Multidisciplinary assessment of tumor response after internal and external radiation therapy for hepatocellular carcinoma

Abstract

Treatment of hepatocellular carcinoma with both internal and external radiation therapy is becoming more common, with the recent incorporation of internal radiation therapy (transarterial radioembolization) into the Barcelona Clinic Liver guidelines. With the increasing use of radiation therapy for the treatment of liver cancer, it is essential to understand the expected imaging findings after therapy and establish a consensus on the management of these patients. Recent insights into the unique post-treatment imaging features of HCC treated with radiation have prompted updates to treatment response algorithms to improve inter-reader response assessment. One must understand the type of locoregional treatment, the time interval of post-treatment imaging and the sequence of the treatment strategy to provide an accurate treatment response assessment. Although imaging response systems attempt to predict treatment efficacy, many of these complex cases should be discussed in a multidisciplinary setting for management recommendations.

Keywords

Hepatocellular carcinoma / radiation / LI-RADS / LIRADS-TRA / treatment response

References

[1] Pan YX,Hu DD.Stereotactic Body radiotherapy vs. radiofrequency ablation in the treatment of hepatocellular carcinoma: a meta-analysis.Front Oncol2020;10:1639 PMCID:PMC7658324

[2] Rim CH,Yang DS.External beam radiation therapy to hepatocellular carcinoma involving inferior vena cava and/or right atrium: a meta-analysis and systemic review.Radiother Oncol2018;129:123-9

[3] Salem R,Kim E.Yttrium-90 radioembolization for the treatment of solitary, unresectable HCC: the LEGACY study.Hepatology2021;74:2342-52 PMCID:PMC8596669

[4] Yamashita H,Murakami N.Japanese Radiological Society multi-institutional SBRT study group (JRS-SBRTSG)Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma.J Radiat Res2015;56:561-7 PMCID:PMC4426924

[5] Sapisochin G,Doherty M.Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis.J Hepatol2017;67:92-9

[6] Mastrocostas K,Munoz-Schuffenegger P.Radiological tumor response and histopathological correlation of hepatocellular carcinoma treated with stereotactic body radiation therapy as a bridge to liver transplantation.Abdom Radiol (NY)2021;46:1572-85

[7] Lewis S,Barry A,Mohamad I.Stereotactic body radiation therapy for hepatocellular carcinoma: From infancy to ongoing maturity.JHEP Rep2022;4:100498 PMCID:PMC9289870

[8] Hong TS,Yeap BY.Multi-institutional phase ii study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma.J Clin Oncol2016;34:460-8 PMCID:PMC4872014

[9] Mendiratta-Lala M,Shankar PR.Magnetic resonance imaging evaluation of hepatocellular carcinoma treated with stereotactic body radiation therapy: long term imaging follow-up.Int J Radiat Oncol Biol Phys2019;103:169-79 PMCID:PMC6301102

[10] Mendiratta-Lala M,Owen D.Imaging findings within the first 12 months of hepatocellular carcinoma treated with stereotactic body radiation therapy.Int J Radiat Oncol Biol Phys2018;102:1063-9 PMCID:PMC5826807

[11] Jiao Y,Liu H.Radiation-induced cell death and its mechanisms.Health Phys2022;123:376-86 PMCID:PMC9512240

[12] Mendiratta-Lala M,Owen D.Natural history of hepatocellular carcinoma after stereotactic body radiation therapy.Abdom Radiol (NY)2020;45:3698-708

[13] Mendiratta-Lala M,Shampain K.MRI assessment of hepatocellular carcinoma after local-regional therapy: a comprehensive review.Radiol Imaging Cancer2020;2:e190024 PMCID:PMC7983779

[14] Shampain KL,Towfighi S.SBRT for HCC: Overview of technique and treatment response assessment.Abdom Radiol (NY)2021;46:3615-24

