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Intra-tumor metabolic heterogeneity of gastric cancer on 18F-FDG PETCT indicates patient survival outcomes

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Abstract

The present study aimed to investigate the prognostic value of intra-tumor metabolic heterogeneity on 2-[18F] Fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for patients with gastric cancer. Fifty-five patients with advanced gastric cancer that had received neoadjuvant chemotherapy and radical surgery were included. Clinicopathological information, 18F-FDG PET/CT before chemotherapy, pathological response, recurrence or metastasis, progression-free survival (PFS), and overall survival (OS) of the patients were collected. The maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1) was calculated as SUVmean divided by the standard deviation, and heterogeneity index-2 (HI-2) was evaluated through linear regressions of MTVs according to different SUV thresholds. Associations between these parameters and patient survival outcomes were analyzed. None of the parameters on PET were associated with tumor recurrence. Pathological responders had significantly smaller TLR, MTV and HI-2 values than non-responders (P = 0.017, 0.017 and 0.013, respectively). In multivariate analysis of PFS, only HI-2 was an independent factor (hazard ratio [HR] = 2.693, P = 0.005) after adjusting for clinical tumor-node-metastasis (TNM) stage. In multivariate analysis of OS, HI-2 was also an independent predictive factor (HR = 2.281, P = 0.009) after adjusting for tumor recurrence. Thus, HI-2 generated from baseline 18F-FDG PET/CT is significantly associated with survival of patients with gastric cancer. Preoperative assessment of HI-2 by 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

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Availability of data and materials

The dataset used and/or analyzed in current study are available from the corresponding author on reasonable request.

Abbreviations

18F-FDG:

2-[18F] Fluoro-2-deoxy-d-glucose

PET/CT:

Positron emission tomography/computed tomography

SUVmax:

Maximum standard uptake value

SUVpeak :

Peak standard uptake value

MTV:

Metabolic tumor volume

TLG:

Total lesion glycolysis

TLR:

Tumor-to-liver ratio

HI:

Heterogeneity index

VOI:

Volume of interest

PFS:

Progression-free survival

OS:

Overall survival

HR:

Hazard ratio

WDA:

Well differentiated adenocarcinoma

MDA:

Moderate differentiated adenocarcinoma

PDA:

Poorly differentiated adenocarcinoma

SRC:

Signet-ring cell carcinoma

MAC:

Mucinous adenocarcinoma

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Acknowledgements

The authors would like to express their gratitude to the staff of the Department of Nulcear Medicine of Zhongshan Hospital, Fudan University, for the support of this study.

Funding

This study was funded by the National Natural Science Foundation of China (Grant Number: 81701730), the training program for excellent young medical talents of Zhongshan Hospital of Fudan University (Grant Number: 2019ZSYQ28), and the Shanghai “Rising Stars of Medical Talent”—–Youth Development Program (Grant Number: HWJRS2019-72). The funding body had no role in the design, data collection, analysis, interpretation or manuscript writing of this study.

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Author notes

  1. Guobing Liu and Hongyan Yin have contributed equally to this article.

Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 in Fenglin Road, Shanghai, 200032, People’s Republic of China

    Guobing Liu, Hongyan Yin, Yan Hu & Hongcheng Shi

  2. Department of Medical Oncology, Center of Evidence-based Medicine, Zhongshan Hospital, Fudan University, No. 180 in Fenglin Road, Shanghai, 200032, People’s Republic of China

    Xi Cheng, Yan Wang & Tianshu Liu

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  1. Guobing Liu
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Contributions

GL and YH conceived and wrote this article. GL, HY, and XC collected the study materials or patients. XC, YW and YH performed the data analysis and interpretation. TL and HS controlled the quality of the study. All authors have read and approved the manuscript for publication.

Corresponding authors

Correspondence to Tianshu Liu or Hongcheng Shi.

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The authors declare that there is no conflict of interest regarding this article.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Zhongshan Hospital of Fudan University (Approval Number: IRB2015-098). Written informed consents were obtained from all patients.

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Written informed consents were obtained from included patients for publication.

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Liu, G., Yin, H., Cheng, X. et al. Intra-tumor metabolic heterogeneity of gastric cancer on 18F-FDG PETCT indicates patient survival outcomes. Clin Exp Med 21, 129–138 (2021). https://doi.org/10.1007/s10238-020-00659-8

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  • DOI: https://doi.org/10.1007/s10238-020-00659-8

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