Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass and strength. This condition is associated with physical disability, decreased quality of life, and increased mortality. Therefore, reducing the prevalence of sarcopenia could significantly lower healthcare costs. Sarcopenia can be classified into primary and secondary sarcopenia. The former is related to aging and begins after the fourth decade of life; after that, there is a muscle loss of around 8% per decade until age 70 years, which subsequently increases to 15% per decade. On the other hand, secondary sarcopenia can affect all individuals and may result from various factors including physical inactivity, malnutrition, endocrine disorders, neurodegenerative diseases, inflammation, and cachexia. Understanding the multiple mechanisms involved in the onset and progression of sarcopenia allows for us to develop strategies that can prevent, treat, or at least mitigate muscle loss caused by increased protein breakdown. One potential treatment of sarcopenia is based on nutritional interventions, including adequate caloric and protein intake and specific nutrients that support muscle health. Such nutrients include natural food rich in whey protein and omega-3 fatty acids as well as nutritional supplements like branched-chain amino acids, β-hydroxy-β-methylbutyrate, and vitamin D along with food for special medical purposes. It is important to emphasize that physical exercises, especially resistance training, not only promote muscle protein synthesis on their own but also work synergistically with nutritional strategies to enhance their effectiveness.

Cachexia is a common complication in advanced gastric cancer (AGC). Eicosapentaenoic acid (EPA) may ameliorate cachexia. This single-arm, phase II study assessed the potential benefit of an oral nutritional supplement containing EPA (ONS-EPA) for cachexia in AGC patients.

Chemotherapy-naive AGC patients with cachexia, defined by serum albumin < 3.5 g/dl and C-reactive protein ≥ 0.5 mg/dl, were included. Patients received an EPA-enriched supplement (Prosure®, 1.056 g EPA/pack) twice daily during first-line chemotherapy. The primary endpoint was time to treatment failure (TTF) in patients adhering to ≥ 25% of the planned ONS-EPA dose in the first two weeks (per-protocol set, PPS). Secondary analyses evaluated adherence impact on treatment outcomes.

Of 72 enrolled patients, 65 were evaluated. Median adherence was 42.8%. Median TTF in the PPS group was 4.8 months (95% CI 3.6-5.5), below the pre-set 4-month threshold. The PPS group had a higher proportion of patients who improved their nutritional and inflammatory status during treatment, along with better TTF and overall survival (OS) compared to those with poor adherence. Adjusted median TTF was 4.6 vs. 2.5 months (hazard ratio: 0.56; 95% CI 0.28-1.12, p = 0.105).

Although the primary endpoint was not achieved, the study suggests that ONS-EPA may benefit AGC patients with cachexia.

The MOUSEION-010 Meta-Analysis assessed the association between nutritional status and clinical outcomes such as Progression Free Survival (PFS) and Overall Survival (OS) among cancer patients treated with immune checkpoint inhibitors (ICIs).

Nutritional status was assessed based on the Prognostic Nutrition Index (PNI), Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) indexes. Databases consulted were: Embase, PubMed, Scopus and Web of Science.

PNI and GNRI indexes did not show a significant association with both PFS and OS, while CONUT index displayed a significant difference in PFS between the two groups, in favor of the control group (Z = 4.04; p < 0.01) also without any publication bias (β= -1.27; 95% CI = [-2.13; -0.42]; p = 0.10]). The same trend was recorded in OS, too (Z = 4.24; p < 0.01). However, publication bias was present (β = 1.89; 95% CI = [1.26; 2.54]; p = 0.028]) and the numerosity of the studies did not reveal the sufficient statistical power to obtain reliable results.

Malnutrition could negatively impact cancer patients, especially in advanced phases. Our findings could be associated with the reduction of physical ability and daily activity performance, lower compliance with treatment protocols, and shorter survival outcomes.

Cancer cachexia is a multifactorial syndrome characterized by persistent skeletal muscle loss, with or without fat loss, which cannot be completely reversed by traditional nutritional support and leads to impaired organ function. Cachexia seriously reduces the quality of life of (QOL) patients, affects the therapeutic effect against cancers, increases the incidence of complications, and is an important cause of death for patients with advanced cancers. To date, no effective medical intervention has completely reversed cachexia, and no medication has been agreed upon. Here, we describe recent advances in the diagnosis, molecular mechanism and treatment of cancer-related cachexia.

