术后脑转移灶切除后与结论性脑蛛网膜结节病相关的基因组变异。
Genomic alterations associated with postoperative nodular leptomeningeal disease after resection of brain metastases.
发表日期:2023 Jul 28
作者:
Ramin A Morshed, Daniel D Cummins, Minh P Nguyen, Satvir Saggi, Harish N Vasudevan, Steve E Braunstein, Ezequiel Goldschmidt, Edward F Chang, Michael W McDermott, Mitchel S Berger, Philip V Theodosopoulos, Mariza Daras, Shawn L Hervey-Jumper, Manish K Aghi
来源:
JOURNAL OF NEUROSURGERY
摘要:
大脑转移切除术与结节性蛛网膜炎(nLMD)风险之间的关系尚不清楚。本研究研究了在大脑转移瘤中发现的基因组改变,旨在确定临床和治疗因素背景下与术后nLMD相关的改变。我们对2014年至2022年期间接受大脑转移瘤切除术且具备临床和基因组数据的患者进行了回顾性单中心研究。术后nLMD是我们主要感兴趣的终点。我们对大脑转移瘤进行了超过500个癌基因的靶向下一代测序。我们进行Cox比例风险分析,以确定与nLMD相关的临床特征和基因组改变。
共有101名患有多种癌症类型的患者构成了该队列。其中有15名患者出现了nLMD(占总队列的14.9%),从手术至nLMD诊断的中位时间为8.2个月。两个监督式机器学习算法一致地确定了CDKN2A/B共删和ERBB2扩增是与术后nLMD相关的最重要的预测因子,适用于所有癌症类型。在包括队列中观察到的临床因素和基因组改变的多变量Cox比例风险分析中,肿瘤体积(×10 cm3;HR 1.2,95% CI 1.01-1.5;p = 0.04)、CDKN2A/B共删(HR 5.3,95% CI 1.7-16.9;p = 0.004)和ERBB2扩增(HR 3.9,95% CI 1.1-14.4;p = 0.04)与术后nLMD的时间缩短相关。
除了增大的切除肿瘤体积外,ERBB2扩增和CDKN2A/B缺失是与多种癌症类型术后nLMD风险增加独立相关的。需要进一步研究确定在术后环境中,靶向治疗是否能降低这种风险。
The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors.A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of > 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD.The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm3; HR 1.2, 95% CI 1.01-1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7-16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4; p = 0.04) were associated with a decreased time to postoperative nLMD.In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.