Elsevier

Ophthalmology

Volume 126, Issue 10, October 2019, Pages 1445-1453
Ophthalmology

Original Article
Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D

Presented in part at: Retina Society Annual Meeting (J. Donald M. Gass Award), September 2019, London, United Kingdom.
https://doi.org/10.1016/j.ophtha.2019.04.027Get rights and content

Purpose

The Cancer Genome Atlas (TCGA) classification has been validated for uveal melanoma (UM) prognostication. We applied TCGA classification to UM biopsied using fine-needle aspiration biopsy (FNAB) to determine the predictability for metastasis and death.

Participants

Patients with UM treated with plaque radiotherapy at Wills Eye Hospital, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, who completed genetic analysis of chromosomes 3 and 8 after FNAB.

Methods

Tumors were classified as A, B, C, or D and were compared using the chi-square test, Fisher exact test, analysis of variance, and Kaplan-Meier analysis.

Main Outcome Measures

Metastasis and death.

Results

Six hundred fifty-eight UM patients were categorized accordingly as TCGA class A (n = 342 [52%]), B (n = 91 [14%]), C (n = 118 [18%]), and D (n = 107 [16%]). More advanced tumor classification revealed older mean patient age (56 vs. 53 vs. 60 vs. 63 years, respectively; P < 0.001), worse presenting visual acuity (20/20–20/50: 81% vs. 67% vs. 71% vs. 66%, respectively; P < 0.001), greater distance from the optic disc (3.5 vs. 4.9 vs. 5.7 vs. 5.3 mm, respectively; P < 0.001), larger tumor basal diameter (10.3 vs. 12.9 vs. 13.9 vs. 15.3 mm, respectively; P < 0.001), and greater tumor thickness (4.3 vs. 6.1 vs. 6.6 vs. 7.5 mm, respectively; P < 0.001). After mean follow-up (47.6 vs. 47.6 vs. 42.9 vs. 28.7 months, respectively; P < 0.001), more advanced TCGA class was associated with increased risk of metastasis (3% vs. 10% vs. 25% vs. 41%, respectively; P < 0.001) and death (1% vs. 0% vs. 3% vs. 9%, respectively; P < 0.001). Compared with class A, the 5-year hazard ratio for metastasis increased at 4.1 (B vs. A; P = 0.01), 10.1 (C vs. A; P < 0.001), and 30.0 (D vs. A; P < 0.001). The 5-year hazard ratio for death increased at 3.1 (C vs. A; P = 0.11) and 13.7 (D vs. A; P < 0.001) with no deaths in class B.

Conclusions

Grouping of UM using TCGA classification predicts the risk of melanoma-related metastasis and death.

Section snippets

Methods

The medical and imaging records of all patients diagnosed with UM at the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, were reviewed. All patients with UM who completed FNAB for genetic analysis (analysis of chromosomes 3 and 8) were included. Patients without complete genetic analysis, including both chromosomes 3 and 8, were excluded. This study was conducted in accordance with the

Results

One thousand five tumors from 1304 patients were treated with plaque radiotherapy during the study period. Six hundred forty-six patients were excluded because of insufficient sample for genetic analysis, only chromosome 3 analysis, or declination of genetic testing. Six hundred fifty-eight tumors from 658 patients were able to be classified according to TCGA classification into class A (n = 342 [52%]), B (n = 91 [14%]), C (n = 118 [18%]), and D (n = 107 [16%]), as described in Table 1.

Discussion

Despite excellent local ocular tumor control for primary UM in the era of plaque radiotherapy, death resulting from metastatic disease remains prevalent, with metastasis in nearly 50% of all patients.15 Although clinical tumor features have prognostic value in UM, the oncology landscape has shifted toward genetic testing for cancer prognostication, and clinical trial eligibility for novel therapies that could prevent metastasis often depends on genetic testing results. Therefore, to identify

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    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported in part by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (C.L.S.). The funders had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. Carol L. Shields, MD, has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at Wills Eye Hospital approved the study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.

    No animal subjects were included in this study.

    Author Contributions:

    Conception and design: Vichitvejpaisal, Dalvin, Mazloumi, Shields

    Analysis and interpretation: Vichitvejpaisal, Dalvin, Mazloumi, Ewens, Ganguly, Shields

    Data collection: Vichitvejpaisal, Ewens, Ganguly

    Obtained funding: Shields

    Overall responsibility: Vichitvejpaisal, Dalvin, Mazloumi, Ewens, Ganguly, Shields

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