1Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; and.
Neurosurg Focus. 2023 Aug;55(2):E15. doi: 10.3171/2023.5.FOCUS23214.
The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery.
This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses.
The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039).
Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.
本研究旨在探讨术后辅助放射外科治疗时发现的切除脑转移瘤中基因组改变与快速局部和远处中枢神经系统（CNS）复发之间的关系。
这是一项对接受颅内脑转移瘤切除术的患者进行的回顾性研究。对脑转移瘤标本进行了超过 500 个编码基因的下一代测序。比较术后和放射外科前磁共振成像（MRI）以识别快速复发。使用名义回归分析将基因组数据与脑转移瘤的快速局部和远处 CNS 复发相关联。
该队列包含 92 例患者和 92 个脑转移瘤。13 例（14.1%）患者出现快速局部复发，64 例（69.6%）患者在术后辅助放射外科时出现快速远处 CNS 进展，中位时间为手术切除后 25 天（范围 3-85 天）。该队列中分别有 8.7%和 9.8%的患者存在 RB1 和 CTNNB1 突变，两者均与快速局部复发的风险显著增加相关（RB1：OR 13.6，95%CI 2.0-92.39，p=0.008；CTNNB1：OR 11.97，95%CI 2.25-63.78，p=0.004）。未发现与快速远处 CNS 进展相关的基因。然而，多变量分析显示，存在颅外疾病与快速远处复发的风险显著增加相关（OR 4.06，95%CI 1.08-15.34，p=0.039）。
RB1 或 CTNNB1 中的基因组改变与切除部位的快速复发显著相关。尽管没有基因组改变与快速远处复发相关，但在切除后辅助放疗时存在活动性颅外疾病是新病变的危险因素。
