Abstract
Purpose
Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of 18F–fluorodeoxyglucose positron emission tomography (18F–FDG PET) for predicting tumour progression during sorafenib treatment.
Methods
We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing 18F–FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured.
Results
Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis.
Conclusion
Pretreatment tumour metabolic activity assessed by 18F–FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.
Similar content being viewed by others
References
Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018. https://doi.org/10.1038/nrdp.2016.18.
Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with Hepatocellular carcinoma. Gastroenterology. 2016;150:835–53. https://doi.org/10.1053/j.gastro.2015.12.041.
Na SJ, Oh JK, Hyun SH, Lee JW, Hong IK, Song BI, et al. 18F-FDG PET/CT can predict survival of advanced hepatocellular carcinoma patients: a multicenter retrospective cohort study. J Nucl Med. 2016. https://doi.org/10.2967/jnumed.116.182022.
Kim DY, Kim HJ, Han KH, Han SY, Heo J, Woo HY, et al. Real-life experience of Sorafenib treatment for Hepatocellular carcinoma in Korea: from GIDEON data. Cancer Res Treat. 2016;48:1243–52. https://doi.org/10.4143/crt.2015.278.
Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016. Clin Mol Hepatol. 2016;22:7–17. https://doi.org/10.3350/cmh.2016.22.1.7.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90. https://doi.org/10.1056/NEJMoa0708857.
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34. https://doi.org/10.1016/S1470-2045(08)70285-7.
Shao YY, Hsu CH, Cheng AL. Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: are we getting there? World J Gastroenterol. 2015;21:10336–47. https://doi.org/10.3748/wjg.v21.i36.10336.
Lee JH, Park JY, Kim DY, Ahn SH, Han KH, Seo HJ, et al. Prognostic value of 18F-FDG PET for hepatocellular carcinoma patients treated with sorafenib. Liver Int. 2011;31:1144–9. https://doi.org/10.1111/j.1478-3231.2011.02541.x.
Sugiyama M, Sakahara H, Torizuka T, Kanno T, Nakamura F, Futatsubashi M, et al. 18F-FDG PET in the detection of extrahepatic metastases from hepatocellular carcinoma. J Gastroenterol. 2004;39:961–8. https://doi.org/10.1007/s00535-004-1427-5.
Hong CM, Ahn BC, Jang YJ, Jeong SY, Lee SW, Lee J. Prognostic value of metabolic parameters of 18F-FDG PET/CT and apparent diffusion coefficient of MRI in Hepatocellular carcinoma. Clin Nucl Med. 2017;42:95–9. https://doi.org/10.1097/rlu.0000000000001478.
Hyun SH, Eo JS, Lee JW, Choi JY, Lee KH, Na SJ, et al. Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with Barcelona clinic liver cancer stages 0 and a hepatocellular carcinomas: a multicenter retrospective cohort study. Eur J Nucl Med Mol Imaging. 2016;43:1638–45. https://doi.org/10.1007/s00259-016-3348-y.
Eo JS, Paeng JC, Lee DS. Nuclear imaging for functional evaluation and theragnosis in liver malignancy and transplantation. World J Gastroenterol. 2014;20:5375–88. https://doi.org/10.3748/wjg.v20.i18.5375.
Lee JW, Paeng JC, Kang KW, Kwon HW, Suh KS, Chung JK, et al. Prediction of tumor recurrence by 18F-FDG PET in liver transplantation for hepatocellular carcinoma. J Nucl Med. 2009;50:682–7. https://doi.org/10.2967/jnumed.108.060574.
Kitamura K, Hatano E, Higashi T, Seo S, Nakamoto Y, Yamanaka K, et al. Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma. Ann Surg Oncol. 2012;19:156–62. https://doi.org/10.1245/s10434-011-1990-y.
Kornberg A, Kupper B, Thrum K, Katenkamp K, Steenbeck J, Sappler A, et al. Increased 18F-FDG uptake of hepatocellular carcinoma on positron emission tomography independently predicts tumor recurrence in liver transplant patients. Transplant Proc. 2009;41:2561–3. https://doi.org/10.1016/j.transproceed.2009.06.115.
