Cachexia In Cancer Patients Research Articles

The association of the Prognostic Nutritional Index (PNI) and Neutrophil-Lymphocyte Ratio (NLR) with cachexia in cancer patients

The association of the Prognostic Nutritional Index (PNI) and Neutrophil-Lymphocyte Ratio (NLR) with cachexia in cancer patients

Cachexia-related consequences of glycemic metabolism: A multivariable and two-step Mendelian randomization study

BackgroundCachexia is a global burden that is caused by chronic diseases such as cancer. It is characterized by inflammation and progressive loss of muscle and adipose tissue, aggravating the patient’s health. Glycemic metabolism disorders exacerbate cachexia and mutually reinforce each other. Thus far, no research has established a connection between the two. Therefore, we aim to explore the influence of glucose metabolism on cachexia using Mendelian randomization (MR) and provide a theoretical basis for the early prediction of cachexia. MethodsWe used glycemic traits (type 2 diabetes (T2D), fasting glucose (FG), fasting insulin (FI), hemoglobin A1c (HbA1c), and 2-hour postprandial glucose (2hPG)) as exposures; and cachexia traits (hand grip strength (HGS), appendicular lean mass (ALM), and walking pace (WP)) as outcomes. 22 mediators were included for mediating effects. Multivariable and mediation MR were used to assess the impact of glycemic metabolism on cachexia. ResultsIn univariate MR, higher FI increased HGS (β = 0.113, 95% confidence interval (CI): 0.060–0.166) and WP (β = 0.066, 95% CI: 0.021–0.112). Higher HbA1c was associated with higher ALM (β = 0.067, 95% CI: 0.017–0.117). Higher 2hPG was associated with weaker HGS (β = −0.037, 95% CI: −0.054 to −0.021). In multivariable MR, only FI maintained a relationship with HGS after adjustments for T2D (β = 0.103, 95% CI: 0.026–0.181), FG (β = 0.101, 95% CI: 0.034–0.169), HbA1c (β = 0.115, 95% CI: 0.055–0.176), and 2hPG (β = 0.101, 95% CI: 0.033–0.169). In mediation MR, three mediators were found to be significant between FI and HGS: waist circumference (WC) (48.1%), lumbar spine bone mineral density (LSBMD) (21.3%) and insulin-like growth factor 1 (IGF-1) (6.7%). ConclusionsUsing multivariable and mediation MR, our finding suggests that higher FI increases HGS with an independent effect. WC, LSBMD, and IGF-1 mediate between FI and HGS. This study offers a theoretical framework for the early prediction and assessment of the prognosis of cachexia in cancer patients with glycemic metabolism disorders.

Prescription Pattern of Anamorelin; a Therapeutic Agent for Cancer Cachexia.

Background: The commercial availability of anamorelin, Japan's first therapeutic agent for cancer cachexia in 2021, led to an investigation into its prescription patterns at Toyama University Hospital. Objective: We aimed to analyze anamorelin prescription trends and outcomes among cancer cachexia patients. Methods: A retrospective study from July 2021 to December 2022 examined 88 cases, assessing demographics, cancer types, prescription locations, and meal intake changes. Results: Anamorelin usage was predominant during chemotherapy, especially for pancreatic cancer in outpatient settings. Approximately 30% experienced increased meal intake. Chemotherapy-initiated cases had a longer median duration (55 days) compared with best supportive care only cases (12 days). Conclusion: Anamorelin demonstrated significant prescription patterns, particularly during chemotherapy for pancreatic cancer in outpatient settings, suggesting potential efficacy enhancements when administered with chemotherapy in cancer cachexia management. The study underscores the importance of tailored approaches to optimize anamorelin's therapeutic benefits.

Masseter muscle thickness is predictive of cancer cachexia in patients with head and neck cancer.

