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Imaging HCC treated with radioembolization: review of the literature and clinical examples of choline PET utility

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Abstract

Purpose

In this review we summarize the current evidence on the role of PET/CT with different probes for radioembolization therapy monitoring in HCC patients. Typical clinical examples are also provided to underline the utility of choline PET in this context.

Methods

PubMed database was searched from 2000 until March 2020.

Results

Overall, 11C-acetate and radiolabeled choline PET have a higher sensitivity in the diagnosis of primary or recurrent HCC as compared to 18F-FDG. On the other hand, 18F-FDG PET/CT can provide useful prognostic information, especially for palliative treatments. Radiolabeled choline better predicts response to loco-regional treatment and provides a better differentiation of disease recurrence from treatment-related changes, as compared to other morphological imaging.

Conclusion

HCC staging is better performed with PET/CT, thus allowing for a more adequate selection of patients candidate to transarterial radioembolization.

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References

  1. Sarfaraz M, Kennedy AS, Lodge MA et al (2004) Radiation absorbed dose distribution in a patient treated with yttrium-90 microspheres for hepatocellular carcinoma. Med Phys 31:2449–2453

    PubMed  Google Scholar 

  2. Sacco R, Conte C, Tumino E et al (2016) Transarterial radioembolization for hepatocellular carcinoma: a review. J Hepatocell Carcinoma 25(3):25–29

    Google Scholar 

  3. Bozkurt MF, Salanci BV, Uğur Ö (2016) Intra-arterial radionuclide therapies for liver tumors. Semin Nucl Med 46(4):324–339

    PubMed  Google Scholar 

  4. Kennedy A, Coldwell D, Sangro B, Wasan H, Salem R (2012) Integrating radioembolization ((90)Y microspheres) into current treatment options for liver tumors: introduction to the international working group report. Am J Clin Oncol 35:81–90

    PubMed  Google Scholar 

  5. Kennedy A, Nag S, Salem R et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 68:13–23

    PubMed  Google Scholar 

  6. Sangro B, Iñarrairaegui M, Bilbao JI (2012) Radioembolization for hepatocellular carcinoma. J Hepatol 56:464–473

    PubMed  Google Scholar 

  7. Mikell JK, Dewaraja YK, Owen D (2020) Transarterial radioembolization for hepatocellular carcinoma and hepatic metastases: clinical aspects and dosimetry models. Semin Radiat Oncol 30(1):68–76

    PubMed  Google Scholar 

  8. Braat MN, Samim M, van den Bosch MA et al (2016) The role of (90)Yradioembolization in downstaging primary and secondary hepatic malignancies: a systematic review. Clin Transl Imaging 4:283–295

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Fidelman N, Kerlan RK Jr (2015) Transarterial chemoembolization and (90)Y radioembolization for hepatocellular carcinoma: review of current applications beyond intermediate-stage disease. AJR Am J Roentgenol 205:742–752

    PubMed  Google Scholar 

  10. Riaz A, Gates VL, Atassi B et al (2011) Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol 79:163–171

    Google Scholar 

  11. Vouche M, Lewandowski RJ, Atassi R et al (2013) Radiation lobectomy: time-dependent analysis of future liver remnant volume in unresectable liver cancer as a bridge to resection. J Hepatol 59:1029–1036

    PubMed  PubMed Central  Google Scholar 

  12. Vilgrain V, Pereira H, Assenat E et al (2017) Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol 18:1624–1636

    CAS  PubMed  Google Scholar 

  13. Chow PKH, Gandhi M, Tan SB et al (2018) SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 36:1913–1921

    CAS  PubMed  Google Scholar 

  14. Riaz A, Gabr A, Abouchaleh N et al (2018) Radioembolization for hepatocellular carcinoma: statistical confirmation of improved survival in responders by landmark analyses. Hepatology 67:873–883

    PubMed  Google Scholar 

  15. Vogel A, Cervantes A, Chau I et al (2018) Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29(Supplement 4):iv238–iv255

    CAS  PubMed  Google Scholar 

  16. Salem R, Gordon AC, Mouli S et al (2016) Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 151(115–1163):e2

    Google Scholar 

  17. Maturen KE, Feng MU, Wasnik AP et al (2013) Imaging effects of radiation therapy in the abdomen and pelvis: evaluating “innocent bystander” tissues. Radiographics 33:599–619

    PubMed  Google Scholar 

  18. Singh P, Anil G (2013) Yttrium-90 radioembolization of liver tumors: what do the images tell us? Cancer Imaging 13:645–657

