结直肠癌 (CRC) 的脑转移 (BM) 与不良预后相关。当考虑以 BM 为导向的治疗时，需要更好的方法来识别具有不良肿瘤结果风险的患者，以便优化患者选择以进行更密切的监测或升级治疗。作者试图确定 CRC BM 接受立体定向放射外科 (SRS) 治疗后生存和颅内疾病进展的临床基因组预测因子。纳入了 2009 年至 2022 年间接受 SRS 治疗的新诊断 CRC BM 患者，这些患者拥有可用的下一代基因组测序数据。无框架 SRS 分 1-5 次单独或在神经外科切除术后进行。结果包括总生存期 (OS) 和颅内进展 (IP)，根据接受 SRS 治疗的每位患者进行评估，以及局部进展 (LP)，根据 BM 进行评估。使用 Cox 回归和竞争风险回归评估基线临床基因组特征和结果之间的关联，其中死亡作为竞争风险。该分析包括 123 名患有 299 例 BM 的患者。 BM诊断时，111名患者（90%）患有进展性颅外疾病，79名患者（64%）有≥3个部位的颅外转移。每个患者的 BM 中位数 (IQR) 为 2 (1-3)。中位 (IQR) 生物有效剂量 (BED) 为 51.3 (51.3-65.1) Gy，相当于分 3 次服用 27 Gy 的处方。 SRS 术后 1 年的 OS、IP 和 LP 估计值分别为 36%、55% 和 12%。 OS 与进行性颅外疾病（HR 4.26，95% CI 1.63-11.2，p = 0.003）和≥ 3 个颅外转移部位（HR 1.84，95% CI 1.12-3.01，p = 0.02）独立相关。当 BM 接受 BED ≥ 51.3 Gy 时，LP 发生的可能性较小（HR 0.24，95% CI 0.07-0.78，p = 0.02），与 BM 直径无关（HR 1.21/cm，95% CI 0.8-1.84，p = 0.4）。 IP 与基因组改变独立相关； TP53 驱动程序改变与 IP 风险较高相关（HR 2.71，95% CI 1.26-5.79，p = 0.01），而 MYC 通路改变与较低风险相关（HR 0.15，95% CI 0.03-0.68，p = 0.01）作者确定了与 CRC BM SRS 后不良后果相关的临床基因组特征。进行性和广泛的颅外转移预示着更差的 OS。 SRS 剂量不足预示着 LP 的风险更大。野生型 TP53 和 MYC 通路的改变与较低的 IP 风险独立相关。 IP 高风险患者可考虑接受更密切的监测或升级治疗。

Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS).Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk.This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01).The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.