Cancer cachexia is prevalent in head and neck cancer patients. The L3 skeletal muscle index (SMI) is often used to assess sarcopenia and cachexia but is infrequently able to be measured in this population. Masseter muscle thickness (MT) may serve as an alternative predictor of cachexia. SMI and MT were calculated from 20 trauma (CTRL) and 40 cachectic (CA-CX) and non-cachectic (CA-NCX) head and neck cancer patients. Area Under the Curve of the Receiver Operating Characteristics (AUC-ROC) analysis was performed for SMI and MT. Both SMI and MT were significantly decreased in CA-CX patients (vs. CA-NCX mean difference -19.5 cm2/m2 and -2.06 mm, respectively) and significant predictors of CA-CX (AUC = 0.985 and 0.805, respectively). When analyzed by sex, the same findings were observed for MT in males and trended toward significance in females. Compared with SMI, MT is a good alternative prognostic biomarker to determine CA-CX status in HNC patients.

Effects of Adjuvant Exercise and Nutrition Therapy on Muscle Fibre Biomechanics in Gastrointestinal Cancer Patients.

Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca2+-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca2+ sensitivity and the quality of contraction were unaltered (pCa50: 5.6-5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L0). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L0), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L0). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC.

Breaking Down Cachexia: A Narrative Review on the Prevalence of Cachexia in Cancer Patients and Its Associated Risk Factors.

Cachexia is an irreversible condition that involves a significant loss of body weight, muscle mass, and adipose tissue. It is a complex condition that involves a variety of metabolic, hormonal, and immune-related factors, with the precise mechanisms not yet fully understood. In this review, the prevalence of cachexia in different types of cancer as well as the potential risk factors was evaluated from literature retrieved from databases such as ScienceDirect, PubMed and Scopus. Potential risk factors evaluated here include tumor-related factors such as location, and stage of the cancer, as well as patient-related factors such as age, gender, and comorbidities. Several findings were observed where cachexia is more prevalent in male cancer patients than females, with higher incidences of weight loss and poorer outcomes. This may be due to the different muscle compositions between gender. Additionally, cachexia is more prevalent at the later stages, which may be brought about by the late-stage diagnosis of certain cancers. The anatomical location of certain cancers such as the pancreas and stomach may play a significant factor in their high prevalence of cachexia. These are sites of the synthesis of digestive enzymes and hormones regulating appetite. Cachexia is an issue faced by cancer patients which could affect their recovery. However, it is poorly understood, which limit therapeutic options. Hence, understanding this disease from different perspectives (clinical and pre-clinical), and bridging those findings could further improve our comprehension and consequently improve therapeutic options.

Astaxanthin Ameliorates Skeletal Muscle Atrophy in Mice With Cancer Cachexia

Astaxanthin (AST) is a natural marine carotenoid with a variety of biological activities. This study aimed to demonstrate the possible mechanisms by which AST improves skeletal muscle atrophy in cancer cachexia. In this study, the effects of different doses of AST (30 mg/kg b.w., 60 mg/kg b.w. and 120 mg/kg b.w.) on skeletal muscle functions were explored in mice with cancer cachexia. The results showed that AST (30, 60 and 120 mg/kg b.w.) could effectively protect cachexia mice from body weight and skeletal muscle loss. AST dose-dependently ameliorated the decrease in myofibres cross-sectional area and increased the expression of myosin heavy chain (MHC). AST treatment decreased both the serum and muscle level of IL-6 but not TNF-α in C26 tumor-bearing cachexia mice. Moreover, AST alleviated skeletal muscle atrophy by decreasing the expression of two muscle-specific E3 ligases MAFBx and MuRF-1. AST improved mitochondrial function by downregulating the levels of muscle Fis1, LC3B and Bax, upregulating the levels of muscle Mfn2 and Bcl-2. In conclusion, our study show that AST might be expected to be a nutritional supplement for cancer cachexia patients.

Abstract 6816: Prevention of cancer cachexia by inhibition of soluble epoxide hydrolase

