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

Research output: Contribution to journalArticle

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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
Pages (from-to)2426-2441
Number of pages16
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume45
Issue number13
DOIs
Publication statusPublished - 2018

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Peptide Receptors
Radioisotopes
Neoplasms
Therapeutics
Neuroendocrine Tumors
PubMed
MEDLINE
Multicenter Studies
Germany
Language
Databases
Peptides

Keywords

  • Absorbed dose correlations
  • Dose–effect
  • Dose–toxicity
  • Dosimetry
  • Peptide receptor radionuclide therapy (PRRT)
  • creatinine
  • dotatate y 90
  • dotatoc y 90
  • lutetium 177
  • radiopharmaceutical agent
  • unclassified drug
  • yttrium 90
  • bibliographic database
  • cancer patient
  • clinical practice
  • comparative study
  • creatinine clearance
  • dose response
  • dosimetry
  • drug efficacy
  • drug potency
  • follow up
  • glomerulus filtration rate
  • human
  • national health organization
  • nephrotoxicity
  • neuroendocrine tumor
  • peptide receptor radionuclide therapy
  • practice guideline
  • radioisotope therapy
  • renal protection
  • Review
  • risk factor
  • treatment planning
  • world health organization

Cite this

@article{c937886e150a4531af93e52f95c631f9,
title = "Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning",
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. {\circledC} 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",
keywords = "Absorbed dose correlations, Dose–effect, Dose–toxicity, Dosimetry, Peptide receptor radionuclide therapy (PRRT), creatinine, dotatate y 90, dotatoc y 90, lutetium 177, radiopharmaceutical agent, unclassified drug, yttrium 90, bibliographic database, cancer patient, clinical practice, comparative study, creatinine clearance, dose response, dosimetry, drug efficacy, drug potency, follow up, glomerulus filtration rate, human, national health organization, nephrotoxicity, neuroendocrine tumor, peptide receptor radionuclide therapy, practice guideline, radioisotope therapy, renal protection, Review, risk factor, treatment planning, world health organization",
author = "M. Cremonesi and M.E. Ferrari and L. Bodei and C. Chiesa and A. Sarnelli and C. Garibaldi and M. Pacilio and L. Strigari and P.E. Summers and R. Orecchia and C.M. Grana and F. Botta",
note = "Cited By :3 Export Date: 5 February 2019 CODEN: EJNMA Correspondence Address: Grana, C.M.; Istituto Europeo di Oncologia, Via Ripamonti, Italy; email: chiara.grana@ieo.it Chemicals/CAS: creatinine, 19230-81-0, 60-27-5; lutetium 177, 14265-75-9; yttrium 90, 10098-91-6 References: Bodei, L., Kwekkeboom, D.J., Kidd, M., Modlin, I.M., Krenning, E.P., Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer (2016) Semin Nucl Med, 46 (3), pp. 225-238. , PID: 27067503; Strosberg, J., El-Haddad, G., Wolin, E., Hendifar, A., Yao, J., Chasen, B., Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors (2017) N Engl J Med, 376 (2), pp. 125-135. , COI: 1:CAS:528:DC{\%}2BC2sXhtlSnsLnM, PID: 5895095; Cybulla, M., Weiner, S.M., Otte, A., End-stage renal disease after treatment with 90Y-DOTATOC (2001) Eur J Nucl Med, 28 (10), pp. 1552-1554. , COI: 1:CAS:528:DC{\%}2BD3MXmvFSlu7g{\%}3D, PID: 11685499; Imhof, A., Brunner, P., Marincek, N., Briel, M., Schindler, C., Rasch, H., Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers (2011) J Clin Oncol, 29, pp. 2416-2423. , COI: 1:CAS:528:DC{\%}2BC3MXovFKqt7s{\%}3D, PID: 21555692; 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year = "2018",
doi = "10.1007/s00259-018-4044-x",
language = "English",
volume = "45",
pages = "2426--2441",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",
number = "13",

}

TY - JOUR

T1 - Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning

AU - Cremonesi, M.

AU - Ferrari, M.E.

AU - Bodei, L.

AU - Chiesa, C.

AU - Sarnelli, A.

AU - Garibaldi, C.

AU - Pacilio, M.

AU - Strigari, L.

AU - Summers, P.E.

AU - Orecchia, R.

AU - Grana, C.M.

AU - Botta, F.

N1 - Cited By :3 Export Date: 5 February 2019 CODEN: EJNMA Correspondence Address: Grana, C.M.; Istituto Europeo di Oncologia, Via Ripamonti, Italy; email: chiara.grana@ieo.it Chemicals/CAS: creatinine, 19230-81-0, 60-27-5; lutetium 177, 14265-75-9; yttrium 90, 10098-91-6 References: Bodei, L., Kwekkeboom, D.J., Kidd, M., Modlin, I.M., Krenning, E.P., Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer (2016) Semin Nucl Med, 46 (3), pp. 225-238. , PID: 27067503; Strosberg, J., El-Haddad, G., Wolin, E., Hendifar, A., Yao, J., Chasen, B., Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors (2017) N Engl J Med, 376 (2), pp. 125-135. , COI: 1:CAS:528:DC%2BC2sXhtlSnsLnM, PID: 5895095; Cybulla, M., Weiner, S.M., Otte, A., End-stage renal disease after treatment with 90Y-DOTATOC (2001) Eur J Nucl Med, 28 (10), pp. 1552-1554. , COI: 1:CAS:528:DC%2BD3MXmvFSlu7g%3D, PID: 11685499; Imhof, A., Brunner, P., Marincek, N., Briel, M., Schindler, C., Rasch, H., Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers (2011) J Clin Oncol, 29, pp. 2416-2423. , COI: 1:CAS:528:DC%2BC3MXovFKqt7s%3D, PID: 21555692; 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PY - 2018

Y1 - 2018

N2 - 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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

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

KW - Absorbed dose correlations

KW - Dose–effect

KW - Dose–toxicity

KW - Dosimetry

KW - Peptide receptor radionuclide therapy (PRRT)

KW - creatinine

KW - dotatate y 90

KW - dotatoc y 90

KW - lutetium 177

KW - radiopharmaceutical agent

KW - unclassified drug

KW - yttrium 90

KW - bibliographic database

KW - cancer patient

KW - clinical practice

KW - comparative study

KW - creatinine clearance

KW - dose response

KW - dosimetry

KW - drug efficacy

KW - drug potency

KW - follow up

KW - glomerulus filtration rate

KW - human

KW - national health organization

KW - nephrotoxicity

KW - neuroendocrine tumor

KW - peptide receptor radionuclide therapy

KW - practice guideline

KW - radioisotope therapy

KW - renal protection

KW - Review

KW - risk factor

KW - treatment planning

KW - world health organization

U2 - 10.1007/s00259-018-4044-x

DO - 10.1007/s00259-018-4044-x

M3 - Article

VL - 45

SP - 2426

EP - 2441

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

SN - 0340-6199

IS - 13

ER -