Impact of the branched‐chain amino acid to tyrosine ratio and branched‐chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Kitabatake, Shusuke; Yama, Tsuyoki

doi:10.1111/jgh.12954

Cited by 25 publications

(32 citation statements)

References 35 publications

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“…Mizuguchi et al 15 previously reported that pre‐treatment BTR could be a useful marker to predict postoperative complications, disease‐free survival, and OS of HCC patients after hepatectomy. Tada et al 16 also reported that low pre‐treatment BTR (≤4.4) was significantly associated with poor prognosis in patients with HCC. These reports indicate that BTR is not only a crucial nutritional indicator, but also a prognostic factor for patients with HCC.…”

Section: Discussionmentioning

confidence: 97%

Branched‐chain amino acid to tyrosine ratio is an essential pre‐treatment factor for maintaining sufficient treatment intensity of lenvatinib in patients with hepatocellular carcinoma

Eso

Nakano

Mishima

et al. 2020

J Hepato Biliary Pancreat

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More than 500 000 cases of hepatocellular carcinoma (HCC) are diagnosed every year; and HCC is one of the leading causes of cancer-related deaths worldwide. 1 For patients with early-stage HCC, either surgical resection or ablation are offered. 2 However, the treatment options for unresectable advanced-stage HCC are limited, and the prognosis is still poor because of the high potential for intra-and extra-hepatic recurrence. An oral tyrosine kinase inhibitor sorafenib was approved in 2007 as the first

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Section: Discussionmentioning

confidence: 97%

Branched‐chain amino acid to tyrosine ratio is an essential pre‐treatment factor for maintaining sufficient treatment intensity of lenvatinib in patients with hepatocellular carcinoma

Eso

Nakano

Mishima

et al. 2020

J Hepato Biliary Pancreat

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“…Although there was no significant correlation between the CONUT score and PFS in lenvatinib treatment in our study (p = 0.1505), it may be worth reconsidering in a more extensive cohort study. The impact of BTR as a prognostic factor in patients with HCC or liver cirrhosis was well documented [23][24][25]. Tada et al recently reported that BCAA therapy improved both OS and disease-specific survival in HCC patients with low BTR levels [25].…”

Section: Discussionmentioning

confidence: 99%

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Eso

Nakano

Mishima

et al. 2019

Cancers

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Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 days) by comparing the relationship between 2M-DBR, 2M-RDI (RDI at 60 days), and the therapeutic response. The therapeutic response to lenvatinib was evaluated in 45 patients who underwent computed tomography 8-12 weeks after treatment initiation. We also investigated the clinical factors associated with high 2M-DBR. The area under the receiver operating characteristic of 2M-DBR that predicts the response to lenvatinib was higher than that of 2M-RDI (0.8004 vs. 0.7778). Patients with high 2M-DBR achieved significantly better objective responses and disease control rates than those with low 2M-DBR (p < 0.0001 and 0.0008). Patients with high 2M-DBR experienced significantly longer progression-free survival (PFS) than those with low 2M-DBR (p = 0.0001), while there was no significant correlation between 2M-RDI levels and PFS (p = 0.2198). Patients who achieved higher levels of 2M-DBR had a significantly better modified ALBI grade (p = 0.0437), better CONUT score (p = 0.0222), and higher BTR (p = 0.0281). Multivariate analysis revealed that high 2M-DBR was the only significant factor associated with longer PFS. In conclusion, 2M-DBR could be an important factor that reflects treatment intensity and useful for predicting the response to lenvatinib against HCC, instead of 2M-RDI.Cancers 2020, 12, 49 2 of 12 based on the two Phase III studies [4,5]. However, due to its various adverse events (AEs) and limited efficacy, identification of novel MTA compounds has been required. Recently, lenvatinib (Lenvima ® , Eisai Co., Ltd., Tokyo, Japan) was approved as a novel first-line MTA for unresectable HCC in the EU, USA, and Asia, including Japan, China, Korea, and Taiwan, based on the Phase III REFLECT trial [6].In order to optimize and maximize the therapeutic effects of pharmacotherapy, especially in the case of anticancer drug treatment, it is essential to appropriately evaluate the patient's condition before administration, sufficiently manage AEs after initiation, and keep the dose intensity (DI) high. The practicality of relative dose intensity (RDI), calculated as the percentage of the delivered DI divided by the standard DI, has been shown to be an indicator of the treatment intensity of anticancer drugs [7]. The correlations between RDI and therapeutic efficacy were reported in various types of cancers, including breast cancer [8], pancreatic ductal adenocarcinoma [9], renal cell carcinoma [10], malignant lymphoma [11], and HCC [12]. However, since lenvatinib is the first oral MTA that is dosed by the patient's weight (8 mg once...

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“…9 Various clinical markers such as age, sex, tumour marker levels (eg α-foetoprotein), liver function, liver fibrosis and HCC stage have been reported as predictors of survival in patients treated with treatment of HCC. 1,3,[10][11][12][13] However, predictors of survival in patients with unresectable HCC treated with lenvatinib have not been sufficiently investigated.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil‐to‐lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib

Tada

Kumada

Hiraoka

et al. 2020

Liver International

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Background and aims Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil‐to‐lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. Methods A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut‐off NLR levels for associating overall survival using hazard ratio (HR) spline curves. Results Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097‐3.119), α‐foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188‐3.265) and modified albumin‐bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267‐3.555) were independently associated with overall survival. Cumulative progression‐free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268‐2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028‐2.236) were independently associated with progression‐free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0‐4.5 is an appropriate cut‐off for associating overall survival. Conclusions NLR can be associated with outcomes in patients with HCC treated with lenvatinib.

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Impact of the branched‐chain amino acid to tyrosine ratio and branched‐chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis

Abstract: Intervention involving BCAA therapy improved survival in patients with HCC versus untreated controls, regardless of BTR. In addition, low BTR was associated with poor prognosis in patients who did not receive BCAA therapy.

Cited by 25 publications

References 35 publications

Branched‐chain amino acid to tyrosine ratio is an essential pre‐treatment factor for maintaining sufficient treatment intensity of lenvatinib in patients with hepatocellular carcinoma

Branched‐chain amino acid to tyrosine ratio is an essential pre‐treatment factor for maintaining sufficient treatment intensity of lenvatinib in patients with hepatocellular carcinoma

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Neutrophil‐to‐lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib

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