]), and metastasis in 3%. At 6 years, radiation complications included corneal epitheliopathy in 6%, scleral necrosis in 3%, cataract in 53%, elevated intraocular pressure (from tumor or radiotherapy) in 19%, and macular edema in 6%. CONCLUSIONS: Iodine-125 plaque radiotherapy is effective in the management of residual or recurrent iris melanoma after surgical resection, providing tumor control in 87% of patients at 6 years and avoiding enucleation in most cases.

Plaque radiotherapy for juxtapapillary choroidal melanoma: tumor control in 650 consecutive cases.

PURPOSE: To evaluate treatment of juxtapapillary choroidal melanoma with plaque radiotherapy and to investigate the role of supplemental transpupillary thermotherapy (TTT). DESIGN: Retrospective, comparative case series. PARTICIPANTS: We included 650 consecutive eyes with juxtapapillary choroidal melanoma within 1 mm of the optic disc. METHODS: Eyes with juxtapapillary choroidal melanoma receiving plaque radiotherapy over a 31-year period from October 1974 to November 2005 were included in the study. The TTT and no TTT groups were analyzed separately and compared. MAIN OUTCOME MEASURES: Local tumor control, metastasis, and tumor-related mortality. RESULTS: The median basal tumor diameter was 10 mm (range, 1.5-21) and median thickness was 3.5 mm (range, 0.5-14.8). In 481 eyes (74%), the tumor was directly adjacent to the optic disc and in 169 eyes (26%) the posterior tumor margin was between 0.1 and 1.0 mm from the optic disc. The circumpapillary extent of the tumor was <4 clock-hours in 321 eyes (50%), 4-8 clock-hours in 250 eyes (38%), and >8 clock-hours in 79 eyes (12%). Plaque radiotherapy using iodine-125 in 616 eyes (95%), cobalt-60 in 19 eyes (3%), iridium-192 in 12 eyes (2%), and ruthenium-106 in 3 eyes (<1%) delivered a median radiation dose of 8000 cGy (range, 3600-15 500) to the tumor apex and adjunctive TTT was used in 307 eyes (56%). Kaplan-Meier estimates for tumor recurrence, metastasis, and death were 14%, 11%, and 4% at 5 years and 21%, 24%, and 9% at 10 years, respectively. Eyes treated with additional TTT showed slight (statistically nonsignificant) reduction in recurrence and metastasis. Using multivariable analysis, factors predictive of tumor recurrence included foveolar tumor requiring TTT (hazard ratio, 5.07; P<0.001) and greater tumor thickness (hazard ratio, 1.29 per mm increase; P<0.001). Factors predictive of metastasis included greater tumor base (hazard ratio, 1.21 per mm increase; P<0.001) and increasing intraocular pressure (hazard ratio, 1.11 per mmHg increase; P = 0.020). CONCLUSIONS: Plaque radiotherapy for juxtapapillary melanoma provides local tumor control in approximately 80% of eyes at 10 years. In subjects who received TTT, there was slight but nonsignificant improved local tumor control and lower metastatic rate.

Plaque Radiotherapy for Medulloepithelioma in 6 Cases From a Single Center.

PURPOSE: To describe outcomes of 6 patients treated with plaque radiotherapy for medulloepithelioma. DESIGN: Retrospective review. METHODS: Computerized medical records were reviewed for patients with cytopathologically confirmed medulloepithelioma and treated with plaque radiotherapy from January 1970 to December 2017. Clinical and radiotherapy parameters along with outcomes of tumor regression, globe salvage, and metastatic disease were recorded. RESULTS: Of 6 patients with medulloepithelioma, plaque radiotherapy was primary (n = 5) or secondary (n = 1) treatment. The median patient age at diagnosis was 41 months (mean, 145; range, 10-624 months). Patient demographics included white race (n = 6) and female sex (n = 5). Patients presented with strabismus (n = 1), decreased vision (n = 1), ocular pain (n = 1), hyphema (n = 1), corectopia (n = 1), and visible iris lesion (n = 1). The mean tumor basal diameter was 11.2 mm (median, 10.0; range, 7.0-16.0 mm), and mean tumor thickness was 6.8 mm (median, 6.4; range, 3.1-11.0 mm). Related findings included cataract (n = 2), iris neovascularization (n = 5), secondary glaucoma (n = 2), and ectropion uveae (n = 2). The mean radiation dose to tumor apex was 44 Gy (median, 38; range, 35-70 Gy). At a mean follow-up of 59 months (range, 12-210 months), tumor control was achieved in 5 eyes (83%) with globe salvage in 4 eyes (67%). No patient had evidence of metastases or death at the last follow-up visit. CONCLUSIONS: Plaque radiotherapy is a reasonable alternative treatment for localized, small- to medium-size medulloepithelioma. Tumors larger than 11.0 mm, with retrolental cyclitic membrane or extrascelral extension, might still require enucleation.