    Google Scholar 

  19. Bester L, Hobbins PG, Wang SC, Salem R (2011) Imaging characteristics following 90yttrium microsphere treatment for unresectable liver cancer. J Med Imaging Radiat Oncol 55:111–118

    PubMed  Google Scholar 

  20. Bruix J, Sherman M, Llovet JM et al (2001) EASL panel of experts on HCC European association for the study of the liver: clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. J Hepatol 35:421–430

    CAS  PubMed  Google Scholar 

  21. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60

    CAS  Google Scholar 

  22. Kudo M, Kubo S, Takayasu K et al (2010) Response evaluation criteria in cancer of the liver (RECICL) proposed by the liver cancer study group of Japan (2009 revised version). Hepatol Res 40:686–692

    PubMed  Google Scholar 

  23. Kudo M, Ueshima K, Kubo S et al (2016) Response evaluation criteria in cancer of the liver (RECICL) (2015 revised version). Hepatol Res 46:3–9

    PubMed  Google Scholar 

  24. Kim S, Kim DY, An C et al (2019) Evaluation of early response to treatment of hepatocellular carcinoma with yttrium-90 radioembolization using quantitative computed tomography analysis. Korean J Radiol 20:449–458

    PubMed  PubMed Central  Google Scholar 

  25. Kele PG, van der Jagt EJ (2010) Diffusion weighted imaging in the liver. World J Gastroenterol 16:1567–1576

    PubMed  PubMed Central  Google Scholar 

  26. Parsai A, Zerizer I, Roche O, Gkoutzios P, Miquel ME (2015) Assessment of diffusion-weighted imaging for characterizing focal liver lesions. Clin Imaging 39:278–284

    PubMed  Google Scholar 

  27. Zhu X, Sobhani F, Xu C et al (2016) Quantitative volumetric functional MR imaging: an imaging biomarker of early treatment response in hypo-vascular liver metastasis patients after yttrium-90 transarterial radioembolization. Abdom Radiol 41:1495–1504

    Google Scholar 

  28. Lee YJ, Lee JM, Lee JS, Lee HY, Park BH, Kim YH, Han JK, Choi BI (2015) Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and metaanalysis. Radiology 275:97–109

    PubMed  Google Scholar 

  29. Roberts LR, Sirlin CB, Zaiem F, Almasri J, Prokop LJ, Heimbach JK, Murad MH, Mohammed K (2018) Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology 67:401–421

    PubMed  Google Scholar 

  30. Kierans AS, Kang SK, Rosenkrantz AB (2016) The diagnostic performance of dynamic contrast-enhanced MR imaging for detection of small hepatocellular carcinoma measuring up to 2 cm: a meta-analysis. Radiology 278:82–94

    PubMed  Google Scholar 

  31. Jiang HY, Chen J, Xia CC et al (2018) Noninvasive imaging of hepatocellular carcinoma: from diagnosis to prognosis. World J Gastroenterol 24(22):2348–2362

    PubMed  PubMed Central  Google Scholar 

  32. Tovoli F, Renzulli M, Granito A, Golfieri R, Bolondi L (2017) Radiologic criteria of response to systemic treatments for hepatocellular carcinoma. Hepat Oncol 4(4):129–137

    PubMed  PubMed Central  Google Scholar 

  33. Lanza E, Donadon M, Felisaz P et al (2017) Refining the management of patients with hepatocellular carcinoma integrating 11C-choline PET/CT scan into the multidisciplinary team discussion. Nucl Med Commun 38(10):826–836

    PubMed  Google Scholar 

  34. Filippi L, Schillaci O, Bagni O (2019) Recent advances in PET probes for hepatocellular carcinoma characterization. Expert Rev Med Devices 16(5):341–350

    CAS  PubMed  Google Scholar 

  35. Lu RC, She B, Gao WT et al (2019) Positron-emission tomography for hepatocellular carcinoma: current status and future prospects. World J Gastroenterol 25(32):4682–4695

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Haug AR (2017) Imaging of primary liver tumors with positron-emission tomography. Q J Nucl Med Mol Imaging 61(3):292–300

    PubMed  Google Scholar 

  37. Li YC, Yang CS, Zhou WL, Li HS, Han YJ, Wang QS, Wu HB (2018) Low glucose metabolism in hepatocellular carcinoma with GPC3 expression. World J Gastroenterol 24:494–503

