Understanding sex differences in the regulation of cancer-induced muscle wasting

Montalvo, Ryan; Counts, Brittany R.; Carson, James A.

doi:10.1097/spc.0000000000000380

Cited by 62 publications

(56 citation statements)

References 136 publications

(223 reference statements)

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“…Our results are consistent with the literature; men are at greater risk, and reasons for this are not fully understood. Possible explanations may be related to sex differences associated with metabolic changes (eg, inflammation) and endocrine dysfunction, which were not collected in the current study . Collectively, these results show that the population is rife with features of cancer‐associated malnutrition (eg, weight loss, reduced food intake), including profound skeletal muscle depletion and fatty infiltration of the muscle, all of which are significantly and independently associated with mortality.…”

Section: Discussionmentioning

confidence: 60%

“…Possible explanations may be related to sex differences associated with metabolic changes (eg, inflammation) and endocrine dysfunction, which were not collected in the current study. 25 Collectively, these results show that the population is rife with features of cancerassociated malnutrition (eg, weight loss, reduced food intake), including profound skeletal muscle depletion and fatty infiltration of the muscle, all of which are significantly and independently associated with mortality. As a result, there is interest in determining whether currently existing nutrition screening tools can reveal any facets of body composition that place patients at greater risk for adverse outcomes; however, this seems unlikely, based on current findings.…”

Section: Discussionmentioning

confidence: 85%

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Cancer‐Associated Malnutrition and CT‐Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients

Martin

Gioulbasanis²,

Sénesse

et al. 2019

J Parenter Enteral Nutr

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Background Overweight/obese patients’ large fat mass can mask the loss of skeletal muscle, which is associated with mortality in the oncology setting. We investigated the prevalence of computed tomography (CT)‐defined sarcopenia and myosteatosis across different levels of nutrition risk assessed by the Patient‐Generated Subjective Global Assessment Short Form (PG‐SGA SF). We also evaluated whether the PG‐SGA SF, sarcopenia, and myosteatosis were prognostic of overall survival. Methods This was a prospective, observational study. Consecutive patients with body mass index ≥25.0 kg/m2 with newly diagnosed head and neck cancer (any stage) or lung and gastrointestinal tract cancer (locally recurrent or metastatic) were screened at presentation to oncology clinics. Nutrition risk was assigned based on PG‐SGA SF triage recommendations. Based on CT, patients were classified with sarcopenia and/or myosteatosis using published cutoffs. Survival analyses were conducted. Results Patients (n=1157) were 63.6 ± 11.4 years, 64% male, and 61% had stage IV disease. Sarcopenia and myosteatosis were prevalent across PG‐SGA SF nutrition risk categories (scores 0–1 [no risk; 36% sarcopenic; 44% myosteatotic], scores 2–3 [37%; 37%], scores 4–8 [40%; 41%], and scores ≥9 [high risk; 50%; 49%]). In multivariable survival analysis, PG‐SGA SF scores ≥9 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.66‐2.60, P<0.001), sarcopenia (HR 1.25, 95% CI 1.06‐1.46, P=0.006), and myosteatosis (HR 1.25, 95% CI 1.07‐1.46, P<0.001) independently predicted reduced survival. Conclusion CT‐defined sarcopenia and myosteatosis are prevalent across different levels of nutrition risk in overweight/obese patients with cancer. Assessment of skeletal muscle using CT adds prognostic value to the PG‐SGA SF.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 85%

Cancer‐Associated Malnutrition and CT‐Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients

Martin

Gioulbasanis²,

Sénesse

et al. 2019

J Parenter Enteral Nutr

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“…In their study, the males had clear muscle mass loss at the end of life, which was not observed in females. Various hormones, cytokines, and the immune system are associated with cachexia progression and muscle depletion [37,38] and are considered vital factors that cause sex differences. Elucidation of the mechanism of the sex difference is one of the keys to measures for muscle depletion and requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Muscle Depletion in Palliative Care Patients With Incurable Cancer: A Retrospective Study

