Ocular Tumors
Visual Outcomes of Parapapillary Uveal Melanomas Following Proton Beam Therapy

https://doi.org/10.1016/j.ijrobp.2015.12.011Get rights and content

Purpose

In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with respect to visual acuity after proton therapy.

Methods and Materials

Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported.

Results

A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively.

Conclusions

A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.

Introduction

Uveal melanoma is the most frequently diagnosed primary ocular tumor. Several studies (randomized and large retrospective ones) have validated the use of conservative treatments against enucleation owing to similar survival rates and no increased risk of metastasis with either treatment (1). Parapapillary melanomas refer to tumors close to the optic disk, whereas juxtapapillary melanomas refer to tumors abutting the optic disk, and both can be difficult to treat with brachytherapy (2). Hypofractionated proton therapy is performed in approximately 12 centers worldwide (3) and yields eye conservation and 5-year tumor relapse-free rates of approximately 90% and 94% to 96%, respectively 4, 5. In parapapillary melanoma patients, full dose to the papilla is commonly unavoidable, and radiation-induced optic neuropathy (RION), maculopathy, neovascular glaucoma (NVG), retinal detachment, and intraocular hemorrhage are associated with visual deterioration. Considering that the optic nerve has a serial architecture, full-dose irradiation of its section proximal to the retina theoretically leads to vision loss. However, it has been suggested that the optic nerve has a mixed behavior and that more complex dose volume effects have been reported with external beam irradiation (6). Moreover, observations suggest that patients receiving the maximal dose to their whole papillary surface with proton therapy recover some vision 7, 8. We investigated the impact of personalized optic nerve sparing despite papillary irradiation on visual acuity (VA) in a series of consecutive parapapillary melanoma patients treated with computed tomography (CT)-based proton therapy planning.

Section snippets

Treatment planning

Eye proton therapy started in 1991, using the 65-MeV dedicated hospital-based cyclotron of Nice, France. Four tantalum fiducial markers (clips) were positioned on the sclera under anesthesia, using transillumination 9, 10. Clip-to-clip, tumor-to-clips, tumor-to-macula and papilla distances, thicknesses, and diameters were reported in ophthalmology reports based on transillumination, fundus (or retinography/angiography), and ultrasonography. Proton therapy was performed 2 to 4 weeks after clip

Results

There were 4224 uveal melanoma patients (among 5205 ocular tumor patients). The selected 865 parapapillary melanoma patients were younger than the overall population. Diameter, thickness and stage were smaller and extrascleral extension, involvement of the ciliary body and iris root less frequent while retinal detachment was more frequent Baseline VA was worse than in the overall population Other initial characteristics were similar (data not shown). There was a center effect with respect to

Discussion

Consistent with previous observations, this 865-patient series suggests that effective visual preservation can be obtained in parapapillary melanomas treated with hypofractionated proton therapy, with good local control 7, 9, 13, 14. In patients with baseline VA of ≥20/200 in the treated eye, Lane et al (13) showed that some vision was retained in 50% and 20% of patients at 2 and 5 years after irradiation and that 50% could count fingers (13). Similar to the study by Meyer et al (7), we chose 2

Conclusions

VA is a complex endpoint that depends on factors other than just the dose to the papilla and optic nerve length. Similarly, the optic nerve has a complex behavior as some patients recover some vision 5 years after the onset of papillopathy (8). We showed that other initial parameters, either related to the patient or disease, and complications highly influenced VA. Optic nerve length sparing appeared relevant. More systematic use of angiography during follow-up would probably help to

Acknowledgments

We thank Marie-Laure Peyrichon for careful reading of the manuscript and dosimetric studies.

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Conflict of interest: none.

J.T., J.H., and J-P.C. contributed equally to the manuscript.

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