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Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma

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Abstract

Objective

We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma.

Methods

We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models.

Results

Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1–3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1–3, p = 0.006, < 0.001, and = 0.224, respectively).

Conclusion

The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

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Data Availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.

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Acknowledgements

The authors wish to thank the staff from the Lung Cancer Research Team of Buddhist Tzu Chi General Hospital for their assistance in retrieving the data of patients with lung adenocarcinoma. We also thank the Grant provided from Buddhist Tzu Chi Medical Foundation (TCMF-A 107-01-02(111)).

Funding

This research was funded by The Ministry of Science and Technology in Taiwan, Grant number: 110–2314-B-303–015-; Buddhist Tzu Chi Medical Foundation, Grant number: TCMF-A 107–01-02(111).

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Yu-Hung Chen

  2. School of Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan

    Yu-Hung Chen, Yen-Chang Chen & Sung-Chao Chu

  3. Department of Anatomical Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Yen-Chang Chen & Ming-Hsun Li

  4. Department of Medical Imaging and Radiological Sciences, Tzu Chi University of Science and Technology, Hualien, Taiwan

    Yu-Hung Chen & Kun-Han Lue

  5. Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Sung-Chao Chu

  6. Department of Cardiothoracic Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Bee-Song Chang

  7. Epidemiology and Biostatistics Consulting Center, Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Ling-Yi Wang

  8. Graduate Institute of Clinical Pharmacy, Tzu Chi University, Hualien, 97002, Taiwan

    Ling-Yi Wang

  9. Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 97002, Taiwan

    Chih-Bin Lin

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  1. Yu-Hung Chen
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Correspondence to Kun-Han Lue or Sung-Chao Chu.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board and Ethics Committee of Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (protocol code IRB110-258-B and date of approval: Dec. 13th, 2021). The requirement of informed consent for this study was waived due to its retrospective nature.

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The requirement of informed consent for this study was waived due to its retrospective nature.

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Chen, YH., Chen, YC., Lue, KH. et al. Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma. Ann Nucl Med 37, 139–150 (2023). https://doi.org/10.1007/s12149-022-01811-y

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