立体定向放射外科治疗结直肠癌脑转移后生存期和颅内进展的临床基因组学预测因素。

IF 3.5 2区 医学 Q1 CLINICAL NEUROLOGY Journal of neurosurgery Pub Date : 2024-08-30 DOI:10.3171/2024.5.JNS24534
Chengcheng Gui, Henry S Walch, Kirin D Mueller, Lillian A Boe, A Turan Ilica, James Strong, Jordan E Eichholz, Kenny K H Yu, Jessica A Wilcox, Paolo Manca, Yao Yu, Yoshiya Yamada, Brandon S Imber, Steven B Maron, Michael B Foote, Rona Yaeger, Nikolaus Schultz, Luke R G Pike
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引用次数: 0

摘要

目的:结直肠癌(CRC)脑转移(BM)与预后不良有关。在考虑以脑转移灶为导向的治疗时,需要更好的方法来识别有不良肿瘤预后风险的患者,以便优化患者选择,进行更严密的监测或升级治疗。作者试图找出CRC BM接受立体定向放射手术(SRS)治疗后生存和颅内疾病进展的临床基因组学预测因素:方法:纳入2009年至2022年间接受SRS治疗的新确诊CRC BM患者,这些患者均有新一代基因组测序数据。无框架 SRS 分 1-5 次进行,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)(按每位接受 SRS 治疗的患者评估),以及局部进展(LP)(按每位 BM 评估)。基线临床基因组学特征与结果之间的关系通过Cox回归和竞争风险回归进行评估,死亡为竞争风险:该分析纳入了 123 名患有 299 例骨髓瘤的患者。在确诊骨髓瘤时,111名患者(90%)颅外疾病进展,79名患者(64%)颅外转移部位≥3个。每位患者的骨髓瘤中位数(IQR)为2(1-3)个。生物有效剂量(BED)的中位数(IQR)为51.3(51.3-65.1)Gy,对应处方为27Gy,分3次进行。SRS术后1年的OS、IP和LP估计值分别为36%、55%和12%。OS与颅外进展性疾病(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的可能性较低(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驱动基因改变与较高的IP风险相关(HR 2.71,95% CI 1.26-5.79,p = 0.01),而MYC通路改变与较低的风险相关(HR 0.15,95% CI 0.03-0.68,p = 0.01):作者发现了与CRC BM SRS术后不良预后相关的临床基因组学特征。进展期和广泛的颅外转移预示着较差的OS。SRS剂量不足预示着更大的LP风险。野生型TP53和MYC通路的改变与较低的IP风险独立相关。IP风险较高的患者可考虑接受更严密的监测或升级治疗。
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Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

Objective: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

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来源期刊
Journal of neurosurgery
Journal of neurosurgery 医学-临床神经学
CiteScore
7.20
自引率
7.30%
发文量
1003
审稿时长
1 months
期刊介绍: The Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of Neurosurgery: Pediatrics, and Neurosurgical Focus are devoted to the publication of original works relating primarily to neurosurgery, including studies in clinical neurophysiology, organic neurology, ophthalmology, radiology, pathology, and molecular biology. The Editors and Editorial Boards encourage submission of clinical and laboratory studies. Other manuscripts accepted for review include technical notes on instruments or equipment that are innovative or useful to clinicians and researchers in the field of neuroscience; papers describing unusual cases; manuscripts on historical persons or events related to neurosurgery; and in Neurosurgical Focus, occasional reviews. Letters to the Editor commenting on articles recently published in the Journal of Neurosurgery, Journal of Neurosurgery: Spine, and Journal of Neurosurgery: Pediatrics are welcome.
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