There is a lack of evidence for compliance with and the acceptability of oral nutritional supplements (ONS) by post-acute care patients. Therefore, the present study examined compliance with fat-free ONS, which are easy to drink. Patients who started oral intake in the general ward after being transferred from the Emergency Department were offered three ONS including fat-free ONS: Isocal Clear, Maybalance Mini, and Medimil, three times a day for three days. On days 1 and 3, patients evaluated each ONS using a questionnaire. Thirty-five eligible patients participated in the present study, which began a median of 10 days after their admission. Median taste ratings for Isocal Clear, Maybalance, and Medimil on day 1 were 8, 7, and 3, respectively, while median ease-to-drink ratings were 8, 7, and 5, respectively. In contrast, median taste ratings on day 3 were 5, 0, and 0, respectively, while median ease-to-drink ratings were 7, 1, and 0, respectively. Intakes of the prescribed diet during the three days had a median value as low as 30-50%. In conclusion, good compliance with fat-free ONS by post-acute care patients may be achieved.

There is general consensus that an improper diet negatively impacts health and that nutrition is a primary tool for the prevention of non-communicable diseases. Unfortunately, the importance of studying body composition, which can reveal early predictors of gender-related diseases, is still not well understood in this context. Currently, individuals are still classified as obese based solely on their body mass index, without considering the amount of fat, its distribution, and the quantity of muscle and bone mass. In this regard, the body composition phenotype defined as "osteosarcopenic obesity" affects approximately 6-41 % of postmenopausal women, with prevalence increasing with age due to the hormonal and metabolic changes that occur during this period. This particular phenotype arises from the strong relationship between visceral fat, muscle, bone, and gut microbiota and predispose postmenopausal women to frailty. Frailty is a complex clinical phenomenon with significant care and economic implications for our society. Recent studies suggest that women have a higher prevalence of frailty syndrome and its individual components, such as osteoporosis, fractures and sarcopenia, compared to men. Here, we provide a comprehensive overview of recent advances regarding the impact of gender on body composition and frailty. Furthermore, we reflect on the crucial importance of personalized nutritional interventions, with a focus on reducing visceral fat, increasing protein intake and optimizing vitamin D levels. A review of the scientific literature on this topic highlights the importance of studying body composition for a personalized and gender-specific approach to nutrition and dietetics, in order to identify frailty syndrome early and establish personalized treatments. This new method of researching disease predictors could likely help clarify the controversial results of studies on vitamin D, calcium and proteins, translate into practical wellness promotion across diverse elderly populations.

Energy requirement assessment is a cornerstone for nutrition practice. The extent to which total energy expenditure (TEE; indicator of energy requirements) has been measured in adults with chronic diseases has not been explored.

This systematic review aimed to characterize evidence on TEE among individuals with chronic diseases and describe TEE across chronic diseases and in comparison to controls without a chronic disease.

A literature search using terms related to doubly labeled water and TEE was conducted in PubMed, MEDLINE, Web of Science, and Embase. Eligible articles included those that measured TEE using doubly labeled water in adults with a major chronic disease. Methodological quality was determined using the Academy of Nutrition and Dietetics quality criteria checklist. Sample size-weighted TEE was calculated in each chronic disease subgroup.

Fifty studies were included, of which 15 had a control group. Median sample size was 20 participants, and approximately half of studies were published over 10 y ago. Thirty-five (70%) studies reported resting energy expenditure, and approximately half (k = 26) reported physical activity level. Methodological quality was neutral (k = 25) or positive (k = 23) for most studies. TEE among individual studies ranged from 934 to 3274 kcal/d. Mean weighted TEE was lowest among gastrointestinal (1786 kcal/d) and neurologic (2104 kcal/d) subgroups and highest among cancer (2903 kcal/d), endocrine (2661 kcal/d), and autoimmune (2625 kcal/d) subgroups. Excluding 1 article in cancer survivors resulted in a low TEE in the cancer subgroup (2112 kcal/d). Most studies with a control group reported no differences in TEE between controls and patients; however, only 1 study was powered for between-group comparisons.

Energy requirements vary across chronic diseases, although there is insufficient evidence to suggest that TEE in patients with chronic disease is different than that among controls. Further research is needed to inform energy requirement recommendations that consider chronic disease. This review was registered at PROSPERO as CRD42022336500 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336500).

