Case Study

Plaque Radiotherapy for the Treatment of Choroidal Melanoma

AKRIT SODHI, MD, PhD · CATHY DIBERNARDO, RN · JULIA HALLER, MD · JAMES HANDA, MD

The incidence of malignant melanoma in North America is estimated at approximately 7 per million per year, or 1200 to 1400 new melanomas annually. Although most ophthalmologists agree that malignant melanomas of the choroid require treatment, there is little information regarding the natural history of uveal melanoma. Small historic studies indicate that many untreated melanomas lead to metastatic disease and death.¹ With larger tumors, and tumors with documented evidence of rapid growth, patients are more likely to develop early metastasis.² Conversely, small melanomas, even if growing, are unlikely to metastasize if the tumor volume remained less than 98 mm³.³

BACKGROUND

Before the 1970s, enucleation was the most common management of malignant melanoma. However, in a landmark paper, Zimmerman and colleagues⁴ suggested that enucleation itself might be associated with increased risk of metastatic disease. Controversy over the effectiveness of enucleation for the treatment of uveal melanoma prompted the Collaborative Ocular Melanoma Study (COMS) in 1986.⁵ The trial included 3 substudies: a large-size tumor trial comparing enucleation vs enucleation preceded by external radiation; a medium-size tumor trial comparing enucleation and brachytherapy; and a natural history study of small melanomas.⁶ In the first arm of the study, patients with large-size melanomas (more than 8 mm in thickness and/or greater than 16 mm in longest base diameter) were randomized between enucleation alone and enucleation preceded by external radiation (2000 centigrays).⁷ At 5- and 8-year follow-ups, radiation neither favorably nor unfavorably influenced outcomes in terms of local orbital complications or 5-year survival. Adjunct radiation therapy for large-size tumors has subsequently fallen out of favor.

In the second arm of the study, patients with a medium-size melanomas (3.1 mm to 8 mm in thickness and no more than 16 mm in longest base diameter) were randomized between enucleation and brachytherapy (using iodine 125).⁸ Mortality rates were not found to differ between the 2 groups up to 12 years after treatment. Plaque radiotherapy is now the first line of treatment for patients with medium-size melanomas. In the natural history study of small melanomas (1 to 3 mm in apical height and at least 5 mm in diameter), delay or refusal of treatment was associated with an increased incidence of metastatic disease and/or early death when compared with 5-year mortality rates of a relatively comparable group of patients who received prompt treatment within the COMS;⁹ although not statistically significant, this evidence did support the concept that treatment of choroidal melanoma is generally indicated to prevent metastatic disease.

Here we describe the use of plaque radiotherapy using iodine-125 for the treatment of a patient with a medium-size choroidal melanoma.

METHODS

Under local sedation, a 360° peritomy was fashioned and the 4 rectus muscles were identified and isolated. Using transillumination, the tumor was identified in the infero-temporal quadrant and was marked on the globe with diathermy. After confirming optimal positioning using a dummy plaque, a 20-mm plaque containing 24 iodine 125 seeds with a total radioactivity of 56.07 millicuries was placed on the eye overlying the tumor and sutured in place. The plaque was checked and verified to be in position with indirect ophthalmoscopy and scleral depression. The conjunctiva and Tenon's capsule were closed. Approximately 4 days later, the patient returned to the operating room where, under local sedation, a partial peritomy was fashioned at the temporal and inferotemporal quadrant and Tenon's capsule and conjunctiva were reflected back to expose the plaque that was removed from the globe. The plaque was inspected and found to contain all of its seeds. The Tenon's capsule and conjunctiva were closed. The total treatment time was 98.96 hours, with the apex of the tumor receiving 88.73 grays.

RESULTS

A 55-year-old man presenting for a second opinion regarding a melanocytic mass in the right eye diagnosed approximately 1 month prior to presentation. When first examined in our office, visual acuity (VA) measured 20/30 in the right eye and 20/25+ in the left eye. His confrontation visual fields on the right eye showed a superior scotoma and was full on the left. Slit lamp examination demonstrated a normal anterior segment in both eyes. Dilated fundoscopic examination of the right eye revealed a 16 × 15 × 3 mm melanocytic lesion with some drusen deposits overlying the lesion just inferior to the macula and an associated inferior exudative retinal detachment over 180° that does not appear to involve the fovea (Figures 1A and B). B-scan ultrasonography demonstrated multilobed lesion with adjacent retinal detachment (Figures 1C and D) and that the lesion measured 14.2 mm laterally × 16.7 mm radially, with a maximum thickness of 3.2 mm by A-scan (Figures 1E and F). After a lengthy discussion of treatment options, which included a number of different radiation modalities, plaque radiotherapy was ultimately recommended after a routine metastatic screening. The patient underwent surgical placement of a 20-mm iodine 125 radioactive plaque in the right eye 3 weeks later with a total treatment time of 98.96 hours; the apex of the tumor received 88.73 grays.

