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Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2018

01-11-2018 | Original Article

Radioembolization with 90Y glass microspheres for hepatocellular carcinoma: significance of pretreatment 11C-acetate and 18F-FDG PET/CT and posttreatment 90Y PET/CT in individualized dose prescription

Authors: Chi Lai Ho, Sirong Chen, Shing Kee Cheung, Yim Lung Leung, Kam Chau Cheng, Ka Nin Wong, Yuet Hung Wong, Thomas Wai Tong Leung

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2018

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Abstract

Purpose

The aim of this study was to establish an algorithm for the prescription of 90Y glass microsphere radioembolization (90Y-GMRE) of HCC in individual patients based on the relationship between tumour dose (TD) and response validated by 90Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters.

Methods

The study group comprised 62 HCC patients prospectively recruited for 90Y-GMRE who underwent pretreatment dual-tracer (11C-acetate and 18F-FDG) PET/CT as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to-nontumour ratio on 99mTc-MAA SPECT/CT (T/NTMAA) was correlated with posttreatment 90Y PET/CT T/NT90Y after quantification validation. The TD–response relationship for HCC of different tracer groups was assessed on follow-up PET/CT 2 months after treatment.

Results

90Y PET/CT was accurate in the measurement of recovery of injected 90Y activity (81.9–99.9%, median 94.8%). Pretreatment SPECT/CT T/NTMAA was strongly correlated with posttreatment 90Y PET/CT T/NT90Y (5.6 ± 3.2 versus 5.9 ± 3.5, T/NT90Y 1.01 × T/NTMAA + 0.161, r = 0.918, P < 0.05). The response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well, moderately and poorly differentiated HCC, respectively. The cut-off TD for a good response was significantly different between poorly differentiated and well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2% sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the T/NTMAA thresholds for predicting a good response in poorly differentiated and well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity (70.3%) and specificity (76%).

