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Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning

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Abstract

Purpose

Peptide receptor radionuclide therapy (PRRT) with 90Y-labelled and 177Lu-labelled peptides is an effective strategy for the treatment of metastatic/nonresectable neuroendocrine tumours (NETs). Dosimetry provides important information useful for optimizing PRRT with individualized regimens to reduce toxicity and increase tumour responses. However, this strategy is not applied in routine clinical practice, despite the fact that several dosimetric studies have demonstrated significant dose–effect correlations for normal organ toxicity and tumour response that can better guide therapy planning. The present study reviews the key relationships and the radiobiological models available in the literature with the aim of providing evidence that optimization of PRRT is feasible through the implementation of dosimetry.

Methods

The MEDLINE database was searched combining specific keywords. Original studies published in the English language reporting dose–effect outcomes in patients treated with PRRT were chosen.

Results

Nine of 126 studies were selected from PubMed, and a further five were added manually, reporting on 590 patients. The studies were analysed and are discussed in terms of weak and strong elements of correlations.

Conclusion

Several studies provided evidence of clinical benefit from the implementation of dosimetry in PRRT, indicating the potential contribution of this approach to reducing severe toxicity and/or reducing undertreatment that commonly occurs. Prospective trials, possibly multicentre, with larger numbers of patients undergoing quantitative dosimetry and with standardized methodologies should be carried out to definitively provide robust predictive paradigms to establish effective tailored PRRT.

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Authors and Affiliations

  1. Istituto Europeo di Oncologia, Via Ripamonti, 435 20141, Milano, Italy

    Marta Cremonesi, Mahila Esmeralda Ferrari, Cristina Garibaldi, Paul Eugene Summers, Roberto Orecchia, Chiara Maria Grana & Francesca Botta

  2. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lisa Bodei

  3. Istituto Nazionale di Tumori, Milano, Italy

    Carlo Chiesa

  4. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy

    Anna Sarnelli

  5. Policlinico Umberto I, University Hospital, Roma, Italy

    Massimiliano Pacilio

  6. Istituto Nazionale dei Tumori Regina Elena, Roma, Italy

    Lidia Strigari

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  1. Marta Cremonesi
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Correspondence to Chiara Maria Grana.

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Conflicts of interest

L.B. acted as a consultant for Advanced Accelerator Applications (AAA) and Ipsen, and has received speaker honorarium from AAA, for work not related to the present paper.

C.C. was a consultant for Alfasigma and discloses funding from BTG Biocompatibles for work not related to the present paper.

M.P. was a consultant for Bayer Healthcare Pharmaceuticals Inc. as a member of the Targeted Alpha Therapy Working Group Advisory Board.

M.C., M.E.F., A.S., C.G., L.S., P.E.S., R.O., C.M.G. and F.B. declare that they have no conflicts of interest.

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Cremonesi, M., Ferrari, M.E., Bodei, L. et al. Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning. Eur J Nucl Med Mol Imaging 45, 2426–2441 (2018). https://doi.org/10.1007/s00259-018-4044-x

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