van Elmpt Wouter, Zegers Catharina M L, Reymen Bart, Even Aniek J G, Dingemans Anne-Marie C, Oellers Michel, Wildberger Joachim E, Mottaghy Felix M, Das Marco, Troost Esther G C, Lambin Philippe
Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Pulmonology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):240-248. doi: 10.1007/s00259-015-3169-4. Epub 2015 Sep 4.
Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level.
A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes.
At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia.
The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia.
如今有多种成像技术可用于临床体内肿瘤生物学可视化。氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(FDG PET/CT)可识别肿瘤代谢增加,缺氧正电子发射断层扫描可显示肿瘤氧合情况,动态对比增强(DCE)CT可表征血管系统和形态。我们在患者层面和肿瘤亚体积层面探讨了非小细胞肺癌(NSCLC)患者这些生物学特征之间的关系。
来自两项正在进行的临床试验(NCT01024829和NCT01210378)的14例NSCLC患者在放化疗前接受了FDG PET/CT、HX4 PET/CT和DCE CT扫描。计算FDG和缺氧HX4 PET/CT扫描中原发肿瘤的标准化摄取值(SUV)。对于缺氧成像,还定义了缺氧体积、分数和肿瘤与血液比值(TBR)。从DCE CT成像中获取血流量和血容量。采用肿瘤亚体积分析来量化亚体积之间的空间重叠。
在患者层面,观察到血流量与缺氧参数(TBR>1.2)之间存在负相关:缺氧体积(-0.65,p = 0.014)、缺氧分数(-0.60,p = 0.025)和TBR(-0.56,p = 0.042)。在肿瘤亚体积层面,缺氧和代谢活跃的亚体积显示重叠率为53±36%。缺氧亚体积与高血流量和血容量亚体积之间的重叠较小:分别为15±17%和28±28%。一半的患者在血流量增加和缺氧之间表现出空间不匹配(重叠<5%)。
NSCLC肿瘤中定义的生物学成像特征在患者间和肿瘤内显示出很大的变异性。大多数肿瘤中缺氧和代谢活跃的亚体积之间存在重叠,高血流量区域和缺氧增加区域之间存在空间不匹配。