Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy

Abstract

Objective: To assess oncological and ophthalmological outcomes after international referral of uveal melanoma patients for proton therapy. Materials and Methods: This is a retrospective study among Dutch uveal melanoma patients who were treated in Switzerland with 60.0 CGE proton therapy (in 4 fractions) from 1987 to 2019. All patients were ineligible for brachytherapy due to tumour size and/or proximity to the optic nerve. Time-to-event analyses were performed using Kaplan–Meier’s methodology and Cox proportional hazards models. Results: There were 103 patients (104 eyes) with a median largest tumour diameter of 19 mm (range 6–26 mm). Tumours were localised centrally (11%), mid-peripherally (65%) or peripherally (34%). Median follow-up was 7 years. Five-year local control, distant metastasis-free survival and eye preservation rates were 94%, 70% and 81% respectively. At five years, severe, moderate and mild visual impairment was observed in respectively 79%, 4% and 6% of the patients. Larger tumour volumes and more central tumour localisation were associated with severe visual impairment. After correction for these factors, dose to the macula, optic disc and retina, but not optic nerve was significantly associated with severe visual impairment. Conclusion: International referral for proton therapy yielded good tumour control and eye preservation rates, but risk of distant metastasis and severe visual impairment were substantial, possibly due to the selection of advanced tumour stages and/or central localisation. Dose to the macula may be more relevant than dose to the optic nerve for preservation of visual acuity, which is relevant for the treatment planning of proton therapy.

MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma

“…Given the heterogeneity of UM, also in terms of perfusion, an analysis which separately evaluates these distinct tumour parts might be more appropriate [ 30 ]. Furthermore, in accordance with the high rates of local control of 95% and 94% for ruthenium brachytherapy and PBT respectively [ 36 , 37 ], no recurrences were present in our cohort. A study with a longer follow-up is therefore warranted to determine if the observed biomarkers of therapy response are also indicative of a good response with no local recurrences on the longer term.…”

“…Patients were included in the study between March 2019 and March 2021. Following national guidelines, patients with small to intermediate-sized choroidal melanomas with a tumour prominence ≤ 7 mm and basal diameters ≤ 16 mm were considered eligible for ruthenium-106 brachytherapy, while larger tumours and juxtapapillary located tumours were referred for PBT at the HollandPTC (Delft, the Netherlands) [ 36 ]. For patients treated with brachytherapy, the dose to the tumour apex was 130 Gy, with a maximum scleral dose of 1000 Gy, as described by Marinkovic et al [ 37 ].…”

Automatic Three-Dimensional Magnetic Resonance-based measurements of tumour prominence and basal diameter for treatment planning of uveal melanoma

“…Although the benefit of including MRI in radiotherapy planning requires further study, we expect less benefit for patients treated with brachytherapy, due to the limited degrees of freedom with the currently available applicators. For PBT, however, the currently relatively large margins of up to 3 mm are in part needed for the uncertainties introduced by the ultrasound measurements [47] , [48] , [49] . Given the earlier reported benefits of including MRI for ocular PBT planning, we would recommend to perform an MRI for these patients and use the proposed 3D prominence and basal diameter definitions to resolve the discrepancies observed for complexly shaped tumours between MRI and ultrasound [25] , especially until fully image-based 3D treatment planning systems for UM are clinically available [21] , [50] , [51] , [52] .…”

Correction Method for Optical Scaling of Fundoscopy Images: Development, Validation, and First Implementation

“… 4 Currently, the tumor location and extent in ocular proton beam therapy are primarily modeled using tantalum clips and surgical measurements. 32 One of the steps toward clipless treatment would be to use fundus photographs to determine the tumor location relative to the macula. We assessed the impact of the varying scale of fundus images for a patient with an apparent 12.5-mm tumor–macula distance ( Fig.…”