Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study

  • Keith T. Chan
  • Adam M. Alessio
  • Guy E. Johnson
  • Sandeep Vaidya
  • Sharon W. Kwan
  • Wayne Monsky
  • Ann E. Wilson
  • David H. Lewis
  • Siddharth A. Padia
Clinical Investigation

Abstract

Purpose

To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET.

Materials and Methods

This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child–Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2.

Results

The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0–133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child–Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy.

Conclusion

Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy.

ClinicalTrials.gov identifier: NCT02848638.

Keywords

Radioembolization Yttrium-90 PET Hepatocellular carcinoma Dosimetry 

Notes

Acknowledgements

Grants for this study: Philips Healthcare. IRB statement: This study was performed under IRB approval at the University of Washington.

Compliance with Ethical Standards

Conflict of interest

S. Padia: Consultant for BTG International and the other authors have no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018

Authors and Affiliations

  1. 1.Division of Interventional Radiology, Department of RadiologyUniversity of WashingtonSeattleUSA
  2. 2.Department of RadiologyUniversity of WashingtonSeattleUSA
  3. 3.Division of Nuclear Medicine, Department of RadiologyHarborview Medical CenterSeattleUSA
  4. 4.Division of Interventional Radiology, Department of RadiologyDavid Geffen School of Medicine at University of California Los AngelesLos AngelesUSA

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