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      Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index

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          Abstract

          Introduction

          Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.

          Methods

          We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm 2/m 2 (male) and < 33.9 cm 2/m 2 (female) using ROC curve.

          Results

          Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia ( P< 0.001), decreasedBMI and SMI during chemotherapy ( P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia ( P< 0.001) and decreased SMI ( P = 0.001), the OS of female patients was influenced with overweight at diagnosis ( P = 0.006), decreased BMI ( P = 0.032) and decreased SMI ( P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI ( P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002).

          Conclusions

          Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.

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          Most cited references13

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          Epidemiology of sarcopenia among the elderly in New Mexico.

          Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.
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            Appendicular skeletal muscle mass: effects of age, gender, and ethnicity.

            This study tested the hypothesis that skeletal muscle mass is reduced in elderly women and men after adjustment first for stature and body weight. The hypothesis was evaluated by estimating appendicular skeletal muscle mass with dual-energy X-ray absorptiometry in a healthy adult cohort. A second purpose was to test the hypothesis that whole body 40K counting-derived total body potassium (TBK) is a reliable indirect measure of skeletal muscle mass. The independent effects on both appendicular skeletal muscle and TBK of gender (n = 148 women and 136 men) and ethnicity (n = 152 African-Americans and 132 Caucasians) were also explored. Main findings were 1) for both appendicular skeletal muscle mass (total, leg, and arm) and TBK, age was an independent determinant after adjustment first by stepwise multiple regression for stature and weight (multiple regression model r2 = approximately 0.60); absolute decrease with greater age in men was almost double that in women; significantly larger absolute amounts were observed in men and African-Americans after adjustment first for stature, weight, and age; and >80% of within-gender or -ethnic group between-individual component variation was explained by stature, weight, age, gender, and ethnicity differences; and 2) most of between-individual TBK variation could be explained by total appendicular skeletal muscle (r2 = 0.865), whereas age, gender, and ethnicity were small but significant additional covariates (total r2 = 0.903). Our study supports the hypotheses that skeletal muscle is reduced in the elderly and that TBK provides a reasonable indirect assessment of skeletal muscle mass. These findings provide a foundation for investigating skeletal muscle mass in a wide range of health-related conditions.
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              Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients

              Background: Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib. Methods: Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation. Results: Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m−2. Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m−2 experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3–13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009). Conclusion: Patients with sarcopenia and a BMI<25 kg m−2 experienced significantly more DLTs during the first cycle of treatment.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 October 2015
                2015
                : 10
                : 10
                : e0139749
                Affiliations
                [1 ]Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
                [2 ]Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
                Centro Nacional de Investigaciones Oncológicas (CNIO), SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: YC DYO. Performed the experiments: YC DYO TK KHL SWH SAI TYK. Analyzed the data: YC DYO TK KHL SWH SAI TYK. Contributed reagents/materials/analysis tools: YC DYO TK KHL SWH SAI TYK YJB. Wrote the paper: YC DYO.

                [¤]

                Current address: Department of Internal Medicine, Dongguk University Gyeongju Hospital, Gyeongsangbuk-do, Korea

                Article
                PONE-D-15-21303
                10.1371/journal.pone.0139749
                4593598
                26437072
                4a829ff9-eba5-42f8-8fc0-76c845c994f5
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 19 May 2015
                : 15 September 2015
                Page count
                Figures: 4, Tables: 6, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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