It remains unclear what causes esophageal cancer (EC), but blood metabolites have been connected to it. Our study performed a Mendelian randomization (MR) analysis to assess the causality from genetically proxied 1400 blood metabolites to EC level. A two-sample MR analysis was employed to evaluate the causal relationship between 1400 blood metabolites and EC. Initially, the EC genome-wide association study (GWAS) data (from Jiang L et al) were examined, leading to the identification of certain metabolites. Subsequently, another set of EC GWAS data from FINNGEN was utilized to validate the findings. Causality was primarily determined through inverse variance weighting, with additional support from the MR-Egger, weighted median, and MR-PRESSO models. Heterogeneity was assessed using the MR Cochran Q test. The MR-Egger intercept and MR-PRESSO global methods were employed to detect multicollinearity. In this study, Bonferroni corrected P value was used for significance threshold. We found 2 metabolites with overlaps, which are lipids. Docosatrienoate (22:3n3) was found to be causally associated with a decreased risk of EC, as evidenced by the EC GWAS data (from Jiang et al) (odds ratio [OR] = 0.620, 95% confidence interval [CI] = 0.390-0.986, P = .044) and the EC GWAS data (from FINNGEN) (OR = 0.77, 95% CI = 0.6-0.99, P = .042), these results were consistent across both data sets. Another overlapping metabolite, glycosyl-N-(2-hydroxyneuramoyl)-sphingosine, was associated with the risk of ES, with EC GWAS data (from Jiang L et al) (OR = 1.536, 95% CI = 1.000-2.360, P = .049), while EC GWAS data (from FINNGEN) (OR = 0.733, 95% CI = 0.574-0.937, P = .013), the 2 data had opposite conclusions. The findings of this study indicate a potential association between lipid metabolites (Docosatrienoate (22:3n3) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1 (2OH))) and the risk of esophageal carcinogenesis.

Accurate assessment of dietary intake, especially energy and protein intake, is crucial for optimizing nutritional care and outcomes in patients with cancer. Validation of dietary assessment methods is necessary to ensure accuracy, but the validity of these methods in patients with cancer, and especially in those with cancer cachexia, is uncertain. Validating nutritional intake is complex because of the variety of dietary methods, lack of a gold standard method, and diverse validation measures. Here, we review the literature on validations of dietary intake methods in patients with cancer, including those with cachexia, and highlight the gap between current validation efforts and the need for accurate dietary assessment methods in this population.

We analyzed eight studies involving 1479 patients with cancer to evaluate the accuracy and reliability of 24-hour recalls, food records, and food frequency questionnaires in estimating energy and protein intake. We discuss validation methods, including comparison with biomarkers, indirect calorimetry, and relative validation of dietary intake methods.

Few have validated dietary intake methods against objective markers in patients with cancer. While food records and 24-hour recalls show potential accuracy for energy and protein intake, this may be compromised in hypermetabolic patients. Additionally, under- and overreporting of intake may be less frequent, and the reliability of urinary nitrogen as a protein intake marker in patients with cachexia needs further investigation. Accurate dietary assessment is important for enhancing nutritional care outcomes in cachexia trials, requiring validation at multiple time points throughout the cancer trajectory.

Meta-analyses have been conducted with conflicting results on this topic. Due to missing several eligible studies in previous meta-analysis by Lam et al., we conducted an extensive systematic review and dose-response meta-analysis of randomized controlled trials in this regard. A comprehensive search was conducted across various databases, including MEDLINE/PubMed, ISI Web of Knowledge, Scopus, and Google Scholar, until November 2023. Based on the analysis of 33 studies comprising 2,047 individuals, it was found that there was a significant increase in body weight for each 1 g/day increase in omega-3 lipids (standardized MD [SMD], 0.52 kg; 95% confidence interval [CI], 0.31, 0.73; I2 = 95%; Grading of Recommendations Assessment, Development and Evaluation [GRADE] = low). Supplementation of omega-3 fatty acids did not yield a statistically significant impact on body mass index (BMI) (SMD, 0.12 kg/m2; 95% CI, -0.02, 0.27; I2 = 79%; GRADE = very low), lean body mass (LBM) (SMD, -0.02 kg; 95% CI, -0.43, 0.39; I2 = 97%; GRADE = very low), fat mass (SMD, 0.45 kg; 95% CI, -0.25, 1.15; I2 = 96%; GRADE = low), and body fat (SMD, 0.30%; 95% CI, -0.90, 1.51; I2 = 96%; GRADE = very low). After excluding 2 studies, the findings were significant for BMI. Regarding the results of the dose-response analysis, body weight increased proportionally by increasing the dose of omega-3 supplementation up to 4 g/day. Omega-3 fatty acid supplementation can improve body weight, but not BMI, LBM, fat mass, or body fat in cancer patients; large-scale randomized trials needed for more reliable results.