Visual Outcome and Millimeter Incremental Risk of Metastasis in 1780 Patients With Small Choroidal Melanoma Managed by Plaque Radiotherapy.

Importance: Early detection of choroidal melanoma at a small tumor size is emphasized in the literature. However, there is little published information on the specific risks of plaque-irradiated small choroidal melanoma on visual acuity and metastasis. Objective: To analyze outcomes of plaque radiotherapy for small choroidal melanoma 3 mm in thickness or less. Design, Setting, and Participants: This retrospective noncomparative series at a tertiary referral center included 1780 consecutive patients who had received plaque radiotherapy treatment for small choroidal melanoma. Main Outcomes and Measures: Visual acuity outcomes and melanoma-associated metastasis, assessed by Kaplan-Meier analyses. Results: The mean (SD) patient age at melanoma diagnosis was 58 (14) years. Of 1780 patients, 908 were female (51.0%), and 1752 were white (98.4%). Visual acuity was 20/40 OU or better in 1276 of the patients (71.7%), and the mean (SD) visual acuity was 20/40 (20/50) OU (median, 20/30; range, 20/20 to counting fingers). The mean (SD) tumor basal dimension was 8.8 (2.9) mm (median, 8.0 mm; range, 2.0-20.0 mm) and mean (SD) tumor thickness was 2.6 (0.5) mm (median, 2.7; range, 0.2-3.4 mm). Mean (SD) distance to the foveola was 3.4 (3.9) mm and to the optic disc was 3.7 (3.7) mm. The Kaplan-Meier rate of visual acuity loss (≥3 Snellen lines) was 9.5% (95% CI, 8.2%-11.0%) at 1 year, 39.2% (95% CI, 36.5%-42.0%) at 5 years, and 48.9% (95% CI, 45.6%-52.3%) at 10 years, whereas poor visual acuity (≤20/200) was 7.1% (95% CI, 5.9%-8.4%) at 1 year, 38.2% (95% CI, 35.5%-41.1%) at 5 years, and 53.5% (95% CI, 50.1%-57.1%) at 10 years. Regarding melanoma-associated metastasis, the rate was 0.2% (95% CI, 0.09%-0.6%) at 1 year, 4.5% (95% CI, 3.4%-5.9%) at 5 years, and 8.8% (95% CI, 6.9%-11.1%) at 10 years. Using 1.0-mm thickness increments, the 10-year risk for metastasis was 25.0% (95% CI, 3.9%-87.2%) at 0-mm to 1.0-mm thickness, 5.9% (95% CI, 2.5%-13.5%) at 1.1-mm to 2.0-mm thickness, 8.1% (95% CI, 5.9%-11.0%) at 2.1-mm to 3.0-mm thickness, and 13.4% (95% CI, 8.7%-20.4%) at thicknesses greater than 3.0 mm. The greater relative risk (RR) for metastasis in thinnest tumors was 1.83 (95% CI, 1.09-3.07), which likely represented more aggressive diffuse (flat) melanoma. By multivariable analysis, clinical features predictive of melanoma-associated metastasis included increasing patient age (RR, 1.32 [95% CI, 1.07-1.63] per decade; P = .01), tumor diameter (RR, 1.15 [95% CI, 1.06-1.24] per mm; P < .001), tumor thickness (RR, 2.22 [95% CI, 1.22-4.05] per mm; P = .01), photopsia symptoms (RR, 2.45 [95% CI, 1.35-4.43]; P = .003), and prior treatment before plaque radiotherapy (RR, 3.31 [95% CI, 1.31-8.33]; P = .01). Conclusions and Relevance: This retrospective study suggests that small choroidal melanoma treated with plaque radiotherapy has a 10-year risk for visual acuity loss of 48.9% (95% CI, 45.6%-52.3%) and a 10-risk of systemic metastasis of 8.8% (95% CI, 6.9%-11.1%). In this analysis, each millimeter of increasing thickness and diameter contributed risk for metastatic disease.

Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma).

