Uveal melanoma: Molecular pattern, clinical features, and radiation response

• PURPOSE: To characterize the clinical spectrum of class 1 and class 2 uveal melanomas and their relationship with intraocular proton radiation response. • DESIGN: Masked retrospective case series of uveal melanoma patients with fine needle biopsy- based molecular profiles. • METHODS: A total of 197 uveal melanoma patients from a single institution were analyzed for pathology, clinical characteristics, and response to radiation therapy. • RESULTS: A total of 126 patients (64%) had class 1 tumors and 71 (36%) had class 2 tumors. Patients with class 2 tumors had more advanced age (mean: 64 years vs 57 years; P = .001), had thicker initial mean ultrasound measurements (7.4 mm vs 5.9 mm; P = .0007), and were more likely to have epithelioid or mixed cells on cytopathology (66% vs 38%; P = .0004). Although mean pretreatment and posttreatment ultrasound thicknesses were significantly different between class 1 and class 2 tumors, there was no difference in the mean change in thickness 24 months after radiation therapy (mean difference: class 1=-1.64 mm, class 2=-1.47; P = .47) or in the overall rate of thickness change (slope: P = .64). Class 2 tumors were more likely to metastasize and cause death than class 1 tumors (DSS: P < .0001). • CONCLUSIONS: At the time of radiation therapy, thicker tumors, epithelioid pathology, and older patient age are significantly related to class 2 tumors, and class 2 tumors result in higher tumor-related mortality. We found no definitive clinical marker for differentiating class 1 and class 2 tumors.