18 F-Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma as a Useful Predictor of an Extremely Rapid Response to Lenvatinib

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Abstract

Background and Aims: This study aimed to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of the response of hepatocellular carcinoma (HCC) to lenvatinib. Methods: We evaluated 28 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT. The tumor-to-normal liver standardized uptake value ratio (TLR) of the target tumor was measured before treatment using 18F-FDG-PET/CT, with a TLR ≥2 classified as a high potential for malignant HCC. The treatment response was evaluated 2 weeks after the initiation of lenvatinib using modified Response Evaluation Criteria in Solid Tumors. Results: Of the 28 patients, 12 (43%) presented with a TLR ≥2. Evaluation of the treatment response at 2 weeks in these 12 patients revealed that 2 (17%) exhibited a complete response, 8 (67%) a partial response, 2 (17%) stable disease, and none with progressive disease. Therefore, 10 of the 12 patients (83%) experienced an objective response to lenvatinib. On the other hand, 7 of the 16 patients with a TLR <2 (44%) experienced an objective response. Thus, the objective response rate was higher in patients with a TLR ≥2 than in those with a TLR <2. Multivariate logistic regression analysis revealed that a TLR ≥2 (odds ratio 10.53; p = 0.028) is a useful predictor of an early objective response at 2 weeks. Conclusion: Patients with unresectable HCC showed a good early treatment response to lenvatinib. High TLR (≥2) may be a useful predictor of an extremely rapid treatment response.

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Transarterial Chemoembolization Failure/Refractoriness: JSH-LCSGJ Criteria 2014 Update

Masatoshi Kudo, Osamu Matsui, Namiki Izumi … (2014)

In the 2010 version of the Japan Society of Hepatology (JSH) consensus-based treatment algorithm for the management of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) failure/refractoriness was defined assuming the use of superselective lipiodol TACE, which has been widely used worldwide and particularly in Japan, and areas with lipiodol deposition were considered to be necrotic. However, this concept is not well accepted internationally. Furthermore, following the approval of microspheres, an embolic material that does not use lipiodol, in February 2014 in Japan, the phrase ‘lipiodol deposition' needed to be changed to ‘necrotic lesion or viable lesion'. Accordingly, the respective section in the JSH guidelines was revised to define TACE failure as an insufficient response after ≥2 consecutive TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, even after chemotherapeutic agents have been changed and/or the feeding artery has been reanalyzed. In addition, the appearance of a higher number of lesions in the liver than that recorded at the previous TACE procedure (other than the nodule being treated) was added to the definition of TACE failure/refractoriness. Following the discussion of other issues concerning the continuous elevation of tumor markers, vascular invasion, and extrahepatic spread, descriptions similar to those in the previous version were approved. The revision of these TACE failure definitions was approved by over 85% of HCC experts. © 2014 S. Karger AG, Basel

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Fluorine-18 fluorodeoxyglucose positron emission tomography predicts tumor differentiation, P-glycoprotein expression, and outcome after resection in hepatocellular carcinoma.

Keiko Iwaisako, Shinji Uemoto, Nobuyuki Tamaki … (2007)

To investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for prediction of tumor differentiation, P-glycoprotein (P-gp) expression, and outcome in hepatocellular carcinoma (HCC) patients. Seventy HCC patients who underwent curative resection were prospectively enrolled in the study. FDG-PET was done 2 weeks preoperatively, and the standardized uptake value (SUV) and the tumor to nontumor SUV ratio (TNR) were calculated from FDG uptake. Tumor differentiation and P-gp expression were examined with H&E and immunohistochemical staining, respectively. SUV and TNR were significantly higher in poorly differentiated HCCs than in well-differentiated (P = 0.001 and 0.002) and moderately differentiated HCCs (P or =2.0) group were significantly lower than in the low TNR (<2.0) group (P = 0.0001 and 0.0002). In multivariate analysis, a high alpha-fetoprotein level (risk ratio, 5.46; P = 0.003; risk ratio, 8.78; P = 0.006) and high TNR (risk ratio, 1.3; P = 0.03; risk ratio, 1.6; P = 0.02) were independent predictors of postoperative recurrence and overall survival. The results suggest that preoperative FDG-PET reflects tumor differentiation and P-gp expression and may be a good predictor of outcome in HCC.

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The Significance of Fibroblast Growth Factor Receptor 2 Expression in Differentiation of Hepatocellular Carcinoma

Norifumi Harimoto, Kenichi Taguchi, Ken Shirabe … (2010)

Fibroblast growth factor receptors (FGFRs) have been reported to be involved in the progression of many cancers. The aim of this study is to clarify the significance of FGFR2 expression in the differentiation of hepatocellular carcinoma (HCC). One nodule-in-nodule HCC sample was obtained from a patient to analyze the different expression in well- to moderately differentiated HCC and poorly differentiated HCC using microarray technique. The expression of FGFR2 in 46 patients with surgically resected HCC was immunohistochemically examined and analyzed in relation to their clinicopathological factors. Fgfr2 was 4.7 times up-regulated in poorly differentiated HCC from a nodule-in-nodule sample. The high expression group was 16 cases and the low expression group was 30 cases. The high FGFR2 expression correlated significantly with a poor histological differentiation, a higher incidence of portal vein and a high level of alpha-fetoprotein. The overall survival rates and the disease-free survival rates in high expression were significantly worse than those in low. In conclusion, a high FGFR2 expression plays an important role in poor differentiation, portal vein invasion, high alpha-fetoprotein production, and poor prognosis. These data suggest that FGFR2 may be a potentially useful biological marker of tumor invasiveness in HCC as well as a novel molecular target for HCC.

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Author and article information

Journal

Journal ID (publisher-id): LIC

Journal ID (pmc): LIC

Journal ID (doi): 10.1159/issn.1664-5553

Title: Liver Cancer

Publisher: S. Karger AG

ISSN (Print): 2235-1795

ISSN (Electronic): 1664-5553

Publication date Subscription-year: 2020

Publication date (Print): January 2020

Publication date (Electronic): 13 November 2019

Volume: 9

Issue: 1

Pages: 84-92

Affiliations

[_a] _aDepartment of Hepatology, Toranomon Hospital, Tokyo, Japan

[_b] _bHepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan

[_c] _cOkinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan

Author notes

*Yusuke Kawamura, MD, PhD, Department of Hepatology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470 (Japan), E-Mail k-yusuke@toranomon.gr.jp

Author information

Norio Akuta https://orcid.org/0000-0001-5386-9672

Article

Publisher ID: 503577 Pmcid ID: PMC7024860 Other ID: Liver Cancer 2020;9:84–92

DOI: 10.1159/000503577

PMC ID: PMC7024860

PubMed ID: 32071912

SO-VID: 9c24681c-b135-4416-a811-b095f01b4351

License:

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 08 August 2019

Date accepted : 18 September 2019

Page count

Figures: 3, Tables: 2, Pages: 9

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