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Peptide receptor radionuclide therapy as a two-step strategy for initially unresectable liver disease from neuroendocrine tumors: a single-center experience

  • Endocrine Surgery
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Abstract

Purpose

In this study, we describe our experience with peptide receptor radionuclide therapy (PRRT) for initially unresectable liver disease as a two-steps therapeutic strategy, first in neoadjuvant intention before surgery and then later on in case of disease relapse.

Methods

We performed a retrospective evaluation of four cases of unresectable liver metastases of NET of different origins treated with neoadjuvant Lu-177-DotaTATE for conversion into resectability first and as rechallenging treatment after disease relapse.

Results

After treatment with Lu-177-DotaTAE, resectability was reached in three of four cases. In one case, SIRT was additionally performed preoperatively. Relapse occurred in three of four cases after 32, 34, and 37 months, respectively, and was managed with Re-PRRT-treatment.

Conclusion

Although more data are needed, our retrospective study suggests that treatment with Lu-177-DotaTATE is an important adjunct to surgery not only in neoadjuvant intention but also for treating disease relapse. A register study might deliver more evidence for supporting this strategy.

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Data availability

All data are available at our university center and can be requested.

References

  1. J. Strosberg et al. Phase 3 trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N. Engl. J. Med. 376(2), 125–135 (2017)

    Article  CAS  Google Scholar 

  2. S.-J. Kim, K. Pak, P.J. Koo et al. The efficacy of 177Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur. J. Nucl. Med Mol. Imaging 42, 1964–1970 (2015)

    Article  CAS  Google Scholar 

  3. S.F. Dannoon, S.A. Alenezi, A.H. Elgazzar, The efficacy of the available peptide receptor radionuclide therapy for neuroendocrine tumors: a meta-analysis. Nucl. Med. Commun. 38, 1085–1093 (2017)

    Article  Google Scholar 

  4. B. Saravana-Bawan, A. Bajwa, J. Paterson, A.J.B. McEwan, T.P.W. McMullen, Efficacy of 177Lu peptide receptor radionuclide therapy for the treatment of neuroendocrine tumors: a meta-analysis. Clin. Nucl. Med 44(9), 719–727 (2019)

    Article  Google Scholar 

  5. T. Traub-Weidinger et al. Improved quality of life in patients treated with peptide radionuclides. World J. Nucl. Med. 10(2), 115–121 (2011)

    Article  CAS  Google Scholar 

  6. J.J. Teunissen, D.J. Kwekkeboom, E.P. Krenning, Quality of life in patients withgastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J. Clin. Oncol. 22(13), 2724–2729 (2004)

    Article  CAS  Google Scholar 

  7. S. Khan, et al. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrinetumors treated with [177Lu-DOTA0,Tyr3]octreotate. J. Nucl. Med. 52(9), 1361–1368 (2011)

    Article  CAS  Google Scholar 

  8. T. Liu, J. Liao, J. Dang, G. Li, Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis. Ther. Adv. Med. Oncol. 11(May), 1758835919853673 (2019)

    CAS  PubMed  PubMed Central  Google Scholar 

  9. E.A. Carlsen, N. Fazio, D. Granberg, S. Grozinsky-Glasberg, H. Ahmadzadehfar, C.M. Grana, W.T. Zandee, J. Cwikla, M.A. Walter, P.S. Oturai, A. Rinke, A. Weaver, A. Frilling, S. Gritti, A.K. Arveschoug, A. Meirovitz, U. Knigge, H. Sorbye, Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocr. Relat. Cancer 26(2), 227–239 (2019)

    Article  CAS  Google Scholar 

  10. J. Zhang, H.R. Kulkarni, A. Singh, K. Niepsch, D. Müller, R.P. Baum, Peptide receptor radionuclide therapy in grade 3 neuroendocrine neoplasms: safety and survival analysis in 69 patients. J. Nucl. Med. 60(3), 377–385 (2019). https://doi.org/10.2967/jnumed.118.215848

    Article  CAS  PubMed  Google Scholar 

  11. S.P. Thang, M.S. Lung, G. Kong, M.S. Hofman, J. Callahan, M. Michael, R.J. Hicks, Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN)—a single-institution retrospective analysis. Eur. J. Nucl. Med. Mol. Imaging 45(2), 262–277 (2018)

    Article  CAS  Google Scholar 

  12. W.A. van der Zwan, T. Brabander, B.L.R. Kam, J.J.M. Teunissen, R.A. Feelders, J. Hofland, E.P. Krenning, W.W. de Herder, Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate inpatients with bronchial and gastroenteropancreatic neuroendocrine tumours. Eur. J. Nucl. Med. Mol. 46(3), 704–717 (2019)

    Article  Google Scholar 

  13. N. Hirmas, R. Jadaan, A. Al-Ibraheem, Peptide receptor radionuclide therapy and the treatment of gastroentero-pancreatic neuroendocrine tumors: current findings and future perspectives. Nucl. Med. Mol. Imaging 52(3), 190–199 (2018). https://doi.org/10.1007/s13139-018-0517-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. I. Perysinakis, C. Aggeli, G. Kaltsas, G.N. Zografos, Neoadjuvant therapy for advanced pancreatic neuroendocrine tumors: an emerging treatment modality. Hormones. 15, 15–22 (2016)

