Rationale and Objective
The objective of this study was to evaluate whether quantitative enhancement or perfusion measurements on preprocedure triphasic computed tomography (CT) can be used to predict response or overall survival after embolization of hepatocellular carcinoma.
Materials and Methods
The institutional review board approved this retrospective review of 63 patients with hepatocellular carcinoma treated with particle embolization between March 2009 and December 2014. Quantitative enhancement and perfusion measurements were performed on the target tumor and the background liver on the triphasic CT performed before treatment. Microvascular invasion (MVI) and degree of differentiation were determined from a core biopsy specimen. Quantitative enhancement and perfusion values were then correlated with pathology (two-tailed t test), response to embolization on modified Response Evaluation Criteria In Solid Tumors (two-tailed t test), and overall survival after embolization (Cox proportional hazards model).
Results
Arterial enhancement did not predict immediate response or overall survival after embolization. The degree of differentiation or presence of MVI also did not predict immediate response or overall survival after embolization. However, high hepatic artery coefficient or low portal vein coefficient, both in the tumor ( P = .011 and P = .004) and in the background liver ( P = .015 and P = .009), were associated with worse survival. Hepatic artery coefficient, both in the tumor ( P = .025) and in the background liver ( P = .013), were independent predictors of survival in a multivariate model including the Child-Pugh score and the BCLC stage.
Conclusions
Tumor and liver perfusion parameters estimated from preprocedure triphasic CT were predictive of survival after embolization. Arterial-phase enhancement and histology (degree of differentiation or MVI) did not predict immediate response or overall survival after particle embolization.
Introduction
Treatment options for unresectable and unablatable hepatocellular carcinoma (HCC) include transarterial embolization (TAE), transarterial chemoembolization (TACE) using either lipiodol or drug-eluting beads, radioembolization, and sorafenib. Recent randomized trials have shown no difference in overall survival for these treatment options, although there are differences in response rates and quality of life .
Regardless of the treatment, there are a subset of patients who do not respond . Although overall survival after the various different treatment options for unresectable HCC appears to be similar, there might be subgroups that do better with one treatment compared to another . Predicting which patients will have poor outcomes with one treatment option could potentially allow these patients to be directed to a different treatment option.
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Materials and Methods
Patient Selection
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Transarterial Embolization
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Imaging Protocol
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Image Evaluation
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Statistical Analysis
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Results
Patient Characteristics
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TABLE 1
Patient Characteristics
n (%) Child-Pugh score A 58 (92) B 5 (8) C 0 (0) BCLC stage 0 1 (1) A 18 (29) B 34 (54) C 10 (16) Etiology of liver disease HBV 10 (16) HCV 18 (29) Alcoholism 6 (10) NASH 5 (8) Other 18 (29) Multiple 5 (8) Cirrhosis Yes 37 (59) No 26 (41) Pathology (degree of differentiation) Well differentiated 12 (19) Moderately differentiated 26 (41) Poorly differentiated 6 (10) Undifferentiated 0 (0) Fibrolamellar 2 (3) Not specified 8 (13) Core biopsy not performed 9 (14) Pathology (MVI) Yes 9 (14) No 45 (71) Core biopsy not performed 9 (14)
BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus; HCV, hepatitis C virus; MVI, microvascular invasion; NASH, nonalcoholic steatohepatitis.
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Predicting Response to Embolization
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TABLE 2
Hepatocellular Carcinoma Enhancement, Perfusion Parameters, and Pathology Did Not Predict CR After Embolization
CR (Av. ± SD) Non-CR (Av. ± SD)P Value HAC 0.03 ± 0.22 0.08 ± 0.29 .45 PVC 0.44 ± 0.27 0.31 ± 0.41 .14 AEF 0.74 ± 0.25 0.94 ± 0.83 .21 Arterial-phase enhancement (HU) 44 ± 17 45 ± 36 .86 Portal venous-phase enhancement (HU) 60 ± 15 53 ± 20 .13 Moderate to poorly differentiated 12/16 20/28 1.0 MVI 5/25 4/29 .72
AEF, arterial enhancement fraction; Av., average; CR, complete response; HAC, hepatic artery coefficient; MVI, microvascular invasion; PVC, portal vein coefficient; SD, standard deviation.
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Predicting Overall Survival After Embolization
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TABLE 3
Predictors of Overall Survival After Embolization of Hepatocellular Carcinoma (Cox Proportional Hazards Model)
Univariate Model
Relative Risk ( P Value) Multivariate Model
Relative Risk ( P Value) Tumor HAC 3.85 (.011 \* ) 4.38 (.025 \* ) PVC 0.32 (.004 \* ) AEF 1.39 (.115) Arterial-phase enhancement (HU) 1 (.73) PV-phase enhancement (HU) 0.99 (.28) Liver HAC 1.27 (.015 \* ) 1.33 (.013 \* ) PVC 0.75 (.009 \* ) Child-Pugh score 1.04 (.83) 1.08 (.684) BCLC stage 0 or A 0.69 (.34) 1 (n/a) B 0.55 (.084) 0.86 (.725) C 6.77 (2.9 × 10 −6 \* ) 6.31 (.00016 \* )
AEF, arterial enhancement fraction; BCLC, Barcelona Clinic Liver Cancer; HAC, hepatic artery coefficient; n/a, not applicable; PV, portal venous; PVC, portal vein coefficient.
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Predicting Pathology From Imaging
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TABLE 4
Higher Arterial or Portal Venous-phase Enhancement Predicts Moderate to Poorly Differentiated Hepatocellular Carcinoma
Well-differentiated (Av. ± SD) Moderately to Poorly Differentiated (Av. ± SD)P Value Arterial-phase enhancement (HU) 29 ± 16 52 ± 52 .004 \* PV-phase enhancement (HU) 43 ± 19 58 ± 58 .028 \* HAC 0.02 ± 0.19 0.10 ± 0.10 .345 PVC 0.27 ± 0.34 0.37 ± 0.37 .415 AEF 0.94 ± 0.99 0.91 ± 0.91 .922
AEF, arterial enhancement fraction; Av., average; HAC, hepatic artery coefficient; PV, portal venous; PVC, portal vein coefficient; SD, standard deviation.
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Discussion
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Supplementary Data
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Appendix S1
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