Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients

Abstract

Objective

Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis.

Methods

Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS.

Results

Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0–4 vs. 5–6 points) (OR, 9.20; 95% CI: 4.68–18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13–7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0–4 vs. 5–6 points) (HR, 1.73; 95% CI: 1.19–2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0–4 points group had shorter OS than those in the FLIS 5–6 points group [20 months (95% CI, 14.7–25.3) vs. 43 months (95% CI, 27.7–58.3); P=0.001].

Conclusion

Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.

References

[1] SungH, FerlayJ, SiegelRL, et al. . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2021, 71(3): 209-249

[2] FornerA, ReigM, BruixJ, et al. . Hepatocellular carcinoma. Lancet, 2018, 391(10127): 1301-1314

[3] LiuZY, KanXF, ZhangJ, et al. . Transarterial chemoembolization combined with apatinib for treatment of advanced hepatocellular carcinoma: analysis of survival and prognostic factors. Curr Med Sci, 2022, 42(5): 1015-1021

[4] RichNE, PhenS, DesaiN, et al. . Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis. Clin Gastroenterol Hepatol, 2022, 20(5): e1157-e1169

[5] BaracosVE, MartinL, KorcM, et al. . Cancer-associated cachexia. Nat Rev Dis Primers, 2018, 4: 17105

[6] KumarNB, KaziA, SmithT, et al. . Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol, 2010, 11(3–4): 107-117

[7] BrownJL, Rosa-CaldwellME, LeeDE, et al. . Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice. J Cachexia Sarcopenia Muscle, 2017, 8(6): 926-938

[8] AnkerMS, HolcombR, MuscaritoliM, et al. . Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review. J Cachexia Sarcopenia Muscle, 2019, 10(1): 22-34

[9] RoelandEJ, BohlkeK, BaracosVE, et al. . Management of Cancer Cachexia ASCO Guideline. J Clin Oncol, 2020, 38(21): 2438-2453

[10] FearonK, StrasserF, AnkerSD, et al. . Definition and classification of cancer cachexia: an international consensus. Lancet Oncol, 2011, 12(5): 489-495

[11] KojimaY, Mishiro-SatoE, FujishitaT, et al. . Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia. Nat Commun, 2023, 14(1): 6246

[12] FonsecaG, FarkasJ, DoraE, et al. . Cancer cachexia and related metabolic dysfunction. Int J Mol Sci, 2020, 21(7): 2321

[13] Rosa-CaldwellME, BrownJL, LeeDE, et al. . Hepatic alterations during the development and progression of cancer cachexia. Appl Physiol Nutr Metab, 2020, 45(5): 500-512

[14] BarcellosPS, BorgesN, TorresDP. Resting energy expenditure in cancer patients: agreement between predictive equations and indirect calorimetry. Clin Nutr ESPEN, 2021, 42: 286-291

[15] KimSE, KimDJ. Sarcopenia as a prognostic indicator of liver cirrhosis. J Cachexia Sarcopenia Muscle, 2022, 13(1): 8-10

[16] BastatiN, BeerL, MandorferM, et al. . Does the Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predict Outcomes in Chronic Liver Disease?. Radiology, 2020, 294(1): 98-107

[17] BastatiN, WibmerA, TamandlD, et al. . Assessment of Orthotopic Liver Transplant Graft Survival on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging Using Qualitative and Quantitative Parameters. Invest Radiol, 2016, 51(11): 728-734

[18] BastatiN, BeerL, Ba-SsalamahA, et al. . Gadoxetic acid-enhanced MRI-derived functional liver imaging score (FLIS) and spleen diameter predict outcomes in ACLD. J Hepatol, 2022, 77(4): 1005-1013

[19] LeeHJ, HongSB, LeeNK, et al. . Validation of functional liver imaging scores (FLIS) derived from gadoxetic acid-enhanced MRI in patients with chronic liver disease and liver cirrhosis: the relationship between Child-Pugh score and FLIS. Eur Radiol, 2021, 31(11): 8606-8614

[20] HeimbachJK, KulikLM, FinnRS, et al. . AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology, 2018, 67(1): 358-380

[21] RichNE, MurphyCC, YoppAC, et al. . Sex disparities in presentation and prognosis of 1110 patients with hepatocellular carcinoma. Aliment Pharmacol Ther, 2020, 52(4): 701-709

[22] Poetter-LangS, AmbrosR, MessnerA, et al. . Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid-enhanced MRI? A large-cohort study. Eur Radiol, 2024, 34(8): 1-13

[23] KangHJ, KimH, LeeDH, et al. . Gadoxetate-enhanced MRI Features of Proliferative Hepatocellular Carcinoma Are Prognostic after Surgery. Radiology, 2021, 300(3): 572-582

[24] SadeghiM, Keshavarz-FathiM, BaracosV, et al. . Cancer cachexia: Diagnosis, assessment, and treatment. Crit Rev Oncol Hematol, 2018, 127: 91-104

[25] WiegertEVM, de OliveiraLC, Calixto-LimaL, et al. . New cancer cachexia staging system for use in clinical practice. Nutrition, 2021, 90: 111271

[26] JiangY, WuHH, ZhaoYF, et al. . Abnormal ^[18F]FDG uptake in liver and adipose tissue: a potential imaging biomarker for cancer-associated cachexia. Eur Radiol, 2023, 33(4): 2561-2573

[27] NakamotoR, OkuyamaC, IshizuK, et al. . Diffusely Decreased Liver Uptake on FDG PET and Cancer-Associated Cachexia With Reduced Survival. Clin Nucl Med, 2019, 44(8): 634-642

[28] LiXX, LiuB, ZhaoYF, et al. . Predicting cachexia in hepatocellular carcinoma patients: a nomogram based on MRI features and body composition. Acta Radiol, 2024, 65(8): 898-906

[29] FeierD, BalassyC, BastatiN, et al. . Liver fibrosis: histopathologic and biochemical influences on diagnostic efficacy of hepatobiliary contrast-enhanced MR imaging in staging. Radiology, 2013, 269(2): 460-468

[30] AslanS, EryurukU, TasdemirMN, et al. . Determining the efficacy of functional liver imaging score (FLIS) obtained from gadoxetic acid-enhanced MRI in patients with chronic liver disease and liver cirrhosis: the relationship between Albumin-Bilirubin (ALBI) grade and FLIS. Abdom Radiol (NY), 2022, 47(7): 2325-2334

[31] MinamiguchiK, IrizatoM, UchiyamaT, et al. . Hepatobiliaryphase gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid MRI for pretreatment prediction of efficacy-to-standard-therapies based on Barcelona Clinic Liver Cancer algorithm: an up-to-date review. Eur Radiol, 2023, 33(12): 8764-8775