[15] Mendiratta-Lala M,Maturen KE.LI-RADS Treatment response algorithm: performance and diagnostic accuracy with radiologic-pathologic explant correlation in patients with sbrt-treated hepatocellular carcinoma.Int J Radiat Oncol Biol Phys2022;112:704-14 PMCID:PMC9400832

[16] Riaz A,Lewandowski RJ.Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres.Hepatology2009;49:1185-93

[17] Chen G,Peng S.Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes?.Eur Radiol2022;32:7307-19 PMCID:PMC9474341

[18] Vincenzi B,Silletta M.Prognostic relevance of objective response according to easl criteria and mrecist criteria in hepatocellular carcinoma patients treated with loco-regional therapies: a literature-based meta-analysis.PLoS One2015;10:e0133488 PMCID:PMC4521926

[19] Zhou M,Nie J.Response Evaluation and Survival Prediction Following PD-1 Inhibitor in Patients With Advanced Hepatocellular Carcinoma: Comparison of the RECIST 1.1, iRECIST, and mRECIST Criteria.Front Oncol2021;11:764189 PMCID:PMC8697350

[20] Prajapati HJ,Hanish SI.mRECIST and EASL responses at early time point by contrast-enhanced dynamic MRI predict survival in patients with unresectable hepatocellular carcinoma (HCC) treated by doxorubicin drug-eluting beads transarterial chemoembolization (DEB TACE).Ann Oncol2013;24:965-73

[21] Ghosn M,Kharrat R.Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria.Diagn Interv Imaging2021;102:35-44

[22] Wang D,Jin B.Perfusion reduction at transcatheter intraarterial perfusion MR imaging: a promising intraprocedural biomarker to predict transplant-free survival during chemoembolization of hepatocellular carcinoma.Radiology2014;272:587-97 PMCID:PMC4263646

[23] Ippolito D,Bonaffini PA.Quantitative evaluation of CT-perfusion map as indicator of tumor response to transarterial chemoembolization and radiofrequency ablation in HCC patients.Eur J Radiol2014;83:1665-71

[24] Kanamoto M,Terashima K,Fuwa N.Preliminary study of apparent diffusion coefficient assessment after ion beam therapy for hepatocellular carcinoma.Radiol Phys Technol2016;9:233-9

[25] Yu JI,Lim DH.The role of diffusion-weighted magnetic resonance imaging in the treatment response evaluation of hepatocellular carcinoma patients treated with radiation therapy.Int J Radiat Oncol Biol Phys2014;89:814-21

[26] Cao Y,Evans J,Chang DT.Is apparent diffusion coefficient established as an imaging biomarker for stereotactic body radiation therapy assessment in hepatocellular carcinoma?.Cancer J2023;29:238-42 PMCID:PMC10372684

[27] Lo CH,Hsiang CW.Prognostic significance of apparent diffusion coefficient in hepatocellular carcinoma patients treated with stereotactic ablative radiotherapy.Sci Rep2019;9:14157 PMCID:PMC6775098

[28] Qiong L,Zhong Z.Detection of hepatocellular carcinoma in a population at risk: iodine-enhanced multidetector CT and/or gadoxetic acid-enhanced 3.0 T MRI.BMJ Open2022;12:e058461 PMCID:PMC8860074

[29] Pfeiffer D,Patino M,Rummeny EJ.Iodine material density images in dual-energy CT: quantification of contrast uptake and washout in HCC.Abdom Radiol (NY)2018;43:3317-23

[30] Bargellini I,Turini FM.Response assessment by volumetric iodine uptake measurement: preliminary experience in patients with intermediate-advanced hepatocellular carcinoma treated with Yttrium-90 radioembolization.Cardiovasc Intervent Radiol2018;41:1373-83

[31] Thaiss WM,Kaufmann S.Dose optimization of perfusion-derived response assessment in hepatocellular carcinoma treated with transarterial chemoembolization: comparison of volume perfusion CT and iodine concentration.Acad Radiol2019;26:1154-63

