Skip to main content
SpringerLink
Log in

Voxel-based tumor dose correlates to complete pathologic necrosis after transarterial radioembolization for hepatocellular carcinoma

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The transarterial radioembolization (TARE) dose is traditionally calculated using the single-compartment Medical Internal Radiation Dose (MIRD) formula. This study utilized voxel-based dosimetry to correlate tumor dose with explant pathology in order to identify dose thresholds that predicted response.

Methods

All patients with HCC treated with TARE using yttrium-90 [90Y] glass microspheres at a single institution between January 2015 – June 2023 who underwent liver transplantation were eligible. The [90Y] distribution and dose-volume histograms were determined using Simplicity90 (Mirada Medical, Oxford UK) with a Bremsstrahlung SPECT/CT. A complete response was assigned if explant pathology showed complete necrosis and the patient had not undergone additional treatments to the same tumor after TARE. Logistic regression and receiver operator characteristic (ROC) curves were constructed to evaluate dose thresholds correlated with response.

Results

Forty-one patients were included. Twenty-six (63%) met criteria for complete response. Dose to 95% (D95), 70% (D70), and 50% (D50) of the tumor volume were associated with likelihood of complete response by logistic regression (all p < 0.05). For lesions with complete response versus without, the median D95 was 813 versus 232 Gy, D70 was 1052 versus 315 Gy, and D50 was 1181 versus 369 Gy (all p < 0.01). A D95 > 719 Gy had the highest accuracy at 68% (58% sensitivity, 87% specificity) for predicting complete response. Median percent of tumor volume receiving at least 100 Gy (V100), 200 Gy (V200), 300 Gy (V300), and 400 Gy (V400) also differed by pathologic response: the median V100, V200, V300, and V400 was 100% versus 99%, 100% versus 97%, 100% versus 74%, and 100% versus 43% in the complete response versus non-complete response groups, respectively (all p < 0.05).

Conclusion

Voxel-based dosimetry was well-correlated with explant pathology. The D95 threshold had the highest accuracy, suggesting the D95 may be a relevant target for multi-compartment dosimetry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76. https://doi.org/10.1053/j.gastro.2007.04.061.

    Article  CAS  PubMed  Google Scholar 

  2. Galle PR, Forner A, Llovet JM, et al. EASL Clinical Practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. https://doi.org/10.1016/j.jhep.2018.03.019.

    Article  Google Scholar 

  3. Fujiki M, Aucejo F, Kim R. General overview of neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: necessity or option? Liver Int. 2011;31(8):1081–9. https://doi.org/10.1111/j.1478-3231.2011.02473.x.

    Article  PubMed  Google Scholar 

  4. DiNorcia J, Florman SS, Haydel B, et al. Pathologic response to Pretransplant Locoregional Therapy is predictive of patient Outcome after Liver Transplantation for Hepatocellular Carcinoma: analysis from the US Multicenter HCC Transplant Consortium. Ann Surg. 2020;271(4):616. https://doi.org/10.1097/SLA.0000000000003253.

    Article  PubMed  Google Scholar 

  5. Ravaioli M, Grazi GL, Ercolani G, et al. Partial necrosis on Hepatocellular Carcinoma Nodules Facilitates Tumor Recurrence after liver transplantation. Transplantation. 2004;78(12):1780. https://doi.org/10.1097/01.TP.0000145892.97114.EE.

    Article  PubMed  Google Scholar 

  6. Gabr A, Kulik L, Mouli S, et al. Liver transplantation following Yttrium-90 radioembolization: 15‐Year experience in 207‐Patient cohort. Hepatology. 2021;73(3):998. https://doi.org/10.1002/hep.31318.

    Article  CAS  PubMed  Google Scholar 

  7. Salem R, Johnson GE, Kim E, et al. Yttrium-90 radioembolization for the Treatment of Solitary, Unresectable HCC: the LEGACY study. Hepatology. 2021;74(5):2342–52. https://doi.org/10.1002/hep.31819.

