Wysong Ashley, Somani Ally-Khan, Ibrahim Sherrif F, Cañueto Javier, Fitzgerald Alison L, Siegel Jennifer J, Prasai Anesh, Goldberg Matthew S, Farberg Aaron S, Regula Christie, Bar Anna, Kasprzak Julia, Brodland David G, Koyfman Shlomo A, Arron Sarah T
Department of Dermatology, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Dermatol Ther (Heidelb). 2024 Mar;14(3):593-612. doi: 10.1007/s13555-024-01111-5. Epub 2024 Mar 1.
The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old.
This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP.
Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models).
The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.
经过验证的40基因表达谱（40-GEP）检测可独立对具有高危临床病理特征的皮肤鳞状细胞癌（cSCC）肿瘤发生区域或远处转移的风险进行分层。本研究在一大群具有一个或多个高危因素的肿瘤以及临床相关亚组中评估了40-GEP检测的风险分层情况，这些亚组包括美国国立综合癌症网络（NCCN）高危和极高危组中的肿瘤、较低分期的布莱根妇女医院（BWH）T1和T2a肿瘤以及年龄>65岁的患者。
这项针对40-GEP的多中心（n = 58）性能研究纳入了897例患者。进行了Kaplan-Meier分析，以评估40-GEP 1类（低）、2A类（较高）和2B类（最高）风险组的风险分层情况，同时使用嵌套Cox回归模型比较临床病理风险分类系统与结合40-GEP的风险分类系统的风险预测。
被分类为40-GEP 1类、2A类或2B类的患者具有显著不同的转移风险情况（p < 0.0001）。将40-GEP结果整合到包含个体临床病理风险因素或风险分类系统（布莱根妇女医院、美国癌症联合委员会第8版分期手册）以及NCCN的模型中，在转移事件预测准确性方面有显著提高（模型偏差的方差分析，所有模型的p < 0.0001）。
40-GEP检测显示出准确、独立且具有临床可操作性的转移风险分层，并且在整合到风险分类系统中时可提高预测准确性。通过40-GEP检测纳入肿瘤生物学信息时风险评估准确性的提高确保了更符合风险情况的个性化患者管理决策。