Figure 1. Appearance of lesion on presentation. A and B. Fundus photographs of the right eye of the patient on initial presentation demonstrating a melanocytic lesion with some drusen deposits overlying the lesion. There is evidence of an inferior exudative retinal detachment that does not appear to involve the macula. B. Transverse B-scan showing a multilobed lesion with adjacent retinal detachment (arrows). C. Longitudinal B-scan showing the radial extent of the tumor (arrow) and its relationship to the optic nerve. D. Standardized A-scan at tissue sensitivity showing the moderate reflectivity (arrow). Vascularity was noted during the dynamic examination. E and F. Standardized A-scan at decreased gain setting to obtain appropriate measurements from the surface of the tumor to the inner scleral spike (double arrow). The lesion had a maximum thickness of 3.2 mm and measures 14.2 mm laterally × 16.7 mm radially.

ALL IMAGES APPEAR COURTESY OF THE AUTHORS.

At his 1-month postoperative follow-up, the patient noted that his vision remained blurry out of the right eye and complained of occasional diplopia. On exam, he had a VA of 20/100 in the right eye. Slit lamp examination of the right eye was notable for local conjunctival injection in the inferotemporal quadrant on the right. Dilated fundoscopic examination of the right eye revealed a small amount of subfoveal fluid. The melanocytic lesion and subretinal fluid otherwise appeared unchanged.

The patient returned for his 6-month follow-up. On examination, his VA was 20/60 +2 in the right eye and his slit lamp examination revealed a normal anterior segment. Dilated fundoscopic examination of the right eye revealed a 16 × 15 × >2 mm collapsed melanocytic lesion seen inferiorly and slightly temporally, and adjacent to this was a small area of subretinal fluid. A- and B-scan ultrasound were performed and demonstrated an irregular contour of the lesion with a maximum thickness of 2.3 mm. The patient was followed every 6 months and continued to improve over the next 3 years. At his most recent follow-up, approximately 5 years after plaque radiotherapy, his VA was 20/100 +1 in the right eye. His extraocular movements were full, and he was orthophoric. Slit lamp examination of the anterior segment of the right eye was notable for a moderate cataract. Dilated fundoscopic examination of the right eye demonstrated a 10 × 10 × 1 mm melanocytic lesion with marked scarring within the lesion. B-scan ultrasound demonstrated a maximum thickness of 1 mm (Figure 2).

Figure 2. Five years post-treatment. A. transverse and B. longitudinal B-scans showing only mild irregular fundus thickening (less than 1 mm) in the area of the treated tumor (arrows). ON represents the shadow of the retrobulbar optic nerve.

DISCUSSION

The treatment of choroidal melanomas with radiation began in 1929 with the use of radon seeds,¹⁰ and later with cobalt 60.¹¹ Plaque radiotherapy remains the gold standard for the treatment of medium-size choroidal melanomas, as in the current case. However, it is not without its critics, who point out the relatively disappointing long-term results associated with depressed vision; nearly one-half of the patients treated with I-125 brachytherapy in the medium-size tumor arm of the COMS lost substantial vision (loss of 6 or more lines from the baseline) by 3 years. Other side effects include neovascular glaucoma, radiation retinopathy, cataracts, and corneal injuries.

Every patient deserves a thoughtful individual assessment before therapeutic avenues are pursued. Management of choroidal melanoma depends on several factors including patient age, tumor size and location, systemic health of the patient, and the status of the other eye. While recent advances in the management of patients with choroidal melanomas have expanded our therapeutic arsenal (eg, photocoagulation, transpupillary thermotherapy, plaque radiotherapy, charged-particle irradiation, local resection, enucleation, orbital exenteration, chemotherapy, immunotherapy, and various combinations of thesemethods), enucleation and plaque radiotherapy remain the mainstays of treatment. Future studies examining the efficacy of combination therapy, and mechanism-based gene–product-targeted therapies, as well as the value of earlier treatment of small melanomas, may ultimately be required for the successful management of this lethal disease. RP

REFERENCES

1. Raivio I. Uveal melanoma in Finland. An epidemiological, clinical, histological and prognostic study. Acta Ophthalmol Suppl. 1977;133:1-64.
2. Char DH, Kroll S, Phillips TL. Uveal melanoma. Growth rate and prognosis. Arch Ophthalmol. 1997;115:1014-1018.
3. Thomas JV, Green WR, Maumenee AE. Small choroidal melanomas. A long-term follow-up study. Arch Ophthalmol. 1979;97:861-864.
4. Zimmerman LE, McLean IW, Foster WD. Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells. Br J Ophthalmol. 1978;62:420-425.
5. Straatsma BR, Fine SL, Earle JD, Hawkins BS, Diener-West M, McLaughlin JA. Enucleation versus plaque irradiation for choroidal melanoma. Ophthalmology. 1988;95:1000-1004.
6. Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study. COMS Report No. 3. Control Clin Trials. 1993;14:362-391.
7. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma II: initial mortality findings. COMS report no. Am J Ophthalmol. 1998;125:779-796.
8. 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. 2001;119:969-982.
9. Mortality in patients with small choroidal melanoma. COMS report no. 4. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. 1997;115:886-893.
10. Moore R. Choroidal sarcoma treated by intraocular insertion of radon seeds. Br J Ophthalmol. 1930;14:145.
11. Stallard HB. Radiotherapy for malignant melanoma of the choroid. Br J Ophthalmol. 1966;50:147-155.