PROSPERO Identifier: CRD42023395341.

Malnutrition is a common condition in lung cancer, and it is an independent prognostic factor. The main objective of this study was to determine whether an early improvement at 3 months in the nutritional status (NS) of patients undergoing immune checkpoint inhibitor (ICI) is associated with a tumor response to treatment at 6-month follow-up. The clinical data of 106 patients initiating ICI for bronchopulmonary non-small cell lung cancer (NCSLC) were retrospectively reviewed. NS was defined according to the HAS 2019 recommendation, depending on BMI, percentage of weight loss, and albuminemia. NS was assessed at baseline (M0) and 3 months (M3) after ICI treatment initiation according to 3 categories: well-nourished, malnourished, and very malnourished. The NS evolution of the 92 patients who were still alive at 3 months was determined. The proportion of patients with malnutrition at M0 and M3 was 39.6% and 43.3%. Median follow-up was 18.7 months. OS and PFS were longer for patients in the M0 well-nourished group than in the malnourished and very malnourished groups. Patients who remained well-nourished had a significantly better ICI success rate at 6 months than patients who remained malnourished or improved or deteriorated their NS. OS was significantly longer for remaining well-nourished patients compared to the amelioration group and the degradation group. PFS was not significantly modified between the 4 evolution groups. Maintaining good NS during the first months of ICI treatment leads to better OS and objective response rate than remaining malnourished or early deteriorating NS. However, an early improvement in NS does not seem to predict a good tumor response to treatment and not a better OS either.

Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE).

A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015.

A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis.

MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.

The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia.

In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses.

The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia.

The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Introduction: energy metabolism in cancer patients is influenced by different factors. However, the effect of antineoplastic treatment is not clear, especially in women. Objective: to evaluate resting energy expenditure (REE) by indirect calorimetry (IC) before (T0) and after (T1) first cycle period of antineoplastic therapy: radiotherapy (RT), chemotherapy (CT), and concomitant chemoradiation therapy (CRT), quality of life (QoL) and accuracy of REE were compared with international guidelines recommendations per kilogram (European Society for Clinical Nutrition and Metabolism [ESPEN]). Methods: an observational, longitudinal study was conducted in women with gynecological cancer diagnosis undergoing antineoplastic treatment: RT, CT and CRT. Weight loss, actual body weight and height were measured. REE was evaluated in T0-T1 and compared with ESPEN recommendations. Kruskal-Wallis test and Bland-Alman analysis were used to determine the agreement (± 10 % of energy predicted) of REE adjusted by physical activity (TEE) compared with ESPEN recommendations, respectively. Results: fifty-four women with cancer were included: 31.5 % (n = 17) for RT group, 31.5 % (n = 17) for CT group and 37 % (n = 20) for CRT group. REE showed statistical differences between T0 and T1 in the total population (p = 0.018), but these were not associated with anticancer therapy groups (p > 0.05). QoL had no significant changes after treatment (p > 0.05). Accuracy of 25 and 30 kcal/kg compared to TEE was less than 30 %. Conclusion: REE in women with gynecological cancer decreased after antineoplastic treatments but this is not associated with a particular antineoplastic therapy. It is needed to develop research to determine the accuracy of ESPEN recommendations with TEE estimated by IC and clinical factors in women with cancer.

Cancer cachexia is a debilitating syndrome associated with marked body loss because of muscular atrophy and fat loss. There are several mechanisms contributing to the pathogenesis of cachexia. The presence of the tumor releases cytokines from inflammatory and immune cells, which play a significant role in activating and deactivating certain pathways associated with protein, carbohydrate, and lipid metabolism. This review focuses on various cascades involving an imbalance between protein synthesis and degradation in the skeletal muscles.

This study aimed to elucidate the mechanisms involved in skeletal muscle wasting phenomenon over the last few years.

