Skip to main content
SpringerLink
Log in

Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization

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

Abstract

Purpose

To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC).

Methods

Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors’ dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3 months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters.

Results

Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9 Gy; Glass: 254.7 Gy), maximum TD (Resin: 162.9 Gy; Glass: 591 Gy), minimum TD (Resin: 53.7 Gy; Glass: 149.1 Gy).

Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75 Gy or maximum TD ≥ 150 Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150 Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031).

Conclusion

TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC.

Level of Evidence

Level 3, Retrospective Study.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ibrahim SM, Nikolaidis P, Miller FH, Lewandowski RJ, Ryu RK, Sato KT, et al. Radiologic findings following Y90 radioembolization for primary liver malignancies. Abdom Imaging. 2009;34(5):566–81. https://doi.org/10.1007/s00261-008-9454-y.

    Article  PubMed  Google Scholar 

  2. Jia Z, Paz-Fumagalli R, Frey G, Sella DM, McKinney JM, Wang W. Resin-based Yttrium-90 microspheres for unresectable and failed first-line chemotherapy intrahepatic cholangiocarcinoma: preliminary results. J Cancer Res Clin Oncol. 2017;143(3):481–9. https://doi.org/10.1007/s00432-016-2291-4.

    Article  CAS  PubMed  Google Scholar 

  3. Ni Q, Shen W, Zhang M, Yang C, Cai W, Wu M, et al. Prognostic analysis of radical resection for intrahepatic cholangiocarcinoma: a retrospective cohort study. Oncotarget. 2017;8(43):75627–37. https://doi.org/10.18632/oncotarget.18465.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Helms RA, Quan DJ. Textbook of therapeutics: drug and disease management. Lippincott Williams & Wilkins (2006).

  5. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–79. https://doi.org/10.1016/S0140-6736(13)61903-0.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Feisthammel J, Schoppmeyer K, Mössner J, Schulze M, Caca K, Wiedmann M. Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial. Am J Clin Oncol. 2007;30(3):319–24.

    Article  CAS  Google Scholar 

  7. de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29(23):3140–5. https://doi.org/10.1200/jco.2011.35.6519.

    Article  PubMed  Google Scholar 

  8. Marsh RdW, Alonzo M, Bajaj S, Baker M, Elton E, Farrell TA, et al. Comprehensive review of the diagnosis and treatment of biliary tract cancer Diagnosis-clinical staging and pathology. J SurgOncol. 2012;106(3):332–8. https://doi.org/10.1002/jso.23028.

    Article  Google Scholar 

  9. Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96(6):896–902. https://doi.org/10.1038/sj.bjc.6603648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bhangoo MS, Karnani DR, Hein PN, Giap H, Knowles H, Issa C, et al. Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma. J Gastrointest Oncol. 2015;6(5):469–78. https://doi.org/10.3978/j.issn.2078-6891.2015.056.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gangi A, Shah J, Hatfield N, Smith J, Sweeney J, Choi J, et al. Intrahepatic cholangiocarcinoma treated with transarterial Yttrium-90 glass microsphere radioembolization: results of a single institution retrospective study. J VascIntervRadiol. 2018;29(8):1101–8. https://doi.org/10.1016/j.jvir.2018.04.001.

    Article  Google Scholar 

  12. Piscaglia F, Ogasawara S. Patient selection for transarterial chemoembolization in hepatocellular carcinoma: importance of benefit/risk assessment. Liver Cancer. 2018;7(1):104–19. https://doi.org/10.1159/000485471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cremonesi M, Chiesa C, Strigari L, Ferrari M, Botta F, Guerriero F, et al. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol. 2014. https://doi.org/10.3389/fonc.2014.00210.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Salem R, Thurston KG. Radioembolization with 90Yttrium Microspheres: a state-of-the-art brachytherapy treatment for primary and secondary Liver malignancies: Part 1: technical and methodologic considerations. J VascIntervRadiol. 2006;17(8):1251–78. https://doi.org/10.1097/01.RVI.0000233785.75257.9A.

    Article  Google Scholar 

  15. Kokabi N, Galt JR, Xing M, Camacho JC, Barron BJ, Schuster DM, et al. A simple method for estimating dose delivered to hepatocellular carcinoma after Yttrium-90 Glass-based radioembolization therapy: preliminary results of a proof of concept study. J VascIntervRadiol. 2014;25(2):277–87. https://doi.org/10.1016/j.jvir.2013.11.007.

    Article  Google Scholar 

  16. Camacho JC, Kokabi N, Xing M, Prajapati HJ, El-Rayes B, Kim HS. Modified response evaluation criteria in solid tumors and European association for the study of the liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following Yttrium-90 radioembolization. J VascIntervRadiol. 2014;25(2):256–65. https://doi.org/10.1016/j.jvir.2013.10.056.

    Article  Google Scholar 

  17. NationalCancerInstitute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. (2017).

  18. Elsayed M, Ermentrout RM, Sethi I, Bercu ZL, Galt JR, Whitmore M, et al. Incidence of radioembolization-induced liver disease and liver toxicity following repeat 90Y-radioembolization: outcomes at a large tertiary care center. ClinNucl Med. 2020;45(2):100–4. https://doi.org/10.1097/rlu.0000000000002828.

    Article  Google Scholar 

  19. Edeline J, Touchefeu Y, Guiu B, Farge O, Tougeron D, Baumgaertner I, et al. Radioembolization Plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):51–9. https://doi.org/10.1001/jamaoncol.2019.3702.

