PET- and CT-Based Imaging Criteria for Response Assessment of Gastroenteropancreatic Neuroendocrine Tumors Under Radiopharmaceutical Therapy

Felix L. Herr, Christian Dascalescu, Matthias P. Fabritius, Gabriel T. Sheikh, Mathias J. Zacherl, Vera Wenter, Lena M. Unterrainer, Matthias Brendel, Adrien Holzgreve, Christoph J. Auernhammer, Christine Spitzweg, Tanja Burkard, Jens Ricke, Maurice M. Heimer, Clemens C. Cyran
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Abstract

Despite well-documented limitations, current guidelines recommend the use of size-based RECIST 1.1 for response assessment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) under radiopharmaceutical therapy (RPT). We hypothesize that functional criteria are superior to RECIST 1.1 for response assessment and progression-free survival (PFS) prediction, and molecular scores can be used in prognosticating PFS. Methods: This single-center, retrospective study included 178 patients with GEP-NETs (G1 and G2) who were treated with at least 2 consecutive cycles of RPT with [177Lu]Lu-DOTATATE and who underwent somatostatin receptor PET/CT at baseline and after 2 cycles of RPT (follow-up). PFS was defined as the time between baseline and clinical progression, as reported by a GEP-NET multidisciplinary tumor board (MDT) assessment or reported death. The differences in categorization and PFS between RECIST 1.1, Choi (functional criteria), and the MDT were evaluated, and 3-y PFS with MDT defined PFS as the reference. The predictive values of the different scores in somatostatin receptor standardized reporting and data system and Krenning (molecular scores) for PFS were analyzed. Results: Choi criteria classified a higher number of patients as having progressive disease and partial response and a lower number of patients as having stable disease compared with RECIST 1.1 (P < 0.01). The PFS of patients with progressive disease according to RECIST 1.1 and Choi criteria was shorter than that of patients with stable disease and partial response (P < 0.05). Choi criteria showed a nonsignificantly higher concordance with the MDT than with RECIST 1.1. There was a shift in category from a Krenning score of 4 to a score of 3 between baseline and follow-up (P < 0.01). At baseline, a Krenning score of 3 was associated with a shorter median PFS compared with a score of 4 (P < 0.05). Conclusion: In addition to RECIST 1.1, further PET- and CT-based imaging criteria have the potential to assess response and predict PFS in patients with GEP-NETs undergoing RPT. Our data support the assumption to use Choi criteria for prediction of PFS and agreement in response assessment. At baseline, the Krenning score can be used to predict therapy response after 2 cycles of RPT.

基于PET和ct的胃肠胰神经内分泌肿瘤放射药物治疗反应评价的影像学标准
尽管有充分证据表明存在局限性,但目前的指南建议使用基于大小的RECIST 1.1来评估放射药物治疗(RPT)下胃肠胰神经内分泌肿瘤(GEP-NETs)的疗效。我们假设功能标准在反应评估和无进展生存(PFS)预测方面优于RECIST 1.1,分子评分可用于预测PFS。方法:这项单中心、回顾性研究纳入178例GEP-NETs (G1和G2)患者,这些患者至少连续2个周期使用[177Lu]Lu-DOTATATE进行RPT治疗,并在基线和2个周期RPT(随访)后接受生长抑素受体PET/CT检查。PFS定义为基线和临床进展之间的时间,由GEP-NET多学科肿瘤委员会(MDT)评估报告或报告死亡。评估RECIST 1.1、Choi(功能标准)和MDT在分类和PFS上的差异,并以MDT定义的PFS为参考进行3-y PFS。分析生长抑素受体标准化报告和数据系统中不同评分和Krenning(分子评分)对PFS的预测价值。结果:与RECIST 1.1相比,Choi标准将更多的患者分类为疾病进展和部分缓解,而将更少的患者分类为疾病稳定(P <;0.01)。根据RECIST 1.1和Choi标准,进展性疾病患者的PFS短于病情稳定且部分缓解的患者(P <;0.05)。Choi标准与MDT的一致性高于与RECIST 1.1的一致性。在基线和随访期间,Krenning评分从4分变为3分(P <;0.01)。在基线时,与Krenning评分为4分相比,3分与较短的中位PFS相关(P <;0.05)。结论:除了RECIST 1.1,进一步的PET和ct成像标准有可能评估接受RPT的GEP-NETs患者的反应和预测PFS。我们的数据支持使用Choi标准预测PFS和反应评估一致性的假设。在基线时,Krenning评分可用于预测2个周期RPT后的治疗反应。
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