Morshed Ramin A, Nguyen Minh P, Cummins Daniel D, Saggi Satvir, Young Jacob S, Haddad Alexander F, Goldschmidt Ezequiel, Chang Edward F, McDermott Michael W, Berger Mitchel S, Theodosopoulos Philip V, Hervey-Jumper Shawn L, Daras Mariza, Aghi Manish K
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Division of Neurosurgery, Miami Neuroscience Institute, Miami, FL, USA.
Neurooncol Adv. 2023 Jan 28;5(1):vdad007. doi: 10.1093/noajnl/vdad007. eCollection 2023 Jan-Dec.
While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.
A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.
A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included (64%), (37%), (29%), (23%), (14%), (14%), and (13%), all of which occurred across multiple cancer types. co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, = 0.025) CNS progression. Median survival and length of follow-up were not different based on mutation status.
co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.
虽然之前已经对脑转移瘤（BMs）的基因改变进行了探索，但关于其与手术切除后复发的关联的数据有限。本研究旨在确定多种癌症类型中与手术后中枢神经系统（CNS）复发相关的脑转移瘤内的基因改变。
对接受脑转移瘤切除术且有可用临床和基因测序数据的患者进行了一项回顾性单中心研究。局部和远处CNS复发是主要研究结局。对脑转移瘤标本进行了500多个癌基因编码区的二代测序。进行Cox比例风险分析以确定与CNS复发相关的临床特征和基因组改变。
共有90例接受91个脑转移瘤切除术的患者组成了该队列。该队列中最常发生突变的基因包括（64%）、（37%）、（29%）、（23%）、（14%）、（14%）和（13%），所有这些基因的突变均出现在多种癌症类型中。在多种癌症类型的21个（23.1%）脑转移瘤中发现了共缺失。在包括患者、肿瘤和治疗因素的多变量Cox比例风险分析中，脑转移瘤中的共缺失与局部（风险比[HR] 4.07，95%置信区间[CI] 1.32 - 12.54，P = 0.014）和远处（HR 2.28，95% CI 1.11 - 4.69，P = 0.025）CNS进展风险增加相关。基于突变状态的中位生存期和随访时间无差异。
在脑转移瘤中检测到的共缺失与手术切除后CNS复发增加相关。需要进一步研究以确定对具有这种突变的患者进行更积极的治疗是否可以改善预后。
