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Optimizing 90Y Particle Density Improves Outcomes After Radioembolization

  • Clinical Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

A Correction to this article was published on 31 May 2022

This article has been updated

Abstract

Purpose

To determine how particle density affects dose distribution and outcomes after lobar radioembolization.

Methods

Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm3) and dose (Gy) were determined. Tumor-to-normal ratio was measured on both 99mTc-MAA SPECT/CT and post-90Y bremsstrahlung SPECT/CT. Microdosimetry simulations were used to calculate first percentile dose, which is the dose in the cold spots between microspheres. Local progression-free survival (LPFS) and overall survival were analyzed.

Results

As more particles were delivered, doses on 90Y SPECT/CT became more uniform throughout the treatment volume: tumor and liver doses became more similar (p = 0.04), and microscopic cold spots between particles disappeared. For hypervascular tumors (tumor-to-normal ratio ≥ 2.6 on MAA scan), delivering fewer particles (< 6000 particles/cm3 treatment volume) was associated with better LPFS (p = 0.03). For less vascular tumors (tumor-to-normal ratio < 2.6), delivering more particles (≥ 6000 particles/cm3) was associated with better LPFS (p = 0.02). In matched pairs of patients, using the optimal particle density resulted in improved overall survival (11.5 vs. 6.8 months, p = 0.047), compared to using suboptimal particle density. Microdosimetry resulted in better predictions of LPFS (p = 0.03), and overall survival (p = 0.02), compared to conventional dosimetry.

Conclusion

The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.

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References

  1. Garin E, Tselikas L, Guiu B, et al. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(1):17–29.

    Article  Google Scholar 

  2. Hermann AL, Dieudonne A, Ronot M, et al. Relationship of tumor radiation–absorbed dose to survival and response in hepatocellular carcinoma treated with transarterial radioembolization with (90)Y in the SARAH Study. Radiology. 2020;296(3):673–84.

    Article  Google Scholar 

  3. Ridouani F, Soliman MM, England RW, et al. Relationship of radiation dose to efficacy of radioembolization of liver metastasis from breast cancer. Eur J Radiol. 2021;136:109539.

    Article  Google Scholar 

  4. van den Hoven AF, Rosenbaum CE, Elias SG, et al. Insights into the dose-response relationship of radioembolization with resin 90Y-microspheres: a prospective cohort study in patients with colorectal cancer liver metastases. J Nucl Med. 2016;57(7):1014–9.

    Article  Google Scholar 

  5. Boas FE, Bodei L, Sofocleous CT. Radioembolization of colorectal liver metastases: indications, technique, and outcomes. J Nucl Med. 2017;58(Suppl 2):104S-111S.

    Article  CAS  Google Scholar 

  6. Spreafico C, Maccauro M, Mazzaferro V, Chiesa C. The dosimetric importance of the number of 90Y microspheres in liver transarterial radioembolization (TARE). Eur J Nucl Med Mol Imaging. 2014;41(4):634–8.

    Article  Google Scholar 

  7. Walrand S, Hesse M, Jamar F, Lhommel R. A hepatic dose-toxicity model opening the way toward individualized radioembolization planning. J Nucl Med. 2014;55(8):1317–22.

    Article  Google Scholar 

  8. Pasciak AS, Abiola G, Liddell RP, et al. The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure. Eur J Nucl Med Mol Imaging. 2020;47(4):816–27.

    Article  CAS  Google Scholar 

  9. Sarwar A, Ali A, Ljuboja D, et al. Neoadjuvant Yttrium-90 transarterial radioembolization with resin microspheres prescribed using the medical internal radiation dose model for intrahepatic cholangiocarcinoma. J Vasc Interv Radiol. 2021;32(11):1560–8.

    Article  Google Scholar 

  10. Horsman MR, Overgaard J. The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res. 2016;57(Suppl 1):i90–8.

    Article  Google Scholar 

  11. Boas FE, Sofocleous CT. Embolotherapy for the management of liver malignancies other than hepatocellular carcinoma. In: Mauro MA, Murphy KP, Thomson KR, Venbrux AC, Morgan RA, editors. Image-guided interventions. 3rd ed. Philadelphia: Elsevier; 2020.

    Google Scholar 

  12. Stabin MG, Eckerman KF, Ryman JC, Williams LE. Bremsstrahlung radiation dose in yttrium-90 therapy applications. J Nucl Med. 1994;35(8):1377–80.

    CAS  PubMed  Google Scholar 

  13. Braat MN, van Erpecum KJ, Zonnenberg BA, van den Bosch MA, Lam MG. Radioembolization-induced liver disease: a systematic review. Eur J Gastroenterol Hepatol. 2017;29(2):144–52.

    Article  CAS  Google Scholar 

  14. Budczies J, Klauschen F, Sinn BV, et al. Cutoff finder: a comprehensive and straightforward web application enabling rapid biomarker cutoff optimization. PLoS ONE. 2012;7(12):e51862.

