Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA)

Blum, David; Stene, Guro Birgitte; Solheim, Tora Skeidsvoll; Fayers, Peter; Hjermstad, Marianne Jensen; Baracos, Vickie E.; Fearon, K. C. H.; Strasser, Florian; Lieve, Van den Block; Meeussen, Koen; Brearley, Sarah; Caraceni, Augusto; Cohen, Joachim; Massimo, Costantini; Anneke, Francke; Harding, Richard; Higginson, Irene J; Kaasa, Stein; Linden, Karen; Miccinesi, Guido; Bregje, Onwuteaka-Philipsen; Pardon, Koen; Roeline, Pasman; Sophie, Pautex; Payne, Sheila; Deliens, Luc

doi:10.1093/annonc/mdu086

Cited by 203 publications

(200 citation statements)

References 16 publications

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“…Data from a heterogeneous population of patients with incurable metastatic or locally advanced cancer diagnosis (13) indicated a prevalence of 14% while a prevalence of 23% was found in patients with nonsmall cell lung cancer (14). In the present study population, the prevalence of precachexia was 15%, which was close to the finding by Blum et al (13). The study included a relatively large group with cancer in the digestive organs, which may be comparable with our cohort.…”

Section: Discussionsupporting

confidence: 88%

“…The consensus classification suggested 3 stages of cachexia with clinical relevance, of which precachexia is the initial stage. Precachectic patients are considered responsive to interventions and it is therefore important to be able to identify these patients (13). However, the cutoff points of the precachectic domains are not accurately defined by the international consensus (1).…”

Section: Introductionmentioning

confidence: 99%

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Comparing Two Classifications of Cancer Cachexia and Their Association with Survival in Patients with Unresected Pancreatic Cancer

Wesseltoft-Rao

Hjermstad

Ikdahl

et al. 2015

Nutrition and Cancer

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There is no universally accepted definition of cancer cachexia. Two classifications have been proposed; the 3-factor classification requiring ≥ 2 of 3 factors; weight loss ≥ 10%, food intake ≤ 1500 kcal/day, and C-reactive protein ≥ 10 mg/l, and the consensus classification requiring weight loss >5% the past 6 mo, or body mass index <20 kg/m(2) or sarcopenia, both with ongoing weight loss >2%. Precachexia is the initial stage of the cachexia trajectory, identified by weight loss ≤ 5%, anorexia and metabolic change. We examined the consistency between the 2 classifications, and their association with survival in a palliative cohort of 45 (25 men, median age of 72 yr, range 35-89) unresected pancreatic cancer patients. Computed tomography images were used to determine sarcopenia. Height/weight/C-reactive protein and survival were extracted from medical records. Food intake was self-reported. The agreement for cachexia and noncachexia was 78% across classifications. Survival was poorer in cachexia compared to noncachexia (3-factor classification, P = 0.0052; consensus classification, P = 0.056; when precachexia was included in the consensus classification, P = 0.027). Both classifications showed a trend toward lower median survival (P < 0.05) with the presence of cachexia. In conclusion, the two classifications showed good overall agreement in defining cachectic pancreatic cancer patients, and cachexia was associated with poorer survival according to both.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Comparing Two Classifications of Cancer Cachexia and Their Association with Survival in Patients with Unresected Pancreatic Cancer

Wesseltoft-Rao

Hjermstad

Ikdahl

et al. 2015

Nutrition and Cancer

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“…Additionally, mice in the early phase of the cachexia trajectory exhibited abnormally elevated markers of thermogenesis in brown, but not white, adipose tissue and elevated energy expenditure when food intake was considered. Our observations suggest that different lipid metabolic responses may occur in different stages 40 and/or models of cancer cachexia. 41 Studies of both early and late cachexia consistently demonstrate that reduced food intake alone cannot explain loss of body weight 5,20 or fat mass.…”

Section: Discussionmentioning

confidence: 76%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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“…7,8 While these guidelines represent significant improvements, there is still a lack of simple clinical indicators and markers to allow for earlier and straightforward classification of CAC. 8 Despite increased awareness of this condition, CAC is still very common and treatments are inadequate, 9 suggesting that a comprehensive understanding of the molecular and physiologic pathways leading to the development and progression of CAC is still lacking. The large inter-individual variability in the prevalence and severity of CAC in patients with the same tumor type 10,11 further supports the need for improving the knowledge of the pathophysiologic mechanisms responsible for CAC.…”

Section: Introduction: the Clinical Problem -Cac History Definitionmentioning

confidence: 99%

The role of adipose tissue in cancer-associated cachexia

Vaitkus

Celi

2016

Exp Biol Med (Maywood)

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Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype – “beige” or “brite” adipose tissue – in a process referred to as “browning.” While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots – white, brown, and beige – to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing experiments, studies, and clinical trials.

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Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA)

Cited by 203 publications

References 16 publications

Comparing Two Classifications of Cancer Cachexia and Their Association with Survival in Patients with Unresected Pancreatic Cancer

Comparing Two Classifications of Cancer Cachexia and Their Association with Survival in Patients with Unresected Pancreatic Cancer

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

The role of adipose tissue in cancer-associated cachexia

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