Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX.
J Clin Oncol. 2024 Oct;42(28):3319-3329. doi: 10.1200/JCO.24.00447. Epub 2024 Jul 25.
PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS).RESULTS15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; .001), followed by status (HR, 1.82 [95% CI, 1.42 to 2.33]; .001). The only clinical variable demonstrating additional prognostic value was tumor diameter.CONCLUSIONIn the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/ classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.
目的
在葡萄膜黑色素瘤（UM）中，经过验证且准确的预后检测对精准医学至关重要。我们的目的是：（1）前瞻性验证一种综合预后分类器，该分类器结合了 15 个基因表达谱（15-GEP）和 RNA 表达；（2）确定可增强 15-GEP/分类器预后准确性的临床变量。
材料和方法
本研究纳入了 1577 名患有脉络膜和/或睫状体 UM 的患者，这些患者均来自协作眼肿瘤学组研究 2（COOG2），并在北美 26 个中心进行了前瞻性监测。所有患者的 15-GEP（1 类或 2 类）和 RNA 表达状态（阴性或阳性）检测结果均可获得。主要终点是无转移生存率（MFS）。
结果
15-GEP 在 1082 名患者（68.6%）中为 1 类，在 495 名患者（31.4%）中为 2 类。在 1106 名患者（70.1%）中为 RNA 阴性，在 471 名患者（29.9%）中为 RNA 阳性。1 类/（-）患者的 5 年 MFS 为 95.6%（95%CI，93.9%至 97.4%），1 类/（+）患者为 80.6%（95%CI，73.9%至 87.9%），2 类/（-）患者为 58.3%（95%CI，51.1%至 66.4%），2 类/（+）患者为 44.8%（95%CI，37.9%至 52.8%）。多变量 Cox 比例风险分析显示，15-GEP 是 MFS 的最重要独立预测因素（风险比[HR]，5.95[95%CI，4.43 至 7.99]；.001），其次是 RNA 表达状态（HR，1.82[95%CI，1.42 至 2.33]；.001）。唯一具有附加预后价值的临床变量是肿瘤直径。
结论
在我们所知的迄今为止针对 UM 进行的最大规模的前瞻性多中心预后生物标志物研究中，COOG2 研究验证了综合 15-GEP/分类器比 15-GEP 单独和临床预后变量具有更高的预后准确性。发现肿瘤直径是唯一提供附加预后信息的临床变量。该预后分类器为 UM 患者的风险调整性转移监测和辅助试验分层提供了一个先进的资源。
