Iravani Amir, Osman Medhat M, Weppler Alison M, Wallace Roslyn, Galligan Anna, Lasocki Arian, Hunter Morgan O, Akhurst Tim, Hofman Michael S, Lau Peter K H, Kee Damien, Au-Yeung George, Sandhu Shahneen, Hicks Rodney J
Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Eur J Nucl Med Mol Imaging. 2020 Nov;47(12):2776-2786. doi: 10.1007/s00259-020-04815-w. Epub 2020 Apr 21.
We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma.
We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation.
Thirty-one consecutive patients, median age 60 years (range, 30-78), were identified from 2016 to 2018. The median number of combination-ICI cycles to the first post-FDG-PET/CT response assessment was 3 (interquartile range (IQR), 2-4). The best-overall responses were complete metabolic response (CMR) in 25 (80%), partial metabolic response (PMR) in 3 (10%), and progressive metabolic disease (PMD) in 3 (10%) patients. Patients with PMD had significantly higher pre-treatment wbMTV (p = 0.009). At a median follow-up of 21.5 months, 26 (84%) patients were alive with median progression-free and overall survival not reached. Secondary progression occurred in 9/31 (29%) patients at a median of 8.2 months (IQR, 6.9-15.5), of those majority (78%) was detected by FDG-PET/CT. Of 36 findings on post-FDG-PET/CT suggestive of irAE, 29 (80%) had clinical confirmation. In 3 (7%), the FDG-PET/CT findings preceded clinical presentation. The most common FDG-PET/CT detectable irAEs were endocrinopathies (36%) and enterocolitis (35%).
FDG-PET/CT response evaluation predicts the long-term outcome of patients treated with first-line combination-ICIs. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.
我们旨在研究氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG-PET/CT）在晚期黑色素瘤一线联合免疫检查点抑制剂（联合ICI）治疗后反应监测及免疫相关不良事件（irAE）中的作用。
我们回顾性分析了以下患者的结局：（1）接受一线纳武单抗加伊匹木单抗治疗；（2）分别在开始ICI治疗后的2个月和4个月内进行治疗前和治疗后的FDG-PET/CT扫描（治疗前FDG-PET/CT和治疗后FDG-PET/CT）；（3）至少有一个病灶可根据实体瘤PET反应标准（PERCIST）进行评估。通过每3个月进行一次FDG-PET/CT监测颅外反应。在治疗前和治疗后测量全身代谢肿瘤体积（wbMTV），并将其与结局相关联。irAE的FDG-PET/CT表现定义为治疗后FDG-PET/CT上新出现的非肿瘤性摄取增加，并与临床表现相关联。
从2016年至2018年共纳入31例连续患者，中位年龄60岁（范围30-78岁）。至首次治疗后FDG-PET/CT反应评估时联合ICI治疗的中位周期数为3（四分位间距（IQR），2-4）。最佳总体反应为25例（80%）患者达到完全代谢反应（CMR），3例（10%）患者达到部分代谢反应（PMR），3例（10%）患者为进行性代谢疾病（PMD）。PMD患者治疗前的wbMTV显著更高（p = 0.009）。中位随访21.5个月时，26例（84%）患者存活，中位无进展生存期和总生存期未达到。9/31例（29%）患者发生继发性进展，中位时间为8.2个月（IQR，6.9-15.5），其中大多数（78%）通过FDG-PET/CT检测到。在治疗后FDG-PET/CT上提示irAE的36项发现中，29项（80%）得到临床证实。3例（7%）患者中，FDG-PET/CT发现先于临床表现。最常见的FDG-PET/CT可检测到的irAE为内分泌病（36%）和小肠结肠炎（35%）。
FDG-PET/CT反应评估可预测接受一线联合ICI治疗患者的长期结局。通过FDG-PET/CT对颅外继发性进展进行长期治疗反应监测是可行的。除反应评估外，FDG-PET/CT经常检测到临床上相关的irAE，其可能同时或在不同时间点累及多个系统，并且可能先于临床诊断。
