Pettersson Olof, Fröss-Baron Katarzyna, Crona Joakim, Sundin Anders
Section of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Front Oncol. 2020 Feb 21;10:193. doi: 10.3389/fonc.2020.00193. eCollection 2020.
Therapy monitoring of cancer treatment by contrast-enhanced CT (CECT), applying response evaluation criteria in solid tumors criteria version 1. 1 (RECIST 1.1) is less suitable for neuroendocrine tumors (NETs) which, when responding, tend to show stabilization rather than shrinkage. New methods are needed to further classify patients in order to identify non-responders at an early stage and avoid unnecessary adverse effects and costs. Changes in arterial tumor attenuation and contrast-enhancement could be used to identify the effect of therapy, perhaps even in early stages of treatment. Patients with metastatic pancreatic NETs (PNETs) receiving peptide receptor radionuclide therapy (PRRT) with Lu-DOTATATE underwent CECT at baseline, mid-treatment (PRRT cycles 3-5) and at follow-up, 3 months after the last PRRT cycle. At baseline CECT, the liver metastasis with the highest arterial attenuation was identified in each patient. The fold changes in arterial tumor attenuation (Hounsfield Units, HU), contrast-enhancement (HU), and transversal tumor area (cm) between CECT at baseline, mid-treatment and follow-up were calculated. Correlation of the tumor metrics to outcome parameters such as progression-free survival (PFS) and time to best response was performed. Fifty-two patients were included (27 men, 25 women), median age 60 years (range 29-80), median Ki-67 8% (range 1-30). Six patients had grade 1 PNETs, forty had grade 2 and four had grade 3 tumors. As an internal control, it was first tested and established that the tumor contrast-enhancement was not merely related to that of the abdominal aorta. The mean ± SD arterial attenuation of the liver metastases was similar at baseline, 217 ± 62 HU and at mid-treatment, 238 ± 80 HU and then decreased to 198 ± 62 HU at follow-up, compared to baseline ( = 0.024, = 52) and mid-treatment ( = 0.0004, = 43). The transversal tumor area decreased 25% between baseline and follow-up ( = 0.013, = 52). Tumor contrast-enhancement increased slightly from baseline to mid-treatment and these fold changes correlated with PFS ( = 0.33, = 0.0002, = 37) and with time to best response ( = 0.34, < 0.0001, = 37). Early changes in contrast-enhancement and arterial attenuation in PNET liver metastases may for CECT monitoring of PRRT yield complementary information to evaluation by RECIST 1.1.
采用实体瘤疗效评价标准1.1版（RECIST 1.1），通过对比增强CT（CECT）对癌症治疗进行疗效监测，不太适用于神经内分泌肿瘤（NETs），因为这类肿瘤在产生反应时往往表现为稳定而非缩小。需要新的方法来进一步对患者进行分类，以便在早期识别无反应者，避免不必要的不良反应和费用。动脉期肿瘤衰减和对比增强的变化可用于确定治疗效果，甚至可能在治疗早期。接受镥[177Lu] DOTATATE肽受体放射性核素治疗（PRRT）的转移性胰腺神经内分泌肿瘤（PNETs）患者在基线期、治疗中期（PRRT第3 - 5周期）和随访期（最后一次PRRT周期后3个月）接受了CECT检查。在基线期CECT检查时，确定每位患者肝转移灶中动脉期衰减最高的病灶。计算基线期、治疗中期和随访期CECT之间动脉期肿瘤衰减（亨氏单位，HU）、对比增强（HU）和肿瘤横截面积（cm）的变化倍数。对肿瘤指标与无进展生存期（PFS）和最佳反应时间等预后参数进行相关性分析。纳入52例患者（27例男性，25例女性），中位年龄60岁（范围29 - 80岁），中位Ki - 67为8%（范围1 - 30）。6例患者为1级PNETs，40例为2级，4例为3级肿瘤。作为内部对照，首先进行测试并确定肿瘤对比增强不仅仅与腹主动脉的对比增强相关。肝转移灶的平均±标准差动脉期衰减在基线期为217±62 HU，治疗中期为238±80 HU，与基线期相比（P = 0.024，n = 52）和治疗中期相比（P = 0.0004，n = 43），随访期降至198±62 HU。肿瘤横截面积在基线期和随访期之间减少了25%（P = 0.013，n = 52）。肿瘤对比增强从基线期到治疗中期略有增加，这些变化倍数与PFS相关（r = 0.33，P = 0.0002，n = 37），与最佳反应时间相关（r = 0.34，P < 0.0001，n = 37）。PNET肝转移灶对比增强和动脉期衰减的早期变化可能为PRRT的CECT监测提供与RECIST 1.1评估互补的信息。
