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Endocrine

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Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

  • Antongiulio FaggianoEmail author
  • Silvana Di Maio
  • Carmela Mocerino
  • Margaret Ottaviano
  • Chiara De Divitiis
  • Valentina Guarnotta
  • Pasquale Dolce
  • Roberta Modica
  • Ivana Puliafito
  • Lucia Tozzi
  • Antonella Di Sarno
  • Silvana Leo
  • Ferdinando Riccardi
  • Giovannella Palmieri
  • Salvatore Tafuto
  • Antonella Bianco
  • Giuseppe Badalamenti
  • Annamaria Colao
  • on behalf of ELIOS
Original Article
  • 113 Downloads

Abstract

Purpose

Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET.

Methods

A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation.

Results

Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03).

Conclusions

SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.

Keywords

Neuroendocrine tumors Sequence of treatments Somatostatin analogues High-dose somatostatin analogs PRRT Targeted therapy 

Notes

Acknowledgements

Thanks to all the participants to the ELIOS (Educational Learning Investigational Observational Study) Multicentre Study for their support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted in accordance with the 1964 Declaration of Helsinki and approved by the ethics committee of each institution. All patients gave written informed consent.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Antongiulio Faggiano
    • 1
    Email author
  • Silvana Di Maio
    • 2
  • Carmela Mocerino
    • 3
  • Margaret Ottaviano
    • 4
  • Chiara De Divitiis
    • 5
  • Valentina Guarnotta
    • 6
  • Pasquale Dolce
    • 7
  • Roberta Modica
    • 2
  • Ivana Puliafito
    • 8
  • Lucia Tozzi
    • 9
  • Antonella Di Sarno
    • 10
  • Silvana Leo
    • 11
  • Ferdinando Riccardi
    • 3
  • Giovannella Palmieri
    • 4
  • Salvatore Tafuto
    • 5
  • Antonella Bianco
    • 10
  • Giuseppe Badalamenti
    • 12
  • Annamaria Colao
    • 2
  • on behalf of ELIOS
  1. 1.Department of Experimental MedicineSapienza University of RomeRomeItaly
  2. 2.Division of Endocrinology, Department of Clinical Medicine and SurgeryFederico II University of NaplesNaplesItaly
  3. 3.Oncology UnitAzienda Ospedaliera Antonio CardarelliNaplesItaly
  4. 4.Oncology Unit, Department of Clinical Medicine and SurgeryFederico II University of NaplesNaplesItaly
  5. 5.Medical Oncology UnitIstituto Nazionale per lo studio e la cura dei tumori “Fondazione G. Pascale”-IRCCSNaplesItaly
  6. 6.Division of Endocrinology, Diabetology and Metabolism, DIBIMISUniversity of PalermoPalermoItaly
  7. 7.Department of Public HealthFederico II University of NaplesNaplesItaly
  8. 8.Oncology Unit, Department of Medical OncologyIOM—Istituto Oncologico del MediterraneoCataniaItaly
  9. 9.Fondazione IRCCS Casa Sollievo della SofferenzaUO di OncologiaSan Giovanni RotondoItaly
  10. 10.Oncology UnitAO dei Colli, Monaldi UnitNaplesItaly
  11. 11.Oncology UnitOspedale CivicoLecceItaly
  12. 12.Division of Oncology, Department of Surgical and Oncological SciencesUniversity of PalermoPalermoItaly

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