Conclusion

90Y PET/CT can provide accurate dosimetry for 90Y-GMRE. Pretreatment T/NTMAA predicts posttreatment T/NT90Y. The TD thresholds for a good response are tracer-dependent, with a strong correlation between HCC radiosensitivity and cellular differentiation and other PET-based parameters. These cytokinetic factors improve treatment efficacy while minimizing organ damage for the prescription of personalized 90Y-GMRE.
Literature
1.
go back to reference 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 Vasc Interv Radiol. 2006;17(8):1251–78.CrossRefPubMed 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 Vasc Interv Radiol. 2006;17(8):1251–78.CrossRefPubMed
2.
go back to reference Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol. 2006;17(9):1425–39.CrossRefPubMed Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol. 2006;17(9):1425–39.CrossRefPubMed
3.
go back to reference Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol. 2006;17(10):1571–93.CrossRefPubMed Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol. 2006;17(10):1571–93.CrossRefPubMed
4.
go back to reference Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.CrossRefPubMedCentralPubMed Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.CrossRefPubMedCentralPubMed
5.
go back to reference Benson R, Madan R, Kilambi R, Chander S. Radiation induced liver disease: a clinical update. J Egypt Natl Canc Inst. 2016;28(1):7–11.CrossRefPubMed Benson R, Madan R, Kilambi R, Chander S. Radiation induced liver disease: a clinical update. J Egypt Natl Canc Inst. 2016;28(1):7–11.CrossRefPubMed
6.
go back to reference Cao X, He N, Sun J, Tan J, Zhang C, Yang J, et al. Hepatic radioembolization with yttrium-90 glass microspheres for treatment of primary liver cancer. Chin Med J. 1999;112(5):430–2.PubMed Cao X, He N, Sun J, Tan J, Zhang C, Yang J, et al. Hepatic radioembolization with yttrium-90 glass microspheres for treatment of primary liver cancer. Chin Med J. 1999;112(5):430–2.PubMed
7.
go back to reference Garin E. Radioembolization with (90)Y-loaded microspheres: high clinical impact of treatment simulation with MAA-based dosimetry. Eur J Nucl Med Mol Imaging. 2015;42(8):1189–91.CrossRefPubMed Garin E. Radioembolization with (90)Y-loaded microspheres: high clinical impact of treatment simulation with MAA-based dosimetry. Eur J Nucl Med Mol Imaging. 2015;42(8):1189–91.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
9.
go back to reference Kao YH, Steinberg JD, Tay YS, Lim GK, Yan J, Townsend DW, et al. Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting. EJNMMI Res. 2013;3(1):56.CrossRefPubMedCentralPubMed Kao YH, Steinberg JD, Tay YS, Lim GK, Yan J, Townsend DW, et al. Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting. EJNMMI Res. 2013;3(1):56.CrossRefPubMedCentralPubMed
10.
go back to reference Willowson KP, Tapner M, QUEST Investigator Team, Bailey DL. A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres: the QUEST Phantom Study. Eur J Nucl Med Mol Imaging. 2015;42(8):1202–22.CrossRefPubMedCentralPubMed Willowson KP, Tapner M, QUEST Investigator Team, Bailey DL. A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres: the QUEST Phantom Study. Eur J Nucl Med Mol Imaging. 2015;42(8):1202–22.CrossRefPubMedCentralPubMed
11.
go back to reference Ilhan H, Goritschan A, Paprottka P, Jakobs TF, Fendler WP, Bartenstein P, et al. Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization. J Nucl Med. 2015;56(3):333–8.CrossRefPubMed Ilhan H, Goritschan A, Paprottka P, Jakobs TF, Fendler WP, Bartenstein P, et al. Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization. J Nucl Med. 2015;56(3):333–8.CrossRefPubMed
12.
go back to reference Leung WT, Lau WY, Ho SK, Chan M, Leung NW, Lin J, et al. Measuring lung shunting in hepatocellular carcinoma with intrahepatic-arterial technetium-99m macroaggregated albumin. J Nucl Med. 1994;35(1):70–3.PubMed Leung WT, Lau WY, Ho SK, Chan M, Leung NW, Lin J, et al. Measuring lung shunting in hepatocellular carcinoma with intrahepatic-arterial technetium-99m macroaggregated albumin. J Nucl Med. 1994;35(1):70–3.PubMed
13.
go back to reference Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.CrossRefPubMed Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.CrossRefPubMed
14.
go back to reference Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med. 1997;24(3):293–8.PubMed Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med. 1997;24(3):293–8.PubMed
15.
go back to reference Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Sposito C, et al. A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres. Q J Nucl Med Mol Imaging. 2012;56(6):503–8.PubMed Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Sposito C, et al. A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres. Q J Nucl Med Mol Imaging. 2012;56(6):503–8.PubMed
16.
