The vertebral 3'-deoxy-3'-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer.
The vertebral 3'-deoxy-3'-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer.
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椎体 3-脱氧-3-18F-氟胸苷摄取可预测肺癌患者全身化疗后的血液学毒性。
DOI：
10.1007/s00330-019-06161-4
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发表时间：
2019
期刊：
影响因子：
5.9
通讯作者：
Ishizuka T.
中科院分区：
文献类型：
--
作者：
Umeda Y;Tsujikawa T;Anzai M;Morikawa M;Waseda Y;Kadowaki M;Shigemi H;Ameshima S;Mori T;Kiyono Y;Okazawa H;Ishizuka T.
目的尽管血液学毒性 (HT) 是全身化疗的主要不良事件，但严重 HT 的估计具有挑战性。最近，PET 积累的 3'-脱氧-3'-[18F]-氟胸苷 (18F-FLT) 被认为是细胞增殖的生物标志物。本研究旨在阐明 18 F-FLT 的椎体积聚是否可以评估铂类双药化疗期间的严重 HT。 方法 在这项机构审查委员会批准的回顾性研究中，50 名原发性肺癌患者在铂类双药化疗前接受了 18 F-FLT PET 扫描。我们评估了椎体（Th4、Th8、Th12和L4）的标准化摄取值、总椎体增殖（TVP）和TVP/体表面积（TVP/BSA），然后评估这些参数与铂类双药化疗期间严重HT频率之间的关联。结果在第一个周期中有40.0%的患者观察到严重HT（3/4级）。 ROC 曲线分析表明，L4 的 TVP/BSA 是预测严重 HT 的 PET 参数中最具辨别力的参数。多变量逻辑回归分析显示，L4 的 TVP/BSA（比值比 [OR]，0.94；p= 0.0036）和既往临床试验中 3/4 级血液学毒性的频率（OR，1.03；p= 0.023）是独立的预测因素。此外，L4 截止值 68.7 的 TVP/BSA 预测 3/4 级 HT 的敏感性、特异性和准确性分别为 80.0%、86.7% 和 84.0%。 L4 的低 TVP/BSA (< 68.7) 作为二元变量是严重 HT 的显着指标 (OR, 26.0;p= 0.000026)。 结论 下椎体中低 18F-FLT 摄取是接受铂类双药化疗的肺癌患者发生严重 HT 的预测因子。 试验注册试验注册：UMIN000027540Key要点• PET 椎体 18 F-FLT 摄取是第一周期铂类双药化疗期间严重血液毒性的独立预测因子。• L4 椎体中 18 F-FLT 摄取比上椎体（Th4、Th8 和 Th12）更好地估计血液毒性。• 使用 18 F-FLT 评估骨髓腔中造血细胞的数量和活性PET 成像可以提供严重血液毒性的预测数据，并帮助确定晚期恶性疾病患者的适当药物组合或剂量强度。
ObjectivesAlthough hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) accumulation with PET has been considered a biomarker of the cell proliferation. This study aims to elucidate whether the vertebral accumulation of18F-FLT could estimate severe HT during platinum-doublet chemotherapy.MethodsIn this Institutional Review Board–approved retrospective study, 50 patients with primary lung cancer underwent18F-FLT PET scan before platinum-doublet chemotherapy. We evaluated the standardized uptake value, total vertebral proliferation (TVP), and TVP/body surface area (TVP/BSA) of the vertebral body (Th4, Th8, Th12, and L4), and then the associations between those parameters and frequency of severe HT during platinum-doublet chemotherapy were assessed.ResultsSevere HT (grade 3/4) was observed in 40.0% of patients during the first cycle. The ROC curve analyses revealed that the TVP/BSA of L4 was the most discriminative parameter among PET parameters for the prediction of severe HT. The multivariate logistic regression analysis revealed the TVP/BSA of L4 (odds ratio [OR], 0.94;p= 0.0036) and the frequency of the grade 3/4 hematological toxicity in previous clinical trials (OR, 1.03;p= 0.023) were independent predictors. Furthermore, the sensitivity, specificity, and accuracy of the TVP/BSA of L4 cut-off of 68.7 to predict grade 3/4 HT were 80.0%, 86.7%, and 84.0%, respectively. A low TVP/BSA of L4 (< 68.7) as a binary variable was a significant indicator of severe HT (OR, 26.0;p= 0.000026).ConclusionsThe low18F-FLT uptake in the lower vertebral body is a predictor of severe HT in patients with lung cancer who receive platinum-doublet chemotherapy.Trial registrationTrial registration: UMIN000027540Key Points• The vertebral18F-FLT uptake with PET is an independent predictor of the severe hematological toxicity during the first cycle of platinum-doublet chemotherapy.• The18F-FLT uptake in L4 vertebral body estimated hematological toxicities better than that in the upper vertebra (Th4, Th8, and Th12).• The evaluation of the amount and activity of hematopoietic cells in the bone marrow cavity using18F-FLT PET imaging could provide predictive data of severe hematological toxicities and help determine an appropriate drug combination or dose intensity in patients with advanced malignant diseases.