Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients

Viganò, Antonio; Morais, José A.; Ciutto, Lorella; Rosenthall, Léonard; Tomasso, Jonathan di; Khan, Sarah; Olders, Henry; Borod, Manuel; Kilgour, Robert D.

doi:10.1016/j.clnu.2016.09.008

Cited by 53 publications

(40 citation statements)

References 50 publications

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“…Cachexia is a devastating syndrome that is characterized by the loss of skeletal muscle mass and fat mass that accompanies many chronic pro-inflammatory diseases including cancer [ 1 ]. Cancer-associated cachexia (CAC), an important adverse prognostic factor, not only increases patient morbidity and mortality but also reduces the efficacy of treatment [ 2 ]. However, there is no explicit mechanism about for tumour-derived factors in simulating catabolism in muscle and adipose tissue, and these are considered the main characteristics of cachexia progression.…”

Section: Main Textmentioning

confidence: 99%

RETRACTED ARTICLE: Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression

et al. 2018

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Emerging evidence supports the pivotal roles of cancer-associated cachexia in breast cancer progression. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. In vitro the use of propranolol ameliorates tumour exosomes-associated cachectic wasting through upregulating the PPARγ expression. These results demonstrate that cancer-derived exosomes reprogram systemic energy metabolism and accelerate cancer-associated cachexia to facilitate tumour progression.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0899-5) contains supplementary material, which is available to authorized users.

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Section: Main Textmentioning

confidence: 99%

RETRACTED ARTICLE: Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression

et al. 2018

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“…26 Vigano et al suggested to define CAX stages using non-nutritional criteria such as white blood cell count, serum albumin, or haemoglobin. 27 The present study describes early protein metabolism dysfunction and a staging method that is supported by the significant association of CAX stages with QoL and physical activity levels. While these definitions would be more robust if they had been associated to survival, this study was not designed for that purpose.…”

Section: Discussionmentioning

confidence: 72%

Staging of nutrition disorders in non‐small‐cell lung cancer patients: utility of skeletal muscle mass assessment

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et al. 2019

J cachexia sarcopenia muscle

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Background An international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia [skeletal muscle mass (SMM) loss], inflammation, and anorexia. The aim of this study was to stage CAX in non‐small‐cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters. Methods This was a cross‐sectional and non‐interventional multicentre study. SMM was assessed by analysing L3 computed tomography‐scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ‐C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ). Results Patients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0–1, and the tumour stage was mainly IIIB‐IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre‐CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K‐RAS+, and 43.2% in patients with no molecular abnormality ( P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL ( P < 0.001) and International Physical Activity Questionnaire ( P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre‐CAX patients. Overall, 43.8% of pre‐CAX patients had only sarcopenia with limited weight loss (≤2%) and no anorexia. Conclusions This is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX.

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“…For example, it is estimated that approximately half of all cancer patients experience cachexia (von Haehling & Anker, , ). It is well established that onset of cachexia negatively impacts disease outcome, reducing the effectiveness of primary disease treatment and increasing patient morbidity and mortality (Andreyev et al , ; Prado et al , ; Utech et al , ; Vaughan et al , ; Vigano et al , ).…”

Section: Introductionmentioning

confidence: 99%

The AMPK agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation‐associated cachectic muscle wasting

et al. 2018

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Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.

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Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients

Cited by 53 publications

References 50 publications

RETRACTED ARTICLE: Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression

RETRACTED ARTICLE: Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression

Staging of nutrition disorders in non‐small‐cell lung cancer patients: utility of skeletal muscle mass assessment

The AMPK agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation‐associated cachectic muscle wasting

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