Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

Open Access 01-07-2013 | Original Article

Boosted selective internal radiation therapy with ⁹⁰Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

Authors: E. Garin, L. Lenoir, J. Edeline, S. Laffont, H. Mesbah, P. Porée, L. Sulpice, K. Boudjema, M. Mesbah, A. Guillygomarc’h, E. Quehen, M. Pracht, J. L. Raoul, B. Clement, Y. Rolland, E. Boucher

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2013

Abstract

Purpose

To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with ⁹⁰Y-loaded glass microspheres (TheraSphere®).

Methods

TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS).

Results

The response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100 % and overall accuracy of 90 %. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4 %), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2–9.5 months) and 11.5 months (2–31 months), respectively, in patients with TD <205 Gy and 13 months (10–16 months) and 23.2 months (17.5–28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2–7 months) and 5 months (2–8 months), respectively, in patients with TD <205 Gy and 10 months (6–15.2 months) and 21.5 months (12–28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18–28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83 % and overall accuracy of 97 %.

Conclusion

Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340:745–50.PubMedCrossRef

Raoul JL, Guyader D, Bretagne JF, Duvauferrier R, Bourguet P, Bekhechi D, et al. Randomized controlled trial for hepatocellular carcinoma with portal vein thrombosis: intra-arterial iodine-131-iodized oil versus medical support. J Nucl Med. 1994;35:1782–7.PubMed

Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138(1):52–64.PubMedCrossRef

Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52(5):1741–9.PubMedCrossRef

Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, et al. Yttrium(90) radioembolization for intermediate-advanced hepatocarcinoma: A phase II study. Hepatology. 2012. doi:10.1002/hep.26014.

Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, et al.; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54(3):868–78.PubMedCrossRef

Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920–8.PubMedCrossRef

Memon K, Kulik L, Lewandowski RJ, Wang E, Riaz A, Ryu RK, et al. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology. 2011;141(2):526–35, 535.e1-2.PubMedCrossRef

Jelic S, Sotiropoulos GC; ESMO Guidelines Working Group. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(5):v59–64.PubMedCrossRef

10.

Sangro B, Iñarrairaegui M, Bilbao JI. Radioembolization for hepatocellular carcinoma. J Hepatol. 2012;56(2):464–73.PubMedCrossRef

11.

Lau WY, Lai EC, Leung TW. Current role of selective internal irradiation with yttrium-90 microspheres in the management of hepatocellular carcinoma: a systematic review. Int J Radiat Oncol Biol Phys. 2011;81(2):460–7.PubMedCrossRef

12.

Salem R, Lewandowski RJ, Gates VL, Nutting CW, Murthy R, Rose SC, et al.; Technology Assessment Committee; Interventional Oncology Task Force of the Society of Interventional Radiology. Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol. 2011;22(3):265–78.PubMedCrossRef

13.

Chiesa C, Maccauro M, Romito R, Spreafico C, Pellizzari S, Negri A, et al. Need, feasibility and convenience of dosimetric treatment planning in liver selective internal radiation therapy with 90Y microspheres: the experience of the National Tumor Institute of Milan. Q J Nucl Med Mol Imaging. 2011;55(2):168–97.PubMed

14.

Garin E, Lenoir L, Rolland Y, Edeline J, Mesba H, Laffont S, et al. 99mTc-MAA SPECT/CT based dosimetry accurately predicts tumour response and survival in HCC patients treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53(2):255–63.PubMedCrossRef

15.

Garin E, Rolland Y, Lenoir L, Pracht M, Mesbah H, Porée P, et al. Utility of quantitative Tc-MAA SPECT/CT for yttrium-labelled microsphere treatment planning: calculating vascularized hepatic volume and dosimetric approach. Int J Mol Imaging. 2011;2011:398051.PubMed

16.

Forner A, Ayuso C, Varela M, Rimola J, Hessheimer AJ, de Lope CR, et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer. 2009;115(3):616–23.PubMedCrossRef

17.

Sato KT, Omary RA, Takehana C, Ibrahim S, Lewandowski RJ, Ryu RK, et al. The role of tumor vascularity in predicting survival after yttrium-90 radioembolization for liver metastases. J Vasc Interv Radiol. 2009;20(12):1564–9.PubMedCrossRef

18.

