脑转移瘤（BM）患者常见且具有明显的致残性癫痫。尽管手术切除可以控制癫痫，但BM患者中的一部分可能在术后继续遭受癫痫的困扰。基因组BM特征可能影响哪些患者存在术后癫痫的风险。本研究探讨了基因组变异与BM切除术后癫痫风险之间的相关性。所有患者在单个机构接受BM切除术，拥有超过500个癌基因的可用临床和测序数据。术前和术后记录临床癫痫。采用随机森林机器学习分类确定与术后癫痫相关的潜在基因组变异，并使用Cox比例风险模型将临床和顶级基因组变量与术后癫痫相关联。共有112例BM患者接受了114次手术，并进行了至少一个月的术后随访。术前有26例（22.8%）患者出现癫痫，术后有25例（21.9%）患者出现癫痫。术前癫痫患者6个月内Engel分级为第I类的有13例（50%），第II类的有6例（23.1%），第III类的有5例（19.2%），第IV类的有2例（7.7%）。术后癫痫发作者中，只有8例（32.0%）术前有癫痫发作，术前癫痫不是术后癫痫的显著预测因子（HR 1.84，95% CI 0.79-4.37，p = 0.156）。在随机森林分类和多因素Cox分析中，控制复发、切除程度和BM数量等因素，CDKN2A变异与术后癫痫相关（HR 3.22，95% CI 1.27-8.16，p = 0.014）。与其他原发性恶性肿瘤相比，黑色素瘤BM与术后癫痫的风险更高（HR 5.23，95% CI 1.37-19.98，p = 0.016）。在39个具有CDKN2A变异的BM中，35.9%（14/39）患者在术后出现了癫痫，而没有CDKN2A变异的患者中有14.7%（11/75）患者出现了癫痫。黑色素瘤的BM术后癫痫发作率为42.9%（15/35），而其他所有原发性恶性肿瘤的BM术后癫痫发作率为12.7%（10/79）。CDKN2A变异和黑色素瘤原发性肿瘤与BM切除术后癫痫风险增加相关。这些结果有助于指导接受BM切除术患者的术后癫痫预防。

Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection.All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models.There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies.CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.