The vertebral 3′-deoxy-3′-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer
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Although 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 of 18F-FLT could estimate severe HT during platinum-doublet chemotherapy.
In this Institutional Review Board–approved retrospective study, 50 patients with primary lung cancer underwent 18F-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.
Severe 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).
The low 18F-FLT uptake in the lower vertebral body is a predictor of severe HT in patients with lung cancer who receive platinum-doublet chemotherapy.
Trial registration: UMIN000027540
• The vertebral 18 F-FLT uptake with PET is an independent predictor of the severe hematological toxicity during the first cycle of platinum-doublet chemotherapy.
• The 18 F-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 using 18 F-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.
KeywordsThymidine Positron emission tomography (PET) Lung cancer Chemotherapy Lumbar vertebrae
Area under the curve
Body mass index
Body surface area
Eastern Cooperative Oncology Group
Granulocyte colony–stimulating factor
Maximum intensity projection
- NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
Negative predictive value
Positive predictive value
Proliferative vertebral volume
Standardized uptake value
Total vertebral proliferation
Volume of interest
White blood cell
This work was supported by MEXT KAKENHI (Grant Number JP22790752) and a grant-in-aid from the scientific research program “Seeds of Advanced Medicine” of the University of Fukui Hospital, Japan.
Compliance with ethical standards
The scientific guarantor of this publication is Dr. Y. Umeda.
Conflict of interest
The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
Three of the authors have significant statistical expertise.
Written informed consent was waived by the Institutional Review Board.
Institutional Review Board approval was obtained.
• Diagnostic study or prognostic study
• Performed at one institution
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