Sachpekidis Christos, Hillengass J, Goldschmidt H, Wagner B, Haberkorn U, Kopka K, Dimitrakopoulou-Strauss A
Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69210, Heidelberg, Germany.
Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):50-62. doi: 10.1007/s00259-016-3502-6. Epub 2016 Aug 29.
The aim of this study was to assess the combined use of the radiotracers F-FDG and F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).
Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with F-FDG and F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).
An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, F-FDG PET/CT-based treatment response revealed CR in 14 patients (F-FDG PET/CT CR), PR in 11 patients (F-FDG PET/CT PR) and progressive disease in four patients (F-FDG PET/CT PD). In terms of F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, F-NaF PET/CT depicted 56 of the 129 F-FDG positive lesions (43 %). Follow-up F-NaF PET/CT showed persistence of 81.5 % of the baseline F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to F-FDG negative. Treatment response according to F-NaF PET/CT revealed CR in one patient (F-NaF PET/CT CR), PR in five patients (F-NaF PET/CT PR), SD in 12 patients (F-NaF PET/CT SD), and PD in seven patients (F-NaF PET/CT PD). Dynamic F-FDG and F-NaF PET/CT studies showed that SUV, SUV, as well as the kinetic parameters K, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001).
F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, F-NaF PET/CT does not seem to add significantly to F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.
本研究旨在通过静态(全身)和动态PET/CT(dPET/CT)评估放射性示踪剂F-FDG和F-NaF联合使用在一组接受大剂量化疗(HDT)后进行自体干细胞移植(ASCT)的多发性骨髓瘤(MM)患者治疗反应评估中的应用。
34例计划接受HDT后ASCT治疗的初发、未经治疗的MM患者纳入本研究。所有患者在治疗前后均接受了F-FDG和F-NaF的PET/CT扫描。根据欧洲癌症研究与治疗组织(EORTC)1999标准通过PET/CT评估治疗反应。dPET/CT研究的评估基于定性评估、半定量(SUV)计算以及基于双组织房室模型和非房室方法的定量分析,从而提取分形维数(FD)。
对29例患者进行了分析:3例临床完全缓解(CR),26例非CR(13例接近完全缓解-nCR,4例非常好的部分缓解-VGPR,9例部分缓解-PR)。治疗后,F-FDG PET/CT在14/29例患者中为阴性,在15/29例患者中为阳性,敏感性为57.5%,特异性为100%。根据EORTC 1999标准,基于F-FDG PET/CT的治疗反应显示14例患者为CR(F-FDG PET/CT CR),11例患者为PR(F-FDG PET/CT PR),4例患者为疾病进展(F-FDG PET/CT PD)。就F-NaF PET/CT而言,4/29例患者(13.8%)基线扫描为阴性,因此未能显示MM。对于可行直接病灶间比较的患者,F-NaF PET/CT显示129个F-FDG阳性病灶中的56个(43%)。随访F-NaF PET/CT显示,治疗后81.5%的基线F-NaF阳性MM病灶持续存在,尽管其中64.7%已转为F-FDG阴性。根据F-NaF PET/CT的治疗反应显示1例患者为CR(F-NaF PET/CT CR),5例患者为PR(F-NaF PET/CT PR),12例患者为疾病稳定(F-NaF PET/CT SD),7例患者为疾病进展(F-NaF PET/CT PD)。动态F-FDG和F-NaF PET/CT研究表明,SUV、SUV以及来自参考骨髓和骨骼的动力学参数K、流入和FD对治疗有显著下降反应(p < 0.001)。
F-FDG PET/CT在MM治疗反应评估中显示出57.7% 的敏感性和100% 的特异性。尽管其敏感性有限,但F-FDG PET/CT的表现令人满意,因为随访扫描中6/9例假阴性患者(66.7%)临床特征为nCR,这是一个肿瘤负荷非常低的疾病阶段。另一方面,在接受HDT和ASCT的MM患者治疗反应评估中,至少在治疗后不久,F-NaF PET/CT似乎并未显著补充F-FDG PET/CT的评估。