Muscle mass as a target to reduce fatigue in patients with advanced cancer

Abstract

BackgroundCancer‐related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF.MethodsA total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy‐fatigue questionnaire (cut‐off for fatigue <34). Multiple linear regression analyses were conducted to study the association between SMI and CRF adjusting for relevant confounders.ResultsIn this group of patients with advanced cancer, the median fatigue score was 36 (interquartile range 26–44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B − 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy‐fatigue score was found (n = 82).ConclusionsThe association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies.

Dysregulation of metabolic‐associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin‐15 targeting fatigue

“…40 In contrast, in patients that do not experience significant body weight or muscle mass loss, pathways in skeletal muscle could promote alterations in mitochondrial function, which would predispose these patients to greater muscle fatigue. 4 Bioinformatics analysis also suggested a dysregulation of IL-15 signalling and activation in muscle of breast cancer patients, and il15 gene expression was lower in muscles from our mouse model of mammary cancer. Skeletal muscle overexpression of IL-15, and subsequent secretion into the circulation, attenuated muscle fatigue in response to mammary tumour growth in mice, suggesting that IL-15-based therapies may be useful to counter breast cancer-associated muscle fatigue.…”

“…In cancer patients that have lost significant amounts of body weight and/or muscle mass, pathways in skeletal muscle would promote muscle atrophy and alterations in protein turnover, which would predispose these patients to lower strength levels . In contrast, in patients that do not experience significant body weight or muscle mass loss, pathways in skeletal muscle could promote alterations in mitochondrial function, which would predispose these patients to greater muscle fatigue . Bioinformatics analysis also suggested a dysregulation of IL‐15 signalling and activation in muscle of breast cancer patients, and il15 gene expression was lower in muscles from our mouse model of mammary cancer.…”

“…1,2 The underlying mechanisms that can promote muscle wasting are not necessarily the same as those that can promote muscle fatigue, 3 and patients may experience muscle fatigue without significant loss of skeletal muscle mass. 4 Although a relatively small percentage of patients with breast cancer demonstrates evidence of body weight loss 5 and reduced skeletal muscle strength, 6,7 a large percentage of breast cancer patients reports moderate to severe fatigue, which can be exacerbated during radiation therapy and chemotherapy 3,[8][9][10] and can last for years after cancer treatments conclude. 8,9 Notably, one study reported that up to 99% of patients with breast cancer report some degree of fatigue.…”

Recent advances in cardio‐oncology: a report from the ‘Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019’

“…2 These patients often suffer from multiple different co-morbidities that may develop as consequences from anti-cancer therapies. Frequent problems include, but are not limited to, chronic kidney disease, 3,4 liver dysfunction, 5,6 gastrointestinal disease, 7,8 anaemia, 9,10 fatigue, 11,12 infections, 13,14 anorexia 15,16 , muscle wasting, 17,18 pain, 19,20 and heart failure (HF). 21,22 Depending on the cancer diagnosis and the type of anti-cancer treatment, cardiotoxicity rates may vary from 0% to 48% of patients, with HF being a predominant presentation.…”

Metabolic disorders in heart failure and cancer

“…11,12 It is also known that modern day anti-cancer treatments are commonly associated with cardiotoxicity which can aggravate or precipitate acute or chronic heart failure. [36][37][38][39] Registries also allow us the unique possibility to examine the wide-range of co-morbidities of heart failure patients. 16,17 Once heart failure develops it is associated with high 5-year mortality rates of 50% or more.…”