BACKGROUND: Cachexia is associated with lower overall survival in patients with cancer; however, the relationship between the two is reported to differ according to the definitive criteria for diagnosing cachexia.
OBJECTIVE: We aimed to investigate the (1) difference in the prevalence of cachexia in patients with cancer and (2) association between cachexia and overall survival, depending on the definitive criteria for diagnosing cachexia in patients with cancer.
METHODS: We searched PubMed and Web of Science from their inception until July 31, 2023 to identify eligible studies. We conducted a systematic review of the prevalence of cachexia in patients with cancer and performed a meta-analysis to investigate its relationship with overall survival.
RESULTS: A total of 125 articles comprising 137,960 patients were included in the systematic review, and 26 articles consisting of 11,118 patients underwent meta-analysis. The overall prevalence of cachexia in patients with cancer was 33.0% (95% confidence interval [CI], 32.8-33.3); however, it varied according to the definitive criteria for diagnosing cachexia (13.9-56.5%). According to the Fearon 2011 criteria, the prevalence of cachexia was associated with a high hazard ratio (HR) for overall survival compared to that of non-cachexia (HR: 1.58 [95% CI, 1.45-1.73]); according to the other criteria, the HR was 2.78 (95% CI, 1.88-4.11), indicating significant subgroup differences (p = 0.006). The dose-response curve indicated that the HR for overall survival plateaued at a cachexia prevalence range of 40-50% (L-shaped relationship).
CONCLUSIONS: The prevalence of cachexia in patients with cancer may vary depending on the definitive criteria used to diagnose cachexia. The HR for overall survival was higher for low cachexia prevalence. The definitive criteria should be carefully considered when assessing cachexia in patients with cancer. This study was registered with PROSPERO as CRD42023435474.
CONCLUSIONS: This study provides crucial insights into the prognostic impact of the differential diagnostic criteria for cancer cachexia in clinical practice. We provide quantitative and qualitative evidence of a significant difference in the overall survival and prevalence of cachexia, depending on the definitive criteria for diagnosing cachexia in patients with cancer.

BACKGROUND: Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated.
OBJECTIVE: This meta-analysis and systematic review aimed to explore the CXI\'s prognostic value in patients with cancer.
METHODS: The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis.
METHODS: The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response.
METHODS: The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001).
CONCLUSIONS: A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.

Chronic inflammation is a hallmark of cancer cachexia. Polyunsaturated fatty acids (ω-3 PUFAs): eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to contribute to the reduction of inflammation, preservation of lean body mass and total body weight, and reduction of cancer-related symptoms, such as anorexia or neuropathy. This systematic review aimed to assess whether the ratio of EPA to DHA used in supplementation in cancer patients matters in the context of the resolution of inflammation and reduction of the risk of cachexia. The analysis included 20 randomized clinical trials with acceptable quality identified from the Pubmed/MEDLINE database. The significant results concerning the resolution of inflammation or improvement in nutritional status were the highest in the case of a low EPA/DHA ratio, i.e., 67%, and decreased, reaching 50% and 36% for the moderate and high ratios, respectively. Most results concerning body weight from high and moderate EPA/DHA ratios showed no benefit or were insignificant. A significant benefit in reducing any reported inflammatory markers was seen in the low EPA/DHA ratio subgroup at 63%, in the moderate at 29%, and in the high ratio subgroup at 11%. The greatest benefit in CRP reduction was obtained by patients during chemotherapy. The review questions the anticachectic and anti-inflammatory effect of ω-3 PUFAs supplementation with doses of EPA higher than DHA. A population that particularly benefits from ω-3 PUFAs supplementation are patients undergoing chemotherapy for advanced cancer.

BACKGROUND: Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue.
OBJECTIVE: To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia.
METHODS: We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis.
RESULTS: From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease.
CONCLUSIONS: Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

BACKGROUND: Cancer cachexia is a clinical condition characterized by recognizable \"sickness behaviors\" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.
METHODS: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).
RESULTS: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001).
CONCLUSIONS: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention\'s mechanism of action and/or intended patient benefit.