OBJECTIVE: To report results of plaque radiotherapy for choroidal melanoma that completely encircles the optic disc (circumpapillary melanoma). METHODS: Retrospective medical record review over a 31-year period of 37 consecutive patients. The main outcome measures were treatment complications, long-term visual acuity, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age at treatment was 69 years (range, 20-86 years). The presenting complaint was visual loss in 19 eyes (51%), photopsia in 5 (14%), and visual field loss in 3 (8%). All tumors touched and encircled the optic disc for 360 degrees . The quadrantic location of the main tumor epicenter was superior in 8 eyes (22%), nasal in 10 (27%), inferior in 9 (24%), and temporal in 10 (27%). The median tumor basal diameter was 11 mm (range, 4.8-20 mm) and median tumor thickness was 3.6 mm (range, 1.8-14.8 mm). The optic disc was obscured to some extent by overhanging tumor in 19 cases (52%). The most commonly used isotope for plaque radiotherapy was iodine 125 (n = 34 cases; 92%), and a notched plaque design was used in 34 cases (92%). Planned adjunctive treatment included transpupillary thermotherapy in 17 cases (49%) and argon laser photocoagulation in 6 of 35 cases (17%) with follow-up. Of the 28 eyes with more than 5 months' follow-up (mean, 52 months; median, 46 months; range, 5-234 months), treatment complications included nonproliferative and proliferative retinopathy in 11 (39%) and 7 eyes (25%); maculopathy in 7 (25%); papillopathy in 9 eyes (32%); neovascular glaucoma in 5 (18%); and vitreous hemorrhage in 13 (46%). Pars plana vitrectomy was required in only 2 of 13 eyes (15%) with persistent vitreous hemorrhage. Long-term visual acuity of 20/200 or worse was observed in 13 eyes (62%), and 12 eyes (57%) lost more than 5 Snellen visual acuity lines, excluding 7 cases (25%) in which enucleation was necessary. Recurrence was noted in 4 cases (14%), of which 3 were treated with enucleation and 1 with transpupillary thermotherapy. Systemic metastasis occurred in 1 patient (4%) and there were no melanoma-specific deaths during the study period. CONCLUSIONS: Custom-designed plaque radiotherapy is a potential treatment for selected patients with circumpapillary choroidal melanoma. We found satisfactory local tumor control, and globe retention was achieved in 75% of eyes with more than 5 months' follow-up.

Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment.

The present report is the follow-up of patients enrolled in a phase II clinical trial using I-MAb 425 as an adjuvant treatment for high grade gliomas. Patient median survivals support published data from an earlier preliminary report. From January 29, 1987 to January 25, 1997, 180 patients diagnosed with astrocytoma with anaplastic foci (AAF) and glioblastoma multiforme (GBM) were treated as outpatients with an average of three weekly intravenous or intraarterial injections of radiolabeled MAb 425. The mean dose was 140 mCi (5.2 GBq). Only one patient who received a single dose of more than 60 mCi (2.2 GBq) experienced acute toxicity. Patients received prior surgery and radiation therapy, with and without chemotherapy. Overall median survival for patients with GBM and AAF was 13.4 and 50.9 months, respectively, with Karnofsky Performance Status (KPS) ranging from 40 to 100 and age ranging from 11 to 75 years. Prognostic factors (KPS and age) correlated positively with increased survival, with KPS the most important determinant of median survival. Data analysis was performed on patients followed 5 years or longer. We conclude that the administration of I-MAb 425 with intensive medical management demonstrates a significant increase in median survival and should be considered a therapeutic regimen for the management of patients with high grade gliomas.

Plaque radiotherapy in the management of scleral-invasive conjunctival squamous cell carcinoma: an analysis of 15 eyes.

