Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Memorial Sloan Kettering Cancer Center, New York, New York.
Neuro Oncol. 2019 May 6;21(5):596-605. doi: 10.1093/neuonc/noy201.
Update 3 of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recognizes amplification of epidermal growth factor receptor (EGFR) as one important aberration in diffuse gliomas (World Health Organization [WHO] grade II/III). While these recommendations endorse testing, a cost-effective, clinically relevant testing paradigm is currently lacking. Here, we use real-world clinical data to propose a financially effective diagnostic test algorithm in the context of new guidelines.
To determine the prevalence, distribution, neuroradiographic features (Visually Accessible REMBRANDT Images [VASARI]), and prognostic relevance of EGFR amplification in lower-grade gliomas, we assembled a consecutive series of diffuse gliomas. For validation we included publicly available data from The Cancer Genome Atlas. For a cost-utility analysis we compared combined EGFR and isocitrate dehydrogenase (IDH) testing, EGFR testing based on IDH results, and no EGFR testing.
In n = 71 WHO grade II/III gliomas, we identified EGFR amplification in 28.2%. With one exception, all EGFR amplifications occurred in IDH-wildtype gliomas. Comparison of overall survival showed that EGFR amplification denotes a significantly more aggressive subset of tumors (P < 0.0001, log-rank). The radiologic phenotype in the EGFR-amplified tumors includes diffusion restriction (15%, P = 0.02), >5% tumor contrast enhancement (75%, P = 0.016), and mild (not avid) enhancement (P = 0.016). The proposed testing algorithm reserves EGFR fluorescence in situ hybridization (FISH) testing for IDH-wildtype cases. Implementation would result in ~37.9% cost reduction at our institution, or about $1.3-4 million nationally.
EGFR-amplified diffuse gliomas are "glioblastoma-like" in their behavior and may represent undersampled glioblastomas, or subsets of IDH-wildtype diffuse gliomas with inherently aggressive biology. EGFR FISH after IDH testing is a financially effective and clinically relevant test algorithm for routine clinical practice.
神经肿瘤分子实践分类共识联盟（cIMPACT-NOW）更新 3 版将表皮生长因子受体（EGFR）扩增认定为弥漫性神经胶质瘤（世界卫生组织 [WHO] 分级 II/III 级）的一个重要异常。虽然这些建议支持进行检测，但目前缺乏具有成本效益的、临床相关的检测模式。在这里，我们使用真实世界的临床数据，根据新指南提出一种经济有效的诊断测试算法。
为了确定 EGFR 扩增在低级别胶质瘤中的流行率、分布、神经影像学特征（可视觉访问的 REMBRANDT 图像 [VASARI]）和预后相关性，我们收集了一系列连续的弥漫性神经胶质瘤病例。为了验证，我们纳入了来自癌症基因组图谱的公开数据。对于成本效益分析，我们比较了联合 EGFR 和异柠檬酸脱氢酶（IDH）检测、基于 IDH 结果的 EGFR 检测和不进行 EGFR 检测。
在 n = 71 例 WHO 分级 II/III 级神经胶质瘤中，我们发现 28.2%存在 EGFR 扩增。除了一个例外，所有 EGFR 扩增均发生在 IDH 野生型神经胶质瘤中。总体生存比较显示，EGFR 扩增表示肿瘤具有更具侵袭性的亚组（P < 0.0001，对数秩检验）。EGFR 扩增肿瘤的放射学表型包括弥散受限（15%，P = 0.02）、>5%的肿瘤对比增强（75%，P = 0.016）和轻度（非活跃）增强（P = 0.016）。提出的测试算法将 IDH 野生型病例的 EGFR 荧光原位杂交（FISH）检测保留下来。在我们的机构实施该测试算法将导致约 37.9%的成本降低，或全国范围内约减少 130 万至 400 万美元的成本。
EGFR 扩增的弥漫性神经胶质瘤在行为上类似于胶质母细胞瘤，可能代表采样不足的胶质母细胞瘤，或 IDH 野生型弥漫性神经胶质瘤中具有固有侵袭性生物学特性的亚组。在 IDH 检测后进行 EGFR FISH 是一种经济有效的、具有临床相关性的常规临床实践测试算法。
