Single-masked Randomized Phase II Study Assessing Two Forms of Hypofractionated Proton Therapy in Patients with Large Choroidal Melanomas
Mené entre 2015 et 2017 sur 32 patients atteints d'un mélanome uvéal de stade T3/T4 et refusant une énucléation (âge moyen : 64 ans ; durée médiane de suivi : 56,7 mois), cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans récidive à 2 ans et de l'absence d'énucléation, de deux types de protonthérapie
Background: Patients with large uveal melanomas are at major risk of liver metastases. Some patients are reluctant to undergo the standard treatment, i.e., immediate enucleation. Proton therapy yields five-year local control rates and eyeball retention of >85% and ≈20% in large uveal melanomas. Patients with T3/T4 uveal melanomas refusing enucleation were randomized between standard 4-13Gy-fraction or moderately hypofractionated 8-6.5Gy-fraction proton therapy. The main endpoint was the two-year local recurrence-free survival without enucleation. Material and methods: A single-masked 1:2 randomized phase II trial was conducted between 2015 and 2017; with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse. Results: The 32 patients mean age 64 yo, had T3/4 (N=17/15), M1 (N=2) uveal melanomas, of mean tumor diameter and thickness of 16.5mm and 9.1mm and of posterior location in 56.5%. Median follow-up was 56.7 months. The two-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The two year-overall survival was 72% (95% confidence interval 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution (logMAR) was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (p=0.39). Conclusion: A 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.
International Journal of Radiation Oncology, Biology, Physics 2023