    Article  CAS  PubMed  Google Scholar 

  8. Gabr A, Riaz A, Johnson GE, et al. Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants. Eur J Nucl Med Mol Imaging. 2021;48(2):580–3. https://doi.org/10.1007/s00259-020-04976-8.

    Article  CAS  PubMed  Google Scholar 

  9. Toskich B, Vidal LL, Olson MT, et al. Pathologic Response of Hepatocellular Carcinoma Treated with Yttrium-90 glass Microsphere Radiation Segmentectomy Prior to Liver Transplantation: a validation study. J Vasc Interv Radiol. 2021;32(4):518–e5261. https://doi.org/10.1016/j.jvir.2020.12.019.

    Article  PubMed  Google Scholar 

  10. Riaz A, Gates VL, Atassi B, et al. Radiation Segmentectomy: a Novel Approach to increase Safety and Efficacy of Radioembolization. Int J Radiation Oncology*Biology*Physics. 2011;79(1):163–71. https://doi.org/10.1016/j.ijrobp.2009.10.062.

    Article  Google Scholar 

  11. Vouche M, Habib A, Ward TJ, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014;60(1):192–201. https://doi.org/10.1002/hep.27057.

    Article  PubMed  Google Scholar 

  12. Kim E, Sher A, Abboud G, et al. Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study. Lancet Gastroenterol Hepatol. 2022;7(9):843–50. https://doi.org/10.1016/S2468-1253(22)00091-7.

    Article  PubMed  Google Scholar 

  13. Montazeri SA, De la Garza-Ramos C, Lewis AR, et al. Hepatocellular carcinoma radiation segmentectomy treatment intensification prior to liver transplantation increases rates of complete pathologic necrosis: an explant analysis of 75 tumors. Eur J Nucl Med Mol Imaging. 2022;49(11):3892–7. https://doi.org/10.1007/s00259-022-05776-y.

    Article  CAS  PubMed  Google Scholar 

  14. Mikell JK, Dewaraja YK, Owen D. Transarterial Radioembolization for Hepatocellular Carcinoma and hepatic metastases: clinical aspects and Dosimetry models. Semin Radiat Oncol. 2020;30(1):68. https://doi.org/10.1016/j.semradonc.2019.08.005.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gulec SA, Mesoloras G, Stabin M. Dosimetric techniques in 90Y-Microsphere therapy of Liver Cancer: the MIRD equations for dose calculations. J Nucl Med. 2006;47(7):1209–11.

    CAS  PubMed  Google Scholar 

  16. Thomas MA, Mahvash A, Abdelsalam M, Kaseb AO, Kappadath SC. Planning dosimetry for 90Y radioembolization with glass microspheres: evaluating the fidelity of 99mTc-MAA and partition model predictions. Med Phys. 2020;47(10):5333–42. https://doi.org/10.1002/mp.14452.

    Article  CAS  PubMed  Google Scholar 

  17. Strigari L, Sciuto R, Rea S, et al. Efficacy and toxicity related to Treatment of Hepatocellular Carcinoma with 90Y-SIR spheres: Radiobiologic considerations. J Nucl Med. 2010;51(9):1377–85. https://doi.org/10.2967/jnumed.110.075861.

    Article  CAS  PubMed  Google Scholar 

  18. Knight GM, Gordon AC, Gates V, et al. Evolution of Personalized Dosimetry for Radioembolization of Hepatocellular Carcinoma. J Vasc Interv Radiol. 2023;34(7):1214–25. https://doi.org/10.1016/j.jvir.2023.03.011.

    Article  PubMed  Google Scholar 

  19. American College of Radiology Committee on LI-RADS® (Liver). LI-RADS® v2018 CT/MRI Manual. Accessed October 31. 2023. https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS.