    Article  CAS  Google Scholar 

  15. Pasciak AS, McElmurray JH, Bourgeois AC, Heidel RE, Bradley YC. The impact of an antireflux catheter on target volume particulate distribution in liver-directed embolotherapy: a pilot study. J Vasc Interv Radiol. 2015;26(5):660–9.

    Article  Google Scholar 

  16. Titano JJ, Fischman AM, Cherian A, et al. End-hole versus microvalve infusion catheters in patients undergoing drug-eluting microspheres-TACE for solitary hepatocellular carcinoma tumors: a retrospective analysis. Cardiovasc Interv Radiol. 2019;42(4):560–8.

    Article  Google Scholar 

  17. Core JM, Frey GT, Sharma A, et al. Increasing Yttrium-90 dose conformality using proximal radioembolization enabled by distal angiosomal truncation for the treatment of hepatic malignancy. J Vasc Interv Radiol. 2020;31(6):934–42.

    Article  Google Scholar 

  18. van den Hoven AF, Smits ML, Rosenbaum CE, Verkooijen HM, van den Bosch MA, Lam MG. The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: a systematic review. PLoS ONE. 2014;9(1):e86394.

    Article  Google Scholar 

  19. Elschot M, Vermolen BJ, Lam MG, de Keizer B, van den Bosch MA, de Jong HW. Quantitative comparison of PET and bremsstrahlung SPECT for imaging the in vivo yttrium-90 microsphere distribution after liver radioembolization. PLoS ONE. 2013;8(2):e55742.

    Article  CAS  Google Scholar 

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Acknowledgements

Assen S. Kirov helped with T/N ratio measurements. Chris Crane suggested looking at the minimum tumor dose, rather than the mean tumor dose. Daniel Kelly wrote queries to extract information from our hospital’s clinical database. This research was funded in part through an NIH/NCI Cancer Center Support Grant to MSKCC (P30 CA008748), and by City of Hope National Medical Center.

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Authors and Affiliations

  1. Department of Diagnostic Imaging, The Warren Alpert Medical School, Brown University, Providence, RI, USA

    Aaron W. P. Maxwell

  2. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Humberto G. Mendoza & Mark P. Dunphy

  3. Radiology Informatics, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Matthew J. Sellitti

  4. Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Juan C. Camacho, Amy R. Deipolyi, Etay Ziv, Constantinos T. Sofocleous, Hooman Yarmohammadi, Majid Maybody & F. Edward Boas

  5. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    John L. Humm & Jazmin Schwartz

  6. Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Krishna Juluru

  7. Department of Radiology, City of Hope Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA

    F. Edward Boas

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  1. Aaron W. P. Maxwell
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  2. Humberto G. Mendoza
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Corresponding author

Correspondence to F. Edward Boas.

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Conflict of interest

FEB is a co-founder of Claripacs, LLC. He received research support (investigator-initiated) from GE Healthcare. He received research grants from the US Department of Defense, Thompson Family Foundation, and Brockman Medical Research Foundation. He received research supplies (investigator-initiated) from Bayer, Steba Biotech, and Terumo. He received a research grant and speaker fees from Society of Interventional Oncology, which were sponsored by Guerbet. He attended research meetings sponsored by Guerbet. He is an investor in Labdoor, Qventus, CloudMedx, Notable Labs, and Xgenomes. He is the inventor and assignee on US patent 8233586, and is an inventor on US provisional patent applications 62/754,139 and 62/817,116. EZ received research grants from: Society of Interventional Radiology, Radiological Society of North America, North American Neuroendocrine Tumor Society, American Association for Cancer Research, Druckenmiller Foundation, Memorial Sloan Kettering Cancer Center, Ethicon, and Novartis. CS received grants from NIH/NCI, Boston Scientific/BTG, Ethicon, and SIRTEX. He received personal fees from Boston Scientific/BTG, Terumo, Varian, Ethicon, and SIRTEX. HY is an advisory board member of BD Medical.

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The original online version of this article was revised: In the original article, the equation for the number of particles delivered (resin) was correct in the PDF, but there was a typesetting problem in the HTML. The correct equation is below \( 44.48 \times 10^{6} \times \frac{{{\text{Delivered dose }}({\text{GBq}})}}{{{\text{Nominal activity at the time of calibration}} \left( {{\text{GBq}}} \right) \times 2^{{ - {\text{treatment time (hours after calibration)}}/64.1}} }} \).

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Maxwell, A.W.P., Mendoza, H.G., Sellitti, M.J. et al. Optimizing 90Y Particle Density Improves Outcomes After Radioembolization. Cardiovasc Intervent Radiol 45, 958–969 (2022). https://doi.org/10.1007/s00270-022-03139-6

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  • DOI: https://doi.org/10.1007/s00270-022-03139-6

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