Skip to main content

Advertisement

SpringerLink
Log in

Peptide Receptor Radionuclide Therapy of Pulmonary Neuroendocrine Neoplasms: a Single-Centre Experience

  • Original Article
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Peptide receptor radionuclide therapy represents a therapeutic option for neuroendocrine neoplasms; to date, experiences with peptide receptor radionuclide therapy of pulmonary neuroendocrine neoplasms are still limited. We report our experience with peptide receptor radionuclide therapy of pulmonary neuroendocrine neoplasm patients.

Materials and Methods

Clinical records of 14 pulmonary neuroendocrine neoplasm patients (7 female and 7 male) who received at least 2 cycles of peptide receptor radionuclide therapy were retrospectively reviewed. Tumoural uptake of somatostatin analogues at pre-treatment imaging was graded as 2 to 3 in all patients. RECIST criteria were used to evaluate response.

Results

No treated patient had significant toxicity. Partial response was found in 3 (21.4%) patients, stable disease in 7 (50%), and progressive disease in 4 (28.6%). A statistically significant difference between disease state at enrolment and after peptide receptor radionuclide therapy was found.

Conclusions

Our data furtherly support peptide receptor radionuclide therapy as a safe and effective treatment of patients affected by pulmonary neuroendocrine neoplasms allowing disease control in about 71% of patients without showing significant toxicity. Other studies are needed to confirm our results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Oberg K, Hellman P, Kwekkeboom D, Ferolla P, Papotti M, ESMO Guidelines Working Group. Neuroendocrine bronchial and thymic tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;2:220–3.

    Article  Google Scholar 

  2. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.

    Article  Google Scholar 

  3. Lloyd RV, Osamura R, Kloppel G, Rosai J. WHO classification of tumours of endocrine organs. 4th ed. Lyon: IARC Press; 2017.

    Google Scholar 

  4. Rindi G. The ENETS guidelines: the new TNM classification system. Tumori. 2010;96:806–9.

    Article  Google Scholar 

  5. Travis WD, Giroux DJ, Chansky K, Crowley J, Asamura H, Brambilla E, et al. International staging committee and participating institutions. The IASLC Lung Cancer Staging Project: proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol. 2008;3:1213–23.

    Article  Google Scholar 

  6. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. World Health Organization classification of tumours. Pathology and genetics of tumors of the lung, pleura, thymus and heart. 3rd ed. Lyon: IARC Press; 2004.

    Google Scholar 

  7. Gridelli C, Rossi A, Airoma G, Bianco R, Costanzo R, Daniele B, et al. Treatment of pulmonary neuroendocrine tumours: state of the art and future developments. Cancer Treat Rev. 2013;39:466–72.

    Article  Google Scholar 

  8. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  CAS  Google Scholar 

  9. Hörsch D, Schmid KW, Anlauf M, Darwiche K, Denecke T, Baum RP, et al. Neuroendocrine tumors of the bronchopulmonary system (typical and atypical carcinoid tumors): current strategies in diagnosis and treatment. Conclusions of an expert meeting February 2011 in Weimar, Germany. Oncol Res Treat. 2014;37:266–76.

    Article  Google Scholar 

  10. Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer. Lancet. 1998;351:417–8.

    Article  CAS  Google Scholar 

  11. Kwekkeboom DJ, Krenning EP, Lebtahi R, Komminoth P, Kos-Kudla B, de Herder WW, et al. Mallorca consensus conference participants; European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology. 2009;90:220–6.

    Article  CAS  Google Scholar 

  12. Campana D, Capurso G, Partelli S, Nori F, Panzuto F, Tamburrino D, et al. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence. Eur J Nucl Med Mol Imaging. 2013;40:1197–205.

    Article  CAS  Google Scholar 

  13. Bergsma H, van Vliet EI, Teunissen JJ, Kam BL, de Herder WW, Peeters RP, et al. Peptide receptor radionuclide therapy (PRRT) for GEP-NETs. Best Pract Res Clin Gastroenterol. 2012;26:867–81.

    Article  CAS  Google Scholar 

  14. Teunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer. 2011;18:S27–51.

    Article  CAS  Google Scholar 

  15. Alexandraki KI, Kaltsas G. Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy. Endocrine. 2012;41:40–52.

    Article  CAS  Google Scholar 

  16. Nisa L, Savelli G, Giubbini R. Yttrium-90 DOTATOC therapy in GEP-NET and other SST2 expressing tumors: a selected review. Ann Nucl Med. 2011;25:75–85.

    Article  CAS  Google Scholar 

  17. Bombardieri E, Ambrosini V, Aktolun C, Baum RP, Bishof-Delaloye A, Del Vecchio S, et al. Oncology Committee of the EANM. 111In-Pentetreotide scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010;37:1441–8.

    Article  Google Scholar 

  18. Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooji PP, de Herder WW, Feelders RA, et al. Radiolabeled somatostatinanalog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005;23:2754–62.

    Article  CAS  Google Scholar 

  19. Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Horsch D, O’Dorisio TM, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40:800–16.

    Article  CAS  Google Scholar 

  20. Chinol M, Paganelli G. Radionuclide peptide cancer therapy. 1st ed. New York: Taylor & Francis Group; 2006.

    Google Scholar 

  21. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  Google Scholar 

  22. Kwekkeboom DJ, Kam BL, van Essen M, Teunissen JJ, van Eijc CH, Valkema R, et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer. 2010;17:R53–73.

