To study the relationship between gene expression profile subclass and clinical features in a multicenter cohort of patients with uveal melanoma.
A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Eligible patients had uveal melanoma and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with gene expression profile testing between January 1, 2010, and October 28, 2014. Data were collected regarding patient demographics, baseline tumor clinical features, and gene expression profile results. Statistical analyses were performed using the Fisher's exact test, Wilcoxon rank-sum test, Kruskal–Wallis test, and proportional-odds cumulative logit modeling.
Inclusion criteria were met for 379 patients. Gene expression profile class divided the cohort into two main groups, Class 1 (n = 263) and Class 2 (n = 113). Class 1 tumors were further subdivided into Class 1a (n = 186) and Class 1b (n = 77). The differences between Class 1 and Class 2 tumors were similar to previous studies, except the finding of Class 2 tumors being more likely to have associated exudative retinal detachment (P < 0.001). There was no statistically significant difference between Class 1 and Class 2 tumors based on the presence of lipofuscin, drusen, or subretinal fluid. Class 1a tumor patients, compared with Class 1b, were significantly older (P = 0.034). Class 2 tumors, when compared with Class 1b, were associated with increasing patient age (P < 0.001), larger tumor height (P = 0.010), ciliary body involvement (P = 0.001), exudative retinal detachment (P = 0.024), and anterior tumor location (P < 0.001). When the tumors were grouped into Collaborative Ocular Melanoma Study size categories, increasing tumor size category was significantly associated with Class 2 status: 6% of small tumors, 32% of medium tumors, and 53% of large tumors were Class 2.
In a multi-institutional setting, we found that the only significant difference in clinical features between Class 1a and Class 1b tumors was that patients with Class 1a tumors were older at the time of diagnosis. We also found that Class 1a and Class 1b have clinical features distinct from Class 2 tumors. The distribution of the gene expression profile subclasses among the size groups was similar to reported time-to-metastasis data among the same size groupings. Our clinical findings support the current molecular classification-based survival data previously reported in uveal melanoma.
A multi-institutional, retrospective analysis of baseline clinical features of uveal melanoma based on gene expression profile subclass.
*Department of Ophthalmology, Duke University, Durham, North Carolina;
†Department of Radiation Oncology, Duke University, Durham, North Carolina;
‡Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas;
§Retina Consultants of Houston, Houston, Texas;
¶The Permanente Medical Group, San Francisco, California, and
**Byers Eye Institute, Stanford University, Stanford, California.
Reprint requests: Amy Schefler, MD, 6560 Fannin Street Suite 750, Houston, TX 77030; e-mail: firstname.lastname@example.org.
P. Mruthyunjaya: Provided by the Childress Family Foundation (NC). A. Skalet: Supported by unrestricted departmental funding from Research to Prevent Blindness (New York, NY) and by Grant P30 EY010572 from the National Institutes of Health (Bethesda, MD).
J. W. Harbour is the inventor of intellectual property used in the study and receives royalties from its commercialization. He is a paid consultant for Castle Biosciences, licensee of intellectual property presented in this article. T. Aaberg, Jr., M. Materin, and P. Mruthyunjaya are consultants for Castle Biosciences. Remaining authors have no any financial/conflicting interests to disclose.
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Ocular Oncology Study Consortium members are listed in Appendix 1.