Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

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

Cancers ◽

10.3390/cancers12082146 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2146 ◽

Cited By ~ 3

Author(s):

Kei Endo ◽

Hidekatsu Kuroda ◽

Jo Kanazawa ◽

Takuro Sato ◽

Yudai Fujiwara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Strength ◽

Grip Strength ◽

Cox Proportional Hazards Model ◽

University Hospital ◽

Poor Prognostic Factor ◽

Skeletal Muscle Index ◽

Increased Risk ◽

The Impact

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

10.20944/preprints202007.0320.v1 ◽

2020 ◽

Author(s):

Kei Endo ◽

Hidekatsu Kuroda ◽

Jo Kanazawa ◽

Takuro Sato ◽

Yudai Fujiwara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Strength ◽

Grip Strength ◽

Cox Proportional Hazards Model ◽

University Hospital ◽

Poor Prognostic Factor ◽

Skeletal Muscle Index ◽

Increased Risk ◽

The Impact

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 separately 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 ALBI2b (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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Pretreatment skeletal muscle depletion as an adverse prognostic factor in metastatic gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.161 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 161-161

Author(s):

Hiroko Hasegawa ◽

Kazumasa Fujitani ◽

Yusuke Yamaoka ◽

Motohiro Hirao ◽

Shoichi Nakazuru ◽

...

Keyword(s):

Gastric Cancer ◽

Skeletal Muscle ◽

Prognostic Factor ◽

Cancer Patients ◽

Performance Status ◽

Metastatic Gastric Cancer ◽

First Line ◽

Skeletal Muscle Index ◽

Pre Treatment ◽

The Impact

161 Background: Body composition has emerged as an important prognostic factor in cancer patients. Especially, skeletal mass depletion has been associated with poor performance status, toxicity of chemotherapy and shortened survival in cancer patients. However, the impact of pre-treatment skeletal muscle index on survival or toxicity in metastatic gastric cancer patients remains uncertain. Methods: In this retrospective study, we reviewed 98 metastatic gastric cancer (mGC) patients who received S-1 based combination chemotherapy as first-line treatment from April 2006 to March 2013. Pre-treatment skeletal muscle mass was quantified by CT cross sectional area at the third lumbar vertebrae and evaluated as lumbar skeletal muscle index (SMI) (cm2/m2) after normalization for stature (m2). Patients were categorized into 2 groups depending on initial SMI: 35 patients with SMI ≤ 40 and 63 patients with SMI > 40. Results: Median overall survival was significantly shorter in the SMI ≤ 40 group than in the SMI >40 group (439 days versus 565 days; p= 0.03). Progression free survival was also better in the SMI> 40 group without statistical significance (175 days versus 151 days; p= 0.17). Toxicity (grade 3 or 4) was more common in the SMI ≤ 40 group than in the SMI >40 group. (41.1% versus 11.1%; p=0.001). In multivariate analysis, performance status of 2 (HR 4.711, 95%CI 1.065 to 20.832, p=0.04), presence of primary tumor (HR 2.322, 95%CI 1.007 to 5.357, p=0.04) and pre-treatment SMI (HR 2.525, 95%CI 1.145 to 5.568, p=0.02) were independent prognostic factors for OS. Conclusions: The present study suggests that skeletal muscle depletion at the initiation of first-line chemotherapy might be an independent prognostic factor for mGC patients.

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Clinical results of radiotherapy for hepatocellular carcinoma with tumor thrombosis.

10.21203/rs.2.20265/v1 ◽

2020 ◽

Author(s):

Takuya Nagano ◽

Akihiko Hoshi ◽

Masayuki Kurosaki ◽

Kazuma Toda ◽

Kaoru Tsuchiya ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factor ◽

Treatment Options ◽

Objective Response ◽

Vena Cava ◽

Equivalent Dose ◽

Treatment Modalities ◽

Significant Prognostic Factor ◽

Combined Chemotherapy ◽

Tumor Thrombosis

Abstract Background: The aim of this study was to evaluate the clinical outcome of radiotherapy (RT) for hepatocellular carcinoma (HCC) with the portal vein (PV), hepatic vein (HV), inferior vena cava (IVC), and bile duct (BD) tumor thrombosis (TT). Methods: Patients who received RT for the treatment of a primary tumor and tumor thrombosis at Musahino Red Cross Hospital between 2011 and 2019 were retrospectively reviewed. We compared patient characteristics, radiation dose, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities. Results: We evaluated 43 patients who were treated with RT, 27 of whom received combined chemotherapy with RT. The total equivalent dose in 2 Gy fractions ranged from 42.25 to 72 Gy (median 48.75 Gy). The median follow-up period after RT was 13 months (range of 2–90 months). Multivariate analysis showed that the length of tumor thrombosis was a unique significant prognostic factor for OS (p = 0.01) and the prescribed equivalent dose of more than 48.75 Gy significantly contributed to ORRs (p = 0.02). When compared, the one-year OS rates of responders (n = 25) and non-responders (n = 18) were 75% and 35%, respectively (p = 0.009). The odds ratio of ORRs between the two total dose groups (42.35 Gy versus more than 48.75 Gy) was 9.8 (95% CI [2.1, 58.9], p = 0.001). Combined chemotherapy with RT was a prognostic factor for OS (p = 0.03), but it was not correlated with response rate (p = 0.53). Conclusion: Local control of tumor thrombosis was found to be a significant prognostic factor for OS in patients with HCC and its tumor thrombosis. Although various drug and treatment options for tumor thrombosis exist, RT provides a better OS.

