Koski Anniina, Ahtinen Helena, Liljenback Heidi, Roivainen Anne, Koskela Anu, Oksanen Minna, Partanen Kaarina, Laasonen Leena, Kairemo Kalevi, Joensuu Timo, Hemminki Akseli
1 Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , 00290 Helsinki, Finland .
Hum Gene Ther. 2013 Dec;24(12):1029-41. doi: 10.1089/hum.2013.123. Epub 2013 Nov 7.
Computed tomography (CT) is the most commonly used radiological response evaluation method in contemporary oncology. However, it may not be optimally suitable for assessment of oncolytic virus treatments because of paradoxical inflammatory tumor swellings, which result from virus treatments, particularly when viruses are armed with immunostimulatory molecules. Here we investigated the prognostic utility of CT and [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oncolytic virus treatments. We also investigated possible appearance of false-positive FDG signals in FDG-PET imaging of humans and hamsters treated with oncolytic adenoviruses. First, immunocompetent Syrian hamsters were treated with intratumoral adenovirus injections, tumor growth was followed up, and [(18)F]-FDG-uptake was quantitated with small animal PET/CT. Second, we describe a retrospective patient series, essentially 17 individual case reports, of advanced cancer patients treated with oncolytic adenoviruses in the context of an Advanced Therapy Access Program (ATAP) who underwent radiological response evaluation with both contrast-enhanced CT and FDG-PET. Third, we collected a retrospective case series of radiological response and survival data of 182 patients treated with oncolytic adenoviruses in ATAP to evaluate the prognostic reliability of CT and FDG-PET. Overall, responses in CT and FDG-PET correlated well with each other and were equally reliable as prognostic markers for long survival after oncolytic adenovirus treatment. Interestingly, we observed that new FDG-avid lymph nodes appearing in FDG-PET after virus treatments may represent inflammatory responses and therefore should not be interpreted as treatment failure in the absence of other signs or verification of disease progression. We also observed indications that FDG-PET might be more sensitive in detection of responses than tumor size.
计算机断层扫描（CT）是当代肿瘤学中最常用的放射学反应评估方法。然而，它可能并非最适合评估溶瘤病毒治疗，因为病毒治疗会导致矛盾的炎症性肿瘤肿胀，尤其是当病毒携带免疫刺激分子时。在此，我们研究了CT和[¹⁸F] - 氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）在溶瘤病毒治疗中的预后效用。我们还研究了在接受溶瘤腺病毒治疗的人类和仓鼠的FDG - PET成像中可能出现的FDG假阳性信号。首先，对具有免疫活性的叙利亚仓鼠进行瘤内注射腺病毒治疗，跟踪肿瘤生长情况，并通过小动物PET / CT对[¹⁸F] - FDG摄取进行定量分析。其次，我们描述了一个回顾性患者系列，本质上是17例个体病例报告，这些晚期癌症患者在高级治疗准入计划（ATAP）的背景下接受了溶瘤腺病毒治疗，并接受了增强CT和FDG - PET的放射学反应评估。第三，我们收集了182例在ATAP中接受溶瘤腺病毒治疗的患者的放射学反应和生存数据的回顾性病例系列，以评估CT和FDG - PET的预后可靠性。总体而言，CT和FDG - PET的反应相互之间相关性良好，并且作为溶瘤腺病毒治疗后长期生存的预后标志物同样可靠。有趣的是，我们观察到病毒治疗后在FDG - PET中出现的新的FDG摄取阳性淋巴结可能代表炎症反应，因此在没有其他疾病进展迹象或证实的情况下，不应将其解释为治疗失败。我们还观察到有迹象表明，FDG - PET在检测反应方面可能比肿瘤大小更敏感。
