Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Enucleation remains the standard therapy for most large choroidal melanomas and melanomas that cause severe glaucoma or invade the optic nerve. One of the two clinical trials of the Collaborative Ocular Melanoma Study (COMS) compared preoperative external-beam radiation therapy plus enucleation to enucleation alone in patients with large choroidal tumors to address the concern that enucleation might precipitate tumor metastasis and shorten survival.[1] After 10 years of follow-up, the cumulative all-cause mortality rate for each treatment arm was 61%. In addition, the 10-year rates of death with histopathologically confirmed melanoma metastasis were not significantly different (45% in the pre-enucleation radiation arm and 40% in the enucleation-alone arm, P = .40).[1][Level of evidence: 1iiA]

Episcleral radionuclide plaque brachytherapy and external-beam, charged-particle radiation therapy offer patients eye-sparing and vision-sparing alternatives to enucleation.[2,3] Both treatment approaches result in relatively slow regression of uveal melanoma during a period of 6 months to 2 years. Most tumors regress to approximately 50% of their original thickness; only occasionally does a tumor regress to a completely flat scar.[2] Local control is achieved in a large proportion of treated eyes with either technique. The probability of visual preservation and of eye retention with either method is related to tumor size and location.

Plaque brachytherapy is the most frequently used eye-sparing treatment for choroidal melanoma. Iodine 125 (¹²⁵I), gold 198 (¹⁹⁸Au), palladium 103 (¹⁰³Pd), and other ophthalmic plaques can be effective in the treatment of medium-sized melanomas.[4-7] ¹²⁵I is the most commonly used isotope because of its good tissue penetration, accessibility, adequate shielding of the source, and lesser risk to other ocular structures and medical personnel. Methods to ensure proper plaque placement are critical to successful radiation therapy.[8-12]

Results from the second COMS clinical trial, which compared ¹²⁵I plaque brachytherapy to enucleation in patients with medium-sized choroidal tumors, revealed no significant difference in cumulative all-cause mortality between the two study arms at 12 years of follow-up (43% for ¹²⁵I plaque brachytherapy vs. 41% for enucleation; risk ratio = 1.04; 95% CI, 0.86–1.24).[13][Level of evidence: 1iiA] In addition, the 12-year rates of death with histopathologically confirmed melanoma metastasis did not differ significantly between the 2 study arms (21% in the ¹²⁵I brachytherapy arm and 17% in the enucleation arm, P = .62). Among the patients treated with ¹²⁵I brachytherapy, 85% retained their eye for 5 years or more, and 37% had visual acuity better than 20/200 in the irradiated eye 5 years after treatment.[14]

Charged-particle radiation therapy can be performed with a proton beam or helium ions.[15,16] Some investigators report better tumor control with helium ion irradiation than with ¹²⁵I episcleral plaque treatment in terms of local tumor control and eye retention; however, more anterior segment complications are found.[15,17]

Another radiation therapy technique occasionally employed but not as extensively studied is Gamma Knife surgery. Preliminary evidence suggests that Gamma Knife surgery may be a feasible treatment option for medium-sized choroidal melanomas.[18]

Standard treatment options:

Tumor growth pattern is a factor in the therapeutic decision. If there is a diffuse melanoma or if there is extraocular extension, enucleation should be considered, but radiation therapy can be employed for less extensive disease.

Medium-sized choroidal melanomas

1. Plaque radiation therapy: Allows eye preservation in most patients, but vision is generally reduced; probability of vision preservation after treatment is related to tumor size and location.[2-12,14,15,19]



2. External-beam, charged-particle radiation therapy: Provides precisely focused radiation with a homogeneous dose distribution pattern and little lateral spread; requires sophisticated equipment available only at selected centers; involves patient cooperation during treatment (voluntarily fixating the eye on a particular point so the tumor is positioned properly in the radiation beam); allows for good local tumor control and reasonable retention of the treated eye for periods of as long as 10 years after treatment, according to reports.[15-17]



3. Local eye-wall resection: Allows for good ocular retention rates and visual results; survival does not appear to be compromised.[20,21]



4. Combined therapy, with ablative laser coagulation or transpupillary thermotherapy to supplement plaque treatment: Can be used to minimize recurrence; transpupillary thermotherapy can be used in conjunction with plaque radiation therapy for medium-sized and larger melanomas as an adjuvant treatment to enhance the effects of radiation therapy and to minimize damage to normal ocular tissue;[22] the addition of laser photocoagulation to plaque radiation therapy for juxtapapillary choroidal melanoma has been reported to increase tumor control substantially;[23] ocular side effects do occur but are usually not clinically significant.