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Effect of Handgrip Strength on Clinical Outcomes of Patients with Hepatocellular Carcinoma Treated with Lenvatinib

Applied Sciences ◽

10.3390/app10165403 ◽

2020 ◽

Vol 10 (16) ◽

pp. 5403

Author(s):

Yurika Kotoh ◽

Issei Saeki ◽

Takahiro Yamasaki ◽

Ryo Sasaki ◽

Norikazu Tanabe ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Prognostic Factors ◽

Clinical Outcomes ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Handgrip Strength ◽

Significant Prognostic Factor ◽

Skeletal Muscle Index ◽

The Individual

Previous studies have reported prognostic factors for hepatocellular carcinoma (HCC) patients receiving lenvatinib; however, no studies have evaluated the effects of both handgrip strength and skeletal muscle mass on the clinical outcomes. Therefore, this retrospective study investigated the individual effect of handgrip strength, skeletal muscle mass, and sarcopenia on clinical outcomes of 53 HCC patients treated with lenvatinib. Before receiving lenvatinib, handgrip strength and skeletal muscle index (SMI) were measured. Low handgrip strength and muscle depletion were defined as <26 and <18 kg and SMI <42 and SMI <38 cm2/m2 in men and women, respectively. Sarcopenia was defined as having low handgrip strength and muscle depletion. Multivariate analysis identified modified albumin–bilirubin grade 1–2a (p = 0.010), Barcelona Clinic Liver Cancer stage A–B (p = 0.011), and absence of low handgrip strength (p = 0.015) as favorable prognostic factors for survival. Furthermore, sarcopenia was an independent significant prognostic factor for survival. Time to treatment failure was associated with handgrip strength and sarcopenia. Our findings suggest that handgrip strength may be a useful marker of clinical outcomes in HCC patients treated with lenvatinib.

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The impact of inflammatory biomarkers, BMI, and sarcopenia on survival in advanced hepatocellular carcinoma treated with immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.553 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 553-553

Author(s):

Mehmet Akce ◽

Yuan Liu ◽

Katerina Mary Zakka ◽

Dylan J. Martini ◽

Amber Draper ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Cox Regression ◽

Statistical Significance ◽

Inflammatory Biomarkers ◽

Advanced Hepatocellular Carcinoma ◽

Skeletal Muscle Index ◽

The Impact ◽

Baseline Bmi ◽

Gender Specific

553 Background: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of inflammatory biomarkers, BMI and sarcopenia on survival in advanced hepatocellular carcinoma (HCC) patients treated with immunotherapy. Methods: We performed a retrospective review of advanced HCC patients treated with immunotherapy-based therapies at Winship Cancer Institute between 2015 and 2019. Baseline computed tomography and magnetic resonance imaging scans were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m)2. Gender-specific sarcopenia was defined by median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall Survival (OS) was set as primary outcome and Cox proportional hazard model was performed. Results: 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% ECOG PS 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9%. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 vs. 14.3 months in sarcopenic vs. non-sarcopenic patients (p=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25 respectively (p=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil to lymphocyte ratio (NLR) ≥ 5.15 vs. NLR < 5.15 (p<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (HR: 4.17, 1.52-11.39, p=0.005). Gender specific sarcopenia showed a trend of worse OS (HR: 1.71, 0.73-4.00, p=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.73, 1.15-6.53, p=0.023). In the association with PFS, neither baseline BMI nor gender specific sarcopenia showed statistical significance. Conclusions: Baseline BMI and NLR may predict OS after immunotherapy treatment. After controlling for baseline Child Pugh Score and NLR, gender specific sarcopenia was not associated with OS significantly.

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Sarcopenia Evaluated Using the Skeletal Muscle Index Is a Significant Prognostic Factor for Metastatic Urothelial Carcinoma

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2015.07.015 ◽

2016 ◽

Vol 14 (3) ◽

pp. 237-243 ◽

Cited By ~ 38

Author(s):

Satoru Taguchi ◽

Nobuhiko Akamatsu ◽

Tohru Nakagawa ◽

Wataru Gonoi ◽

Atsushi Kanatani ◽

...

