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Both fractionated stereotactic radiotherapy with CyberKnife (CK) and ocular proton beam therapy with a dedicated ocular beamline have proven to be successful eye-conserving treatments for uveal melanoma patients. Both modalities have reported a high local tumor control in the literature, but comparative data are lacking regarding the likelihood of post-therapy ocular complications derived from imaging-based planning. This dosimetric study aims to evaluate and compare the potential radiation-induced secondary complications assessed in clinical CK plans vs. proton plans, which were simulated in line with the clinical one-beam practice using a dedicated ocular beamline.

Retrospective CT-based treatment plans of 16 patients with critical posterior tumors in the eye were used in this study. All tumors had T1 T2 staging and were abutting the optic nerve within 3 mm. Patients were previously treated with a total CK dose of 50 GyRBE in 5 fractions prescribed at the 80% isodose line (clinical plans). Corresponding proton plans were simulated with a 60 GyRBE dose prescribed at the 90% isodose line to be delivered in 4 fractions according to clinical protocol. For the proton plans, individual gazing angles were selected to prioritize the optic nerve and macula sparing. Dosimetric parameter values (D_2%, D_20%, D_25%, D_mean) were selected as predictors of radiation-induced toxicity and were compared between both modalities. Patient-specific spider maps were used to compare the dosimetric parameters and the risk and severity of the main radiogenic side-effects with each treatment. Two-sided Wilcoxon signed-rank tests were used to assess the statistical significance (p-value<.05) of the dosimetric differences between modalities.

Tumor coverage was reached for all patients with both modalities: median D_mean=59.8 (CK) vs. 58.9 GyRBE (proton plans). The spider maps are shown in Fig.1A, and the associated ocular risk and severity in Fig.1B. In 11/16 patiens, the CK plans increased the D_2% of the optic nerve compared to the proton plans (median=38.0 vs. 17.9 GyRBE, p-value=0.019, respectively), and the D_2% of the lacrimal gland (median 16.1 vs. 0.0 GyRBE, p-value<0.001, respectively). The same dose level for the D_2% of the macula and D_20% of the sclera was reported. Lastly, a decrease in both D_2% (median=12.9 vs. 42.2 GyRBE, p-value=0.002, respectively) and D_25% (median=8.1 vs. 29.6 GyRBE, p-value=0.038, respectively) of the anterior segment was obtained with CK compared to protons.

Whereas proton therapy has the potential to decrease the risk of optic neuropathy and dry-eye syndrome compared to CK, radiation-induced complications occurring in the anterior segment of the eye (ie neovascular glaucoma) are lower with CK. Radiation-induced indicator tools as presented in this work could support the decision-making process of choosing the most appropriate treatment for uveal melanoma patients.