    Article  Google Scholar 

  15. D. Kaemmerer, V. Prasad, W. Daffner, D. Hörsch, G. Klöppel, M. Hommann, R.P. Baum, Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor. World J. Gastroenterol. 15, 5867–5870 (2009)

    Article  Google Scholar 

  16. O. Stoeltzing, M. Loss, E. Huber, V. Gross, C. Eilles, J. Mueller-Brand, H.J. Schlitt, Staged surgery with neoadjuvant 90Y-DOTATOC therapy for down-sizing synchronous bilobular hepatic metastases from a neuroendocrine pancreatic tumor. Langenbeck’s Arch. Surg. 395, 185–192 (2010)

    Article  Google Scholar 

  17. A. Sowa-Staszczak, D. Pach, R. Chrzan, M. Trofimiuk, A. Stefańska, M. Tomaszuk, M. Kołodziej, R. Mikołajczak, D. Pawlak, A. Hubalewska-Dydejczyk, Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur. J. Nucl. Med. Mol. Imaging 38, 1669–1674 (2011). https://doi.org/10.1007/s00259-011-1835-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. E.I. van Vliet, C.H. van Eijck, R.R. de Krijger, E.J. Van Dijkum, J.J. Teunissen, B.L. Kam, W.W. de Herder, R.A. Feelders, B.A. Bonsing, T. Brabander, E.P. Krenning, Neoadjuvant treatment of nonfunctioning pancreatic neuroendocrine tumors with [177Lu-DOTA0, Tyr3] octreotate. J. Nucl. Med. 56, 1647–1653 (2015)

    Article  Google Scholar 

  19. A. Frilling, A.K. Clift, Therapeutic strategies for neuroendocrine liver metastases. Cancer 121(8), 1172–1186 (2015)

    Article  CAS  Google Scholar 

  20. A. Frilling et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 15(1), e8–e21 (2014)

    Article  Google Scholar 

  21. P.L. Kunz, P.J. Catalano, H. Nimeiri, G.A. Fisher, T.A. Longacre, C.J. Suarez et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: a trial of the ECOG-ACRIN Cancer Research Group (E2211). J. Clin. Oncol. 36(15_suppl), 36 (2018)

    Article  Google Scholar 

  22. L.M. Dilz, T. Denecke, I.G. Steffen, V. Prasad, L.F. von Weikersthal, U.F. Pape, B. Wiedenmann, M. Pavel, Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours. Eur. J. Cancer 51(10), 1253–1262 (2015)

    Article  CAS  Google Scholar 

  23. P.G. Claringbold, R.A. Price, J.H. Turner, Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother. Radiopharm. 27(9), 561–569 (2012). https://doi.org/10.1089/cbr.2012.1276

    Article  CAS  PubMed  Google Scholar 

  24. T.W. Barber et al. The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable. Eur. J. Surg. Oncol. 38(1), 64–71 (2012)

    Article  CAS  Google Scholar 

  25. P.W. McGarrah, G.F.M. Westin, T.J. Hobday, J.A. Scales, J.P. Ingimarsson, B.C. Leibovich, T. R. Halfdanarson, Renal neuroendocrine neoplasms: a single-center experience, Clin Genitourin Cancer. S1558-7673(19)30354-4 (2019). https://doi.org/10.1016/j.clgc.2019.11.003

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Acknowledgements

We thank our colleagues that participate in the endocrine board on a regular basis. We also thank the referring physicians in our region for entrusting their patients to our care.

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Author notes

  1. These authors contributed equally: Matthias Schmidt, Dirk L. Stippel

Authors and Affiliations

  1. Department for General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Costanza Chiapponi, Nadine Lürssen, Roger Wahba & Dirk L. Stippel

  2. Department for Hemato-Oncology, University Hospital of Cologne, Univeristy of Cologne, Cologne, Germany

    Birgit Cremer

  3. Department for Pathology, University Hospital of Cologne, University of Cologne, Cologne, Germany

    Uta Drebber

  4. Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital of Cologne, Univeristy of Cologne, Cologne, Germany

    Michael Faust

  5. Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany

    Matthias Schmidt

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  1. Costanza Chiapponi
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Contributions

Each author has made substantial contributions to the conception of the work. C.C. and N.L. are responsible for the acquisition and the analysis of data, C.C., M.S., B.C., and D.S. for the interpretation of data. C.C., N.L. together with all other authors participated in drafting the work. M.S., B.C., M.F., U.D., R.W., and D.S. revised it critically for important intellectual content; all authors approved the final version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Costanza Chiapponi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

Given the retrospective nature of the research presented in this manuscript no ethical committee was involved. All patients agreed that their data are used anonymously for research purpose, by being treated at a university hospital. There was no financial funding. This paper will not be simultaneously submitted to any other publication during the review process.

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Chiapponi, C., Lürssen, N., Cremer, B. et al. Peptide receptor radionuclide therapy as a two-step strategy for initially unresectable liver disease from neuroendocrine tumors: a single-center experience. Endocrine 70, 187–193 (2020). https://doi.org/10.1007/s12020-020-02341-1

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  • DOI: https://doi.org/10.1007/s12020-020-02341-1

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