Background: Early imaging-based treatment response assessment of brain metastases following stereotactic radiosurgery (SRS) remains challenging. The aim of this study is to determine whether early (within 12 weeks) intratumoral changes in interstitial fluid pressure (IFP) and velocity (IFV) estimated from computational fluid modeling (CFM) using dynamic contrast-enhanced (DCE) MRI can predict long-term outcomes of lung cancer brain metastases (LCBMs) treated with SRS. Methods: Pre- and post-treatment T1-weighted DCE-MRI data were obtained in 41 patients treated with SRS for intact LCBMs. The imaging response was assessed using RANO-BM criteria. For each lesion, extravasation of contrast agent measured from Extended Tofts pharmacokinetic Model (volume transfer constant, Ktrans) was incorporated into a computational fluid model to estimate tumor IFP and IFV. Estimates of mean IFP and IFV and heterogeneity (skewness and kurtosis) were calculated for each lesion from pre- and post-SRS imaging. The Wilcoxon rank-sum test was utilized to assess for significant differences in IFP, IFV, and IFP/IFV change (Δ) between response groups. Results: Fifty-three lesions from 41 patients were included. Median follow-up time after SRS was 11 months. The objective response (OR) rate (partial or complete response) was 79%, with 21% demonstrating stable disease (SD) or progressive disease (PD). There were significant response group differences for multiple posttreatment and Δ CFM parameters: post-SRS IFP skewness (mean -0.405 vs. -0.691, p = 0.022), IFP kurtosis (mean 2.88 vs. 3.51, p = 0.024), and IFV mean (5.75e-09 vs. 4.19e-09 m/s, p = 0.027); and Δ IFP kurtosis (mean -2.26 vs. -0.0156, p = 0.017) and IFV mean (1.91e-09 vs. 2.38e-10 m/s, p = 0.013). Posttreatment and Δ thresholds predicted non-OR with high sensitivity (sens): post-SRS IFP skewness (-0.432, sens 84%), kurtosis (2.89, sens 84%), and IFV mean (4.93e-09 m/s, sens 79%); and Δ IFP kurtosis (-0.469, sens 74%) and IFV mean (9.90e-10 m/s, sens 74%). Conclusions: Objective response was associated with lower post-treatment tumor heterogeneity, as represented by reductions in IFP skewness and kurtosis. These results suggest that early post-treatment assessment of IFP and IFV can be used to predict long-term response of lung cancer brain metastases to SRS, allowing a timelier treatment modification.

中文翻译：

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立体定向放射外科治疗非小细胞肺癌脑转移组织间质液压力和速度的计算模型。

背景：立体定向放射外科（SRS）后基于早期影像学的脑转移治疗反应评估仍然具有挑战性。这项研究的目的是确定使用动态对比增强（DCE）MRI从计算流体模型（CFM）估计的组织间液压力（IFP）和速度（IFV）的早期（12周内）肿瘤内变化是否可以预测长期的SRS治疗的肺癌脑转移（LCBM）的长期预后。方法：在41例接受SRS治疗的完整LCBM患者中，获得了治疗前后的T1加权DCE-MRI数据。使用RANO-BM标准评估成像反应。对于每个病变，根据Extended Tofts药代动力学模型（体积转移常数，将Ktrans）合并到计算流体模型中以估计肿瘤IFP和IFV。从SRS之前和之后的成像计算每个病变的平均IFP和IFV估计值和异质性（偏度和峰度）。使用Wilcoxon秩和检验来评估应答组之间IFP，IFV和IFP / IFV变化（Δ）的显着差异。结果：包括来自41例患者的53个病变。SRS后的中位随访时间为11个月。客观缓解率（部分或完全缓解）为79％，其中21％表示稳定疾病（SD）或进行性疾病（PD）。在多个后处理和ΔCFM参数上，反应组存在显着差异：SRS后IFP偏斜（平均值-0.405与-0.691，p = 0.022），IFP峰度（平均值2.88与3.51，p = 0.024）和IFV均值（5.75e-09与4。19e-09 m / s，p = 0.027）；和ΔIFP峰度（平均值-2.26对-0.0156，p = 0.017）和IFV平均值（1.91e-09对2.38e-10 m / s，p = 0.013）。治疗后和Δ阈值以高灵敏度（sens）预测非手术室：SRS后IFP偏斜（-0.432，sens 84％），峰度（2.89，sens 84％）和IFV平均值（4.93e-09 m / s，感觉79％）; 和ΔIFP峰度（-0.469，感觉74％）和IFV平均值（9.90e-10 m / s，感觉74％）。结论：客观反应与较低的治疗后肿瘤异质性有关，以IFP偏斜和峰度的降低为代表。这些结果表明，IFP和IFV的早期治疗后评估可用于预测肺癌脑转移对SRS的长期反应，从而可以更及时地进行治疗。p = 0.013）。治疗后和Δ阈值以高灵敏度（sens）预测非手术室：SRS后IFP偏斜（-0.432，sens 84％），峰度（2.89，sens 84％）和IFV平均值（4.93e-09 m / s，感觉79％）; 和ΔIFP峰度（-0.469，感觉74％）和IFV平均值（9.90e-10 m / s，感觉74％）。结论：客观反应与较低的治疗后肿瘤异质性有关，以IFP偏斜和峰度的降低为代表。这些结果表明，IFP和IFV的早期治疗后评估可用于预测肺癌脑转移对SRS的长期反应，从而可以更及时地进行治疗。p = 0.013）。治疗后和Δ阈值以高灵敏度（sens）预测非手术室：SRS后IFP偏斜（-0.432，sens 84％），峰度（2.89，sens 84％）和IFV平均值（4.93e-09 m / s，感觉79％）; 和ΔIFP峰度（-0.469，感觉74％）和IFV平均值（9.90e-10 m / s，感觉74％）。结论：客观反应与较低的治疗后肿瘤异质性有关，以IFP偏斜和峰度的降低为代表。这些结果表明，IFP和IFV的早期治疗后评估可用于预测肺癌脑转移对SRS的长期反应，从而可以更及时地进行治疗。sens 74％）和IFV平均值（9.90e-10 m / s，sens 74％）。结论：客观反应与较低的治疗后肿瘤异质性有关，以IFP偏斜和峰度的降低为代表。这些结果表明，IFP和IFV的早期治疗后评估可用于预测肺癌脑转移对SRS的长期反应，从而可以更及时地进行治疗。sens 74％）和IFV平均值（9.90e-10 m / s，sens 74％）。结论：客观反应与较低的治疗后肿瘤异质性有关，以IFP偏斜和峰度的降低为代表。这些结果表明，IFP和IFV的早期治疗后评估可用于预测肺癌脑转移对SRS的长期反应，从而可以更及时地进行治疗。