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Ferda J, Ferdova E, Baxa J et al (2015) The role of 18F-FDG accumulation and arterial enhancement as biomarkers in the assessment of typing, grading and staging of hepatocellular carcinoma using 18F-FDG-PET/CT with integrated dualphase CT angiography. Anticancer Res 35:2241–2246

    CAS  PubMed  Google Scholar 

  39. Ijichi H, Shirabe K, Taketomi A et al (2013) Clinical usefulness of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma. Hepatol Res 43:481–487

    CAS  PubMed  Google Scholar 

  40. Lin CY, Chen JH, Liang JA et al (2012) 18F-FDG PET or PET/CT for detecting extrahepatic metastases or recurrent hepatocellular carcinoma: a systematic review and meta-analysis. Eur J Radiol 81:2417–2422

    PubMed  Google Scholar 

  41. Na SJ, Oh JK, Hyun SH et al (2017) 18F-FDG PET/CT can predict survival of advanced hepatocellular carcinoma patients: a multicenter retrospective cohort study. J Nucl Med 58:730–736

    CAS  PubMed  Google Scholar 

  42. Sposito C, Di Sandro S, Brunero F et al (2016) Development of a prognostic scoring system for resectable hepatocellular carcinoma. World J Gastroenterol 22:8194–8202

    PubMed  PubMed Central  Google Scholar 

  43. Aarntzen EHJG, Heijmen L, Oyen WJG (2018) 18F-FDG PET/CT in local ablative therapies: a systematic review. J Nucl Med 59(4):551–556

    CAS  PubMed  Google Scholar 

  44. Sabet A, Ahmadzadehfar H, Bruhman J et al (2014) Survival in patients with hepatocellular carcinoma treated with 90Y-microsphere radioembolization. Prediction by 18F-FDG PET. Nuklearmedizin 53:39–45

    CAS  PubMed  Google Scholar 

  45. Abuodeh Y, Naghavi AO, Ahmed KA et al (2016) Prognostic value of pre-treatment F-18-FDG PET-CT in patients with hepatocellular carcinoma undergoing radioembolization. World J Gastroenterol 22:10406–10414

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Jreige M, Mitsakis P, Van Der Gucht A et al (2017) 18F-FDG PET/CT predicts survival after 90Y transarterial radioembolization in unresectable hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 44:1215–1222

    CAS  PubMed  Google Scholar 

  47. Soydal C, Keskin O, Kucuk ON et al (2015) Prognostic factors for prediction of survival of hepatocellular cancer patients after selective internal radiation therapy. Ann Nucl Med 29:426–430

    CAS  PubMed  Google Scholar 

  48. Kucuk ON, Soydal C, Araz M et al (2013) Prognostic importance of 18F-FDG uptake pattern of hepatocellular cancer patients who received SIRT. Clin Nucl Med 38:e283–e289

    PubMed  Google Scholar 

  49. Filippi L, Di Costanzo GG, D'Agostini A et al (2018) Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis. Nucl Med Commun 39:845–852

    CAS  PubMed  Google Scholar 

  50. Karanikas G, Beheshti M (2014) 11C-acetate PET/CT imaging: physiologic uptake, variants, and pitfalls. PET Clin 9(3):339–344

    PubMed  Google Scholar 

  51. Park JW, Kim JH, Kim SK et al (2008) A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med 49:1912–1921

    PubMed  Google Scholar 

  52. Cheung TT, Chan SC, Ho CL et al (2011) Can positron emission tomography with the dual tracers [11C]acetate and [18F]fludeoxyglucose predict microvascular invasion in hepatocellular carcinoma? Liver Transplant 17(10):1218–1225

    Google Scholar 

  53. Cheung TT, Ho CL, Lo CM et al (2013) 11C-acetate and 18F-FDG PET/CT for clinical staging and selection of patients with hepatocellular carcinoma for liver transplantation on the basis of Milan criteria: surgeon’s perspective. J Nucl Med 54(2):192–200

    CAS  PubMed  Google Scholar 

  54. Larsson P, Arvidsson D, Bjornstedt M et al (2012) Adding 11C-acetate to 18F-FDG at PET examination has an incremental value in the diagnosis of hepatocellular carcinoma. Mol Imaging Radionucl Ther 21:6–12

    PubMed  PubMed Central  Google Scholar 

  55. Ho CL, Chen S, Yeung DW et al (2007) Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma. J Nucl Med 48(6):902–909

