de Jong Evelyn E C, van Elmpt Wouter, Leijenaar Ralph T H, Hoekstra Otto S, Groen Harry J M, Smit Egbert F, Boellaard Ronald, van der Noort Vincent, Troost Esther G C, Lambin Philippe, Dingemans Anne-Marie C
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, Netherlands.
Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):8-16. doi: 10.1007/s00259-016-3498-y. Epub 2016 Sep 6.
Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival.
A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG.
A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively).
The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders than CT-based response assessment (part of the [18F]FDG PET/CT); this was not correlated to survival. This might be due to timing of the [18F]FDG PET shortly after the bevacizumab infusion.
硝酸甘油（NTG）是一种血管扩张药物，可增加肿瘤血流，从而减少缺氧情况。因此，[18F]氟脱氧葡萄糖正电子发射断层扫描（[18F]FDG PET）摄取模式可能会发生变化。在本分析中，我们研究了[18F]FDG PET用于评估紫杉醇-卡铂-贝伐单抗（PCB）联合或不联合NTG贴片治疗反应的可行性。并且我们比较了[18F]FDG PET反应评估与实体瘤疗效评价标准（RECIST）反应评估及生存率。
共有223例IV期非小细胞肺癌（NSCLC）患者纳入一项II期研究（NCT01171170），随机接受含或不含NTG贴片的PCB治疗。对于60例参与研究的患者，可获得治疗开始后第22至24天之间进行的基线和第二次[18F]FDG PET/计算机断层扫描（CT）。肿瘤反应定义为CT和PET参数降低30%，并与第6周时的RECIST反应进行比较。评估这些评估对无进展生存期（PFS）和总生存期（OS）的预测价值，分为有NTG和无NTG两种情况。
与CT直径评估降低30%相比，SUVpeak评估降低30%可识别出更多患者为反应者（73%对18%），然而，这与OS无关（SUVpeak30 p = 0.833；CTdiameter30 p = 0.557）。与对照组相比，NTG组基线和第二次扫描之间PET参数的变化无显著差异（p值范围为0.159 - 0.634）。与对照组相比，NTG组基于CT（[18F]FDG PET/CT的一部分）的参数在基线和第二次扫描之间显示出显著差异（CT直径降低7±23%对19±14%，p = 0.016）。
在接受化疗联合或不联合NTG治疗的晚期NSCLC患者中，两个治疗组肿瘤FDG摄取的降低无差异。基于PET的早期反应评估显示的肿瘤反应者比基于CT的反应评估（[18F]FDG PET/CT的一部分）更多；这与生存率无关。这可能是由于贝伐单抗输注后不久进行[18F]FDG PET检查的时间问题。