Keyword(s):

Skeletal Muscle ◽

Prognostic Factor ◽

Urothelial Carcinoma ◽

Significant Prognostic Factor ◽

Skeletal Muscle Index ◽

Metastatic Urothelial Carcinoma

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Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients

Diagnostics ◽

10.3390/diagnostics9040206 ◽

2019 ◽

Vol 9 (4) ◽

pp. 206 ◽

Cited By ~ 2

Author(s):

Naomi Nakayama ◽

Kentaro Nakayama ◽

Kohei Nakamura ◽

Sultana Razia ◽

Satoru Kyo

Keyword(s):

Ovarian Cancer ◽

Skeletal Muscle ◽

Cancer Patients ◽

Disease Free Survival ◽

Muscle Volume ◽

Muscle Quality ◽

Prognostic Impact ◽

Poor Prognostic Factor ◽

Skeletal Muscle Index ◽

The Impact

Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival (p = 0.329 and p = 0.3370, respectively) or poor overall survival (p = 0.921 and p = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer.

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Prognostic role of computed tomography-based, artificial intelligence-driven waist skeletal muscle volume in uterine endometrial carcinoma

Insights into Imaging ◽

10.1186/s13244-021-01134-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Se Ik Kim ◽

Joo Yeon Chung ◽

Haerin Paik ◽

Aeran Seol ◽

Soon Ho Yoon ◽

...

Keyword(s):

Artificial Intelligence ◽

Computed Tomography ◽

Skeletal Muscle ◽

Endometrial Cancer ◽

Survival Rate ◽

Muscle Volume ◽

Survival Outcomes ◽

Poor Prognostic Factor ◽

Skeletal Muscle Index ◽

The Impact

Abstract Objectives To investigate the impact of computed tomography (CT)-based, artificial intelligence-driven waist skeletal muscle volume on survival outcomes in patients with endometrial cancer. Methods We retrospectively identified endometrial cancer patients who received primary surgical treatment between 2014 and 2018 and whose pre-treatment CT scans were available (n = 385). Using an artificial intelligence-based tool, the skeletal muscle area (cm2) at the third lumbar vertebra (L3) and the skeletal muscle volume (cm3) at the waist level were measured. These values were converted to the L3 skeletal muscle index (SMI) and volumetric SMI by normalisation with body height. The relationships between L3, volumetric SMIs, and survival outcomes were evaluated. Results Setting 39.0 cm2/m2 of L3 SMI as cut-off value for sarcopenia, sarcopenia (< 39.0 cm2/m2, n = 177) and non-sarcopenia (≥ 39.0 cm2/m2, n = 208) groups showed similar progression-free survival (PFS; p = 0.335) and overall survival (OS; p = 0.241). Using the median value, the low-volumetric SMI group (< 206.0 cm3/m3, n = 192) showed significantly worse PFS (3-year survival rate, 77.3% vs. 88.8%; p = 0.004) and OS (3-year survival rate, 92.8% vs. 99.4%; p = 0.003) than the high-volumetric SMI group (≥ 206.0 cm3/m3, n = 193). In multivariate analyses adjusted for baseline body mass index and other factors, low-volumetric SMI was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.762; 95% CI, 1.051–2.953; p = 0.032) and OS (adjusted HR, 5.964; 95% CI, 1.296–27.448; p = 0.022). Conclusions Waist skeletal muscle volume might be a novel prognostic biomarker in patients with endometrial cancer. Assessing body composition before treatment can provide important prognostic information for such patients.

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Immunotherapy in Hepatocellular Carcinoma

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00886-5 ◽

2021 ◽

Vol 22 (10) ◽

Cited By ~ 1

Author(s):

Claudia A. M. Fulgenzi ◽

Thomas Talbot ◽

Sam M. Murray ◽

Marianna Silletta ◽

Bruno Vincenzi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Treatment Options ◽

Predictive Biomarkers ◽

Intermediate Stage ◽

Routine Practice ◽

Advanced Hcc

Opinion statementPatients with hepatocellular carcinoma (HCC) have been traditionally deprived from highly effective systemic therapy options in the past decades. The multi-targeted tyrosine kinase inhibitor sorafenib, approved in 2008, remained the only treatment option for advanced HCC for over a decade. A number of molecularly targeted therapies such as lenvatinib, regorafenib, cabozantinib, and ramucirumab have significantly widened treatment options in patients with advanced HCC. However, emergence of resistance and long-term toxicity from treatment are barriers to long-term survivorship. Immunotherapy is at the focus of intense research efforts in HCC. Whilst targeting of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte 4 (CTLA-4) is associated with radiologically measurable disease-modulating effects in HCC, monotherapies fell short of demonstrating evidence of significant survival extension in advanced disease. Atezolizumab and bevacizumab were the first immunotherapy regimen to demonstrate clear superiority in improving the survival of patients with unresectable HCC compared to sorafenib, paving the way for immunotherapy combinations. As the treatment landscape of HCC rapidly evolves, with immunotherapy integrating within early- and intermediate-stage disease treatment algorithms, lack of level 1 evidence on sequencing of therapeutic strategies and lack of head-to-head comparisons across immunotherapy combinations will affect prescribing of immunotherapy in routine practice. In the absence of predictive biomarkers, choice of immunotherapy over kinase inhibitors will continue to remain an empirical exercise, guided by balancing anti-tumour efficacy with toxicity considerations in the individual patient.

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