Maeda¹,

Yamanaka²,

Matsuyama³

et al. 2020

Preprint

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Background: Depletion of muscle mass and strength has been proven to be a negative prognostic indicator for patients with cancer receiving anticancer treatment. However, little is known about its role in palliative care patients. The objective of this study was to evaluate the prognostic significance of muscle depletion in predicting survival among patients in palliative care.Methods: We retrospectively examined the association between muscle mass and strength and prognosis in patients with incurable solid cancer who are supported by a palliative care team at a university hospital. Psoas muscle index (PMI) at the level of the fourth lumbar vertebra was employed as the muscle mass index. Pinch grip strength (PGS) was used as the muscle strength index. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival.Results: A total of 78 patients were included in this study (35 male, median age 67 years). Median survival was 87.5 (95% confidence interval [CI] 50–124) days. After adjustment for age, sex, albumin, edema, and performance status as potential confounders, loss of PMI (HR=0.998, 95% CI 0.996–0.999; P=0.003) and PGS (HR=0.73, 95% CI 0.55–0.97; P=0.030) independently predicted the overall survival.Conclusion: Depletion of muscle mass and strength is an independent predictor of survival in patients with incurable solid cancer receiving palliative care. PMI and PGS may help to better assess the prognosis of patients in palliative care.

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“…In addition, it has been suggested that there are sex differences in both how cachexia develops and in the severity of the loss of muscle mass and function (Montalvo, Counts, & Carson, 2018), but few studies have directly addressed these sex differences. Female patients and rodents with cancer appear to benefit from the anti-inflammatory effects of estrogen (Hetzler et al, 2015(Hetzler et al, , 2017Koo et al, 2008), which corresponds with data indicating that male cancer patients lost more body weight, muscle mass and have higher rates of mortality compared with their female counterparts (Baracos, Reiman, Mourtzakis, Gioulbasanis, & Antoun, 2010;Hendifar et al, 2009).…”

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confidence: 99%

Sex differences in skeletal muscle alterations in a model of colorectal cancer

et al. 2020

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Cancer cachexia is the loss of lean muscle mass with or without loss of fat mass that is often highlighted by a progressive loss of skeletal muscle mass and function. The mechanisms behind the cachexia‐related loss of skeletal muscle are poorly understood, including cachexia‐related muscle functional impairments. Existing models have revealed some potential mechanisms, but appear limited to how the cancer develops and the type of tumors that form. We studied the C57BL6/J (B6) ApcMin/+ Tg::Fabp1‐Cre TG::PIK3ca* (CANCER) mouse. In this model, mice develop highly aggressive intestinal cancers. We tested whether CANCER mice develop cancer cachexia, if muscle function is altered and if sex differences are present. Both female and male mice, B6 (CONTROL) and CANCER mice, were analyzed to determine body weight, hindlimb muscle mass, protein concentration, specific force, and fatigability. Female CANCER mice had reduced body weight and hindlimb muscle mass compared with female CONTROL mice, but lacked changes in protein concentration and specific force. Male CANCER mice had reduced protein concentration and reduced specific force, but lacked altered body weight and muscle mass. There were no changes in fatigability in either group. Our study demonstrates that CANCER mice present an early stage of cachexia, have reduced specific force in male CANCER mice and develop a sex‐dependent cachexia phenotype. However, CANCER mice lack certain aspects of the syndrome seen in the human scenario and, therefore, using the CANCER mice as a preclinical model does not seem sufficient in order to maximize the translation of preclinical findings to humans.

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Understanding sex differences in the regulation of cancer-induced muscle wasting

Abstract: Females and males have unique characteristics that effect skeletal muscle's microenvironment and intrinsic signaling. These differences provide a strong rationale for distinct causes for cancer cachexia development and treatment in males and females.

Cited by 62 publications

References 136 publications

Cancer‐Associated Malnutrition and CT‐Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients

Cancer‐Associated Malnutrition and CT‐Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients

Prognostic Role of Muscle Depletion in Palliative Care Patients With Incurable Cancer: A Retrospective Study

Sex differences in skeletal muscle alterations in a model of colorectal cancer

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