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The role of quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT in well-differentiated neuroendocrine tumors: beyond prognosis

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Abstract

Purpose

We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs).

Methods

This study enrolled patients with [68 Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell’s C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden.

Results

A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV30 and liver SRETV30) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658–0.946] and 0.806 [95% CI, 0.664–0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241–1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV30 (P = 0.016) or high liver SRETV30 (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV30 or liver SRETV30 (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS.

Conclusion

Quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR.

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Data availability

The clinical data and imaging files used in this study, though not available in a public repository, are available from the corresponding authors upon reasonable request.

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Acknowledgements

This study was supported by the Guangdong Provincial Basic and Applied Basic Research Fund (grant no. 2021A1515110241). This funder had no role in the design, conduct, or reporting of this work.

Funding

This study was supported by the Guangdong Provincial Basic and Applied Basic Research Fund (grant no. 2021A1515110241). This funder had no role in the design, conduct, or reporting of this work.

Author information

Author notes

  1. Luohai Chen, Nuerailaguli Jumai, and Qiao He contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Luohai Chen, Nuerailaguli Jumai, Man Liu, Min-hu Chen, Zhirong Zeng & Ning Zhang

  2. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Qiao He & Xiangsong Zhang

  3. Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Yuan Lin

  4. Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Yanji Luo

  5. Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Yu Wang

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  1. Luohai Chen
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Contributions

Luohai Chen, Nuerailaguli Jumai, Xiangsong Zhang, and Ning Zhang each contributed to the study conception and design. Data collection was performed by Luohai Chen, Nuerailaguli Jumai, and Qiao He. Data analysis and interpretation of results was also conducted by Luohai Chen, Nuerailaguli Jumai, and Qiao He. Luohai Chen drafted the manuscript, and Nuerailaguli Jumai, Qiao He, Man Liu, Yuan Lin, Yu Wang, Min-hu Chen, and Zhirong Zeng each contributed to the critical revision of the manuscript. All authors reviewed the manuscript and provided approval for the final version of the manuscript.

Corresponding authors

Correspondence to Xiangsong Zhang or Ning Zhang.

Ethics declarations

Ethics approval

This study was approved by the ethics committee of The First Affiliated Hospital, Sun Yat-sen University (approval no. 2022–062) and was conducted in accordance with the principles of the Declaration of Helsinki.

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The requirement for formal consent was waived by the approving ethics committee due to the retrospective nature of this study.

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Not applicable.

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The authors declare no competing interests.

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Chen, L., Jumai, N., He, Q. et al. The role of quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT in well-differentiated neuroendocrine tumors: beyond prognosis. Eur J Nucl Med Mol Imaging 50, 525–534 (2023). https://doi.org/10.1007/s00259-022-05971-x

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