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Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis

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Abstract

Background

Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumors and available systemic therapies are limited.

Aim

To explore the role of peptide receptor radionuclide therapy (PRRT) with Yttrium-90 (90Y) and Lutetium-177 (177Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs).

Methods

We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with 177Lu- or 90Y-DOTA-TATE or –TOC between 1999 to 2017 at our Institute. Overall, 30 patients with confirmed malignant PCCs and PGLs matched inclusion/exclusion criteria and were considered eligible for this analysis.

Results

Thirty (n = 30) patients were treated: 22 with PGLs and 8 with PCCs (12 M and 18 F, median age 47 [IQR: 35–60 years]). Eighteen patients (n = 18) had head and neck PGLs, 3 patients thoracic PGLs and 1 patient abdominal PGL. Sixteen patients (53%) had locally advanced and fourteen (47%) had metastatic disease. Twenty-seven (90%) patients had disease progression at baseline. Four (13%) patients were treated with 90Y, sixteen (53%) with 177Lu and ten (33%) with 90Y + 177Lu respectively. The median total cumulative activity from treatment with 90Y- alone was 9.45 GBq (range 5.11–14.02 GBq), from 177Lu- alone was 21.9 GBq (7.55–32.12 GBq) and from the combination treatment was 4.94 GBq from 90Y- and 6.83 GBq from 177Lu- (ranges 1.04–10.1 and 2.66–20.13 GBq, respectively). Seven out of 30 (23%) patients had partial response and 19 (63%) stable disease. Median follow up was 8.9 years (IQR: 2.9–12). The 5-y and 10-y PFS was 68% (95% CI: 48–82) and 53% (95% CI: 33–69), respectively, whereas 5-y and 10-y OS was 75% (95% CI: 54–87) and 59% (95% CI: 38–75), respectively. Grade 3 or 4 acute hematological toxicity occurred in three patients, two with leucopenia and one with thrombocytopenia, respectively.

Conclusion

PRRT with 177Lu- or 90Y-DOTA-TATE or –TOC is feasible and well tolerated in advanced PGLs and PCCs.

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Author Contributions

C.M.G. and M.R. contributed to the study conception and design. Material preparation, data collection and analysis were performed by G.D.D.S. and M.R. The first draft of the manuscript was written by G.D.D.S. and M. R. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Author notes

  1. These authors contributed equally: Manila Rubino, Giuseppe Danilo Di Stasio

Authors and Affiliations

  1. Onco-Endocrinology Unit, IEO European Institute of Oncology IRCCS, Milano, Italy

    Manila Rubino

  2. Nuclear Medicine Service, Check-Up Polydiagnostic Center, Salerno, Italy

    Giuseppe Danilo Di Stasio

  3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lisa Bodei

  4. Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milano, Italy

    Stefano Papi, Paola Anna Rocca, Riccardo Mei & Francesco Ceci

  5. Medical Physics Unit, IEO European Institute of Oncology IRCCS, Milano, Italy

    Mahila Esmeralda Ferrari

  6. Division of Radiotherapy, Data Management, IEO European Institute of Oncology IRCCS, Milano, Italy

    Cristiana Iuliana Fodor

  7. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milano, Italy

    Vincenzo Bagnardi & Samuele Frassoni

  8. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumours, IEO European Institute of Oncology, IRCCS, Milano, Italy

    Nicola Fazio

  9. Department of Oncology and Hemato-Oncology, University of Milan, Milano, Italy

    Francesco Ceci

  10. Radiometabolic Therapy Unit, Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milano, Italy

    Chiara Maria Grana

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  1. Manila Rubino
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Correspondence to Chiara Maria Grana.

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Conflict of interest

L.B.: nonremunerated consultancy for AAA-Novartis, Ipsen, ITM, Great Point Partners, RayzeBio, Point Biopharma; research grant AAA-Novartis. The other authors have no relevant financial or non-financial interests to disclose regarding this study.

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Rubino, M., Di Stasio, G.D., Bodei, L. et al. Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis. Endocrine 84, 704–710 (2024). https://doi.org/10.1007/s12020-024-03707-5

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