Zhao Kewei, Wang Chunsheng, Mao Qingfeng, Shang Dongping, Huang Yong, Ma Li, Yu Jinming, Li Minghuan
School of Medicine, Shandong University, Wenhua West Road 44, Jinan, 250012, Shandong Province, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, 250117, Shandong Province, China.
EJNMMI Res. 2020 May 29;10(1):57. doi: 10.1186/s13550-020-00647-9.
Perfusion CT can offer functional information about tumor angiogenesis, and F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC).
Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman's rank correlation, Mann-Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan-Meier method, and Cox proportional hazards models.
The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = - 0.547, p = 0.003) and TTP (r = - 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014).
The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.
灌注CT可提供有关肿瘤血管生成的功能信息，而F-FDG PET/CT可量化肿瘤的葡萄糖代谢活性。这项前瞻性研究旨在探讨生物学相关成像生物标志物在预测局部晚期食管鳞状细胞癌（LA ESCC）患者治疗反应和生存结果方面的价值。
纳入27例经病理证实的ESCC患者。所有患者在接受确定性放化疗（dCRT）前，使用不同的成像系统进行了灌注CT和F-FDG PET/CT检查。灌注参数包括血流量（BF）、血容量（BV）和达峰时间（TTP），代谢参数包括最大标准化摄取值（SUVmax）、代谢肿瘤体积（MTV）和总病灶糖酵解（TLG）。血流代谢比值（FMR）定义为BF除以SUVmax。使用的统计方法包括Spearman等级相关性分析、Mann-Whitney U检验或两样本t检验、受试者工作特征（ROC）曲线分析、Kaplan-Meier法和Cox比例风险模型。
中位总生存期（OS）和无进展生存期（PFS）分别为18个月和11.6个月。肿瘤内FMR与BF显著正相关（r = 0.886，p < 0.001），与SUVmax（r = - 0.547，p = 0.003）和TTP（r = - 0.462，p = 0.015）显著负相关。然而，灌注参数与PET参数之间无显著相关性。dCRT后，14例患者（51.9%）被确定为反应者，另外13例为无反应者。反应者的BF和FMR显著高于无反应者（42.05 ± 16.47 vs 27.48 ± 8.55，p = 0.007；3.18 ± 1.15 vs 1.84 ± 0.65，p = 0.001）。ROC曲线表明，FMR[曲线下面积（AUC）= 0.846]比BF（AUC = 0.802）是更好的预测治疗反应的生物标志物。单变量Cox分析显示，在所有成像参数中，只有FMR与总生存期（OS）（p = 0.015）和无进展生存期（PFS）（p = 0.017）显著相关。具体而言，FMR较低的患者生存率较差。多变量分析显示，在调整年龄、临床分期和治疗反应后，FMR仍然是OS（p = 0.026）和PFS（p = 0.014）的独立预测因子。
低FMR所显示的血流代谢不匹配在预测ESCC放化疗敏感性和预后方面具有良好潜力。
