Rapid Depletion of Subcutaneous Adipose Tissue during Sorafenib Treatment Predicts Poor Survival in Patients with Hepatocellular Carcinoma

Abstract

<jats:p>The aim of this study was to assess the annualized changes in body composition, including skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before, during, and after sorafenib treatment in patients with hepatocellular carcinoma (HCC). This retrospective study evaluated 61 HCC patients treated with sorafenib. Annualized changes (Δ; cm2/m2/year) in skeletal muscle index (SMI), SAT index (SATI), and VAT index (VATI), which were defined as the cross-sectional areas (cm2) of those areas on computed tomography normalized by the square of one’s height (m2), before (pre), during (during), and after (post) sorafenib treatment, were calculated. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion group and the effects of these values on survival were analyzed using the Kaplan-Meier analysis and Cox proportional-hazards model. Annualized depletion rates of SMI (ΔSMIpre: −3.5, ΔSMIduring: −3.5, ΔSMIpost: −8.0) and VATI (ΔVATIpre: −3.2, ΔVATIduring: −2.8, ΔVATIpost: −15.1) accelerated after the cancellation of sorafenib, whereas that of SATI (ΔSATIpre: −4.8, ΔSATIduring; −7.6, ΔSATIpost; −8.0) had already accelerated during sorafenib treatment. Patients with rapid depletion of ΔSATIduring experienced significantly worse survival rates (p &lt; 0.001), and it was an independent predictor of survival (p = 0.009), together with therapeutic effect (p &lt; 0.001). Rapid depletion of SAT during sorafenib treatment can be used to predict survival in patients with HCC.</jats:p>

Prognostic value of low skeletal muscle mass in hepatocellular carcinoma patients treated with sorafenib or lenvatinib: A meta-analysis

“…18 records didn't meet the inclusion criteria and were discarded: 2 involving other kinase inhibitors (Nault et al, 2013[ 28 ], 2015[ 29 ]), 9 with overlapped patient data (Antonelli et al, 2018[ 2 ]; Gigante et al, 2015[ 13 ]; Hoshino et al, 2015[ 16 ]; Imai et al, 2015[ 17 ], 2019[ 19 ]; Labeur et al, 2018[ 23 ][ 24 ]; Okada et al, 2019[ 33 ]; Saeki et al, 2019[ 34 ]), 5 lacking HR and 95 % CI (Mir et al, 2012[ 26 ]; Okada et al, 2020[ 32 ]; Saeki et al, 2018[ 35 ]; Uchikawa et al, 2020[ 39 ]; Ueki et al, 2016[ 40 ]), 1 without any interesting outcome (Cheng et al, 2019[ 7 ]) and 1 with low quality and faulty data (Nishikawa et al, 2017[ 30 ]). Thus, 11 retrospective studies (Antonelli et al, 2018[ 3 ]; Endo et al, 2020[ 10 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Labeur et al, 2019[ 25 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Takada et al, 2018[ 38 ]; Uojima et al, 2020[ 41 ]; Wu et al, 2021[ 43 ]; Yamashima et al, 2017[ 45 ]) were included in this meta-analysis, comprising 1148 patients. The flow diagram of this study selection process is shown in Figure 1 (Fig.…”

“…The main results of the crude and adjusted pooled analysis are reported in Figure 2A and 2B (Fig. 2) (References in Figure 2: Antonelli et al, 2018[ 3 ]; Endo et al, 2020[ 10 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Labeur et al, 2019[ 25 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Takada et al, 2018[ 38 ]; Uojima et al, 2020[ 41 ]; Wu et al, 2020[ 43 ]; Yamashima et al, 2017[ 45 ]) respectively. Ten studies involving 1028 patients provided the crude HRs and 95 % CIs of the association between the LSMM and HCC patients treated with sorafenib or lenvatinib (Antonelli et al, 2018[ 3 ]; Endo et al, 2020[ 10 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Labeur et al, 2019[ 25 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Takada et al, 2018[ 38 ]; Uojima et al, 2020[ 41 ]; Yamashima et al, 2017[ 45 ]).…”

“…2) ). Eight studies involving 661 patients provided the adjusted HRs and 95 % CIs (Antonelli et al, 2018[ 3 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Uojima et al, 2020[ 41 ]; Wu et al, 2021[ 43 ]; Yamashima et al, 2017[ 45 ]). One of these studies defined LSMM based on TSM, PM, and RA indices and provided three different corresponding HRs (Wu et al, 2021[ 43 ]), so three adjusted pooled results were obtained.…”

“…When stratifying by types of TKIs, we found significantly negative impact of LSMM on OS in patients treated with sorafenib (p<0.00001), but there was no significant association in patients treated with lenvatinib (p=0.06), probably because of the small number of included studies (n=2) (Figure 4A (Fig. 4) ; References in Figure 4: Antonelli et al, 2018[ 3 ]; Endo et al, 2020[ 10 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Labeur et al, 2019[ 25 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Takada et al, 2018[ 38 ]; Uojima et al, 2020[ 41 ]; Wu et al, 2020[ 43 ]; Yamashima et al, 2017[ 45 ]). Then, we did not find other subgroup analyses to be a significant effect modifier for the association between LSMM and OS (Figure 4 (Fig.…”

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

“…Recently, the prognostic impact of changes in body composition caused by sorafenib has been reported. Previous retrospective studies reported that the rapid depletion of skeletal muscle mass or subcutaneous adipose tissue was a poor prognostic factor for u-HCC patients treated with sorafenib [ 26 , 27 ]. In the present study, we evaluated the skeletal muscle condition only at the start of lenvatinib, so a further study is needed to confirm the prognostic impact of the changes in the body composition, including adipose tissue and muscle, in u-HCC patients treated with lenvatinib.…”