Visual Outcomes after Proton Therapy for Recurrent Uveal Melanoma.

OBJECTIVE: Proton beam reirradiation remains an effective and globe-preserving alternative to enucleation in the treatment of local recurrence in uveal melanoma. The study aimed to assess visual outcomes and prognostic factors in visual acuity following proton beam salvage therapy. DESIGN: Retrospective study SUBJECTS: A retrospective study evaluated patients with recurrent uveal melanoma treated with proton beam irradiation (PBI) from 1984 through 2019 at a single academic tertiary center. METHODS: Patient and tumor characteristics were collected from the medical record, as well as best visual acuity (BVA) and ocular outcomes following treatment of recurrent uveal melanoma with PBI. MAIN OUTCOME MEASURES: The primary outcome of the study was the visual acuity of patients following proton beam irradiation for recurrent uveal melanoma. Additional outcome measures included enucleation rate of patients following salvage PBI and analysis of tumor and patient characteristics in the prognostication of visual acuity. RESULTS: The study comprised 67 patients who received PBI for recurrent uveal melanoma. The median age at recurrence was 67.6 years (range 31.6-91.0 years) and median follow-up from the time of recurrence to last examination was 4.4 years (range 0.23-17.1 years). The median final BVA was hand motion (range 20/20-no light perception) and 6 (9.1%) patients maintained a Snellen VA 20/40 or better. The 5-year probability of visual acuity retention of 20/200 or better was 19%. In a multivariable Cox model, VA at tumor recurrence of less than 20/40 was found to be significantly associated with a VA of 20/200 or worse following retreatment with PBI. Twelve (18%) patients underwent enucleation following retreatment with PBI. CONCLUSIONS: PBI allows for ocular preservation and functional vision in the treatment of recurrent uveal melanoma in select patients.

Survival of patients with recurrent uveal melanoma after treatment with radiation therapy.

BACKGROUND/AIMS: We evaluated a large cohort of patients treated for local recurrence of choroidal or ciliary body melanomas at the Massachusetts Eye and Ear (MEE) to quantify the risk of melanoma-related mortality associated with recurrence, independent of other risk factors. METHODS: Patients treated with radiation therapy from 1982 to 2017 were identified through the Uveal Melanoma Registry at MEE. Competing risks regression was performed to investigate the risk of melanoma-related mortality associated with recurrence, treating recurrence as a time-varying covariate. RESULTS: Of 4196 patients treated, 4043 patients remained recurrence-free and 153 patients experienced a recurrence (median follow-up: 9.9 years). Median time from initial treatment to recurrence was 30.5 months (range: 2.0-238.7). Seventy-nine (69.9%) patients with recurrences and 826 (37.9%) patients in the recurrence-free group died of metastatic uveal melanoma (p<0.001). Median time from initial treatment to melanoma-related death was 4.9 years (1.0-31.8) for patients who developed recurrences and 4.3 years (0.59-33.8) for patients who did not (p=0.17). Five-year and 10-year probabilities of melanoma-related mortality were 9.5% and 15.0%, respectively, in patients without local recurrences compared with 32.0% and 46.6% in patients with recurrences (p<0.001). CONCLUSION: These data confirm previous reports that local recurrence is associated with an increased risk of dying of melanoma and quantify the risk that can be attributed to local recurrence independent of other risk factors. This group of patients should be strongly considered for adjuvant therapies when available.

Proton beam irradiation of uveal melanoma involving the iris, ciliary body and anterior choroid without surgical localisation (light field).

AIMS: To assess treatment outcomes after proton beam irradiation (PBI) without surgical localisation of uveal melanomas involving the iris, ciliary body and anterior choroid. METHODS: Retrospective chart review of 125 patients evaluated at Massachusetts Eye and Ear and treated with PBI using a light field set-up without localisation surgery between November 1975 and April 2017. The tumours were characterised as follows: iris (n=18, 14.4%), ciliary body (n=12, 9.6%), iridociliary (n=58, 46.4%), ciliochoroidal (n=24, 19.2%) and iridociliochoroidal (n=13, 10.4%). The tumours were measured by transillumination and ultrasonography before treatment. Tumours with posterior margin located less than two disc diameters from the ora serrata were treated using the light field technique. Patient outcomes after PBI were evaluated. RESULTS: Most patients had good vision at the time of tumour diagnosis (69.6% had baseline visual acuity (VA) of ≥20/40). Median VA at last follow-up (median follow-up: 72.1 months) was 20/63. Recurrences occurred in 12 patients (9.6%) at a median time of 4.0 years post-treatment. Recurrences were treated by repeat PBI (n=5) or enucleation (n=7). Secondary enucleation was performed in 18 patients (14.4%), and 61.1% of these were due to complications. Neovascular glaucoma (NVG) developed in 21 patients (16.8%). Of seven patients who developed NVG after anti-vascular endothelial growth factor (anti-VEGF) therapies became available, five were treated with intravitreal Avastin injections (23.8% of patients with NVG). Of 69 patients diagnosed with cataract after treatment, 51 (73.9%) were characterised as radiation-related. Death from metastatic uveal melanoma occurred in 20.8% of the cohort, with a median follow-up of 10.1 years. CONCLUSIONS: Patients treated with PBI using a light field set-up technique experience good outcomes after irradiation. Eye preservation and retention of good VA are seen in the majority of cases, and tumour recurrence is low.

Proton beam irradiation for non-AMD CNV: 2-year results of a randomised clinical trial.

AIMS: To evaluate safety and visual outcomes after proton beam irradiation (PBI) therapy for subfoveal choroidal neovascularisation (CNV) secondary to causes other than age-related macular degeneration (AMD). METHODS: This study is a prospective, unmasked and randomised clinical trial using two dosage regimens, conducted in the Massachusetts Eye and Ear Infirmary. The study included 46 patients with CNV secondary to non-AMD and best-corrected visual acuity of 20/320 or better. Patients were randomly assigned to receive 16 or 24 cobalt gray equivalents (CGE) of PBI in two equal fractions. Complete ophthalmological examinations, fundus photography and fluorescein angiography were performed at baseline and 6, 12, 18 and 24 months after treatment. RESULTS: At 1 year after treatment, 82% and 72% lost fewer than 1.5 lines of vision in the 16 CGE and in 24 CGE groups, respectively. At 2 years after therapy, 77% in the lower dose group and 64% in the higher dose group lost fewer than 1.5 lines of vision. Mild radiation complications such as radiation vasculopathy developed in 17.6% of patients. CONCLUSIONS: PBI is a safe and efficacious treatment for subfoveal CNV not due to AMD. The data with respect to visual outcomes and radiation complications trend in favour of the 16 CGE group, although differences do not reach statistical significance. PBI may be considered as an alternative to current therapies.

Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma.

PURPOSE: To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. METHODS AND MATERIALS: Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). RESULTS: At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). CONCLUSIONS: A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence.