Johnbeck Camilla B, Knigge Ulrich, Langer Seppo W, Loft Annika, Berthelsen Anne Kiil, Federspiel Birgitte, Binderup Tina, Kjaer Andreas
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark.
ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
J Nucl Med. 2016 Dec;57(12):1851-1857. doi: 10.2967/jnumed.116.174714. Epub 2016 Jul 28.
Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'-F-fluorothymidine (F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate F-FLT PET as a prognostic marker for NENs in comparison with F-FDG PET and Ki-67 index.
One hundred patients were PET-scanned with both F-FLT and F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and F-FLT uptake was also investigated.
Thirty-seven percent of patients had a positive F-FLT PET scan, and 49% had F-FDG PET-positive foci. Patients with a high F-FLT uptake had a significantly shorter OS and PFS than patients with low or no F-FLT uptake. No correlation was found between Ki-67 index and F-FLT uptake. In a multivariate analysis F-FLT, F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only F-FDG and Ki-67 remained significant.
F-FLT PET has prognostic value in NEN patients but when F-FDG PET and Ki-67 index are also available, a multivariate model revealed that F-FLT PET only adds information regarding PFS but not OS, whereas F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including F-FLT in addition to F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of F-FLT PET in NENs remains to be established.
神经内分泌肿瘤（NENs）是一组异质性肿瘤，起源于各种器官，侵袭性和生存率差异很大。Ki-67增殖指数目前被用作预后的关键标志物，治疗指南很大程度上基于该指数。3'-脱氧-3'-氟胸苷（F-FLT）是一种用于PET成像的增殖示踪剂，在监测各种癌症的疾病进展和治疗反应方面具有重要价值。然而，到目前为止，文献中仅有10例NEN患者的数据。本研究的目的是将F-FLT PET与F-FDG PET和Ki-67指数进行比较，研究其作为NENs预后标志物的价值。
100例患者在同一周内分别接受F-FLT和F-FDG PET扫描，并根据无进展生存期（PFS）和总生存期（OS）评估阳性扫描的预后价值。同时研究Ki-67指数与F-FLT摄取之间的相关性。
37%的患者F-FLT PET扫描呈阳性，49%的患者F-FDG PET有阳性病灶。F-FLT摄取高的患者的OS和PFS明显短于F-FLT摄取低或无摄取的患者。未发现Ki-67指数与F-FLT摄取之间存在相关性。在多变量分析中，F-FLT、F-FDG和Ki-67均是PFS的重要预后标志物。对于OS，只有F-FDG和Ki-67仍然具有显著性。
F-FLT PET对NEN患者具有预后价值，但当同时有F-FDG PET和Ki-67指数时，多变量模型显示F-FLT PET仅增加了关于PFS的信息，而对OS无影响，而F-FDG PET仍然可预测PFS和OS。然而，未能找到一种除F-FDG和Ki-67外还包括F-FLT的临床稳健算法。因此，F-FLT PET在NENs中的确切作用（如果有的话）仍有待确定。
