Nutritional Interventions for Cancer-Induced Cachexia

Cancer cachexia is a type of energy-wasting syndrome characterized by fatigue, anorexia, muscle weakness, fat loss, and systemic inflammation. Baicalein, a flavonoid with bioactive properties, has demonstrated the ability to mitigate cardiac and skeletal muscle atrophy in different experimental settings. This effect is achieved through the inhibition of muscle proteolysis, suggesting its potential in preserving skeletal muscle homeostasis. In this study, we investigated the anti-cancer cachexia effects of baicalein in the regulation of muscle and fat wasting, both in vivo and in vitro. Baicalein attenuated body weight loss, including skeletal muscle and white adipose tissue (WAT), in CT26-induced cachectic mice. Moreover, baicalein increased muscle fiber thickness and suppressed the muscle-specific ubiquitin-protease system, including F-box only protein 32 and muscle RING-finger protein-1, by activating AKT phosphorylation both in vivo and in vitro. The use of LY294002, a particular inhibitor of AKT, eliminated the observed impact of baicalein on the improvement of muscle atrophy. In conclusion, baicalein inhibits muscle proteolysis and enhances AKT phosphorylation, indicating its potential role in cancer cachexia-associated muscle atrophy.

Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC.

This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival.

Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m²), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325–4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016–3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009–3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups.

Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR.

Cancer cachexia is a complex syndrome characterized by progressive weight loss, muscle mass depletion, and systemic inflammation, profoundly affecting the well-being and treatment outcomes of cancer patients. Effective management of cancer cachexia demands a coordinated, multifaceted approach involving various healthcare disciplines and operational strategies. Streamlining care processes is crucial to ensure timely interventions and support, reducing delays in diagnosis and treatment initiation. Multidisciplinary collaboration is pivotal in creating integrated care plans that address the multifactorial nature of cancer cachexia comprehensively. Data-driven decision-making empowers healthcare teams to identify trends, monitor treatment responses, and tailor care plans to individual needs, ultimately leading to improved patient outcomes. Standardized assessment and monitoring play a vital role in maintaining consistent, high-quality care, facilitating early interventions and treatment adjustments. Implementing patient-centered care fosters trust, enhances treatment adherence, and encourages patients to actively engage in their care journey, thereby improving their overall quality of life. This paper underscores the significance of applying operations management principles to optimize care delivery and enhance patient outcomes in the management of cancer cachexia. It provides valuable insights for healthcare institutions and professionals striving to provide comprehensive and effective care for individuals affected by this challenging condition.

It has been proposed that direct measurement of adiposity has a greater accuracy as a prognostic factor in various malignancies than anthropometric measures such as BMI. We evaluated the association of visceral and subcutaneous adiposity with outcomes in patients with hematological malignancies with a systematic review and meta-analysis. This systematic review included patients with hematological malignancies who had the analysis of overall mortality and progression-free survival according to their adiposity status. We identified 3137 articles, of which we included seven studies. Patients with visceral low visceral adiposity had 2 times greater mortality risk (HR 2.02, P = .0004) and 80% higher risk of death or disease progression (HR 2.98, P = 0.0002), than patients with normal visceral obesity. Patients classified with subcutaneous adipopenia had almost 3 times greater mortality risk. In conclusion, hematological malignancy patients having low adiposity (subcutaneous or visceral) have worse outcomes.

Cachexia has been recognized as involuntary weight loss resulting from a decline in food consumption correlated to metabolic dysfunction. It is an impaired metabolism leading to the progressive loss of muscle and functional impairment, as well as a reduction in survival. Several pathophysiological conditions are behind the progression of cachexia induced by cancer, chronic obstructive pulmonary disease (COPD), heart failure, and kidney diseases. From the mechanistic point of view, inflammatory mediators such as nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) play critical roles in the pathogenesis of cachexia. Additionally, apoptosis (e.g., Bax, caspase) and oxidative stress are increased in such situations. Besides, cachexia makes an imbalance in the homeostasis of muscle synthesis or degradation of protein/lipids, and related mediators including muscle atrophy F-box (MAFbx), muscle-specific RING finger-1 (MuRF 1), the ubiquitin-proteasome system (UPS), phosphoinositide 3-kinases (PI3K)/Akt/mammalian target of rapamycin (mTOR). Consequently, it leads to multiorgan damages, not only limited to muscle tissue, but also several other tissues, including brown and white adipose, brain, liver, gut, and heart. However, there is no therapeutic agent possessing high efficacy and lower side effects in combating cachexia. These days, natural products are promising agents in playing useful functions toward the prevention and treatment of cachexia.

In this chapter, dysregulated signaling pathways of cachexia have been developed in cancer, COPD, heart failure, and kidney diseases. Additionally, candidate phytonutrients and related mechanisms of action have been developed in combating cachexia.

Malnutrition is prevalent in upper gastrointestinal cancer patients. The purpose of this study was a comprehensive assessment of nutritional status in newly diagnosed patients with esophageal cancer.

Newly diagnosed esophageal cancer patients were referred to a chemo-radiation referral center in Mashhad, Iran, between February 2017 to February 2019. Anthropometric indices, a Patient-Generated Subjective Global Assessment (PG-SGA) tool, body composition, dietary intake, nutritional-related complications, and laboratory tests were assessed.

One hundred and eighty-nine patients with a mean age of 67.1 ± 12 and a male to female ratio of 98 to 91 were included. Ninety-seven (51.3%) of patients had experienced significant weight loss and 56 (29.6%) were underweight at diagnosis. According to PG-SGA, 179 (94.7%) needed nutritional interventions. Reduced muscle mass and low handgrip strength were observed in 70 (39.4%) and 26 (14.4%) of patients, respectively. Inadequate intakes of energy (less than 24 kcal/kg/day) and protein (less than 1.2 g/kg/day) were found in 146 (77.8%) and 171 (91%) patients, respectively. The mean total daily energy and protein intakes of subjects were 943.8 ± 540 kcal/day, and 30.6 ± 21 g/day, respectively. The most common nutritional-related complications were as follows: dysphagia (84.8%), anorexia (31.6%), constipation (62.1%), esophageal pain (48.4%), and dyspepsia (41.1%).

Our study demonstrated a high prevalence of malnutrition in newly diagnosed esophageal cancer patients. This fact demonstrates the importance of early screening of nutritional status via PG-SGA tool, clinical evaluation, dietary intake evaluations, and laboratory tests, based on which effective nutritional interventions and Symptoms management may be introduced in these patients.