Abstract Background: Cancer cachexia is a devastating syndrome characterized by progressive muscle wasting and hyperinflammation. The underlying mechanisms remain poorly understood with no treatment options available. Cachexia is driven by systemic inflammation, pro-inflammatory cytokines, and apoptotic cell death (debris). The resolution of inflammation as an active biochemical process is regulated by novel pro-resolving lipid mediators. Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are lipid mediators stimulating inflammation resolution. EETs are rapidly metabolized by the enzyme soluble epoxide hydrolase (sEH). sEH is a critical cause of inflammation and a biomarker in several chronic inflammatory diseases. sEH inhibitors promote tissue regeneration and counter-regulate pro-inflammatory cytokines. We hypothesized that pharmacological inhibition of the sEH may prevent cachexia. Methods: We investigated murine cancer cachexia models using genetically engineered pancreatic (KPC) and prostate (TRAMP C1) tumor cell lines, and “TRAMP” mice (transgenic adenocarcinoma of the mouse prostate). We performed LC-MS/MS-based profiling of bioactive lipids in plasma from KPC and colon cancer (CT26)-induced cachectic mice. Results: KPC cells injected intraperitoneally induced 19.7% and 54.1% reduction in muscle weight in the tibialis anterior and soleus, respectively, in immunocompetent C57BL/6 mice compared to non-tumor bearing (NTB) mice. LC-MS/MS revealed KPC and CT26 cachexia induced a pro-inflammatory eicosanoid-driven cytokine storm. The human sEH inhibitor EC5026 delayed the onset of cachexia, leading to sustained survival over 250 days post-injection in the KPC model (n=15 mice/group). sEH expression was increased in the gastrocnemius of KPC mice by day 22 post-tumor cell injection vs. NTB. EC5026 counter-regulated sEH expression compared to vehicle-treated. In the TRAMP model, 5/5 of mice treated with EC5026 survived 230 days post-treatment compared to no survival of vehicle-treated mice (n=5). The transplanted KPC and TRAMP showed reduced CD4+ and CD8+ T lymphocytes and B lymphocytes in the tibialis anterior and gastrocnemius vs. NTB after flow cytometry analysis. EC5026 stimulated a general increase in CD3+ T lymphocytes and counter-regulated an eicosanoid-driven cytokine storm as shown by cytokine assays. EC5026 treatment increased tibialis anterior and gastrocnemius muscle weights and body weights compared to vehicle-treated KPC and TRAMP mice. Conclusions: sEH inhibition may be a novel therapeutic approach to cachexia by targeting the immune response via stimulation of resolution of inflammation without toxicity or immunosuppression. Since sEH inhibitors have proven safe and effective in clinical trials for controlling multiple inflammatory diseases, this study provides a basis for the rapid clinical translation of sEH inhibitors to prevent/reverse cachexia in cancer patients. Citation Format: Rachel L. Bayer, Sarina Virani, Michael Gillespie, Jacqueline Capuano, Keira Smith, Katherine Quinlivan, Kimberly Vasquez, Jun Yang, Haixia Yang, Nicholas Mitsiades, Bruce D. Hammock, Dipak Panigrahy. Prevention of cancer cachexia by inhibition of soluble epoxide hydrolase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6816.

Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study

BackgroundHepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia.MethodsThis multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL).ResultsC-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19–1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25–1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels.ConclusionLow albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.

Quantitative and Qualitative Radiological Assessment of Sarcopenia and Cachexia in Cancer Patients: A Systematic Review.

Sarcopenia, an extremely common condition in cancer patients, is described as a progressive and generalized musculoskeletal disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. By contrast, cachexia is defined as a syndrome characterized by weight loss with the concomitant loss of muscle and/or fat mass. Cancer cachexia leads to functional impairment, reduced physical performance, and decreased survival, and is often accompanied by cancer progression and reduced response to therapy. The literature states that cancer patients with cachexia or sarcopenia have many more complications than patients without these conditions. The interplay between physiologic sarcopenia and cancer cachexia is, in part, responsible for the complexity of studying wasting disorders in the cancer population, particularly in the geriatric population. For these reasons, a comprehensive assessment of the body composition and physical function of these patients is necessary. There are several modalities adapted to measure skeletal muscle mass, such as dual-energy X-ray absorptiometry (DEXA), bioelectrical impedance analysis (BIA), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). The gold standard for the measurement of quantitative and qualitative changes in body composition in patients with cancer is the analysis of tissue density using a CT scan. However, this technique remains poorly implemented in clinical practice because of the use of ionizing radiation. Similarly, DEXA, MRI, and US have been proposed, but their use is limited. In this review, we present and compare the imaging techniques that have been developed so far for the nutritional assessment of cancer patients.

