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Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis

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Abstract

Purpose

Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed.

Patients and methods

We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes.

Results

Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3).

Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048).

Conclusion

Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

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Data availability

IEO shall be classified as autonomous Data Controllers pursuant to Regulation (EU) 2016/679 of the European Parliament and Council of 27 April 2016 (GDPR).

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Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Via Ripamonti 435, 20141, Milan, Italy

    A. Laffi, F. Spada, M. Rubino & N. Fazio

  2. Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Piazza dell’Ateneo Nuovo 1, 20126, Milan, Italy

    V. Bagnardi & S. Frassoni

  3. Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy

    E. Pisa & M. Barberis

Authors
  1. A. Laffi
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  2. F. Spada
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  3. V. Bagnardi
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  4. S. Frassoni
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  5. E. Pisa
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  6. M. Rubino
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  7. M. Barberis
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  8. N. Fazio
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Contributions

All authors discussed the results and contributed to the final manuscript.

Corresponding author

Correspondence to A. Laffi.

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Conflict of interest

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in this study.

Ethical approval

The retrospective analysis complies with the Declaration of Helsinki and was approved by our local internal review board (IRB), and the IEO Data Protection Officer, with the U-ID of 2259.

Research involving human participants and/or animals

The retrospective analysis complies with the Declaration of Helsinki and was approved by our local internal review board (IRB), and the European Institute of Oncology Data Protection Officer, with the U-ID of 2259.

Informed consent

As a retrospective study, a specific informed consent was not needed and all collected data were anonymized. Every patient gave the consent for the research, as required by the Institution regulation.

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Laffi, A., Spada, F., Bagnardi, V. et al. Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis. J Endocrinol Invest 45, 317–325 (2022). https://doi.org/10.1007/s40618-021-01642-0

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  • DOI: https://doi.org/10.1007/s40618-021-01642-0

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