Ocular Oncology Service, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
Tumori Foundation, California Pacific Medical Center, San Francisco.
JAMA Ophthalmol. 2016 Jul 1;134(7):734-40. doi: 10.1001/jamaophthalmol.2016.0913.
Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis.
To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015.
Progression-free survival (PFS). The secondary outcome was overall survival.
The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort.
Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.
葡萄膜黑色素瘤（UM）可以根据前瞻性验证和广泛使用的 15 个基因表达谱（GEP）测试分为具有预后意义的亚组。1 类 UM 转移风险低，2 类 UM 转移风险高。
确定是否有任何临床病理因素提供独立的预后信息，可能会提高 GEP 分类的准确性。
设计、地点和参与者：这项在 2 个眼科肿瘤转诊中心进行的回顾性观察性研究纳入了 339 名原发性队列患者和 241 名验证队列患者，这些患者均来自睫状体和/或脉络膜的 UM。所有患者均接受 GEP 预后检测肿瘤活检。临床病理变量包括患者年龄和性别、肿瘤厚度、最大基底肿瘤直径（LBD）、睫状体受累和病理细胞类型。原发性队列的患者于 1998 年 11 月 1 日至 2012 年 3 月 16 日入组；验证队列的患者于 1996 年 11 月 4 日至 2013 年 11 月 7 日入组。原发性队列的随访于 2013 年 8 月 18 日结束；验证队列的随访于 2013 年 12 月 10 日结束。数据分析于 2013 年 11 月 12 日至 2015 年 11 月 25 日进行。
无进展生存期（PFS）。次要结局是总生存期。
原发性队列包括 339 名患者（175 名女性[51.6%]；平均[SD]年龄 61.8[13.6]岁）。最重要的预后因素是 GEP 分类（exp[b]，10.33；95%CI，4.30-24.84；P < .001）。唯一提供独立预后信息的其他变量是 LBD（exp[b]，1.13；95%CI，1.02-1.26；P = .02）。在 2 类 UM 中，LBD 与 PFS 呈适度但显著相关（exp[b]，1.13；95%CI，1.04-1.24；P = .005）。5 年无转移生存估计（SE）为：LBD 小于 12mm 的 1 类 UM 为 97%（3%），LBD 大于或等于 12mm 的 1 类 UM 为 90%（4%），LBD 小于 12mm 的 2 类 UM 为 90%（9%），LBD 大于或等于 12mm 的 2 类 UM 为 30%（7%）。LBD 和 12mm LBD 截断值的独立预后价值在独立的验证 241 名患者队列中得到了证实。
治疗时 LBD 小于 12mm 的 2 类 UM 预后更好。这些发现可能对患者咨询、原发肿瘤治疗、临床试验入组、转移监测和辅助治疗具有重要意义。