A Review of Olanzapine in the Treatment of Cancer Anorexia-Cachexia Syndrome.

Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Low dose olanzapine (2.5-5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients.

Evaluation and validation of neutrophil to albumin ratio as a promising prognostic marker for all-cause mortality in patients with cancer: a multicenter cohort study

ObjectivesThe practicality and effectiveness of using the prognostic value of the neutrophil-to-albumin ratio (NAR) in evaluating patients with cancer remain unclear, and research is needed to fully understand its potential application in the cancer population. MethodsThe Kaplan–Meier method was used for survival analysis, and the log-rank test was employed for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the prognostic biomarkers, and Logistic regression analysis was conducted to investigate the relationship between NAR and 90-day outcomes and cachexia. ResultsThe study included 14 682 patients with cancer, divided into discovery (6592 patients), internal validation (2820 patients), and external validation groups (5270 patients). Patients with high NAR had higher all-cause mortality than those with low NAR in the discovery (50.15% versus 69.29%, P < 0.001), internal validation (54.18% versus 70.91%, P < 0.001), and external validation cohorts (40.60% versus 66.68%, P < 0.001). In the discovery cohort, high NAR was observed to be independently associated with all-cause mortality in patients (HR 1.16, 95% CI 1.12–1.19; P < 0.001). Moreover, we validated the promising prognostic value of NAR as a predictor of survival in patients with cancer through internal validation (HR 1.21, 95% CI 1.16–1.27, P < 0.001) and external validation cohorts (HR 1.27, 95% CI 1.21–1.34, P < 0.001). Additionally, in the subgroup analysis by tumor type, high NAR was identified as a risk factor for most cancers, except for breast cancer. ConclusionsThis study showed that NAR is a feasible and promising biomarker for predicting prognosis and cancer cachexia in cancer patients.

Healthcare professionals' knowledge of and compliance with the ASCO/ESMO/GLIM guidelines for the diagnosis and management of cancer cachexia (CC): the ASSIST-CC baseline findings in Uganda.

More than 50% of people with advanced cancer suffer from cancer-related cachexia (CC) - a major contributor to morbidity and mortality. Despite the lack of local guidelines on CC diagnosis and management in Uganda, the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO) and the Global Leadership Initiative on Malnutrition (GLIM) developed guidelines on CC screening and management. However, the level of knowledge on CC and compliance with the available guidelines among Ugandan oncology health professionals is unknown. This study aimed to assess the level of awareness and knowledge of CC diagnosis and management and compliance with the ASCO/ESMO/GLIM guidelines on CC among healthcare professionals (HCPs) involved in the care of cancer patients. In this phase one, a self-administered structured questionnaire developed using the ASCO/ESMO and GLIM guidelines on diagnosis and management of CC was used to assess the level of awareness, and knowledge of 200 health professionals from three hospital settings on CC, and compliance with the ASCO/ESMO/GLIM guidelines on CC related core communication, barriers to communication, clinician training in communication, discussing goals of care, treatment options and meeting the needs of the underserved populations. The data were entered into Research Electronic Data Capture software analysed using STATA version 18.0 software. The overall objectively correct knowledge score of CC diagnosis criteria was 67.5% (n = 135), yet there was a much lower level of awareness about ASCO/ESMO/GLIM guidelines on CC at 30% (n = 60) and only 21% (n = 42) of the HCPs have ever assessed Quality of life of CC patients. The compliance with ASCO/ESMO/GLIM guidelines on nutritional interventions for patients with CC varied across the variables markedly, ranging from 25.1% (n = 50) to 81% (n = 162) for the specific ASCO/ESMO/GLIM guidelines' recommendations. Whereas compliance with the guidelines on discussing goals of care, prognosis, treatment options and end-of-life care scored the highest in most variables, most HCPs exhibited low compliance with the discussion about patients' end-of-life preferences early in the course of incurable illness (49.8%, n = 99). There were statistically significant differences between the mean scores of only two variables among the three hospitals in compliance with ASCO/ESMO/GLIM guidelines on the provision. This study indicated that the overall objectively correct knowledge of CC diagnosis criteria was inadequate, with a much lower level of awareness about the ASCO/ESMO/GLIM guidelines on CC and a handful of the HCPs have ever assessed the quality of life of CC patients. Quality improvement interventions on CC diagnosis and management should prioritize improving the level of knowledge on CC, diagnostic criteria and patient-clinician communication, including discussion about patients' end-of-life care using standardised tools such as ASCO/ESMO or GLIM guidelines on CC using a multidisciplinary team approach.

