Pathophysiological mechanisms explaining poor clinical outcome of older cancer patients with low skeletal muscle mass

Abstract

Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as post‐operative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review, we summarize proposed pathophysiological mechanisms underlying the association between low skeletal muscle mass and poor clinical outcomes in older cancer patients including a) systemic inflammation; b) insulin‐dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics of anticancer drugs. The mechanisms of altered myokine balance negatively affecting the innate and adaptive immune system, and altered pharmacokinetics of anticancer drugs leading to a relative overdosage of anticancer drugs are best‐substantiated. The effects of glucose intolerance and circulating mitochondrial DNA as a consequence of low skeletal muscle mass are topics of interest for future research. Restoring myokine balance through physical exercise, exercise mimetics, neuro‐muscular activation and adapting anticancer drug dosing on skeletal muscle mass could be targeted approaches to improve clinical outcomes in older cancer patients with low skeletal muscle mass.

Optimal Skeletal Muscle Mass Index Cut-Off Values for Presarcopenia Evaluated by Computed Tomography against Dual-Energy X-ray Absorptiometry in Patients with Chronic Liver Disease

“…Myokine production is decreased with the loss of SMM [36]. Of the myokines, interleukin (IL)-6 and 15 regulate innate and adaptive immunity systems [37]. Decreased IL-15 caused by low skeletal muscle reduces the number and activity of natural killer cells and worsens the prognosis of cancer patients.…”

Are computed tomography-based measures of specific abdominal muscle groups predictive of adverse outcomes in older cancer patients?

“…Both sarcopenia [13,32], diagnosed by a combination of low skeletal muscle mass and low physical function, and malnutrition [33], are two prevalent geriatric syndromes in older cancer patients that could be of high importance in identifying older cancer patients with a high risk of adverse outcomes. Another interesting factor would be the association between systemic inflammatory markers and individual muscle groups as it has been suggested that systemic inflammation may also be associated with skeletal muscle measures [34] and the risk of adverse outcomes [35,36].…”

Physical exercise—A toxin‐free complement to cancer therapy

“…Looijard et al give a review regarding possible pathophysiological mechanisms behind this phenomenon. 18 These mechanisms include systems similar to those that are supposed to be influenced by physical exercise, such as the inflammatory system, insulin-glucose metabolism, energy regulation of mitochondria and the body's reaction to potentially aggressive cancer drugs. They propose physical exercise or exercise mimetics -the application of substances that mimic the systemic effects of exercise 19 -as approaches to improve clinical outcomes in cancer patients.…”

“…Low skeletal muscle mass is associated with poor clinical outcomes especially in older patients. Looijard et al give a review regarding possible pathophysiological mechanisms behind this phenomenon 18 . These mechanisms include systems similar to those that are supposed to be influenced by physical exercise, such as the inflammatory system, insulin‐glucose metabolism, energy regulation of mitochondria and the body's reaction to potentially aggressive cancer drugs.…”