Skeletal Muscle Mass Influences Tolerability and Prognosis in Hepatocellular Carcinoma Patients Treated with Lenvatinib

Uojima, Haruki; Chuma, Makoto; Tanaka, Yoshiaki; Hidaka, Hiroyoshi; Nakazawa, Takahide; Iwabuchi, Shogo; Kobayashi, Satoshi; Hattori, Nobuhiro; Ogushi, Katsuaki; Morimoto, Manabu; Kagawa, Tatehiro; Tanaka, Katsuaki; Kako, Makoto; Koizumi, Wasaburo

doi:10.1159/000504604

Cited by 69 publications

(103 citation statements)

References 28 publications

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“…Furthermore, a cohort study of European Caucasian cirrhotic patients with advanced HCC treated with sorafenib showed that low SMI was a predictor of reduced survival and cancer treatment toxicity [ 58 ]. Recently, Uojima et al showed the number of severe adverse advents during the first two months of lenvatinib treatment was significantly associated with low SMI in 100 patients with HCC [ 59 ]. Low muscle mass has been already demonstrated to be a strong and independent risk factor for mortality in advanced HCC patients [ 60 ].…”

Section: Implications Of Muscle Wasting In Clinical Outcomes In Pamentioning

confidence: 99%

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges

Rinninella

Cintoni²,

Raoul

et al. 2020

Nutrients

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In cancer patients, loss of muscle mass is significantly associated with low tolerability of chemotherapy and poor survival. Despite the great strides in the treatment of cancer, targeted therapies such as tyrosine kinase inhibitors (TKIs) could exacerbate muscle wasting. Over recent years, the impact of skeletal muscle loss during TKI therapy on clinical outcomes has been in the spotlight. In this review, we focus on the different molecular pathways of TKIs potentially involved in muscle wasting. Then, we report the results of the studies assessing the effects of different TKI therapies—such as sorafenib, regorafenib, sunitinib, and lenvatinib—on muscle mass, and highlight their potential clinical implications. Finally, we discuss an integrative nutritional approach to be adopted during TKI treatment. The assessment of muscle mass from computerized tomography imaging could be helpful in predicting toxicity and prognosis in patients treated with TKI such as sorafenib. Early recognition of low muscle mass and effective personalized nutritional support could prevent or attenuate muscle mass wasting. However, the role of nutrition is still overlooked, and future clinical trials are needed to find the optimal nutritional support to countermeasure muscle mass depletion during TKI therapy.

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Section: Implications Of Muscle Wasting In Clinical Outcomes In Pamentioning

confidence: 99%

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges

Rinninella

Cintoni²,

Raoul

et al. 2020

Nutrients

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“…Recently, sarcopenia has been recognized as a poor prognostic factor in various fields of clinical medicine, including cancer [ 4 , 5 , 6 ]. Sarcopenia has been reported to worsen the prognosis of patients, with u-HCC patients treated with sorafenib and lenvatinib [ 7 , 8 , 9 , 10 ]. Chronic liver disease (CLD), the underlying disease of HCC, is considered a representative cause of secondary sarcopenia, as the liver is a central organ of nutrient metabolism [ 3 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Endo

Kuroda

Kanazawa

et al. 2020

Cancers

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Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We evaluated the impact of sarcopenia-related factors (grip strength (GS) and the skeletal muscle index (SMI)) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that modified albumin-bilirubin-grade (mALBI) 2b (hazard ratio (HR) 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

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“…Moreover, the selection bias was correlated with the outcome. The multivariate analysis showed that an SNP combination pattern of the NOS3 rs2070744 and FGFR4 rs351855 genotypes was an independent factor of lenvatinib response, and a previous report showed that the factors significantly associated with poor OS included skeletal muscle mass index and ALBI grade 42 . Second, there was no control arm in the present study.…”

Section: Discussionmentioning

confidence: 72%

Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib

Azuma

Uojima

Chuma

et al. 2020

Sci Rep

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We investigated whether or not nitric oxide synthase 3 (NOS3) rs2070744 genotypes can affect the response for lenvatinib treatment in patients with hepatocellular carcinoma (HCC). We evaluated the relation of the NOS3 rs2070744 genotypes to the tumor response, progression-free survival (PFS), and overall survival (OS) as the response for lenvatinib. We also examined the association between fibroblast growth factor receptor (FGFR) gene polymorphisms, a potential feature of lenvatinib, and the response. There were no significant differences between the studies for either PFS or OS, even though patients with the TT genotype had a longer mean PFS (hazard ratio [HR] 0.60; p = 0.069) and mean OS (HR 0.46; p = 0.075) than those with the TC/CC genotypes. However, patients with a single-nucleotide polymorphism (SNP) combination pattern of the NOS3 rs2070744 TC/CC and FGFR4 rs351855 CT/TT genotypes had a significantly shorter mean PFS (HR 2.56; p = 0.006) and mean OS (HR 3.36; p = 0.013) than those with the other genotypes. The NOS3 rs2070744 genotypes did not influence the clinical response. However, the SNP combination pattern of the NOS3 rs2070744 and FGFR4 rs351855 genotypes may be helpful as treatment effect predictors and prognostic factors for HCC patients treated with lenvatinib.

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Skeletal Muscle Mass Influences Tolerability and Prognosis in Hepatocellular Carcinoma Patients Treated with Lenvatinib

Cited by 69 publications

References 28 publications

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges

Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib

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