MO55-5 Impact of tumor genomic alterations on development of cancer cachexia in patients with advanced non-small cell lung cancer

MO55-5 Impact of tumor genomic alterations on development of cancer cachexia in patients with advanced non-small cell lung cancer

The Relationship between Exercise Capacity and Muscle Strength, Physical Activity, Fatigue and Quality of Life in Patients with Cancer Cachexia

Background Exercise capacity is a significant determinant of mortality for cancer patients, so knowing the possible determinants of exercise capacity will produce physical and psychological benefits for individuals with cancer cachexia. Purpose To investigate the relationship between exercise capacity on peripheric and respiratory muscle strength, physical activity, fatigue and quality of life in subjects with cancer cachexia. Methods The study included 31 patients diagnosed with cancer cachexia. Functional capacity was assessed by 6-Minute Walk Test, hand grip strength and proximal muscle mass by hand dynamometer, respiratory muscle strength by the Maximum Expiratory Pressure and Maximum Inspiratory Pressure measurements, physical activity by International Physical Activity Questionnaire Short Form, fatigue by Brief Fatigue Inventory, and quality of life by EORT-QLQ-C30. The relationship between functional capacity and continuous independent variables was determined using Spearman’s or Pearson’s tests. Results A strong positive correlation was observed between exercise capacity and expiratory muscle strength (r = 0.75, p < 0.001), activity level (r = 0.68, p < 0.001), and quality of life global health status (r = 0.74, p < 0.001). Conversely, a strong negative correlation was found between exercise capacity and fatigue severity (r = −0.64, p < 0.001). Conclusion Higher exercise capacity in cancer cachexia patients is linked to reduced fatigue, improved respiratory muscle strength, increased physical activity levels, and enhanced quality of life. When designing rehabilitation programs or exercise interventions for individuals with cancer cachexia, it is crucial to assess their exercise capacity and tailor the programs accordingly.

The roles of P-selectin in cancer cachexia.

P-selectin, a cell adhesion molecule of the selectin family, is expressed on the surface of activated endothelial cells (ECs) and platelets. Binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) supports the leukocytes capture and rolling on stimulated ECs and increases the aggregation of leukocytes and activated platelets. Cancer cachexia is asystemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss ofappetite, fat depletion, and progressive muscle atrophy. Cachexia status is associated with increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which activates ECs to release P-selectin. Single-nucleotide polymorphisms (SNPs) loci of P-selectin encoding gene SELP are associated with higher level of plasma P-selectin and increase the susceptibility to cachexia in cancer patients. Elevated P-selectin expression has been observed in the hypothalamus, liver, and gastrocnemius muscle in animal models with cancer cachexia. Increased P-selectin may cause excessive inflammatory processes, muscle atrophy, and blood hypercoagulation, thus facilitating the development of cancer cachexia. In this review, physiological functions of P-selectin and its potential roles in cancer cachexia have been summarized. We also discuss the therapeutic potential of P-selectin inhibitors for the treatment of cancer cachexia.

The effect of anamorelin (ONO-7643) on cachexia in cancer patients: Systematic review and meta-analysis of randomized controlled trials.