Lee JW, Yun M, Cho A, Han KH, Kim DY, Lee SM, et al. The predictive value of metabolic tumor volume on FDG PET/CT for transarterial chemoembolization and transarterial chemotherapy infusion in hepatocellular carcinoma patients without extrahepatic metastasis. Ann Nucl Med. 2015;29:400–8. https://doi.org/10.1007/s12149-015-0956-8.
Kim MJ, Kim YS, Cho YH, Jang HY, Song JY, Lee SH, et al. Use of (18)F-FDG PET to predict tumor progression and survival in patients with intermediate hepatocellular carcinoma treated by transarterial chemoembolization. Korean J Intern Med. 2015;30:308–15. https://doi.org/10.3904/kjim.2015.30.3.308.
Lee JW, Oh JK, Chung YA, Na SJ, Hyun SH, Hong IK, et al. Prognostic significance of (1)(8)F-FDG uptake in Hepatocellular carcinoma treated with Transarterial Chemoembolization or concurrent Chemoradiotherapy: a multicenter retrospective cohort study. J Nucl Med. 2016;57:509–16. https://doi.org/10.2967/jnumed.115.167338.
Lee JW, Hwang SH, Kim DY, Han KH, Yun M. Prognostic value of FDG uptake of portal vein tumor thrombosis in patients with locally advanced Hepatocellular carcinoma. Clin Nucl Med. 2017;42:e35–40. https://doi.org/10.1097/rlu.0000000000001422.
Song MJ, Bae SH, Lee SW, Song DS, Kim HY, Yoo Ie R, et al. 18F-fluorodeoxyglucose PET/CT predicts tumour progression after transarterial chemoembolization in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2013;40:865–73. https://doi.org/10.1007/s00259-013-2366-2.
Jreige M, Mitsakis P, Van Der Gucht A, Pomoni A, Silva-Monteiro M, Gnesin S, et al. 18F-FDG PET/CT predicts survival after 90Y transarterial radioembolization in unresectable hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2017. https://doi.org/10.1007/s00259-017-3653-0.
Hartenbach M, Weber S, Albert NL, Hartenbach S, Hirtl A, Zacherl MJ, et al. Evaluating treatment response of Radioembolization in intermediate-stage Hepatocellular carcinoma patients using 18F-Fluoroethylcholine PET/CT. J Nucl Med. 2015;56:1661–6. https://doi.org/10.2967/jnumed.115.158758.
Sabet A, Ahmadzadehfar H, Bruhman J, Sabet A, Meyer C, Wasmuth JC, et al. Survival in patients with hepatocellular carcinoma treated with 90Y-microsphere radioembolization. Prediction by 18F-FDG PET. Nuklearmedizin. 2014;53:39–45. https://doi.org/10.3413/Nukmed-0622-13-09.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60. https://doi.org/10.1055/s-0030-1247132.
Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P. The Warburg effect: insights from the past decade. Pharmacol Ther. 2013;137:318–30. https://doi.org/10.1016/j.pharmthera.2012.11.003.
Pimiento JM, Davis-Yadley AH, Kim RD, Chen DT, Eikman EA, Berman CG, et al. Metabolic activity by 18F-FDG-PET/CT is prognostic for stage I and II pancreatic cancer. Clin Nucl Med. 2016;41:177–81. https://doi.org/10.1097/RLU.0000000000001098.
Song DS, Song MJ, Bae SH, Chung WJ, Jang JY, Kim YS, et al. A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol. 2015;50:445–54. https://doi.org/10.1007/s00535-014-0978-3.
Edeline J, Boucher E, Rolland Y, Vauleon E, Pracht M, Perrin C, et al. Comparison of tumor response by response evaluation criteria in solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer. 2012;118:147–56. https://doi.org/10.1002/cncr.26255.
Acknowledgements
This work was supported by Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1A2B4010197).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interests
There are no conflicts of interest in this study.
Ethics approval
Ethics approval was provided by the Institutional Ethics Review Board of The Catholic University of Korea (KC17RESI0241).
Electronic supplementary material
ESM 1
(PDF 186 kb)
Rights and permissions
About this article
Cite this article
Sung, P.S., Park, H.L., Yang, K. et al. 18F–fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment. Eur J Nucl Med Mol Imaging 45, 384–391 (2018). https://doi.org/10.1007/s00259-017-3871-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-017-3871-5