IMPORTANCE: Conjunctival squamous cell carcinoma (SCC) is surgically managed with wide surgical excisional biopsy, superficial keratectomy, and cryotherapy. In eyes with residual tumor showing scleral invasion or intraocular involvement, enucleation is advised. OBJECTIVE: To explore the role of plaque radiotherapy for residual invasive conjunctival SCC as an alternative to enucleation. DESIGN, SETTING, AND PARTICIPANTS: Interventional case series involving 15 patients with histopathologically confirmed scleral and/or intraocular invasion of SCC at Wills Eye Hospital. INTERVENTION: Plaque radiotherapy. MAIN OUTCOMES AND MEASURES: Tumor control, treatment complications, and globe salvage. RESULTS: The primary tumor prior to excision displayed a mean basal diameter of 12.1 mm (median, 12 mm; range, 4-25 mm) and mean thickness of 2.6 mm (median, 3 mm; range, 1-5 mm). In all cases, the tumor was managed by primary surgical resection using wide excisional biopsy, limited superficial keratectomy, and cryotherapy to the remaining conjunctival margins. Histopathology confirmed conjunctival SCC in all cases with residual tumor demonstrating scleral invasion (n = 15) and/or anterior chamber invasion (n = 3). The residual tumor measured a mean basal diameter of 10.6 mm (median, 10 mm; range, 2.5-20 mm) and mean thickness of 1.5 mm (median, 1 mm; range, 1-5 mm). Plaque radiotherapy was applied in all cases for a mean apex dose of 56 Gy (median, 50 Gy; range, 50-80 Gy) over a mean of 132 hours (median, 142 hours; range, 93-170 hours). Over a mean follow-up of 41 months (median, 46 months; range, 9-96 months), local tumor control was achieved in all 15 cases (100%). However, 4 cases showed further distant conjunctival tumor recurrence remote from the site of radiotherapy with positive orbital involvement at a mean of 5 months postradiotherapy, necessitating enucleation (n = 2) or orbital exenteration (n = 2). Globe salvage was achieved in 10 cases, as 1 patient required enucleation for chronic ocular irritation. Radiation complications included cataract (n = 13), iris telangiectasia (n = 5), corneal epithelial defect (n = 4), corneal edema (n = 3), and glaucoma (n = 1). There was no evidence of metastasis. CONCLUSIONS AND RELEVANCE: Plaque radiotherapy delivered over a mean of 6 days can be an effective alternative to enucleation for residual scleral-invasive conjunctival SCC following resection. Local tumor control was achieved in all cases.

Plaque radiotherapy for juxtapapillary choroidal melanoma: treatment complications and visual outcomes in 650 consecutive cases.

IMPORTANCE: The treatment of juxtapapillary choroidal melanoma is challenging because of the proximity of the tumor to visually important structures. OBJECTIVE: To report the complications of treatment of juxtapapillary choroidal melanoma with plaque radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case series of patients from the Ocular Oncology Service, Wills Eye Hospital, 650 consecutive eyes with juxtapapillary choroidal melanoma (≤1 mm to optic disc) treated with plaque radiotherapy from October 1, 1974, through November 30, 2005, were studied. MAIN OUTCOMES AND MEASURES: Kaplan-Meier analysis of rates of radiation complications, secondary enucleation, and visual acuity outcomes. RESULTS: The 5-year (10-year) rate of nonproliferative retinopathy was 66% (75%); proliferative retinopathy, 24% (32%); maculopathy, 56% (65%); papillopathy, 61% (77%); cataract, 66% (80%); neovascular glaucoma, 15% (22%); vitreous hemorrhage, 35% (42%); and secondary enucleation, 16% (26%). Visual acuity of 20/200 or worse occurred in 54% (87%), and loss of more than 5 lines of Snellen visual acuity was found in 45% (78%). CONCLUSIONS AND RELEVANCE: Among this case series, plaque radiotherapy for juxtapapillary choroidal melanoma commonly led to retinopathy and papillopathy, but globe retention was 84% at 5 years. Vision loss should be anticipated in 45% by 5 years. Plaque radiotherapy remains a suitable choice for the treatment of juxtapapillary melanoma with a high globe retention rate.

Sp1 facilitates DNA double-strand break repair through a nontranscriptional mechanism.

Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H(2)O(2). Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant γH2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects.

Irradiation toxic effects during intra-arterial chemotherapy for retinoblastoma: should we be concerned?

OBJECTIVE: To evaluate irradiation toxic effects from fluoroscopy during intra-arterial chemotherapy for retinoblastoma. DESIGN: Prospective trial. PARTICIPANTS: Eight patients treated with intra-arterial chemotherapy. MAIN OUTCOME MEASURES: Irradiation toxic effects in vital organs. RESULTS: The mean patient age was 29 months (range, 10-74 months) and 63% were male. The mean irradiation dose to the skin of the affected eye was 0.19173 Gy, to the contralateral eye was 0.03533 Gy, to the chest wall was 0.00296 Gy, and to the abdominal wall was 0.00104 Gy. The estimated irradiation dose to the lens in the treatment eye was 0.16 Gy, which, in accumulated doses, could be cataractogenic. The estimated irradiation dose from a single fluoroscopy session to other organs, including the brain (0.05560 Gy), thyroid (0.00192 Gy), bone marrow (0.00059 Gy), and gonads (0.00015 Gy), was far lower than the minimal toxic level. CONCLUSIONS: Careful use of fluoroscopy during intra-arterial chemotherapy with limited irradiation exposure is advised. Accumulated irradiation toxic effects following multiple sessions of intra-arterial chemotherapy could be cataractogenic and possibly carcinogenic, especially in irradiation-sensitive patients with retinoblastoma.

