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The vertebral 3′-deoxy-3′-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer

  • Oncology
  • Published:
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Abstract

Objectives

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.

Methods

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.

Results

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).

Conclusions

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

Trial registration: UMIN000027540

Key Points

• 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.

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Abbreviations

18F-FLT:

3′-Deoxy-3′-[18F]-fluorothymidine

AUC:

Area under the curve

BMI:

Body mass index

BSA:

Body surface area

CI:

Confidence interval

ECOG:

Eastern Cooperative Oncology Group

G-CSF:

Granulocyte colony–stimulating factor

HT:

Hematological toxicity

L:

Lumbar vertebra

MIP:

Maximum intensity projection

NCI CTCAE:

National Cancer Institute Common Terminology Criteria for Adverse Events

NPV:

Negative predictive value

OR:

Odds ratio

PPV:

Positive predictive value

PPV:

Proliferative vertebral volume

PS:

Performance status

SUV:

Standardized uptake value

Th:

Thoracic vertebra

TVP:

Total vertebral proliferation

VOI:

Volume of interest

WBC:

White blood cell

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Funding

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.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan

    Yukihiro Umeda, Masaki Anzai, Miwa Morikawa, Yuko Waseda, Maiko Kadowaki, Hiroko Shigemi, Shingo Ameshima & Tamotsu Ishizuka

  2. Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan

    Tetsuya Tsujikawa, Tetsuya Mori, Yasushi Kiyono & Hidehiko Okazawa

  3. Department of Internal Medicine, Sakai Municipal Mikuni Hospital, 1-1 Shimoshinjo, Mikuni-cho, Sakai, Fukui, 913-8611, Japan

    Shingo Ameshima

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  1. Yukihiro Umeda
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  2. Tetsuya Tsujikawa
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Correspondence to Yukihiro Umeda.

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Umeda, Y., Tsujikawa, T., Anzai, M. et al. The vertebral 3′-deoxy-3′-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer. Eur Radiol 29, 3908–3917 (2019). https://doi.org/10.1007/s00330-019-06161-4

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