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

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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.

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Acknowledgements

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

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Correspondence to Siddharth A. Padia.

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

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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.

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

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Chan, K.T., Alessio, A.M., Johnson, G.E. et al. Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study. Cardiovasc Intervent Radiol 41, 1363–1372 (2018). https://doi.org/10.1007/s00270-018-1949-5

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  • DOI: https://doi.org/10.1007/s00270-018-1949-5

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