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177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In March 2014, we reported the activity and safety of 177Lu-DOTA-octreotate peptide receptor radionuclide therapy (Lu-PRRT) at two different dosages (18.5 GBq and 27.5 GBq in 5 cycles) in patients with progressive metastatic gastrointestinal neuroendocrine tumors (GI-NETs). Disease control rate (DCR) and toxicity were addressed. Herein, we report the late toxicity, progression-free survival (PFS), and overall survival (OS) in the same cohort after a 10-year follow-up.

Methods

We conducted an open-label, disease-oriented prospective phase II trial. From March 2008 to June 2011, 43 patients received 3.7 GBq or 5.5 GBq of Lu-PRRT every 6 to 8 weeks, each cycle repeated 5 times. All patients showed 68Gallium-DOTA-peptide PET/Octreoscan® positivity (score 3–4 Rotterdam scale) in known lesions. Tumor burden was estimated radiologically. Time-to-event data (PFS and OS) were described using Kaplan-Meier curves and compared with the log-rank test.

Results

Forty-three patients (28 males and 15 females) were evaluable and were monitored for a median period of 118 months (range 12.6–139.6). Median PFS in patients receiving 18.5 GBq was 59.8 months (95% confidence interval [95% CI] 14.3–79.6), identical to that of patients treated with 27.5 GBq (59.8 months, 95% CI 23.4–82.0). Median OS was 71.0 months (95% CI 46.1–107.3) in the group who received 18.5 GBq and 97.6 months (95% CI 64.3-not reached) in the group treated with 27.5 GBq (P = 0.22). Patients with progression limited to lymph nodes showed significantly longer median PFS and OS than those with hepatic lesions (P = 0.02 for PFS and P = 0.04 for OS). Age over 65 years at the time of PRRT was also significant for OS. Of note, no late hematological or renal toxicity was observed in either group.

Conclusions

The long-term follow-up of the IRST phase II study shows that Lu-PRRT is a safe and effective therapy for patients with advanced GI-NET, the most important prognostic factor being tumor burden, hepatic lesions, and age. We believe that Lu-PRRT should be offered to patients with early-stage disease.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors thank Gráinne Tierney for the English revision of the manuscript. We also thank Monica Golinucci and the other members of the Nuclear Medicine and Radiometabolic Medicine Unit team for their support and assistance.

Funding

This study was partially supported by AIRC (Associazione Italiana per la Ricerca sul Cancro).

Author information

Authors and Affiliations

  1. Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy

    Giovanni Paganelli, Maddalena Sansovini, Silvia Nicolini, Ilaria Grassi, Federica Matteucci & Stefano Severi

  2. Radiology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Elena Amadori

  3. Oncology Pharmacy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Valentina Di Iorio

  4. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Manuela Monti & Emanuela Scarpi

  5. Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Toni Ibrahim & Alberto Bongiovanni

  6. Healthcare Administration, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Mattia Altini

  7. Nuclear Medicine Unit, University of Ferrara, Ferrara, Italy

    Luca Urso & Corrado Cittanti

Authors
  1. Giovanni Paganelli
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  2. Maddalena Sansovini
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  3. Silvia Nicolini
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  4. Ilaria Grassi
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  6. Elena Amadori
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  8. Manuela Monti
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  9. Emanuela Scarpi
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  10. Alberto Bongiovanni
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  14. Federica Matteucci
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  15. Stefano Severi
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Contributions

Giovanni Paganelli: study concept and design, manuscript drafting; Stefano Severi: coordinated the different tasks of the project and worked on preparation, treatment, and follow-up of patients; Maddalena Sansovini, Silvia Nicolini, Grassi Ilaria, and Luca Urso: worked on enrolment, preparation, treatment, and follow-up of patients; Elena Amadori: reviewed morphological imaging during enrolment, treatment, and follow-up; Federica Matteucci: worked on the diagnostic and therapeutic scintigraphy examinations of the patients; Corrado Cittanti: reviewed the manuscript; Mattia Altini: reviewed the manuscript; Valentina Di Iorio: prepared the radiopharmaceutical drug; Toni Ibrahim and Alberto Bongiovanni: worked on enrolment and follow-up of patients; Emanuela Scarpi: data analysis; Manuela Monti: data collection; Giovanni Paganelli: coordinated and supervised the different tasks of the project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maddalena Sansovini.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The protocol was approved by the Area Vasta Romagna Ethics Committee (approval no. 2007-005517-20 of October 31, 2007), and by the competent Italian Regulatory Authorities. The study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and with Good Clinical Practice (GCP) guidelines.

Informed consent

All patients gave informed consent. Having an 18FDG-PET scan before PRRT was not a prerequisite for the study but was taken into account as a prognostic factor when available.

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This article is part of the Topical Collection on Oncology - Digestive tract

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Paganelli, G., Sansovini, M., Nicolini, S. et al. 177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study. Eur J Nucl Med Mol Imaging 48, 152–160 (2021). https://doi.org/10.1007/s00259-020-04873-0

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