Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Lee, Jie; Lin, Joseph; Wu, Meng‐Hao; Jan, Ya‐Ting; Chang, Chih‐Long; Huang, Chueh-Yi; Sun, Fang‐Ju; Chen, Yu-Jen

doi:10.1002/jcsm.12440

Cited by 53 publications

(73 citation statements)

References 70 publications

(235 reference statements)

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“…Modulations of muscle IL4/IL4R and IL13/IL13R, as well as of IL4 and IL13 plasma levels, showed that the signalling dependent on these cytokines is likely altered in the C26‐bearing mice, supporting the possibility of improper FAP behaviour and functions. In this regard, an intriguing hypothesis is that FAP degeneration to adipocyte‐like phenotype could contribute to myosteatosis, a common feature in patients affected by chronic inflammation and cachexia . A detailed analysis of muscle biopsies obtained from cancer patients reported intramyocellular lipid droplets and large accumulation of neutral lipids in connective tissues in the rectus abdominis .…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Costamagna¹,

Duelen²,

Penna

et al. 2020

J cachexia sarcopenia muscle

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Background Anorexia, body wasting, inflammation, muscle, and adipose tissue loss are hallmarks of cancer cachexia, a syndrome that affects the majority of cancer patients, impairing their ability to endure chemotherapeutic therapies and reducing their lifespan. In the last 10 years, alterations of protein turnover and impairment of adult myogenesis have been proposed as major contributing factors. Methods Muscle stem cells, including satellite cells, mesoangioblasts, and fibroadipogenic progenitors, were isolated and characterized from C26 colon carcinoma‐bearing (C26) mice. Circulating levels of interleukin‐4/13 (IL4/IL13) were analysed by ELISA, and the effects of IL4 on muscle mass and function, protein synthesis, muscle regeneration, and myogenic progenitor cell number were analysed at both functional (treadmill and grip test) and molecular levels (qRT–PCR, immunofluorescence analysis, surface sensing of translation, and western blot). The Kaplan–Meier test was used to analyse the survival curve of IL4‐treated and IL4‐untreated C26 mice. Results The administration of IL4 to C26 mice rescued muscle mass by increasing protein synthesis. The IL4 treatment improved performances and prolonged survival of C26 mice. IL4 administration re‐established both number and function of satellite cells and fibroadipogenic progenitors without affecting mesoangioblasts in C26 mice, rescuing myogenesis. Upon IL4 treatment, a high number of cytotoxic lymphocytes and type II macrophages were observed with a subsequent increase in necrotic areas of C26 tumours. Conclusions The results here presented shed new light on IL4 signalling during muscle wasting and early stages of muscle regeneration that explain the beneficial effect observed in IL4‐treated C26 mice. These findings might aid to develop therapeutic approaches to improve mobility and quality of life in cachectic patients.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Costamagna¹,

Duelen²,

Penna

et al. 2020

J cachexia sarcopenia muscle

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“…Previous studies demonstrated that myosteatosis, evidenced by a decrease of skeletal muscle radiodensity, was associated with adverse outcomes in various types of cancers [10,23,24]. Kroenke and colleagues demonstrated that in patients with CRC, low SMR was associated with higher overall and CRC-specific mortality [25].…”

Section: Discussionmentioning

confidence: 99%

“…The impact of skeletal muscle depletion (known as sarcopenia) or decreased skeletal muscle radiodensity (known as myosteatosis) has been investigated in various cancers with respect to chemotherapy-or chemoradiotherapy-induced toxicities or survival [6][7][8][9][10]. Sarcopenia, myosteatosis, and visceral obesity have demonstrated substantial value as prognosticators in a number of studies on various cancers including CRC [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer

Chung

Lee

Cho

et al. 2019

Cancers

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The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), −19% (p < 0.001), −3.4% (p = 0.936), and −11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at −2% and −2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel–Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15–0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14–0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.

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“…Although the CT abdominal region is the most frequently used point, there are also studies using peripheral CT for SM evaluation, such as the mid‐thigh image (Lee, Lin, et al , 2019). However, studies reporting peripheral CT approach both in healthy and diseased individuals also take advantage on the examination prescription for clinical diagnosis (i.e.…”

Section: Resultsmentioning

confidence: 99%

Assessing skeletal muscle radiodensity by computed tomography: An integrative review of the applied methodologies

Poltronieri

Paula

Chaves

2020

Clin Physio Funct Imaging

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Low‐radiodensity skeletal muscle has been related to the degree of muscle fat infiltration and seems to be associated with worse outcomes. The aim of this study was to summarize the methodologies used to appraise skeletal muscle radiodensity by computed tomography, to describe the terms used in the literature to define muscle radiodensity and to give recommendations for its measurement standardization. An integrative bibliographic review in four databases included studies published until August 2019 in Portuguese, English or Spanish and performed in humans, adults and/or the elderly, of both sex, which investigated skeletal muscle radiodensity through computed tomography (CT) of the region between the third and fifth lumbar vertebrae and evaluated at least two muscular groups. One hundred and seventeen studies were selected. We observed a trend towards selecting all abdominal region muscle. A significant methodological variation in terms of contrast use, selection of skeletal muscle areas, radiodensity ranges delimitation and their cut‐off points, as well as the terminologies used, was also found. The methodological differences detected are probably due to the lack of more precise information about the correlation between skeletal muscle radiodensity by CT and its molecular composition, among others. Therefore, until the gaps are addressed in future studies, authors should avoid arbitrary approaches when reporting skeletal muscle radiodensity, especially when it comes to prognosis inference. Studies using both CT and direct methods of muscle composition evaluation are encouraged, to enable the definition and validation of the best approach to classify fat‐infiltrated muscle tissue, which will favour the nomenclature uniformization.

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Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Cited by 53 publications

References 70 publications

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer

Assessing skeletal muscle radiodensity by computed tomography: An integrative review of the applied methodologies

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