    Article  PubMed  Google Scholar 

  20. Zhen Y, Liu B, Chang Z, Ren H, Liu Z, Zheng J. A pooled analysis of transarterialradioembolization with Yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma. Onco Targets Ther. 2019;12:4489–98. https://doi.org/10.2147/OTT.S202875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Piana PM, Bar V, Doyle L, Anne R, Sato T, Eschelman DJ, et al. Early arterial stasis during resin-based Yttrium-90 radioembolization: incidence and preliminary outcomes. HPB (Oxford). 2014;16(4):336–41. https://doi.org/10.1111/hpb.12135.

    Article  Google Scholar 

  22. Zhang Z, Fardanesh MR, Machac J, Heiba S, Knesaurek K, Zaretsky V, et al. Comparison of therapeutic response using RECIST criteria: Y-90 SIR-Spheres and TheraSphere treatment of unresectable hepatocellular carcinoma. J Nucl Med. 2013;54(supplement 2):224.

    Google Scholar 

  23. Horsman MR, Overgaard J. The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res. 2016;57(Suppl 1(Suppl 1)):i90–8. https://doi.org/10.1093/jrr/rrw007.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bilbao JI, de Martino A, de Luis E, Díaz-Dorronsoro L, Alonso-Burgos A, Martínez de la Cuesta A, et al. Biocompatibility inflammatory response and recannalization characteristics of nonradioactive resin microspheres histological findings. CardioVascIntervenRadiol. 2009;32(4):727–36. https://doi.org/10.1007/s00270-009-9592-9.

    Article  Google Scholar 

  25. Miller G, Kim A. Rate of stasis and disease response after Y-90 radioembolization. J Vasc Interv Radiol. 2017;28(2):S119–20. https://doi.org/10.1016/j.jvir.2016.12.887.

    Article  Google Scholar 

  26. Nezami N, Kokabi N, Camacho JC, Schuster DM, Xing M, Kim HS. (90)Y radioembolization dosimetry using a simple semi-quantitative method in intrahepatic cholangiocarcinoma: glass versus resin microspheres. Nucl Med Biol. 2018;59:22–8. https://doi.org/10.1016/j.nucmedbio.2018.01.001.

    Article  CAS  PubMed  Google Scholar 

  27. Srinivas SM, Nasr EC, Kunam VK, Bullen JA, Purysko AS. Administered activity and outcomes of glass versus resin (90)Y microsphere radioembolization in patients with colorectal liver metastases. J Gastrointest Oncol. 2016;7(4):530–9. https://doi.org/10.21037/jgo.2016.03.09.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Garin E, Rolland Y, Edeline J, Icard N, Lenoir L, Laffont S, et al. Personalized dosimetry with intensification using 90Y-loaded glass microsphere radioembolization induces prolonged overall survival in hepatocellular carcinoma patients with portal vein thrombosis. J Nucl Med. 2015;56(3):339–46. https://doi.org/10.2967/jnumed.114.145177.

    Article  CAS  PubMed  Google Scholar 

  29. Demirelli S, Erkilic M, Oner AO, Budak ES, Gunduz S, Ozgur O, et al. Evaluation of factors affecting tumor response and survival in patients with primary and metastatic liver cancer treated with microspheres. Nucl Med Commun. 2015;36(4):340–9. https://doi.org/10.1097/mnm.0000000000000257.

    Article  CAS  PubMed  Google Scholar 

  30. Kao YH, Steinberg JD, Tay YS, Lim GK, Yan J, Townsend DW, et al. Post-radioembolization Yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres. EJNMMI Res. 2013;3(1):57. https://doi.org/10.1186/2191-219x-3-57.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chung YE, Kim M-J, Park YN, Choi J-Y, Pyo JY, Kim YC, et al. Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics. 2009;29(3):683–700. https://doi.org/10.1148/rg.293085729.

    Article  PubMed  Google Scholar 

  32. Köhler M, Harders F, Lohöfer F, Paprottka PM, Schaarschmidt BM, Theysohn J, et al. Prognostic factors for overall survival in advanced intrahepatic cholangiocarcinoma treated with Yttrium-90 radioembolization. J Clin Med. 2019;9(1):56. https://doi.org/10.3390/jcm9010056.

    Article  CAS  PubMed Central  Google Scholar 

Download references

Funding

This study was not supported by any funding.

Author information

Authors and Affiliations

  1. Morehouse School of Medicine, 720 Westview Dr SW, Atlanta, GA, 30310, USA

    Bernard Cheng

  2. Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA

    Alex Villalobos, William Wagstaff, Zachary Bercu, Bill Majdalany & Nima Kokabi

  3. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA

    Ila Sethi, James Galt, David Brandon & David M. Schuster

Authors
  1. Bernard Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alex Villalobos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ila Sethi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William Wagstaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James Galt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Brandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David M. Schuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zachary Bercu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bill Majdalany
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nima Kokabi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard Cheng.

Ethics declarations

Conflict of interest

Nima Kokabi conducts research partially funded by Sirtex Medical Ltd. No grant funding has been received for the development of this manuscript. The remaining authors have no financial disclosures.

Ethical Approval

For this type of study formal consent is not required.

Informed Consent

This study has obtained approval from our tertiary center’s IRB and the need for informed consent was waived.

Consent for Publication

For this type of study consent for publication is not required.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, B., Villalobos, A., Sethi, I. et al. Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization. Cardiovasc Intervent Radiol 44, 1194–1203 (2021). https://doi.org/10.1007/s00270-021-02834-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-021-02834-0

Keywords

Search

Navigation