5. Enucleation: Is considered primarily if there is a diffuse melanoma or if there is extraocular extension; radiation complications or tumor recurrence may eventually make enucleation necessary.[22]

Large choroidal melanomas

1. Radiation therapy plus enucleation.[24]
2. Enucleation.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with ciliary body and choroid melanoma, medium/large size. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Hawkins BS; Collaborative Ocular Melanoma Study Group.: The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am J Ophthalmol 138 (6): 936-51, 2004.  [PUBMED Abstract]
   
   
2. Shields CL, Shields JA, Gündüz K, et al.: Radiation therapy for uveal malignant melanoma. Ophthalmic Surg Lasers 29 (5): 397-409, 1998.  [PUBMED Abstract]
   
   
3. Finger PT: Radiation therapy for choroidal melanoma. Surv Ophthalmol 42 (3): 215-32, 1997 Nov-Dec.  [PUBMED Abstract]
   
   
4. Earle J, Kline RW, Robertson DM: Selection of iodine 125 for the Collaborative Ocular Melanoma Study. Arch Ophthalmol 105 (6): 763-4, 1987.  [PUBMED Abstract]
   
   
5. Packer S, Stoller S, Lesser ML, et al.: Long-term results of iodine 125 irradiation of uveal melanoma. Ophthalmology 99 (5): 767-73; discussion 774, 1992.  [PUBMED Abstract]
   
   
6. Finger PT, Berson A, Szechter A: Palladium-103 plaque radiotherapy for choroidal melanoma: results of a 7-year study. Ophthalmology 106 (3): 606-13, 1999.  [PUBMED Abstract]
   
   
7. Karvat A, Duzenli C, Ma R, et al.: The treatment of choroidal melanoma with 198 Au plaque brachytherapy. Radiother Oncol 59 (2): 153-6, 2001.  [PUBMED Abstract]
   
   
8. Finger PT, Romero JM, Rosen RB, et al.: Three-dimensional ultrasonography of choroidal melanoma: localization of radioactive eye plaques. Arch Ophthalmol 116 (3): 305-12, 1998.  [PUBMED Abstract]
   
   
9. Hanna SL, Lemmi MA, Langston JW, et al.: Treatment of choroidal melanoma: MR imaging in the assessment of radioactive plaque position. Radiology 176 (3): 851-3, 1990.  [PUBMED Abstract]
   
   
10. Harbour JW, Murray TG, Byrne SF, et al.: Intraoperative echographic localization of iodine 125 episcleral radioactive plaques for posterior uveal melanoma. Retina 16 (2): 129-34, 1996.  [PUBMED Abstract]
    
    
11. Tabandeh H, Chaudhry NA, Murray TG, et al.: Intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma. Am J Ophthalmol 129 (2): 199-204, 2000.  [PUBMED Abstract]
    
    
12. Finger PT, Iezzi R, Romero JM, et al.: Plaque-mounted diode-light transillumination for localization around intraocular tumors. Arch Ophthalmol 117 (2): 179-83, 1999.  [PUBMED Abstract]
    
    
13. Collaborative Ocular Melanoma Study Group.: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol 124 (12): 1684-93, 2006.  [PUBMED Abstract]
    
    
14. Diener-West M, Earle JD, Fine SL, et al.: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol 119 (7): 969-82, 2001.  [PUBMED Abstract]
    
    
15. Char DH, Quivey JM, Castro JR, et al.: Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial. Ophthalmology 100 (10): 1547-54, 1993.  [PUBMED Abstract]
    
    
16. Fuss M, Loredo LN, Blacharski PA, et al.: Proton radiation therapy for medium and large choroidal melanoma: preservation of the eye and its functionality. Int J Radiat Oncol Biol Phys 49 (4): 1053-9, 2001.  [PUBMED Abstract]
    
    
17. Char DH, Kroll SM, Castro J: Ten-year follow-up of helium ion therapy for uveal melanoma. Am J Ophthalmol 125 (1): 81-9, 1998.  [PUBMED Abstract]
    
    
18. Woodburn R, Danis R, Timmerman R, et al.: Preliminary experience in the treatment of choroidal melanoma with gamma knife radiosurgery. J Neurosurg 93 (Suppl 3): 177-9, 2000.  [PUBMED Abstract]
    
    
19. Melia BM, Abramson DH, Albert DM, et al.: Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology 108 (2): 348-66, 2001.  [PUBMED Abstract]
    
    
20. Char DH, Miller T, Crawford JB: Uveal tumour resection. Br J Ophthalmol 85 (10): 1213-9, 2001.  [PUBMED Abstract]
    
    
21. Peyman GA, Juarez CP, Diamond JG, et al.: Ten years experience with eye wall resection for uveal malignant melanomas. Ophthalmology 91 (12): 1720-5, 1984.  [PUBMED Abstract]
    
    
22. Seregard S, Landau I: Transpupillary thermotherapy as an adjunct to ruthenium plaque radiotherapy for choroidal melanoma. Acta Ophthalmol Scand 79 (1): 19-22, 2001.  [PUBMED Abstract]
    
    
23. Shields JA: The expanding role of laser photocoagulation for intraocular tumors. The 1993 H. Christian Zweng Memorial Lecture. Retina 14 (4): 310-22, 1994.  [PUBMED Abstract]
    
    
24. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma II: initial mortality findings. COMS report no. 10. Am J Ophthalmol 125 (6): 779-96, 1998.  [PUBMED Abstract]
    
    

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