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An Italian real-world multicenter study of patients with advanced mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) of the gastro-entero-pancreatic system treated with chemotherapy

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Abstract

Purpose

The aim of this study is to describe the clinical management of an Italian series of patients with advanced gastro-entero-pancreatic (GEP) MiNENs treated in clinical practice.

Methods

Clinical records of patients from four Italian referral Centers were retrospectively analyzed to correlate clinical/biological data with clinical outcomes. All the surgical specimens were centrally reviewed.

Results

Clinical data and surgical samples of 51 patients during 1995–2015 were analyzed. Sites of origin were: 32 colorectal, 14 gastro-esophageal, and 5 pancreatobiliary. Twenty-one out of fifty-one (42.2%) developed metachronous distant metastases. Only 5/51 (9.8%) patients received peri-operative therapy, and 23/51 (45.1%) first-line chemotherapy, mostly fluoropyrimidines/oxaliplatin. The NEN component was poorly differentiated in the whole population. Patients with Ki67 index < 55% in the NEC component had a significantly longer median overall survival (OS) (35.3 months; 95% CI 27.1–41.0) than those with Ki67 ≥ 55% (11.9 months; 95% CI 9.1–14.0) P = 0.0005. The median OS was 14 months (95% CI 10.1–19.1) in the whole cohort, with 11.4 months (95% CI 6.2–20.2) in patients who received a first-line therapy.

Conclusion

This study confirms that GEP-MiNENs represent a complex disease and that over the past years the clinical management has been predominantly guided by the subjective judgment of the clinicians. Although, in this series, the NEC component appeared mostly responsible for the systemic spread and prognosis on the whole neoplasm, the lack of strong prognostic and predictive factors universally recognized seems to condition their management so far. Future prospective clinical and biomolecular studies could help clinicians to improve clinical management of GEP-MiNENs.

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Data availability

All the data are available at European Institute of Oncology.

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Acknowledgements

The authors thank Mr. William Russel for revising English language and literature search, Prof. Fausto Sessa for suggestions and supervision over the Ph.D. program, and all the Italian pathologists who reviewed the surgical samples for the pathological counterpart of this study already published in 2018.

Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Division of Gastrointestinal Medical Oncology, Neuroendocrine Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy

    Francesca Spada & Nicola Fazio

  2. Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy

    Massimo Milione

  3. Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology, IRCCS, Milan, Italy

    Patrick Maisonneuve

  4. Department of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy

    Natalie Prinzi & Sara Pusceddu

  5. First Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy

    Natalie Prinzi

  6. Medical Oncology Unit, Istituto Clinico Humanitas, IRCCS, via Manzoni 56, Rozzano, Italy

    Valeria Smiroldo & Carlo Carnaghi

  7. Oncology Unit, ASST Rhodense, Rho, Italy

    Valeria Smiroldo

  8. Department of Oncology, Ospedale Di Circolo, Varese, Italy

    Elena Bolzacchini

  9. Oncology Unit, Ospedale Sant’Anna, ASST Lariana, Como, Italy

    Elena Bolzacchini

  10. Medical Oncology, Humanitas Istituto Clinico Catanese, Catania, Sicilia, Italy

    Carlo Carnaghi

  11. Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy

    Fausto Sessa & Stefano La Rosa

  12. Unit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy

    Fausto Sessa & Stefano La Rosa

  13. Pathology Unit, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy

    Silvia Uccella

  14. Pathology Service, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy

    Silvia Uccella

Authors
  1. Francesca Spada
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  2. Massimo Milione
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  9. Fausto Sessa
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  10. Stefano La Rosa
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Contributions

For research articles with several authors, a short paragraph specifying their individual contributions must be provided. The following statements should be used “Conceptualization, FS, MM and NF; methodology, FS, PM and MM; validation, FS, MM, PM and NF; formal analysis, PM; investigation, FS, NP, VS, SP, CC, FS; resources, FS, MM., SLR, NF; data curation, FS, MM, PM, NF; writing-original draft preparation, F.S.; writing-review and editing, FS, MM, PM, SP, SLR, SU, and NF; visualization, FS and NF; supervision, FS, NF.; project administration, FS All authors have read and agreed to the published version of the manuscript.”

Corresponding author

Correspondence to Nicola Fazio.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of National Institute of Oncology, INT, IRCCS, Milan with the approval n° INT 21/16.

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Informed consent was obtained from all subjects involved in this study.

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Spada, F., Milione, M., Maisonneuve, P. et al. An Italian real-world multicenter study of patients with advanced mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) of the gastro-entero-pancreatic system treated with chemotherapy. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02314-5

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