  20. Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S + to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77. https://doi.org/10.1186/1471-2105-12-77.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lam M, Garin E, Maccauro M, et al. A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study. Eur J Nucl Med Mol Imaging. 2022;49(10):3340–52. https://doi.org/10.1007/s00259-022-05774-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kappadath SC, Lopez BP. Single-compartment dose prescriptions for ablative 90Y-Radioembolization segmentectomy. Life (Basel). 2023;13(6):1238. https://doi.org/10.3390/life13061238.

    Article  CAS  PubMed  Google Scholar 

  23. Son MH, Ha LN, Bang MH, et al. Diagnostic and prognostic value of 99mTc-MAA SPECT/CT for treatment planning of 90Y-resin microsphere radioembolization for hepatocellular carcinoma: comparison with planar image. Sci Rep. 2021;11(1):3207. https://doi.org/10.1038/s41598-021-82887-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Smits MLJ, Elschot M, Sze DY, et al. Radioembolization Dosimetry: the Road ahead. Cardiovasc Intervent Radiol. 2015;38(2):261–9. https://doi.org/10.1007/s00270-014-1042-7.

    Article  PubMed  Google Scholar 

  25. Garin E, Rolland Y, Laffont S, Edeline J. Clinical impact of 99mTc-MAA SPECT/CT-based dosimetry in the radioembolization of liver malignancies with 90Y-loaded microspheres. Eur J Nucl Med Mol Imaging. 2016;43:559. https://doi.org/10.1007/s00259-015-3157-8.

    Article  CAS  PubMed  Google Scholar 

  26. Van de Wiele C, Maes A, Brugman E, et al. SIRT of liver metastases: physiological and pathophysiological considerations. Eur J Nucl Med Mol Imaging. 2012;39(10):1646–55. https://doi.org/10.1007/s00259-012-2189-6.

    Article  CAS  PubMed  Google Scholar 

  27. Kokabi N, Arndt-Webster L, Chen B, et al. Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study. Eur J Nucl Med Mol Imaging. 2023;50(6):1743–52. https://doi.org/10.1007/s00259-023-06111-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Veenstra EB, Ruiter SJS, de Haas RJ, Bokkers RPH, de Jong KP, Noordzij W. Post-treatment three-dimensional voxel-based dosimetry after Yttrium-90 resin microsphere radioembolization in HCC. EJNMMI Res. 2022;12(1):9. https://doi.org/10.1186/s13550-022-00879-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. School of Medicine, University of California San Diego, La Jolla, CA, USA

    Kurt T. Pianka

  2. Department of Radiology, University of California San Diego, 200 West Arbor Drive, Mail Code 8756, San Diego, CA, USA

    Mark Barahman, Jeet Minocha, Jonas W. Redmond, Steven C. Rose, Kathryn J. Fowler & Zachary T. Berman

  3. Department of Surgery, University of California San Diego, La Jolla, CA, 92103, USA

    Gabriel T. Schnickel

Authors
  1. Kurt T. Pianka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Barahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeet Minocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonas W. Redmond
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriel T. Schnickel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steven C. Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kathryn J. Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zachary T. Berman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Kurt Pianka, Mark Barahman, and Zach Berman. The first draft of the manuscript was written by Kurt Pianka, Mark Barahman, and Zach Berman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zachary T. Berman.

Ethics declarations

Ethical approval

This retrospective study was Institutional Review Board-approved in accordance with the Health Insurance Portability and Accountability Act by the University of San Diego Office of IRB Administration.

Consent to participate

A waiver for written informed consent was provided as part of the Institutional Review Board approval based on the use of retrospective data alone.

Consent to publish

No individual person’s data in any form is included with this publication.

Competing interests

Author ZTB has received speaking honoraria from Boston Scientific. The other authors disclose no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pianka, K.T., Barahman, M., Minocha, J. et al. Voxel-based tumor dose correlates to complete pathologic necrosis after transarterial radioembolization for hepatocellular carcinoma. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06813-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00259-024-06813-8

Keywords

Search

Navigation