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  • S. Karger AG  (7)
  • Arase, Yasuji  (7)
  • 1
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    Pretreatment Positron Emission Tomography with 〈sup〉18〈/sup〉F-Fluorodeoxyglucose May Be a Useful New Predictor of Overall Prognosis Following Lenvatinib Treatment
    S. Karger AG ; 2021
    In:  Oncology Vol. 99, No. 10 ( 2021), p. 611-621
    Details
    In: Oncology, S. Karger AG, Vol. 99, No. 10 ( 2021), p. 611-621
    Abstract: 〈 b 〉 〈 i 〉 Background and Aim: 〈 /i 〉 〈 /b 〉 The aim of this study was to identify the utility of 〈 sup 〉 18 〈 /sup 〉 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT) as a predictor of overall prognosis in patients with hepatocellular carcinoma treated with lenvatinib. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Forty-eight consecutive patients who received lenvatinib treatment were reviewed. The oncological aggressiveness of tumors estimated using 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT was investigated by the analysis of progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS). Multivariate analysis was used to identify potential confounders for OS during lenvatinib therapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Using the Modified Response Evaluation Criteria in Solid Tumors, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with a better objective response to lenvatinib than a TLR & #x3c;2 (78 vs. 62%), resulting in a similar PFS ( 〈 i 〉 p 〈 /i 〉 = 0.751). Because of a significantly worse PPS, OS with a TLR ≥2 was poor compared to a TLR & #x3c; 2 ( 〈 i 〉 p 〈 /i 〉 = 0.012). Multivariate analysis confirmed that a TLR ≥ 2 was associated with poor OS (hazard ratio, 2.709; 95% CI, 1.140–6.436; 〈 i 〉 p 〈 /i 〉 = 0.024). Analysis of 24 patients who received a repeat 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT showed that daily changes expressed as ΔTLR × 10 〈 sup 〉 3 〈 /sup 〉 /day over the treatment course tended to be different among the types of subsequent treatment. A R0 resection and lenvatinib-TACE sequential therapy provided good disease control (median, −4.593 and −0.024, respectively) compared with other treatments (median, 5.278) ( 〈 i 〉 p 〈 /i 〉 = 0.075). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Lenvatinib has acceptable disease control regardless of estimated tumor differentiation. A high TLR (≥2) is a poor prognostic factor of OS following lenvatinib treatment, while ΔTLR × 10 〈 sup 〉 3 〈 /sup 〉 /day provides useful information of disease control status.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000516565
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 2
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    〈sup〉18〈/sup〉F-Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma as a Useful Predictor of an Extremely Rapid Response to Lenvatinib
    S. Karger AG ; 2020
    In:  Liver Cancer Vol. 9, No. 1 ( 2020), p. 84-92
    Details
    In: Liver Cancer, S. Karger AG, Vol. 9, No. 1 ( 2020), p. 84-92
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 This study aimed to identify the utility of 〈 sup 〉 18 〈 /sup 〉 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT) as a predictor of the response of hepatocellular carcinoma (HCC) to lenvatinib. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We evaluated 28 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT. The tumor-to-normal liver standardized uptake value ratio (TLR) of the target tumor was measured before treatment using 〈 sup 〉 18 〈 /sup 〉 F-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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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 & #x3c;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 & #x3c;2. Multivariate logistic regression analysis revealed that a TLR ≥2 (odds ratio 10.53; 〈 i 〉 p 〈 /i 〉 = 0.028) is a useful predictor of an early objective response at 2 weeks. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 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.
    Type of Medium: Online Resource
    ISSN: 2235-1795 , 1664-5553
    URL: Article
    DOI: 10.1159/000503577
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 2666925-0
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  • 3
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    Pretreatment Positron Emission Tomography with 〈sup〉18〈/sup〉F-Fluorodeoxyglucose May Be a Useful New Predictor of Early Progressive Disease following Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma
    S. Karger AG ; 2022
    In:  Oncology Vol. 100, No. 6 ( 2022), p. 320-330
    Details
    In: Oncology, S. Karger AG, Vol. 100, No. 6 ( 2022), p. 320-330
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 The aim of this study was to identify the utility of 〈 sup 〉 18 〈 /sup 〉 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT) as a predictor of early progressive disease (e-PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Twenty consecutive patients with measurable intrahepatic target nodules who received Atezo/Bev treatment were reviewed. The oncological aggressiveness of tumors estimated by 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT was analyzed using the rate of e-PD within 12 weeks and early progression-free survival (e-PFS) and overall survival (OS). Multivariate analysis was used to identify potential confounders for PD during Atezo/Bev therapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Using the Response Evaluation Criteria in Solid Tumors version 1.1, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with lower objective response rates compared with TLR values & #x3c;2 (18% vs. 33%, respectively). Moreover, TLR values ≥2 were significantly associated with higher e-PD rates compared with TLR values & #x3c;2 (64% vs. 11%, respectively) and worse e-PFS ( 〈 i 〉 p 〈 /i 〉 = 0.021). In multivariate analysis, TLR ≥2 showed marginal significance as a predictor of e-PD ( 〈 i 〉 p 〈 /i 〉 = 0.053), and utility as a predictor for worse e-PFS (hazard ratio, 7.153; 95% confidence interval, 1.258–40.689; 〈 i 〉 p 〈 /i 〉 = 0.027). In contrast, no significant differences in OS with/without e-PD were observed during the treatment course. In this study, 8 patients experienced e-PD and almost 40% of patients experienced acceptable disease control following subsequent lenvatinib treatment. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Pretreatment 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT may be a useful new predictor of e-PD and may enable early decision-making based on early treatment changes following Atezo/Bev treatment of HCC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000523850
