Trigonis Ioannis, Koh Pek Keng, Taylor Ben, Tamal Mahbubunnabi, Ryder David, Earl Mark, Anton-Rodriguez Jose, Haslett Kate, Young Helen, Faivre-Finn Corinne, Blackhall Fiona, Jackson Alan, Asselin Marie-Claude
Institute of Population Health, Wolfson Molecular Imaging Centre, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, M20 3LJ, UK,
Eur J Nucl Med Mol Imaging. 2014 Apr;41(4):682-93. doi: 10.1007/s00259-013-2632-3. Epub 2014 Feb 7.
PURPOSE: Changes in tumour 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. METHODS: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV(mean) and SUV(max)) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. RESULTS: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV(mean) reproducibility in primary tumours (SD 8.9%) was better than SUV(max) reproducibility (SD 12.6%). In nodes, SUV(mean) and SUV(max) reproducibilities (SD 18.0 and 17.2%) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV(mean) decreased significantly by 25% (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31% (p = 0.020) with a larger SUV(mean) decrease of 40% (p < 0.0001). Similar changes were found for SUV(max). CONCLUSION: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.
目的：在两项正电子发射断层扫描（PET）试点研究中，已报道了非小细胞肺癌（NSCLC）患者在同步放化疗期间肿瘤3'-脱氧-3'-[(18)F]氟胸苷（FLT）摄取的变化，时间点各不相同。本研究的目的是评估在不进行同步化疗的情况下，放疗（RT）早期是否会出现FLT变化，以及这种变化是否超过重测变异性。 方法：16例计划进行根治性放疗的NSCLC患者在基线时接受1次/2次FLT PET检查以评估可重复性，和/或在接受5-11次放疗分割后评估反应。在CT上手动勾勒出原发和淋巴结恶性病变，并估计体积、平均和最大标准化摄取值（SUV(mean)和SUV(max)）。分析包括描述性统计和对混合效应模型的参数拟合，该模型考虑了具有不同数量可评估病变的患者。 结果：总共对7例患者共18个病变的35次FLT PET扫描以及12例患者共30个病变的扫描分别进行了可重复性和反应评估。原发肿瘤中SUV(mean)的可重复性（标准差8.9%）优于SUV(max)的可重复性（标准差12.6%）。在淋巴结中，SUV(mean)和SUV(max)的可重复性（标准差18.0%和17.2%）相当，但比原发肿瘤差。在接受5-11次放疗分割后，在无明显体积变化的情况下，原发肿瘤SUV(mean)显著下降25%（p = 0.0001），而转移淋巴结体积下降31%（p = 0.020），SUV(mean)下降幅度更大，为40%（p < 0.0001）。SUV(max)也发现了类似变化。 结论：在这组NSCLC患者中，放疗导致病变FLT摄取早期显著下降，超过重测变异性。这种效应在患者之间存在差异，在原发和转移淋巴结病变之间表现明显，并且在原发肿瘤中低于之前在类似时间点报道的同步放化疗情况。这些结果证实了FLT PET报告放疗反应早期情况以及通过提供可解释的早期药效学终点来促进新型药物-放疗联合方案临床开发的潜力。
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