High local control and low ocular toxicity using ultra-low-dose "boom-boom" radiotherapy for indolent orbital lymphoma.

BACKGROUND: The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity. METHODS: This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation treatment plans were reviewed. Endpoints included response rate, progression, and ocular toxicity per oncologist and ophthalmology reports. RESULTS: A total of 17 patients (12 female and 5 male) with 19 indolent orbital lymphomas were included. Median follow-up was 39 months. Complete, partial, and stable response was achieved in 65%, 24%, and 12% of patients, respectively. Only 1 patient developed local recurrent 47 month after radiation treatment, and was successfully salvaged with standard dose radiation (24 Gy). Five-year distant progression rate is 18%. Oncologist-reported Common Terminology Criteria for Adverse Events (CTCAE) toxicity rates were 6% grade 1 and 0% grade 2+. Ophthalmologist reported 33.3% new post-RT toxicities including dry eye, cataract, and chorioretinal atrophy. There is no significant vision acuity change after RT. CONCLUSIONS: "Boom-Boom" RT (4 Gy in 2 fractions) provides excellent control for indolent orbital lymphoma. While minimal toxicity was documented by radiation oncologists, higher rates were noted by ophthalmologists, highlighting the radiosensitivity of orbital structures and potentially underreported ocular toxicity in "boom-boom" and standard regimens. Further prospective randomized studies are needed to better define the outcome and toxicity of ultra-low-dose (4 Gy) RT for ocular lymphoma.

Randomized study of remote telehealth genetic services versus usual care in oncology practices without genetic counselors.

PURPOSE: To examine the benefit of telehealth over current delivery options in oncology practices without genetic counselors. METHODS: Participants meeting cancer genetic testing guidelines were recruited to this multi-center, randomized trial comparing uptake of genetic services with remote services (telephone or videoconference) to usual care in six predominantly community practices without genetic counselors. The primary outcome was the composite uptake of genetic counseling or testing. Secondary outcomes compare telephone versus videoconference services. RESULTS: 147 participants enrolled and 119 were randomized. Eighty percent of participants in the telehealth arm had genetic services as compared to 16% in the usual care arm (OR 30.52, p < 0.001). Five genetic mutation carriers (6.7%) were identified in the telehealth arm, compared to none in the usual care arm. In secondary analyses, factors associated with uptake were lower anxiety (6.77 vs. 8.07, p = 0.04) and lower depression (3.38 vs. 5.06, p = 0.04) among those who had genetic services. There were no significant differences in change in cognitive or affective outcomes immediately post-counseling and at 6 and 12 months between telephone and videoconference arms. CONCLUSION: Telehealth increases uptake of genetic counseling and testing at oncology practices without genetic counselors and could significantly improve identification of genetic carriers and cancer prevention outcomes.

BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort.

PURPOSE: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA). METHODS AND MATERIALS: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months. CONCLUSIONS: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment.

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.

Strut-based accelerated partial breast irradiation: Report of treatment results for 250 consecutive patients at 5 years from a multicenter retrospective study.

PURPOSE: This registry trial studied the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators and reports on the local control, toxicity, and survival for the first 250 patients treated with this device. METHODS AND MATERIALS: Patients were treated using the strut-based brachytherapy device with conventional dose and fractionation of 34 Gy in 10 twice-daily fractions. Planning goals for the planning target volume were V90 > 90%, V150 < 50 cc, and V200 < 20 cc. Toxicity was graded based on the Common Terminology Criteria for Adverse Events v3.0. Recurrence rates were also calculated. RESULTS: Median followup was 59.5 months for the 250 patients. Grade 2 or higher adverse events at any time for hyperpigmentation, induration, erythema, telangiectasia, breast pain, seroma, and fat necrosis were 0.4%, 3.0%, 3.0%, 3.0%, 3.9%, 4.8%, and 1.3%, respectively. The median V90 was 97%, V95 was 95.1%, V150 was 28.7 cc, and V200 was 14.2 cc. For those patients with a less than a 5-mm or 3-mm-skin bridge, the median skin max doses were 272 and 289 cGy, respectively. The 4-year actuarial recurrence rates for true recurrence/marginal miss and ipsilateral breast tumor recurrence were 2.3% and 3.6%, respectively. The 4-year actuarial rates for overall survival, cause-specific survival, and disease-free survival were 97%, 98%, and 92%, respectively. CONCLUSIONS: The strut-based applicator was designed to simplify APBI compared to interstitial brachytherapy. This report confirms excellent tumor control and survival with low toxicity and supports the evidence that brachytherapy has less normal tissue toxicity than APBI with external beam irradiation.

Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with lower biological effective doses.

OBJECTIVE: Few studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer. METHODS: Two hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival. RESULTS: Twenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported. CONCLUSION: Patients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

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.

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.

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.

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.

Hyperbaric oxygen therapy for radiation-induced cystitis and proctitis.

PURPOSE: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. METHODS AND MATERIALS: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15-84 years). The range of external-beam radiation delivered was 50.0-75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90-120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. RESULTS: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7-70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). CONCLUSIONS: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.

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.

Tumor bed-to-skin distance using accelerated partial-breast irradiation with the strut-adjusted volume implant device.

PURPOSE: Because of the risk of skin toxicity with single dwell position, single-lumen brachytherapy devices are sometimes contraindicated for tumor cavities 5-7mm from the skin surface. We discuss the use of multicatheter device to treat patients with tumor bed-to-skin distances <7mm. METHODS AND MATERIALS: We treated 117 patients with accelerated partial-breast irradiation brachytherapy: 77 single-lumen and 40 multicatheter devices. A subset of 12 patients treated with SAVI(®) had bed-to-skin spacing <7mm. All patients had Tis-2N0 ductal carcinoma with negative margins. A total dose of 34.0Gy in 10 fractions was delivered twice daily. Planning target volume was created using computed tomography-based three-dimensional planning with a 1.0-cm expansion of the lumpectomy cavity. Skin dose was measured dosimetrically, with skin constraints <125% of the prescription. Toxicities were graded, and patients were assessed at various intervals. RESULTS: Of the patients treated with the multicatheter device, 0% (0/12) had their device pulled. At 2 weeks after treatment, fewer than 50% of the patients had skin toxicities of Grades 1-2, all of which resolved by 6 months. The cosmetic outcome was good to excellent at followup. CONCLUSIONS: Multicatheter devices permit well-tolerated accelerated partial-breast irradiation in patients with tumor cavities near the skin surface for which the single-lumen device may not be appropriate.

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.

A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance.

We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I-II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3-15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0-50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1-5) in cohort SLND and 18 (range 7-36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.

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%.