A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme.

OBJECT: This single-institution Phase II study tests the efficacy of adjuvant radioimmunotherapy with (125)I-labeled anti-epidermal growth factor receptor 425 murine monoclonal antibody ((125)I-mAb 425) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: A total of 192 patients with GBM were treated with (125)I-mAb 425 over a course of 3 weekly intravenous injections of 1.8 GBq following surgery and radiation therapy. The primary end point was overall survival, and the secondary end point was toxicity. Additional subgroup analyses were performed comparing treatment with (125)I-mAb 425 (RIT, 132 patients), (125)I-mAb 425 and temozolomide (TMZ+RIT, 60 patients), and a historical control group (CTL, 81 patients). RESULTS: The median age was 53 years (range 19-78 years), and the median Karnofsky Performance Scale score was 80 (range 60-100). The percentage of patients who underwent debulking surgery was 77.6% and that of those receiving temozolomide was 31.3%. The overall median survival was 15.7 months (95% CI 13.6-17.8 months). The 1- and 2-year survivals were 62.5 and 25.5%, respectively. For subgroups RIT and TMZ+RIT, the median survivals were 14.5 and 20.2 months, respectively. No Grade 3 or 4 toxicity was seen with the administration of (125)I-mAb 425. The CTL patients lacked Karnofsky Performance Scale scores, had poorer survival, were older, and were less likely to receive radiation therapy. On multivariate analysis, the hazard ratios for RIT versus CTL, TMZ+RIT versus CTL, and TMZ+RIT versus RIT were 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively. CONCLUSIONS: In this large Phase II study of 192 patients with GBM treated with anti-epidermal growth factor receptor (125)I-mAb 425 radioimmunotherapy, survival was 15.7 months, and treatment was safe and well tolerated.

Plaque radiotherapy for juxtapapillary choroidal melanoma overhanging the optic disc in 141 consecutive patients.

OBJECTIVE: To evaluate tumor control with plaque radiotherapy for juxtapapillary choroidal melanoma that overhangs the optic disc. METHODS: Retrospective medical record review of 141 consecutive patients with data on complications of treatment, final visual acuity, visual loss, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age was 61 years. Presenting symptoms included reduced visual acuity in 72 eyes (51%), photopsia in 14 (10%), and visual field defect in 18 (13%); 35 patients (25%) were asymptomatic. The median tumor basal diameter was 11 mm and the median thickness was 5.2 mm. The tumor overhung 50% or less of the disc in 88 eyes (62%) and more than 50% of the disc in 53 eyes (38%). In 19 cases (13%), the tumor overhung the entire disc. All patients were treated with plaque radiotherapy, using a notched design in 126 eyes (89%) and a round design in 14 eyes (10%), with iodine 125 in 132 eyes (94%) and cobalt 60 in 9 eyes (6%). The median radiation dose to the tumor apex was 8500 cGy. Adjuvant transpupillary thermotherapy was used in 54 eyes (39%). During a mean follow-up of 56 months, complications included nonproliferative retinopathy in 61 eyes (51%), proliferative retinopathy in 26 (22%), maculopathy in 44 (37%), papillopathy in 57 (48%), neovascular glaucoma in 23 (19%), and vitreous hemorrhage in 48 (40%). A final visual acuity of 20/200 or worse was measured in 72 eyes (77%), and visual loss of more than 5 Snellen lines occurred in 59 eyes (63%). Enucleation was necessary in 27 eyes (23%). Tumor recurrence was found in 12 eyes (10%). Metastasis developed in 15 patients (13%) and death in 4 cases (3%). CONCLUSIONS: Using plaque radiotherapy for choroidal melanoma overhanging the optic disc, local tumor control was achieved in 90% of cases. Tumor and radiation effects led to poor visual acuity in 77% of eyes. The metastatic rate was 13% and the mortality rate was 3%.