Cremonesi M, Ferrari M, Bartolomei M, Orsi F, Bonomo G, Aricò D, et al. Radioembolisation with 90Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment. Eur J Nucl Med Mol Imaging. 2008;35(11):2088–96.PubMedCrossRef

19.

Becker S, Laffont S, Rolland Y, Lecloirec J, Boucher E, Raoul JL, et al. Dosimetric evaluation and therapeutic response to vectorized internal radiation therapy of hepatocarcinomas using iodine-131 labelled lipiodol. Nucl Med Commun. 2008;29(9):815–25.PubMedCrossRef

20.

Riaz A, Kulik L, Lewandowski RJ, Ryu RK, Giakoumis Spear G, Mulcahy MF, et al. Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology. 2009;49(4):1185–93.PubMedCrossRef

21.

Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012;57(4):821–9.PubMedCrossRef

22.

Garin E, Rolland Y, Boucher E. Pre-therapeutic dosimetric evaluation and selective internal radiation therapy of hepatocellular carcinoma using yttrium-90-loaded microspheres. J Hepatol. 2013. doi:10.1016/j.jhep.2012.11.050.

23.

Ho S, Lau WY, Leung TWT, Chan M, Johnson PJ, Li AKC. 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;24:293–8.PubMed

24.

Knesaurek K, Machac J, Muzinic M, DaCosta M, Zhang Z, Heiba S. Quantitative comparison of yttrium-90 (90Y)-microspheres and technetium-99m (99mTc)-macroaggregated albumin SPECT images for planning 90Y therapy of liver cancer. Technol Cancer Res Treat. 2010;9(3):253–62.PubMed

25.

Knesaurek K, Machac J, Heiba S, Cacinovic C, Zhang Z. Can correlation between Y-90 and Tc-99m MAA SPECT/CT image predict clinical outcome in hepatic Y-90 microsphere therapy. Eur J Nucl Med Mol Imaging. 2010;37(2):S293. Abstract.

26.

Goin JE, Salem R, Carr BI, Dancey JE, Soulen MC, Geschwind JF, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: a risk-stratification analysis. J Vasc Interv Radiol. 2005;16(2 Pt 1):195–203.PubMedCrossRef

27.

Kennedy AS, McNeillie P, Dezarn WA, Nutting C, Sangro B, Wertman D, et al. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys. 2009;74(5):1494–500.PubMedCrossRef

28.

Strigari L, Sciuto R, Rea S, Carpanese L, Pizzi G, Soriani A, 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.PubMedCrossRef

29.

Awada A, Vandone AM, Aftimos P. Personalized management of patients with solid cancers: moving from patient characteristics to tumor biology. Curr Opin Oncol. 2012;24(3):297–304.PubMedCrossRef

30.

Hodgson DR, Wellings R, Harbron C. Practical perspectives of personalized healthcare in oncology. N Biotechnol. 2012;29(6):656–64.PubMedCrossRef

31.

Dieudonné A, Garin E, Laffont S, Rolland Y, Lebtahi R, Leguludec D, et al. Clinical feasibility of fast 3-dimensionnal dosimetry of the liver for treatment planning of hepatocellular carcinoma with 90Y-microspheres. J Nucl Med. 2011;52(12):1930–7.PubMedCrossRef

Title: Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept
Authors: E. Garin
L. Lenoir
J. Edeline
S. Laffont
H. Mesbah
P. Porée
L. Sulpice
K. Boudjema
M. Mesbah
A. Guillygomarc’h
E. Quehen
M. Pracht
J. L. Raoul
B. Clement
Y. Rolland
E. Boucher
Publication date: 01-07-2013
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2013
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2395-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Boosted selective internal radiation therapy with ⁹⁰Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2013

Congenital isolated H-type tracheo-oesophageal fistula identified by milk scan

The value of 18F-FDG PET/CT in diagnosing infectious endocarditis

Utility of 18F-FDG PET(/CT) in patients with systemic and localized amyloidosis

Factors influencing the sensitivity of 18F-FDG PET/CT in the detection of infective endocarditis

Influence of selected b values on ADC quantification in diffusion-weighted MRI. Comment on Punwani et al.: Diffusion-weighted MRI of lymphoma: prognostic utility and implications for PET/MRI?

Glucose corrected standardized uptake value (SUVgluc) in the evaluation of brain lesions with 18F-FDG PET