3'-脱氧-3'-[F]氟胸苷正电子发射断层扫描-计算机断层扫描作为培加吉酶治疗精氨酸琥珀酸合成酶1缺乏型胸段癌症预测生物标志物的作用
Role of 3'-Deoxy-3'-[F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase.
作者信息
Szyszko Teresa A, Dunn Joel T, Phillips Melissa M, Bomalaski John, Sheaff Michael T, Ellis Steve, Pike Lucy, Goh Vicky, Cook Gary J R, Szlosarek Peter W
机构信息
King's College London and Guy's and St Thomas' PET Centre, St Thomas' Hospital, London, United Kingdom.
Department of Nuclear Medicine, Royal Free Hospital NHS Trust, London, United Kingdom.
出版信息
JTO Clin Res Rep. 2022 Jul 20;3(9):100382. doi: 10.1016/j.jtocrr.2022.100382. eCollection 2022 Sep.
INTRODUCTION
Pegargiminase (ADI-PEG 20I) degrades arginine in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma (MPM) and NSCLC. Imaging with proliferation biomarker 3'-deoxy-3'-[F] fluorothymidine (F-FLT) positron emission tomography (PET)-computed tomography (CT) was performed in a phase 1 study of pegargiminase with pemetrexed and cisplatin (ADIPemCis). The aim was to determine whether FLT PET-CT predicts treatment response earlier than CT.
METHODS
A total of 18 patients with thoracic malignancies (10 MPM; eight NSCLC) underwent imaging. FLT PET-CT was performed at baseline (PET1), 24 hours post-pegargiminase monotherapy (PET2), post one cycle of ADIPemCis (PET3), and at end of treatment (EOT, PET4). CT was performed at baseline (CT1) and EOT (CT4). CT4 (modified) Response Evaluation Criteria in Solid Tumors (RECIST) response was compared with treatment response on PET (changes in maximum standardized uptake value [SUVmax] on European Organisation for Research and Treatment of Cancer-based criteria). Categorical responses (progression, partial response, and stable disease) for PET2, PET3, and PET4 were compared against CT using Cohen's kappa.
RESULTS
ADIPemCis treatment response resulted in 22% mean decrease in size between CT1 and CT4 and 37% mean decrease in SUVmax between PET1 and PET4. PET2 agreed with CT4 response in 62% (8 of 13) of patients ( = 0.043), although decrease in proliferation (SUVmax) did not precede decrease in size (RECIST). Partial responses on FLT PET-CT were detected in 20% (3 of 15) of participants at PET2 and 69% (9 of 13) at PET4 with good agreement between modalities in MPM at EOT.
CONCLUSIONS
Early FLT imaging (PET2) agrees with EOT CT results in nearly two-thirds of patients. Both early and late FLT PET-CT provide evidence of response to ADIPemCis therapy in MPM and NSCLC. We provide first-in-human FLT PET-CT data in MPM, indicating it is comparable with modified RECIST.
引言
培加吉酶（ADI-PEG 20I）可降解精氨琥珀酸合成酶1缺乏的恶性胸膜间皮瘤（MPM）和非小细胞肺癌（NSCLC）患者体内的精氨酸。在一项培加吉酶联合培美曲塞和顺铂（ADIPemCis）的1期研究中，采用增殖生物标志物3'-脱氧-3'-[F]氟胸腺嘧啶核苷（F-FLT）正电子发射断层扫描（PET）-计算机断层扫描（CT）进行成像。目的是确定FLT PET-CT是否比CT更早预测治疗反应。
方法
共有18例胸段恶性肿瘤患者（10例MPM；8例NSCLC）接受成像检查。在基线（PET1）、培加吉酶单药治疗后24小时（PET2）、ADIPemCis一个周期后（PET3）以及治疗结束时（EOT，PET4）进行FLT PET-CT检查。在基线（CT1）和EOT（CT4）进行CT检查。将CT4（改良）实体瘤疗效评价标准（RECIST）反应与PET上的治疗反应（基于欧洲癌症研究与治疗组织标准的最大标准化摄取值[SUVmax]变化）进行比较。使用Cohen's kappa将PET2、PET3和PET4的分类反应（进展、部分反应和疾病稳定）与CT进行比较。
结果
ADIPemCis治疗反应导致CT1和CT4之间平均大小减少22%，PET1和PET4之间SUVmax平均减少37%。62%（13例中的8例）患者的PET2与CT4反应一致（κ = 0.043），尽管增殖（SUVmax）的降低并不先于大小（RECIST）的降低。在PET2时，15例参与者中有20%（3例）检测到FLT PET-CT部分反应，在PET4时为69%（13例中的9例），在EOT时MPM中各模式之间一致性良好。
结论
早期FLT成像（PET2）与EOT CT结果在近三分之二的患者中一致。早期和晚期FLT PET-CT均提供了MPM和NSCLC对ADIPemCis治疗有反应的证据。我们提供了MPM中首次人体FLT PET-CT数据，表明其与改良RECIST相当。
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