    Article  CAS  Google Scholar 

  23. Delpassand ES, Sims-Mourtada J, Saso H, Azhdarinia A, Ashoori F, Torabi F, et al. Safety and efficacy of radionuclide therapy with high-activity In-111 pentetreotide in patients with progressive neuroendocrine tumors. Cancer Biother Radiopharm. 2008;23:292–300.

    Article  CAS  Google Scholar 

  24. de Jong M, Breeman WA, Bernard BF, Bakker WH, Visser TJ, Kooji PP, et al. Tumor response after [(90)Y-DOTA(0), Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size. J Nucl Med. 2001;42:1841–6.

    PubMed  Google Scholar 

  25. Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001;12:941–5.

    Article  CAS  Google Scholar 

  26. Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq(90)Y-DOTATOC. J Nucl Med. 2002;43:610–6.

    CAS  PubMed  Google Scholar 

  27. Bushnell DL Jr, O’Dorisio TM, O’Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, et al. 90Y-endotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28:1652–9.

    Article  CAS  Google Scholar 

  28. Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabelled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23.

    Article  CAS  Google Scholar 

  29. Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011;38:2125–35.

    Article  CAS  Google Scholar 

  30. Filice A, Fraternali A, Frasoldati A, Asti M, Grassi E, Massi L, et al. Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience. J Oncol. 2012;2012:320198.

    Article  CAS  Google Scholar 

  31. van Essen M, Krenning EP, Kam BL, de Herder WW, Feelders RA, Kwekkebom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010;51:383–90.

    Article  Google Scholar 

  32. Mariniello A, Bodei L, Tinelli C, Baio SM, Gilardi L, Colandrea M, et al. Long term results of PRRT in advanced bronchopulmonary carcinoid. Eur J Nucl Med Mol Imaging. 2016;43:441–52.

    Article  CAS  Google Scholar 

  33. Baum R, Kluge AW, Kulkarni H, Schorr-Neufing U, Niepsch K, Bitterlich N, et al. [(177)Lu-DOTA](0)-D-Phe(1)-Tyr(3)-Octreotide ((177)Lu-DOTATOC) for peptide receptor radiotherapy in patients with advanced neuroendocrine tumours: a phase-II study. Theranostics. 2016;6:501–10.

    Article  CAS  Google Scholar 

  34. Minutoli F, Amato E, Sindoni A, Cardile D, Conti A, Herberg A, et al. Peptide receptor radionuclide therapy in patients with inoperable meningiomas: our experience and review of the literature. Cancer Biother Radiopharm. 2014;29:193–9.

    Article  CAS  Google Scholar 

  35. Baldari S, Ferraù F, Alafaci C, Herberg A, Granata F, Militano V, et al. First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary. 2012;15:S57–60.

    Article  Google Scholar 

  36. Buscombe JR, Caplin ME, Hilson AJ. Long-term efficacy of high-activity 111Inpentetreotide therapy in patients with disseminated neuroendocrine tumors. J Nucl Med. 2003;44:1–6.

    CAS  PubMed  Google Scholar 

  37. Valkema R, De Jong M, Bakker WH, Breeman WA, Kooji PP, Lugtenburg PJ, et al. Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Semin Nucl Med. 2002;32:110–22.

    Article  Google Scholar 

  38. Larsson M, Bernhardt P, Svensson JB, Wangberg B, Ahlman H, Forssell-Aronsson E. Estimation of absorbed dose to the kidneys in patients after treatment with 177Lu-octreotate: comparison between methods based on planar scintigraphy. EJNMMI Res. 2012;2:49.

    Article  Google Scholar 

  39. Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008;35:1847–56.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy

    Fabio Minutoli, Davide Cardile, Riccardo Laudicella, Antonio Vento, Benedetta Pagano & Sergio Baldari

Authors
  1. Fabio Minutoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Davide Cardile
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Riccardo Laudicella
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Vento
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benedetta Pagano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sergio Baldari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Content planning: Fabio Minutoli, Davide Cardile, and Sergio Baldari

Literature search: Fabio Minutoli, Davide Cardile, Antonio Vento, and Benedetta Pagano

Literature review: Fabio Minutoli, Davide Cardile, Riccardo Laudicella, and Antonio Vento

Manuscript writing: Fabio Minutoli; Davide Cardile, Riccardo Laudicella, and Sergio Baldari

Manuscript editing: Fabio Minutoli, Riccardo Laudicella, Antonio Vento, and Sergio Baldari

Corresponding author

Correspondence to Riccardo Laudicella.

Ethics declarations

Conflict of Interest

Fabio Minutoli, Davide Cardile, Riccardo Laudicella, Antonio Vento, Benedetta Pagano and Sergio Baldari declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Minutoli, F., Cardile, D., Laudicella, R. et al. Peptide Receptor Radionuclide Therapy of Pulmonary Neuroendocrine Neoplasms: a Single-Centre Experience. Nucl Med Mol Imaging 55, 38–45 (2021). https://doi.org/10.1007/s13139-020-00679-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-020-00679-y

Keywords

Search

Navigation