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Research ArticleDosimetry

The Impact of Radiobiologically Informed Dose Prescription on the Clinical Benefit of 90Y SIRT in Colorectal Cancer Patients

Elliot M. Abbott, Nadia Falzone, Boon Q. Lee, Christiana Kartsonaki, Helen Winter, Tessa A. Greenhalgh, Daniel R. McGowan, Nigar Syed, Ana M. Denis-Bacelar, Philip Boardman, Ricky A. Sharma and Katherine A. Vallis
Journal of Nuclear Medicine November 2020, 61 (11) 1658-1664; DOI: https://doi.org/10.2967/jnumed.119.233650
Elliot M. Abbott
1Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, United Kingdom
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Nadia Falzone
1Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, United Kingdom
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Boon Q. Lee
1Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, United Kingdom
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Christiana Kartsonaki
2Nuffield Department of Population Health, Oxford University, Oxford, United Kingdom
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Helen Winter
3Department of Oncology, Oxford University, Oxford, United Kingdom
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Tessa A. Greenhalgh
3Department of Oncology, Oxford University, Oxford, United Kingdom
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Daniel R. McGowan
4Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Nigar Syed
4Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Ana M. Denis-Bacelar
5National Physical Laboratory, Teddington, United Kingdom; and
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Philip Boardman
4Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Ricky A. Sharma
6Radiation Oncology, University College London, London, United Kingdom
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Katherine A. Vallis
1Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, United Kingdom
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Abstract

The purpose of this study was to establish the dose–response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to 90Y. Methods: Twenty-three mCRC patients with liver metastases refractory to chemotherapy were included. 90Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and volumetric RECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90Y or external beam radiotherapy (EBRT; 6 MV photons) were used in biologically effective dose (BED) calculations. Results: Mean administered radioactivity was 1,469 ± 428 MBq (range, 847–2,185 MBq), achieving a mean absorbed radiation dose to tumor of 35.5 ± 9.4 Gy and mean normal liver dose of 26.4 ± 6.8 Gy. A 1.0 Gy increase in mean, median, and D70 absorbed dose was associated with a reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and an increased probability of a volumetric RECIST response (odds ratio, 1.09, 1.09, and 1.10, respectively). Threshold mean, median and D70 doses for response were 48.3, 48.8, and 41.8 Gy, respectively. EBRT-equivalent BEDs for 90Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90Y SIRT and EBRT, leading to inflation of BED for SIRT and possible undertreatment. Radiobiological parameters for 90Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control.

  • colorectal cancer
  • liver metastases
  • SIRT
  • 90Y
  • BED

Footnotes

  • ↵* Contributed equally to this work.

  • Published online May 1, 2020.

  • © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 61 (11)
Journal of Nuclear Medicine
Vol. 61, Issue 11
November 1, 2020
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The Impact of Radiobiologically Informed Dose Prescription on the Clinical Benefit of 90Y SIRT in Colorectal Cancer Patients
Elliot M. Abbott, Nadia Falzone, Boon Q. Lee, Christiana Kartsonaki, Helen Winter, Tessa A. Greenhalgh, Daniel R. McGowan, Nigar Syed, Ana M. Denis-Bacelar, Philip Boardman, Ricky A. Sharma, Katherine A. Vallis
Journal of Nuclear Medicine Nov 2020, 61 (11) 1658-1664; DOI: 10.2967/jnumed.119.233650

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The Impact of Radiobiologically Informed Dose Prescription on the Clinical Benefit of 90Y SIRT in Colorectal Cancer Patients
Elliot M. Abbott, Nadia Falzone, Boon Q. Lee, Christiana Kartsonaki, Helen Winter, Tessa A. Greenhalgh, Daniel R. McGowan, Nigar Syed, Ana M. Denis-Bacelar, Philip Boardman, Ricky A. Sharma, Katherine A. Vallis
Journal of Nuclear Medicine Nov 2020, 61 (11) 1658-1664; DOI: 10.2967/jnumed.119.233650
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Keywords

  • Colorectal cancer
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