Cachexia is a condition characterized by substantial loss of body weight resulting from the depletion of skeletal muscle and adipose tissue. A considerable fraction of patients with advanced cancer, particularly those who have been diagnosed with pancreatic or gastric cancer, lung cancer, prostate cancer, colon cancer, breast cancer, or leukemias, are impacted by this condition. This syndrome manifests at all stages of cancer and is associated with an unfavorable prognosis. It heightens the susceptibility to surgical complications, chemotherapy toxicity, functional impairments, breathing difficulties, and fatigue. The early detection of patients with cancer cachexia has the potential to enhance both their quality of life and overall survival rates. Regarding this matter, blood biomarkers, although helpful, possess certain limitations and do not exhibit universal application. Additionally, the available treatment options for cachexia are currently limited, and there is a lack of comprehensive understanding of the underlying molecular pathways associated with this condition. Thus, this review aims to provide an overview of molecular mechanisms associated with cachexia and potential therapeutic targets for the development of effective treatments for this devastating condition.

UNASSIGNED: The clinical development of immune checkpoint inhibitors (ICIs) has led to substantial advances in the treatment of lung cancer. In particular, the contribution of ICIs to the long-term survival of certain patients with non-small cell lung cancer (NSCLC) has been reported. With the accumulated experience in the use of ICIs, numerous studies have documented the efficacy and safety of ICIs in patients with diverse backgrounds, including those with problematic indications for drug therapy. In the current review, we summarize the most recent literature-based findings on ICI administration in vulnerable patients with NSCLC and provide an overview of the current status and prospects of ICIs.
UNASSIGNED: Herein, we defined vulnerable as the group of patients with NSCLC and performance status (PS) ≥2 (poor PS), advanced age (≥75 years), or cancer cachexia. We conducted a narrative review of the literature on the efficacy and safety of ICIs in vulnerable patients with advanced NSCLC.
UNASSIGNED: Among the vulnerable patient group, poor PS was a strong, poor prognostic factor, even in patients undergoing ICI therapy. ICI therapy in older patients can be effective, although adverse events (AEs) should be carefully monitored. The efficacy of ICI therapy in patients with cancer cachexia is poor, with further therapeutic development warranted.
UNASSIGNED: Although prior studies have evaluated lung cancer pharmacotherapy in various vulnerable populations, clinical studies on the application of ICIs in patients with vulnerable NSCLC are lacking in both number and quality. Further development of these therapeutic agents, with the emergence of additional evidence regarding their appropriate use in this population, is expected.

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality of life and tolerance to anticancer therapy, and results in a poor prognosis in cancer patients. Dysregulated GDF15 levels have been discovered in patients with CC and animal models, where they have been found to be involved in anorexia and weight loss. Although studies have suggested that GDF15 mediates anorexia and weight loss in CC through its neuroreceptor, glial cell-lineage neurotrophic factor family receptor α-like, the effects of GDF15 on CC and the potential regulatory mechanisms require further elucidation. In the present review, the characteristics of GDF15 and its roles and molecular mechanisms in CC are elaborated. The targeting of GDF15 as a potential therapeutic strategy for CC is also discussed.

The use of total parenteral nutrition (TPN) in patients with gastrointestinal cancers is a well-established practice, yet there is substantial variability in its use across institutions. Decision-making around the initiation of TPN is complex. An interdisciplinary team can help identify patient factors and clinical situations that influence whether a patient is likely to benefit from parenteral nutrition. We present the case of a woman with a gastrointestinal cancer who benefited from the initiation of TPN as a bridge therapy to further cancer treatment. This case highlights the importance of establishing a plan for nutrition with specific goals in mind, such as optimizing patients for more cancer-directed therapy. Although patients with gastrointestinal cancers may be candidates for TPN, many patient-specific factors, such as functional status and opportunities for future treatments, must be considered prior to the initiation of parenteral nutrition. An interdisciplinary approach should be used to make recommendations based on patient goals, with a focus on patient and cancer characteristics that are associated with positive outcomes after initiation of TPN. These characteristics include functional status, nutritional status, degree of symptom control, and ability to safely administer nutrition. It is important to continually assess whether parenteral nutrition is beneficial in respect to a patient\'s preferences and prognosis.