[32] Patel R,Parikh ND.Updates on LI-RADS treatment response criteria for hepatocellular carcinoma: focusing on MRI.J Magn Reson Imaging2023;57:1641-54 PMCID:PMC11078141

[33] Marrero JA,Sirlin CB.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases.Hepatology2018;68:723-50

[34] Lin H,Cong N,Liu C.Transarterial chemoembolization followed by radiotherapy versus sandwich treatment for unresectable or ablative hepatocellular carcinoma.Technol Cancer Res Treat2020;19:1533033820983799 PMCID:PMC7768318

[35] Buckstein M,Özbek U.Combination transarterial chemoembolization and stereotactic body radiation therapy for unresectable single large hepatocellular carcinoma: results from a prospective Phase 2 trial.Int J Radiat Oncol Biol Phys2022;114:221-30

[36] Ning C,Wang Y.Radiation therapy with combination therapy of immune checkpoint inhibitors and antiangiogenic therapy for hepatocellular carcinoma.Int J Radiat Oncol Biol Phys2024;118:1461-71

[37] Cozzi L,Fogliata A.Radiomics based analysis to predict local control and survival in hepatocellular carcinoma patients treated with volumetric modulated arc therapy.BMC Cancer2017;17:829 PMCID:PMC5718116

[38] Park JW,Hong H.Efficacy of radiomics in predicting oncologic outcome of liver-directed combined radiotherapy in locally advanced hepatocellular carcinoma.Cancers (Basel)2023;15:5405 PMCID:PMC10670316

[39] Wei L,Rosen B.A deep survival interpretable radiomics model of hepatocellular carcinoma patients.Phys Med2021;82:295-305 PMCID:PMC8035300

[40] Wang L,Shen L,Yan S.Prognostic value of a CT radiomics-based nomogram for the overall survival of patients with nonmetastatic BCLC stage C hepatocellular carcinoma after stereotactic body radiotherapy.J Oncol2023;2023:1554599 PMCID:PMC9831699

[41] Wu K,Sun W,Pang H.Utility of Radiomics for predicting patient survival in hepatocellular carcinoma with portal vein tumor thrombosis treated with stereotactic body radiotherapy.Front Oncol2020;10:569435 PMCID:PMC7594107

[42] Wu K,Sun W,Pang H.Utility of radiomics for predicting patient survival in hepatocellular carcinoma with portal vein tumor thrombosis treated with stereotactic body radiotherapy.Front Oncol2020;10:569435.

[43] Shen PC,Dai YH.Radiomics-based predictive model of radiation-induced liver disease in hepatocellular carcinoma patients receiving stereo-tactic body radiotherapy.Biomedicines2022;10:597 PMCID:PMC8945465

[44] Onuoha E,Cannon R,Kim H.Perfusion change of hepatocellular carcinoma during atezolizumab plus bevacizumab treatment: a pilot study.J Gastrointest Cancer2023;54:776-81 PMCID:PMC9971356

[45] Choi JY,Park HC.The possibility of radiotherapy as downstaging to living donor liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus.Liver Transpl2017;23:545-51

[46] Montazeri SA,Lewis AR.Hepatocellular carcinoma radiation segmentectomy treatment intensification prior to liver transplantation increases rates of complete pathologic necrosis: an explant analysis of 75 tumors.Eur J Nucl Med Mol Imaging2022;49:3892-7

[47] Wang YF,Lin CS.Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series.Radiat Oncol2021;16:15 PMCID:PMC7807861

[48] Garg R,Movahedi B.Outcomes after stereotactic body radiation therapy as a bridging modality to liver transplantation for hepatocellular carcinoma.Adv Radiat Oncol2021;6:100559 PMCID:PMC7897771

[49] Wei X,Zhang X.Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study.J Clin Oncol2019;37:2141-51 PMCID:PMC6698917