Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis

Yusuke Kawamura; Masahiro Kobayashi; Junichi Shindoh; Yuta Kobayashi; Kayoko Kasuya; Tomoya Sano; Shunichiro Fujiyama; Tetsuya Hosaka; Satoshi Saitoh; Hitomi Sezaki; Norio Akuta; Fumitaka Suzuki; Yoshiyuki Suzuki; Kenji Ikeda; Yasuji Arase; Masaji Hashimoto; Hiromitsu Kumada

doi:10.1159/000505190

Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis

Liver Cancer. 2020 Jun;9(3):275-292. doi: 10.1159/000505190. Epub 2020 Feb 4.

Authors

Yusuke Kawamura^{1

2}, Masahiro Kobayashi^{1

2}, Junichi Shindoh^{3

2}, Yuta Kobayashi^{3

2}, Kayoko Kasuya^{1

2}, Tomoya Sano^{1

2}, Shunichiro Fujiyama^{1

2}, Tetsuya Hosaka^{1

2}, Satoshi Saitoh^{1

2}, Hitomi Sezaki^{1

2}, Norio Akuta^{1

2}, Fumitaka Suzuki^{1

2}, Yoshiyuki Suzuki^{1

2}, Kenji Ikeda^{1

2}, Yasuji Arase^{1

2}, Masaji Hashimoto^{3

2}, Hiromitsu Kumada^{1

2}

Affiliations

¹ Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
² Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
³ Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.

Abstract

Objective: The aim of this study was to evaluate the performance of pretreatment computed tomography (CT) enhancement of hepatocellular carcinoma (HCC) as a potential predictor of response to lenvatinib and its relevance to survival outcomes.

Methods: We evaluated 51 consecutive patients who received lenvatinib treatment for unresectable HCC. On imaging analysis, pretreatment arterial/portal phase dynamic CT images were classified as follows: type 2, homogeneous enhancement pattern with increased arterial blood flow; type 3, heterogeneous enhancement pattern with a septum-like structure; and type 4, heterogeneous enhancement pattern with irregularly shaped ring structures. Treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors at 2-12 weeks after initiation of lenvatinib, and the correlations between the CT enhancement patterns and response to lenvatinib or survival outcomes were investigated.

Results: Of the 51 patients, 38 (75%) experienced an objective response (OR). ORs were significantly more common in heterogeneously enhanced HCC (types 3 and 4) than in homogeneous HCC (type 2) (83 vs. 53%, respectively; p = 0.037). Multivariate analysis revealed that pretreatment heterogeneous enhancement pattern is an independent predictor for response to lenvatinib (odds ratio, 4.75; p = 0.042). Presence of OR was associated with longer progression-free survival (PFS) (hazard ratio, 0.36; p = 0.017), and patients with oncologically aggressive type 3 and 4 tumors showed similar PFS to those harboring type 2 tumors (p = 0.455), reflecting that OR was more common in type 3 or 4 tumors compared with type 2 tumors. Although postprogression survival was extremely poor in patients with type 4 tumors (p = 0.064), overall survival after introduction of lenvatinib was not statistically different among the three groups of patients (p = 0.053).

Conclusion: The CT enhancement pattern of HCC may predict response to lenvatinib. OR seems to occur more frequently in HCC with oncologically aggressive features and may contribute to prolonged survival through a prolonged progression-free interval, even in an oncologically poor-risk group of patients.

Keywords: Computed tomography; Hepatocellular carcinoma; Lenvatinib; Malignant potential; Poorly-differentiated hepatocellular carcinoma.