Ranibizumab for the Prevention of Radiation Complications in Patients Treated With Proton Beam Irradiation for Choroidal Melanoma

Abstract

Purpose: To investigate the safety and potential efficacy of ranibizumab for prevention of radiation complications in patients treated with proton irradiation for choroidal melanoma.

Methods: Forty patients with tumors located within 2 disc diameters of the optic nerve and/or macula were enrolled in this open-label study. Participants received ranibizumab 0.5 mg or 1.0 mg at tumor localization and every 2 months thereafter for the study duration of 24 months. The incidence of adverse events, visual acuity, and other measures of ocular morbidity related to radiation complications were assessed. Historical controls with similar follow-up meeting the eligibility criteria for tumor size, location, and baseline visual acuity were assembled for comparison.

Results: Fifteen patients with large tumors and 25 patients with small/medium tumors were enrolled. Thirty-two patients completed the month 24 visit. No serious ocular or systemic adverse events related to ranibizumab were observed. At 24 months, the proportion of patients with visual acuity ≥ 20/200 was 30/31 (97%) in the study group versus 92/205 (45%) in historical controls (P < .001). The proportion of patients with visual acuity ≥20/40 was 24/31 (77%) in the study group versus 46/205 (22%) in controls at 24 months (P<.001). Clinical evidence of radiation maculopathy at month 24 was seen in 8/24 (33%) patients with small/medium tumors versus 42/62 (68%) of controls (P = .004). Three patients with large tumors developed metastases.

Conclusions: In this small pilot study, prophylactic ranibizumab appears generally safe in patients treated with proton irradiation for choroidal melanoma. High rates of visual acuity retention were observed through 2 years.

Figures

FIGURE 1

Cumulative rates of visual acuity retention of ≥20/200 for overall study cohort. The difference between the curves is statistically significant, P<.001 (Log-rank test).

FIGURE 2

Cumulative rates of visual acuity retention of ≥20/200 for large tumor group. The curves are not significantly different, P=.62 (Log-rank test).

FIGURE 3

Cumulative rates of visual acuity retention of ≥20/200 for small/medium tumor group. The difference between the curves is statistically significant, P=.006 (Log-rank test).

FIGURE 4

Cumulative rates of visual acuity retention of ≥20/40 for small/medium tumor group. The difference between the curves is not statistically significant, P=.11 (Log-rank test).

FIGURE 5

Cumulative rates of vision retention within 3 lines from baseline (P =.04 (Log-rank test)

FIGURE 6

Representative examples of patients from small/medium tumor group. A. Color fundus photograph of a patient at baseline with visual acuity 20/16. B. Same patient at month 24 with some clinical signs of radiation maculopathy. Visual acuity remains 20/16. C. Color fundus photograph of a patient at baseline with visual acuity 20/20. D. Same patient at month 24 with visual acuity 20/20. E. Color fundus photograph of patient at baseline with visual acuity 20/25. F. Same patient at month 24 with no signs of radiation maculopathy but decrease in visual acuity to 20/63.