Cachexia is associated with increased morbidity and mortality rates in patients with cancer. This meta-analysis aims to explore the effect of anamorelin on cancer cachexia markers. We searched MEDLINE/PubMed, SCOPUS, and WOS from their inception until 5 June 2022. A systematic search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We included trials investigating the effect of anamorelin on body weight, lean body mass, fat mass, insulin-like growth factor 1 (IGF-1), handgrip, quality of life insulin-like growth factor-binding protein 3 (IGFBP-3), and in patients with cancer. A random-effects model was run to pooled results. Five articles providing 1331 participants were analyzed in this study. Pooled analysis revealed a significant increase in body weight (weighted mean difference (WMD): 1.56 kg, 95% confidence interval (CI): 1.20, 1.92; I2= 0%), lean body mass (WMD: 1.36 kg, 95% CI: 0.85, 1.86; I2= 53.1%), fat mass (WMD: 1.02 kg, 95% CI: 0.51, 1.53; I2= 60.7%), IGF-1 (WMD: 51.16 ng/mL, 95% CI: 41.42, 60.90, I2= 0%), and IGFBP-3 (WMD: 0.43 μg/mL, 95% CI: 0.17, 0.68, I2= 98.6%). Results showed no significant increase in appetite when analysis run on all studies without considering different doses 0.29 (95% CI: -0.30, 0.89, I2= 73.8%), however, there was a significant increase in appetite without heterogeneity and inconsistency 0.59 (95% CI: 0.32, 0.86; I2= 0%) in the 100 mg/day group compared to anamorelin non-user. Patients with cancer who receive anamorelin as a treatment for cachexia showed a significant increase in body weight, lean body mass, fat mass, IGF-1, and IGFBP-3.

Prevalence of Cachexia in Cancer Patients

Introduction. Cachexia is a syndrome characterized by the loss of musculoskeletal mass, with or without adipose mass, which cannot be reversed by nutritional support. In Chile, there are no data on cachexia in cancer patients that allows for decision making on better interdisciplinary management. In this study, the prevalence of cachexia in inpatient and outpatient cancer patients was investigated. Methods. An observational, descriptive, and cross-sectional study was carried out. Eighty-six inpatients and outpatients were evaluated. Cachexia was evaluated by applying the miniCASCO tool, its weight by bioimpedance, and inflammation by blood parameters. Comparisons and correlations were made considering p &lt; 0.05 as the threshold for statistical significance. Results. Forty patients met the inclusion criteria, 35% were men and 65% were women. In all, 27.5% of patients had cachexia secondary to cancer. Of the total number of patients with the syndrome, approximately 45.4% had mild cachexia, 36.3% had severe cachexia, and 18.1% had moderate cachexia. In addition, there was a significant positive correlation p = 0.0150 and moderately strong (r = 0.7209) match between the final scores and the stage of cancer. Conclusion. The prevalence of cachectic patients is reported for the first time through the application of the miniCASCO tool. A moderate positive match was detected between the final miniCASCO score and the stages of cancer patients. Finally, an early discovery of cachexia would allow therapeutic interventions aimed at improving the prognosis of cancer patients.

The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study.

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.

Effect of Protein and Energy-Dense Nutritional Supplement with Immunonutrients on Cachexia in Cancer Patients: An Open-Label, Single-Arm Study Among Indian Patients

Background Cachexia is highly prevalent in cancer patients and is responsible for as much as 20% of all cancer deaths. Nevertheless, there is little emphasis on cachexia in routine clinical practice. This study looks at the efficacy and tolerability of a protein and energy-dense nutritional supplement with immunonutrients on cachexia in cancer patients. Methods This was a three-month, prospective, open-label study of patients undergoing radiotherapy and/or chemotherapy for head and neck or gastrointestinal or lung cancer. Efficacy endpoints were mean change in muscle strength, acute phase proteins (albumin and pre-albumin), C-reactive protein (CRP) levels, weight, Glasgow prognostic score (GPS), and nutritional status at the end of the study period. Results The study population consists of 47 (79.66%) males and 12 (20.34%) females with a mean age of 47.98 ± 12.16 years. The mean change in muscle strength, albumin, pre-albumin, CRP levels, and weight for the overall study population was 0.17 ± 12.09 kg (P=0.9145), -0.05 ± 0.53 g/dl, (P=0.5888), -0.01 ± 0.09 g/dl (P=0.2951), 0.50 ± 37.41 mg/dl (P=0.9258), -0.59 ± 3.70 kg (P=0.2265), respectively. At the end of the study period, there was a significant improvement in the nutritional status concerning total calories, protein, and fat intake. Conclusion Protein and energy-dense nutritional supplement with immunonutrients might help in the improvement of muscle strength, GPS, and dietary intake. The addition of the supplement to the diet regime of patients with cancer cachexia increases their daily consumption of proteins which might translate to multimodal clinical benefits.