目的:术前立体定向放射外科(SRS)正在成为标准术后SRS的可行替代方案。研究表明,术前SRS可提供可比的肿瘤控制和总生存期(OS),并可能降低软脑膜疾病(LMD)和不良放射影响(ARE)的发生率。它是未知的,然而,如果术前SRS在包括大型脑转移(>14cm3)在内的队列中仍然有效,或者术前SRS影响类固醇锥度/免疫疗法。这里,作者报告了一项2期单臂试验的结果,该试验评估了一项前瞻性获得的26例接受术前SRS的患者,没有体积截止,与30例接受术后SRS治疗的患者的倾向评分匹配队列进行比较,以解决这些突出问题.
方法:人口统计,肿瘤病史,手术细节,和结局从医疗记录中收集.共同主要终点是局部肿瘤控制(LTC)和LTC的复合结局,ARE,还有LMD.其他结果是OS,类固醇锥度细节,免疫疗法恢复。对于生存分析,队列为倾向评分匹配.
结果:术前和术后SRS患者在年龄方面具有可比性,性别,Karnofsky绩效状态得分,肿瘤病史,和操作细节。术前组的大体肿瘤体积(GTV)明显较高(中位数12.2vs5.3cm3,p<0.001)。一年LTC(术前SRS:77.2%,术后SRS:82.5%,p=0.61)和复合结局(68.3%vs72.7%,p=0.38)两组之间没有显着差异。在多变量分析中,术前SRS对LTC无显著影响(HR1.57[95%CI0.38-6.49],p=0.536)或复合结局(HR1.18[95%CI0.38-3.72],p=0.771),尽管置信区间很大。中位OS(术前SRS:17.0,术后SRS:14.0个月,p=0.61)没有显着差异。术前SRS组的LMD发生率没有显著降低(3.8%vs16.7%,p=0.200)。GTV体积增大与类固醇锥度延长(>10天)相关(OR1.24[95%CI1.04-1.55],p=0.032)。然而,在多变量分析中,术前SRS显著减少了类固醇锥度长度(OR0.13[95%CI0.02-0.61],p=0.016)。术前SRS组的免疫治疗时间较短(36[IQR26,76]vsOR228[IQR129,436]天,p=0.02)。
结论:与术后SRS相比,术前SRS是治疗各种规模的脑转移瘤的安全有效的策略,可在不增加不良反应的情况下提供相当的肿瘤控制.值得注意的是,术前SRS使类固醇快速锥度,甚至在较大的肿瘤中。未来的研究应特别检查术前SRS与类固醇使用和恢复全身治疗的相互作用,以及对全身进展和OS的后续影响。
OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions.
METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched.
RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02).
CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.