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 4
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    Potential and Clinical Significance of 〈sup〉18〈/sup〉F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Evaluating Liver Cancer Response to Lenvatinib Treatment
    S. Karger AG ; 2021
    In:  Oncology Vol. 99, No. 3 ( 2021), p. 169-176
    Details
    In: Oncology, S. Karger AG, Vol. 99, No. 3 ( 2021), p. 169-176
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The sensitivity of 〈 sup 〉 18 〈 /sup 〉 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT) in hepatocellular carcinoma (HCC) is low; however, clinical evidence demonstrating its prognostic value in patients with HCC has recently been reported. This study aimed to assess the value of 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT as a tool for evaluating the response of HCC to lenvatinib treatment. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We evaluated 11 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT from April 2018 to December 2019. The tumor-to-normal liver ratio (TLR) of the target tumor was measured before and during the course of lenvatinib treatment with 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT (pre and post analysis, respectively), with a TLR ≥2 classified as PET-positive HCC. At the time of each evaluation, we also used the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the modified RECIST (mRECIST), and the tumor marker alfa-fetoprotein (AFP). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 11 patients, 3 (27%) and 8 (73%) had an objective response to lenvatinib treatment at the time of post-analysis by RECIST 1.1 and mRECIST, respectively. There were 3 (27%) and 7 (64%) patients with PET-positive HCC at the time of pre- and post-analysis, respectively. There was a significant correlation between the rates of change in AFP and TLR during lenvatinib treatment ( 〈 i 〉 r 〈 /i 〉 = 0.69, 〈 i 〉 p 〈 /i 〉 = 0.019). Based on these results, we were able to perform liver resection on 4 patients with PET-positive HCC as conversion therapy. Three samples from these patients showed poorly differentiated tumors. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT has potential as an evaluation tool for describing biological tumor behavior and reflecting disease progression, location, and treatment response. This modality may provide useful information for considering prognosis and subsequent therapy.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000510754
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 5
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    The Impact of Lenvatinib on Tumor Blood Vessel Shrinkage of Hepatocellular Carcinoma during Treatment: An Imaging-Based Analysis
    S. Karger AG ; 2023
    In:  Oncology Vol. 101, No. 2 ( 2023), p. 134-144
    Details
    In: Oncology, S. Karger AG, Vol. 101, No. 2 ( 2023), p. 134-144
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan, were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography before treatment and its change over time (2–12 weeks after lenvatinib initiation). The relationship between changes in TBV diameter and prognosis was also examined. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2–12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage ( 〈 i 〉 p 〈 /i 〉 = 0.039). 〈 b 〉 〈 i 〉 Discussion/Conclusion: 〈 /i 〉 〈 /b 〉 Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of TBVs in imaging analysis may be associated with improved prognosis; however, additional studies are still required.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000526976
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
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  • 6
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    Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma
    S. Karger AG ; 2020
    In:  Liver Cancer Vol. 9, No. 6 ( 2020), p. 756-770
    Details
    In: Liver Cancer, S. Karger AG, Vol. 9, No. 6 ( 2020), p. 756-770
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Heterogeneous enhancement patterns ( 〈 i 〉 Type-3 〈 /i 〉 and 〈 i 〉 -4 〈 /i 〉 ), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern ( 〈 i 〉 Type-2 〈 /i 〉 ) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS ( 〈 i 〉 p 〈 /i 〉 = 0.313). Because of significantly worse PPS, overall survival of 〈 i 〉 Type-4 〈 /i 〉 tumor was poor compared to 〈 i 〉 Type-2 〈 /i 〉 or 〈 i 〉 -3 〈 /i 〉 tumors ( 〈 i 〉 p 〈 /i 〉 = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; 〈 i 〉 p 〈 /i 〉 = 0.023), while 〈 i 〉 Type-4 〈 /i 〉 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; 〈 i 〉 p 〈 /i 〉 = 0.039). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.
    Type of Medium: Online Resource
    ISSN: 2235-1795 , 1664-5553
    URL: Article
    DOI: 10.1159/000510299
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
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  • 7
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    Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis
    S. Karger AG ; 2020
    In:  Liver Cancer Vol. 9, No. 3 ( 2020), p. 275-292
    Details
    In: Liver Cancer, S. Karger AG, Vol. 9, No. 3 ( 2020), p. 275-292
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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; 〈 i 〉 p 〈 /i 〉 = 0.037). Multivariate analysis revealed that pretreatment heterogeneous enhancement pattern is an independent predictor for response to lenvatinib (odds ratio, 4.75; 〈 i 〉 p 〈 /i 〉 = 0.042). Presence of OR was associated with longer progression-free survival (PFS) (hazard ratio, 0.36; 〈 i 〉 p 〈 /i 〉 = 0.017), and patients with oncologically aggressive type 3 and 4 tumors showed similar PFS to those harboring type 2 tumors ( 〈 i 〉 p 〈 /i 〉 = 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 ( 〈 i 〉 p 〈 /i 〉 = 0.064), overall survival after introduction of lenvatinib was not statistically different among the three groups of patients ( 〈 i 〉 p 〈 /i 〉 = 0.053). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 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.
    Type of Medium: Online Resource
    ISSN: 2235-1795 , 1664-5553
    URL: Article
    DOI: 10.1159/000505190
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 2666925-0
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