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Peptide receptor radionuclide therapy with 177Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and 18F-FDG PET

  • Annarita Ianniello
  • Maddalena Sansovini
  • Stefano Severi
  • Silvia Nicolini
  • Chiara Maria Grana
  • Katrin Massri
  • Alberto Bongiovanni
  • Lorenzo Antonuzzo
  • Valentina Di Iorio
  • Anna Sarnelli
  • Paola Caroli
  • Manuela Monti
  • Emanuela Scarpi
  • Giovanni Paganelli
Original Article

Abstract

Purpose

Typical and atypical carcinoids (TC and AC) represent 20 – 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-FDG PET as prognostic factors in patients with advanced TC or AC.

Methods

A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient’s kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients.

Results

The median follow-up was 29 months (range 7 – 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 – 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 – 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 – 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 – 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 – 48.9 months) and 15.3 months (11.7 – 31.1 months) in the FDG PET-positive group.

Conclusion

Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC.

Keywords

Peptide receptor radionuclide therapy with 177Lu-DOTATATE Bronchial carcinoids Thyroid transcription factor 1 18F-FDG PET 

Notes

Acknowledgments

The authors thank Ursula Elbling for editing the manuscript. This study was partially supported by AIRC – Associazione Italiana per la Ricerca sul Cancro (grant number: IG10679).

Authors’ contributions

S.S. coordinated the various stages of the project and was involved in the preparation, treatment and follow-up of patients. A.I., M.S., S.N., C.M.G., K.M. were involved in the enrolment, preparation, treatment and follow-up of patients. P.C. performed the diagnostic and therapeutic scintigraphy scans. A.B. and L.A. were involved in the preparation, treatment and follow-up of patients. V.D.I. prepared the radiopharmaceutical. A.S. was responsible for imaging quality control. M.M. was responsible for data collection. E.S. performed the statistical analysis. A.I. and G.P. drafted the manuscript. G.P. reviewed the manuscript for important intellectual content. All authors read and approved the final version of the paper.

Compliance with ethical standards

Funding

None.

Conflict of interest

None.

Ethical approval

The protocol was approved by the Ethics Committee of the Wide Catchment Area of Romagna-IRST (CEIIAV) and by the competent Italian regulatory authorities. The study was conducted in accordance with the principles of the Declaration of Helsinki and good clinical practice guidelines.

Informed consent

All patients gave written informed consent.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Annarita Ianniello
    • 1
  • Maddalena Sansovini
    • 1
  • Stefano Severi
    • 1
  • Silvia Nicolini
    • 1
  • Chiara Maria Grana
    • 2
  • Katrin Massri
    • 3
  • Alberto Bongiovanni
    • 4
  • Lorenzo Antonuzzo
    • 5
  • Valentina Di Iorio
    • 6
  • Anna Sarnelli
    • 7
  • Paola Caroli
    • 1
  • Manuela Monti
    • 8
  • Emanuela Scarpi
    • 8
  • Giovanni Paganelli
    • 1
  1. 1.Nuclear Medicine and Radiometabolic UnitIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  2. 2.Division of Nuclear MedicineEuropean Institute of Oncology Milan (IEO)MilanItaly
  3. 3.Nuclear Medicine, Department of RadiologyOspedale San LucaLuccaItaly
  4. 4.Osteoncology and Rare Tumors CenterIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  5. 5.SC Oncologia Medica 1AOU CareggiFirenzeItaly
  6. 6.Oncology Pharmacy LaboratoryIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  7. 7.Medical Physics UnitIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  8. 8.Unit of Biostatistics and Clinical TrialsIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly

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