Highly favourable outcomes with peptide receptor radionuclide therapy (PRRT) for metastatic rectal neuroendocrine neoplasia (NEN)

  • Grace KongEmail author
  • Simona Grozinsky-Glasberg
  • Michael S. Hofman
  • Tim Akhurst
  • Amichay Meirovitz
  • Ofra Maimon
  • Yodphat Krausz
  • Jeremy Godefroy
  • Michael Michael
  • David J. Gross
  • Rodney J. Hicks
Original Article



Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres.


Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT.


Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had 177Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia.


Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.


PRRT Rectal Neuroendocrine Lutetium Radionuclide therapy 


Compliance with ethical standards

Conflict of interest

The authors 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. This article does not contain any studies with animals performed by any of the authors.

Informed consent

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


  1. 1.
    Öberg K, Åkerström G, Rindi G, Jelic S. On behalf of the ESMO Guidelines Working Group; Neuroendocrine gastroenteropancreatic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010; 21(suppl-5):v223–7.
  2. 2.
    Lloyd RVOR, Kloppel G, Rosai J, editors. WHO classification of tumours of endocrine organs. 4th ed; 2017.Google Scholar
  3. 3.
    Fazio N, Milione M. Heterogeneity of grade 3 gastroenteropancreatic neuroendocrine carcinomas: new insights and treatment implications. Cancer Treat Rev. 2016;50:61–7. Scholar
  4. 4.
    Perren A, Couvelard A, Scoazec JY, Costa F, Borbath I, Delle Fave G, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: pathology: diagnosis and prognostic stratification. Neuroendocrinology. 2017.
  5. 5.
    Leoncini E, Boffetta P, Shafir M, Aleksovska K, Boccia S, Rindi G. Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms. Endocrine. 2017.
  6. 6.
    Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin N Am. 2011;40(1):1–18, vii. Scholar
  7. 7.
    Niederle MB, Hackl M, Kaserer K, Niederle B. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European neuroendocrine tumour society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer. 2010;17(4):909–18. Scholar
  8. 8.
    Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335–42. Scholar
  9. 9.
    Ramage JK, De Herder WW, Delle Fave G, Ferolla P, Ferone D, Ito T, et al. ENETS consensus guidelines update for colorectal neuroendocrine neoplasms. Neuroendocrinology. 2016;103(2):139–43. Scholar
  10. 10.
    Caplin M, Sundin A, Nillson O, Baum RP, Klose KJ, Kelestimur F, et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology. 2012;95(2):88–97. Scholar
  11. 11.
    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 Off J Am Soc Clin Oncol. 2008;26(18):3063–72. CrossRefGoogle Scholar
  12. 12.
    Weinstock B, Ward SC, Harpaz N, Warner RR, Itzkowitz S, Kim MK. Clinical and prognostic features of rectal neuroendocrine tumors. Neuroendocrinology. 2013;98(3):180–7. Scholar
  13. 13.
    Pavel M, O’Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103(2):172–85. Scholar
  14. 14.
    Caplin ME, Pavel M, Ruszniewski P. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(16):1556–7. Google Scholar
  15. 15.
    Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, et al. ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas. Neuroendocrinology. 2016;103(2):186–94. Scholar
  16. 16.
    Castellano D, Bajetta E, Panneerselvam A, Saletan S, Kocha W, O’Dorisio T, et al. Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-2 study. Oncologist. 2013;18(1):46–53. Scholar
  17. 17.
    Hicks RJ, Kwekkeboom DJ, Krenning E, Bodei L, Grozinsky-Glasberg S, Arnold R, et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabeled somatostatin analogues. Neuroendocrinology. 2017.
  18. 18.
    Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–35. CrossRefGoogle Scholar
  19. 19.
    Kong G, Thompson M, Collins M, Herschtal A, Hofman MS, Johnston V, et al. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT). Eur J Nucl Med Mol Imaging. 2014;41(10):1831–44. Scholar
  20. 20.
    Kong G, Callahan J, Hofman MS, Pattison DA, Akhurst T, Michael M, et al. High clinical and morphologic response using (90)Y-DOTA-octreotate sequenced with (177)Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2017;44(3):476–89. Scholar
  21. 21.
    Kong G, Johnston V, Ramdave S, Lau E, Rischin D, Hicks RJ. High-administered activity in-111 octreotide therapy with concomitant radiosensitizing 5FU chemotherapy for treatment of neuroendocrine tumors: preliminary experience. Cancer Biother Radiopharm. 2009;24(5):527–33. Scholar
  22. 22.
    Hubble D, Kong G, Michael M, Johnson V, Ramdave S, Hicks RJ. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging. 2010;37(10):1869–75. Scholar
  23. 23.
    Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38(2):302–11. Scholar
  24. 24.
    Krenning EP, Valkema R, Kooij PP, Breeman WA, Bakker WH, deHerder WW, et al. Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide. Ital J Gastroenterol Hepatol. 1999;31(Suppl 2):S219–23.Google Scholar
  25. 25.
    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(2):228–47. Scholar
  26. 26.
    Ryan J, Akhurst T, Lynch AC, Michael M, Heriot AG. Neoadjuvant (90) yttrium peptide receptor radionuclide therapy for advanced rectal neuroendocrine tumour: a case report. ANZ J Surg. 2017;87(1–2):92–3. Scholar
  27. 27.
    Abdulrezzak U, Kula M, Tutus A, Buyukkaya F, Karaca H. PET/CT and bremsstrahlung imaging after 90Y DOTANOC therapy for rectal net with liver metastases. Clin Nucl Med. 2015;40(10):799–801. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Grace Kong
    • 1
    • 2
    Email author
  • Simona Grozinsky-Glasberg
    • 3
  • Michael S. Hofman
    • 1
    • 2
  • Tim Akhurst
    • 1
    • 2
  • Amichay Meirovitz
    • 4
  • Ofra Maimon
    • 4
  • Yodphat Krausz
    • 5
  • Jeremy Godefroy
    • 5
  • Michael Michael
    • 2
    • 6
  • David J. Gross
    • 3
  • Rodney J. Hicks
    • 1
    • 2
    • 7
  1. 1.Centre for Cancer ImagingPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Neuroendocrine ServicePeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.Neuroendocrine Tumour Unit, Endocrinology and Metabolism DepartmentHadassah-Hebrew University Medical CentreJerusalemIsrael
  4. 4.Oncology Department and Radiation Therapy UnitHadassah-Hebrew University Medical CenterJerusalemIsrael
  5. 5.Nuclear Medicine DepartmentHadassah-Hebrew University Medical CentreJerusalemIsrael
  6. 6.Divison Cancer MedicinePeter MacCallum Cancer CentreMelbourneAustralia
  7. 7.The Sir Peter MacCallum Department of Oncologythe University of MelbourneParkvilleAustralia

Personalised recommendations