Radiation Oncology/Eye/Ocular melanoma/Randomized

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Ocular Melanoma - Randomized Data

Enucleation vs. RT

 * COMS Medium (1987-1998)
 * Randomized. 1317 patients. Choroidal melanoma, height 2.5 - 10.0 mm, size <=16.0 mm. Ineligible if contiguous with optic disc. Arm 1) Enucleation vs. Arm 2) I-125 brachytherapy
 * Brachytherapy: episcleral plaque, 2-3 mm margin beyond base of tumor (i.e. 4-6 mm larger than maximum basal diameter). If near optic nerve, allowed notches. Dosimetry based on TG43. If tumor height 2.5-4.9 mm, prescription 5 mm from interior surface of sclera; if tumor height >=5 mm, prescription to apex. Dose 85 Gy (dose rate 0.42-1.05 Gy). Organs at risk sclera (1mm from surface of plaque), optic nerve (center of optic disc), macula (foveola), opposite retina (22 mm from scleral surface along diameter of globe)
 * 5-years; 2001 PMID 11448319 -- "The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18." (Diener-West M, Arch Ophthalmol. 2001 Jul;119(7):969-82.). Minimum F/U 2 years, 81% F/U 5+ years, 32% F/U 10+ years
 * Outcome: 5-year OS enucleation 81% vs. I-125 82% (NS); Risk of death from metastatic disease 11% vs. 9% (NS)
 * Predictors: age, height, diameter, distance to optic disc, smoking
 * Toxicity: I-125 5-year visual acuity <20/200 63%, <5/200 45%, enucleation 12%
 * Conclusion: No difference in mortality between enucleation and I-125 brachytherapy
 * 12-years; 2006 PMID 17159027 -- "The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28." (COMS, Arch Ophthalmol. 2006 Dec;124(12):1684-93.). Minimum F/U 5 years, 39% F/U 12+ years
 * Outcome: 12-year OS enucleation 59% vs. I-125 57% (NS); Risk of death from metastatic disease 17% vs. 21%
 * Predictors: age, diameter
 * Conclusion: No survival difference between enucleation and I-125 brachytherapy

Periocular Triamcinolone

 * Thomas Jefferson (2005-2005) -- Plaque RT +/- periocular triamcinolone
 * Randomized. 163 patients, new diagnosed uveal melanoma, I-125 plaque brachytherapy. Arm 1) control vs. Arm 2) periocular injection of triamcinolone acetonide (40 mg in 1 ml) at time of plaque insertion, 4 months, and 8 months later. Optical coherence tomography
 * 2009 PMID 19481812 -- "Periocular Triamcinolone for Prevention of Macular Edema after Plaque Radiotherapy of Uveal Melanoma A Randomized Controlled Trial." (Horgan N, Ophthalmology. 2009 May 28.) Mean F/U >1.5 years
 * Outcome: Macular edema control 58% vs. triamcinolone 36% (SS). NNT 4.5 patients. Moderate vision loss 48% vs. 31% (SS), severe vision loss 15% vs. 5% (SS)
 * Toxicity: elevated IOP (NS), cataract progression (NS)
 * Periocular triamcinolone beneficial in reducing risk of macular edema, and moderate/severe vision loss

Protons

 * MGH; 2000 (1989-1998) PMID 10865313 -- "A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma." (Gragoudas ES, Arch Ophthalmol. 2000 Jun;118(6):773-8.)
 * Randomized. 188 patients with small/medium choroidal melanoma (<15mm diameter, <5mm height), within 4 disc diameters of optic disc or macula. Arm 1) 50 CGE vs. Arm 2) 70 CGE
 * 5-year outcome: visual acuity >20/200 similar at 55%; tumor regrowth similar at ~3%; mets similar at ~8%
 * Toxicity: 50 CGE significantly less visual loss; no difference in radiation papillopathy or maculopathy
 * Conclusion: Lower dose resulted in similar outcome, similar visual acuity loss, but improved visual field loss

Heavy Ions

 * UCSF; 1993 PMID 8414414 -- "Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial." (Char DH, Ophthalmology. 1993 Oct;100(10):1547-54.)
 * Randomized. 184 patients, diameter <15mm, thickness <10 mm. Arm 1) helium ion with vs. Arm 2) I-125 plaque brachytherapy. Dose 70 Gy in both arms, but significantly different in delivery: Helium ion given 70/5 over 2 minutes each vs. I-125 continuous LDR 0.7-0.75 Gy /hr
 * Outcome: local failure He 0% vs. 13%; enucleation 2x more common after plaque. No difference in survival
 * Toxicity: More anterior segment complications after He.
 * Conclusion: RT can be used to manage uveal melanoma, with eye retention. Better control with He ion
 * Comment: Results led to increase in dose and dose-rate of plaque treatments