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Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors

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Abstract

Purpose

To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery.

Methods

This retrospective study included 72 consecutive patients with PanNET (January 2018–March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE.

Results

Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040).

Conclusion

SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients’ management by preoperatively identifying subjects with more aggressive diseases.

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Data Availability

Data will be made available upon request to the corresponding author.

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Author information

Author notes

  1. P. Mapelli and C. Bezzi equally contributed to the paper and therefore they are joint first authors

Authors and Affiliations

  1. Vita-Salute San Raffaele University, Milan, Italy

    Paola Mapelli, Carolina Bezzi, Samuele Ghezzo, Valentina Andreasi, Francesco De Cobelli, Stefano Partelli, Massimo Falconi & Maria Picchio

  2. Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Paola Mapelli, Carolina Bezzi, Samuele Ghezzo, Carla Canevari, Patrizia Magnani, Luigi Gianolli & Maria Picchio

  3. Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Francesca Muffatti, Valentina Andreasi, Stefano Partelli & Massimo Falconi

  4. University of Milano-Bicocca, Milan, Italy

    Francesco Baldassi

  5. Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Marco Schiavo Lena

  6. Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Francesco De Cobelli

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  1. Paola Mapelli
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Correspondence to Maria Picchio.

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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 national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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All patients gave their informed consent to participate in the study.

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Prof. Massimo Falconi was an Advisory Board Member of Advanced Accelerator Application (AAA). All the other authors have no conflicts of interest related to the present paper to disclose.

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Mapelli, P., Bezzi, C., Muffatti, F. et al. Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging 50, 2818–2829 (2023). https://doi.org/10.1007/s00259-023-06210-7

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