Abstract
Purpose :
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM is an especially challenging and rare diagnosis for adolescent and young adult patients, a population for which limited data exists. Multiple risk factors and genetic abnormalities have been implicated in UM, but pathophysiology is poorly understood. We aimed to investigate potential novel associated factors, specifically in young UM patients.
Methods :
Case-control study of 247 UM patients (age ≤45) treated with PBT at a tertiary center and 400 age, sex-matched controls. We obtained demographic and genetic data, social history, environmental exposures, medical and ocular history via retrospective chart review and phone follow-up.
Results :
Median age at diagnosis was 38 years (range 13-45). Median follow-up time was 8 years (0-27). Median time to distant metastasis (DM) progression was 4 years (0-18) in 51 patients (21%). 10-year DM-free rate was 81%, and 10-year overall survival was 83%. Other primary cancers developed in 35 (14%) patients. Gene expression profiling was available in 67 patients, with 54% class IA, 19% class IB, and 27% class 2, and for those with specific genetic mutations available (n=9), most commonly mutated genes were GNAQ (56%), SF3B1 (56%), EIF1AX (33%), and GNA11 (22%). Based on preliminary results, risk factors associated with significantly increased odds ratio (OR) of UM included exposure to cigarette smoke (OR=3.6, p<0.0001), toxic chemicals (5.6, p=0.002), tanning bed use (9.6, p=0.0002), another primary cancer (4.5, p<0.0001), family history of cancer (2.2, p<0.0001), family history of skin (2.9, p=0.005) or ocular (p=0.04) melanoma, prior eye trauma in the UM eye (3.4, p=0.02), light eye color (7.7, p<0.0001), White race (3.8, p<0.0001), Ashkenazi Jewish descent (5, p<0.0001), not wearing eyewear outdoors (2.9, p=0.002), and pregnancy at diagnosis (3.1, p=0.02).
Conclusions :
To our knowledge, this is the first matched case-control study in adolescent and young adult UM patients. Our findings reaffirm certain established and highlight select new associated risk factors for UM in young patients. Further studies are needed to determine whether genetic and environmental factors can be identified to screen earlier for at-risk populations, given the rarity and severity of potential impact from uveal melanoma in young patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.