Foundation Medicine, Inc., Cambridge, MA, USA.
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Oncologist. 2022 Oct 1;27(10):839-848. doi: 10.1093/oncolo/oyac094.
In patients with non-small cell lung cancer (NSCLC), 10%-40% will eventually develop brain metastases. We present the clinicopathologic, genomic, and biomarker landscape of a large cohort of NSCLC brain metastases (NSCLC-BM) samples.
We retrospectively analyzed 3035 NSCLC-BM tested with comprehensive genomic profiling (CGP) during routine clinical care. In addition, we compared the NSCLC-BM to a separate cohort of 7277 primary NSCLC (pNSCLC) specimens. Finally, we present data on 67 paired patients with NSCLC-BM and pNSCLC.
Comprehensive genomic profiling analysis of the 3035 NSCLC-BMs found that the most frequent genomic alterations (GAs) were in the TP53, KRAS, CDKN2A, STK11, CDKN2B, EGFR, NKX2-1, RB1, MYC, and KEAP1 genes. In the NSCLC-BM cohort, there were significantly higher rates of several targetable GAs compared with pNSCLC, including ALK fusions, KRAS G12C mutations, and MET amplifications; and decreased frequency of MET exon14 skipping mutations (all P < .05). In the subset of NSCLC-BM (n = 1063) where concurrent PD-L1 immunohistochemistry (IHC) was performed, 54.7% of the patients with NSCLC-BM were eligible for pembrolizumab based on PD-L1 IHC (TPS ≥ 1), and 56.9% were eligible for pembrolizumab based on TMB-High status. In addition, in a series 67 paired pNSCLC and NSCLC-BM samples, 85.1% (57/67) had at least one additional GA discovered in the NSCLC-BM sample when compared with the pNSCLC sample.
Herein, we defined the clinicopathologic, genomic, and biomarker landscape of a large cohort of patients with NSCLC-BM which can help inform study design of future clinical studies for patients with NSCLC with BM. In certain clinical situations, metastatic NSCLC brain tissue or cerebral spinal fluid specimens may be needed to fully optimize personalized treatment.
在非小细胞肺癌（NSCLC）患者中，有 10%-40%最终会发展为脑转移。我们呈现了一个大型 NSCLC 脑转移（NSCLC-BM）样本的临床病理、基因组和生物标志物图谱。
我们回顾性分析了 3035 例在常规临床护理中接受全面基因组分析（CGP）检测的 NSCLC-BM。此外，我们将 NSCLC-BM 与另一个包含 7277 例原发性 NSCLC（pNSCLC）样本的队列进行了比较。最后，我们展示了 67 对 NSCLC-BM 和 pNSCLC 患者的数据。
对 3035 例 NSCLC-BM 的全面基因组分析发现，最常见的基因组改变（GA）发生在 TP53、KRAS、CDKN2A、STK11、CDKN2B、EGFR、NKX2-1、RB1、MYC 和 KEAP1 基因。在 NSCLC-BM 队列中，与 pNSCLC 相比，几种可靶向的 GA 的发生率明显更高，包括 ALK 融合、KRAS G12C 突变和 MET 扩增；MET 外显子 14 跳跃突变的频率降低（均 P <.05）。在 NSCLC-BM 亚组（n = 1063）中，同时进行 PD-L1 免疫组化（IHC）检测，54.7%的 NSCLC-BM 患者符合 pembrolizumab 的治疗标准，基于 PD-L1 IHC（TPS ≥ 1），56.9%的患者符合 pembrolizumab 的治疗标准，基于 TMB-High 状态。此外，在一系列 67 对 pNSCLC 和 NSCLC-BM 样本中，与 pNSCLC 样本相比，在 NSCLC-BM 样本中发现了 85.1%（57/67）至少存在一种额外的 GA。
本研究确定了一个大型 NSCLC-BM 患者队列的临床病理、基因组和生物标志物图谱，有助于为 NSCLC 伴 BM 患者的未来临床研究设计提供信息。在某些临床情况下，可能需要转移的 NSCLC 脑组织或脑脊液标本来充分优化个体化治疗。