    CAS  PubMed  Google Scholar 

  56. Ho CL, Yu SC, Yeung DW (2003) 11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. J Nucl Med 44(2):213–221

    PubMed  Google Scholar 

  57. Ho CL, Chen S, Cheung SK et al (2018) Radioembolization with (90)Y glass microspheres for hepatocellular carcinoma: significance of pretreatment (11) C-acetate and (18)F-FDG PET/CT and posttreatment (90)Y PET/CT in individualized dose prescription. Eur J Nucl Med Mol Imaging 45(12):2110–2121

    CAS  PubMed  Google Scholar 

  58. Ho CL, Chen S, Cheung SK, Leung TWT (2019) Significant value of 11C-acetate and 18F-flurodeoxyglucose PET/computed tomography on 90Y microspheres radioembolization for hepatocellular carcinoma. PET Clin 14(4):459–467

    PubMed  Google Scholar 

  59. Mertens K, Slaets D, Lambert B et al (2010) PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature. Eur J Nucl Med Mol Imaging 37:2188–2193

    CAS  PubMed  Google Scholar 

  60. D'Agostino GR, Lopci E, Di Brina L et al (2018) Role of 11C-choline PET/CT in radiation therapy planning of patients with prostate cancer. Nucl Med Commun 39(10):951–956

    PubMed  Google Scholar 

  61. Lopci E, Torzilli G, Poretti D et al (2015) Diagnostic accuracy of 11C-choline PET/CT in comparison with CT and/or MRI in patients with hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 42(9):1399–1407

    CAS  PubMed  Google Scholar 

  62. Yamamoto Y, Nishiyama Y, Kameyama R et al (2008) Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET. J Nucl Med 49:1245–1248

    PubMed  Google Scholar 

  63. Talbot JN, Fartoux L, Balogova S et al (2010) Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. J Nucl Med 51:1699–1706

    PubMed  Google Scholar 

  64. Talbot JN, Gutman F, Fartoux L et al (2006) PET/CT in patients with hepatocellular carcinoma using [(18) F]fluorocholine: preliminary comparison with [(18)F]FDG PET/CT. Eur J Nucl Med Mol Imaging 33:1285–1289

    PubMed  Google Scholar 

  65. Wu HB, Wang QS, Li BY et al (2011) F-18 FDG in conjunction with 11C-choline PET/CT in the diagnosis of hepatocellular carcinoma. Clin Nucl Med 36:1092–1097

    PubMed  Google Scholar 

  66. Castilla-Lièvre MA, Franco D, Gervais P et al (2016) Diagnostic value of combining 11C-choline and 18FFDG PET/CT in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 43:852–859

    PubMed  Google Scholar 

  67. Chalaye J, Costentin CE, Luciani A et al (2018) Positron emission tomography/computed tomography with 18F-fluorocholine improve tumour staging and treatment allocation in patients with hepatocellular carcinoma. J Hepatol 69:336–344

    PubMed  Google Scholar 

  68. Kwee SA, Tiirikainen M, Sato MM et al (2019) Transcriptomics associates molecular features with 18F-fluorocholine PET/CT imaging phenotype and its potential relationship to survival in hepatocellular carcinoma. Cancer Res 79(7):1696–1704

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hartenbach M, Weber S, Albert NL et al (2015) Evaluating treatment response of radioembolization in intermediate-stage hepatocellular carcinoma patients using 18F-fluoroethylcholine PET/CT. J Nucl Med 56:1661–1666

    CAS  PubMed  Google Scholar 

  70. Hartenbach M, Weber S, Pilz M et al (2018) Combined [18F]-fluoroethylcholine PET/CT and 99mTc-macroaggregated albumin SPECT/CT predict survival in patients with intermediate-stage hepatocellular carcinoma. Clin Nucl Med 43(7):477–481

    PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the colleagues for the clinical management of HCC patients submitted to radioembolization at the Departments of Nuclear Medicine and Radiology, Humanitas Clinical and Research Center – IRCCS, Rozzano (Milano), Italy.

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  1. Department of Nuclear Medicine, Humanitas Clinical and Research Hospital - IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy

    Angelo Castello & Egesta Lopci

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  1. Angelo Castello
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  2. Egesta Lopci
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Correspondence to Egesta Lopci.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Patients herein described were enrolled in a dedicated clinical study registrered at ClinicalTrials.gov Identifier: NCT02519075.

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Castello, A., Lopci, E. Imaging HCC treated with radioembolization: review of the literature and clinical examples of choline PET utility. Clin Transl Imaging 8, 377–392 (2020). https://doi.org/10.1007/s40336-020-00384-y

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