go back to reference Lau WY, Leung WT, Ho S, Leung NW, Chan M, Lin J, et al. Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer. 1994;70(5):994–9.CrossRefPubMedCentralPubMed Lau WY, Leung WT, Ho S, Leung NW, Chan M, Lin J, et al. Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer. 1994;70(5):994–9.CrossRefPubMedCentralPubMed
17.
go back to reference Gulec SA, Sztejnberg ML, Siegel JA, Jevremovic T, Stabin M. Hepatic structural dosimetry in (90)Y microsphere treatment: a Monte Carlo modeling approach based on lobular microanatomy. J Nucl Med. 2010;51(2):301–10.CrossRefPubMed Gulec SA, Sztejnberg ML, Siegel JA, Jevremovic T, Stabin M. Hepatic structural dosimetry in (90)Y microsphere treatment: a Monte Carlo modeling approach based on lobular microanatomy. J Nucl Med. 2010;51(2):301–10.CrossRefPubMed
18.
go back to reference Haber AH, Rothstein BE. Radiosensitivity and rate of cell division: “law of Bergonie and Tribondeau”. Science. 1969;163(3873):1338–9.CrossRefPubMed Haber AH, Rothstein BE. Radiosensitivity and rate of cell division: “law of Bergonie and Tribondeau”. Science. 1969;163(3873):1338–9.CrossRefPubMed
19.
go back to reference Garin E, Lenoir L, Rolland Y, Edeline J, Mesbah H, Laffont S, et al. Dosimetry based on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53(2):255–63.CrossRefPubMed Garin E, Lenoir L, Rolland Y, Edeline J, Mesbah H, Laffont S, et al. Dosimetry based on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53(2):255–63.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference Ho S, Lau WY, Leung TW, Chan M, Ngar YK, Johnson PJ, et al. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours. Eur J Nucl Med. 1996;23(8):947–52.CrossRefPubMed Ho S, Lau WY, Leung TW, Chan M, Ngar YK, Johnson PJ, et al. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours. Eur J Nucl Med. 1996;23(8):947–52.CrossRefPubMed
22.
go back to reference Ho S, Lau WY, Leung TW, Chan M, Chan KW, Lee WY, et al. Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin. Br J Radiol. 1997;70(836):823–8.CrossRefPubMed Ho S, Lau WY, Leung TW, Chan M, Chan KW, Lee WY, et al. Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin. Br J Radiol. 1997;70(836):823–8.CrossRefPubMed
23.
go back to reference Lau WY, Sangro B, Chen PJ, Cheng SQ, Chow P, Lee RC, et al. Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90. Oncology. 2013;84(5):311–8.CrossRefPubMed Lau WY, Sangro B, Chen PJ, Cheng SQ, Chow P, Lee RC, et al. Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90. Oncology. 2013;84(5):311–8.CrossRefPubMed
24.
go back to reference Srinivas SM, Natarajan N, Kuroiwa J, Gallagher S, Nasr E, Shah SN, et al. Determination of radiation absorbed dose to primary liver tumors and normal liver tissue using post-Radioembolization (90)Y PET. Front Oncol. 2014;4:255.CrossRefPubMedCentralPubMed Srinivas SM, Natarajan N, Kuroiwa J, Gallagher S, Nasr E, Shah SN, et al. Determination of radiation absorbed dose to primary liver tumors and normal liver tissue using post-Radioembolization (90)Y PET. Front Oncol. 2014;4:255.CrossRefPubMedCentralPubMed
25.
go back to reference Lea WB, Tapp KN, Tann M, Hutchins GD, Fletcher JW, Johnson MS. Microsphere localization and dose quantification using positron emission tomography/CT following hepatic intraarterial radioembolization with yttrium-90 in patients with advanced hepatocellular carcinoma. J Vasc Interv Radiol. 2014;25(10):1595–603.CrossRefPubMed Lea WB, Tapp KN, Tann M, Hutchins GD, Fletcher JW, Johnson MS. Microsphere localization and dose quantification using positron emission tomography/CT following hepatic intraarterial radioembolization with yttrium-90 in patients with advanced hepatocellular carcinoma. J Vasc Interv Radiol. 2014;25(10):1595–603.CrossRefPubMed
26.
go back to reference Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(4):928–42.CrossRefPubMed Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(4):928–42.CrossRefPubMed
27.
go back to reference Elschot M, Nijsen JF, Lam MG, Smits ML, Prince JF, Viergever MA, et al. (99m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with 166Ho-microspheres. Eur J Nucl Med Mol Imaging. 2014;41(10):1965–75.CrossRefPubMed Elschot M, Nijsen JF, Lam MG, Smits ML, Prince JF, Viergever MA, et al. (99m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with 166Ho-microspheres. Eur J Nucl Med Mol Imaging. 2014;41(10):1965–75.CrossRefPubMed
Metadata
Title
Radioembolization with 90Y glass microspheres for hepatocellular carcinoma: significance of pretreatment 11C-acetate and 18F-FDG PET/CT and posttreatment 90Y PET/CT in individualized dose prescription
Authors
Chi Lai Ho
Sirong Chen
Shing Kee Cheung
Yim Lung Leung
Kam Chau Cheng
Ka Nin Wong
Yuet Hung Wong
Thomas Wai Tong Leung
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4064-6

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