Dataset Information

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.

ABSTRACT:

Background

Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib.

Methods

We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively. Muscle depletion was defined as an SMI value < 42 cm²/m² in men and < 38 cm²/m² in women. High VFA (H-VFA) was defined as a value ?100 cm². In addition to SMI and VFA, we also analyzed various clinical parameters as potential prognostic factors.

Results

Multivariate analysis showed that having a tumor number < 7 (hazard ratio [HR] = 0.409, p < 0.001), absence of extrahepatic spread (EHS) (HR = 0.562, p < 0.001), absence of muscle depletion (HR = 0.498, p = 0.006), and H-VFA (HR = 0.556, p = 0.031) were significant factors for long-term survival. Therefore, we evaluated the prognosis of those with no muscle depletion with H-VFA. The no muscle depletion with H-VFA group showed significantly longer survival than the other group (median survival time 15.6 vs. 11.0 months, p = 0.003). Multivariate analysis showed that having a tumor number < 7 (HR = 0.454, p = 0.001), absence of EHS (HR = 0.511, p = 0.008), and no muscle depletion with H-VFA (HR = 0.454, p = 0.002) were significant predictors of survival.

Conclusions

We identified no muscle depletion with H-VFA as a novel biomarker for advanced HCC patients treated with sorafenib.

SUBMITTER: Saeki I

PROVIDER: S-EPMC6249591 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.

Saeki Issei I Yamasaki Takahiro T Maeda Masaki M Kawano Reo R Hisanaga Takuro T Iwamoto Takuya T Matsumoto Toshihiko T Hidaka Isao I Ishikawa Tsuyoshi T Takami Taro T Sakaida Isao I

Liver cancer 20180406 4

<h4>Background</h4>Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib.<h4>Methods</h4>We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) ...[more]

PMID: 30488024

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Project description:BackgroundPhase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC.Materials and methodsPatients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ?60 days after diagnosis.ResultsOf 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter.ConclusionSurvival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit.Implications for practiceThe findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.

Project description:Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33-4.17; p = 0.003), total dose (0.44: 0.27-0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53-3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients.

Dataset Information

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.

Background

Methods

Results

Conclusions

Publications

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.

Similar Datasets

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