Challapalli Amarnath, Barwick Tara, Pearson Rachel A, Merchant Shairoz, Mauri Francesco, Howell Elizabeth C, Sumpter Katherine, Maxwell Ross J, Aboagye Eric O, Sharma Rohini
Department of Surgery & Cancer, Imperial College London (ICL), London, UK.
Eur J Nucl Med Mol Imaging. 2015 May;42(6):831-40. doi: 10.1007/s00259-015-3000-2. Epub 2015 Feb 12.
3'-Deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy.
Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy.
Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PETKSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35%). Maximum standardised uptake value at 60 min post-injection (SUV60,max) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV60,max increase of ≥ 12% resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100%, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV60,max were not predictive of survival.
FLT PET/CT detected changes in proliferation, with early increase in SUV60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer.
由于示踪剂在肝脏的生理性摄取较高,3'-脱氧-3'-(18)F-氟胸苷(FLT)正电子发射断层扫描(PET)在腹部成像中的应用有限。我们评估了FLT PET/CT结合基于时间强度信息的体素聚类方法(称为动力学空间滤波,FLT PET/CTKSF),用于早期预测接受吉西他滨化疗的局部晚期和转移性胰腺癌患者的反应和生存结果。
在化疗第一周期前和化疗3周后收集动态FLT PET/CT数据。确定肿瘤FLT PET/CT变量的变化。主要终点是治疗3个月后增强CT上的RECIST 1.1反应。
纳入20例患者。在FLT PETKSF图像中可见肿瘤与正常胰腺之间的视觉区分。所有靶病变(>2 cm),包括所有原发性胰腺肿瘤,均清晰可见。11个肝转移灶中,3个(<2 cm)在动力学滤波后不可见。20例患者中,7例病情进展(35%)。疾病进展患者注射后60分钟的最大标准化摄取值(SUV60,max)显著增加(p = 0.04)。受试者操作特征曲线分析表明,SUV60,max增加≥12%的阈值导致预测疾病进展患者的敏感性、特异性和阳性预测值(PPV)分别为71%、100%和100%[曲线下面积(AUC)0.90,p = 0.0001]。SUV60,max的变化不能预测生存。
FLT PET/CT检测到增殖变化,SUV60,max早期升高以高特异性和PPV预测疾病进展。因此,FLT PET/CT可作为基于吉西他滨化疗的早期反应生物标志物,用于选择可能从晚期和转移性胰腺癌的新型治疗药物中获益的预后不良组。