This article briefly overviews different pathways responsible for muscle atrophy in cancer cachexia. Studies published up to April 2023 were included. Important findings and study contributions were chosen and compiled using several databases including PubMed, Google Scholar, Science Direct, and ClinicalTrials.gov using relevant keywords.

Cancer cachexia is a complex disease involving multiple factors resulting in atrophy of skeletal muscles. Systemic inflammation, altered energy balance and carbohydrate metabolism, altered lipid and protein metabolism, and adipose tissue browning are some of the major culprits in cancer cachexia. Increased protein degradation and decreased protein synthesis lead to muscle atrophy. Changes in signaling pathway like ubiquitin-proteasome, autophagy, mTOR, AMPK, and IGF-1 also lead to muscle wasting. Physical exercise, nutritional supplementation, steroids, myostatin inhibitors, and interventions targeting on inflammation have been investigated to treat cancer cachexia. Some therapy showed positive results in preclinical and clinical settings, although more research on the efficacy and safety of the treatment should be done.

Muscle atrophy in cancer cachexia is the result of multiple complex mechanisms; as a result, a lot more research has been done to describe the pathophysiology of the disease. Targeted therapy and multimodal interventions can improve clinical outcomes for patients.

Malnutrition is prevalent in people with upper gastrointestinal (GI) cancers and is associated with shorter survival and poor quality of life. In order to effectively prevent or treat malnutrition, nutrition interventions must ensure appropriate energy provision to meet daily metabolic demands. In practice, the energy needs of people with cancer are frequently estimated from predictive equations which are not cancer-specific and are demonstrated to be inaccurate in this population. The purpose of this scoping review was to synthesize the existing evidence regarding energy expenditure in people with upper GI cancer. Three databases (Ovid MEDLINE, Embase via Ovid, CINAHL plus) were systematically searched to identify studies reporting on resting energy expenditure using indirect calorimetry and total energy expenditure using doubly labeled water (DLW) in adults with any stage of upper GI cancer at any point from diagnosis. A total of 57 original research studies involving 2,125 individuals with cancer of the esophagus, stomach, pancreas, biliary tract, or liver were eligible for inclusion. All studies used indirect calorimetry, and one study used DLW to measure energy expenditure, which was reported unadjusted in 42 studies, adjusted for body weight in 32 studies, and adjusted for fat-free mass in 13 studies. Energy expenditure in upper GI cancer was compared with noncancer controls in 19 studies and measured compared with predicted energy expenditure reported in 31 studies. There was heterogeneity in study design and in reporting of important clinical characteristics between studies. There was also substantial variation in energy expenditure between studies and within and between cancer types. Given this heterogeneity and known inaccuracies of predictive equations in patients with cancer, energy expenditure should be measured in practice wherever feasible. Additional research in cohorts defined by cancer type, stage, and treatment is needed to further characterize energy expenditure in upper GI cancer.

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB, or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, the fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols. The clinical trial protocol has been registered at the platform for Clinical Trials (NCT05486260).

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 a systemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss of appetite, 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.

Skeletal muscle indices have been associated with improved peri-operative outcomes after surgical resection of non-small-cell lung cancer (NSCLC). However, it is unclear if these indices can predict long term cancer specific outcomes.

NSCLC patients undergoing lobectomy at our institute between 2009-2015 were included in this analysis (N = 492). Preoperative CT scans were used to quantify skeletal muscle index (SMI) at L4 using sliceOmatic software. Cox proportional modelling was performed for overall (OS) and recurrence free survival (RFS).

For all patients, median SMI was 45.7 cm2/m2 (IQR, 40-53.8). SMI was negatively associated with age (R = -0.2; p < 0.05) and positively associated with BMI (R = 0.46; P < 0.05). No association with either OS or RFS was seen with univariate cox modelling. However, multivariable modelling for SMI with patient age, gender, race, smoking status, DLCO and FEV1 (% predicted), American Society of Anesthesiology (ASA) score, tumor histology and stage, and postoperative neoadjuvant therapy showed improved OS (HR = 0.97; P = 0.0005) and RFS (HR = 0.97; P = 0.01) with SMI. Using sex specific median SMI as cutoff, a lower SMI was associated with poor OS (HR = 1.65, P = 0.001) and RFS (HR = 1.47, P = 0.03).

SMI is associated with improved outcomes after resection of NSCLC. Further studies are needed to understand the biological basis of this observation. This study provides additional rationale for designing and implementation of rehabilitation trials after surgical resection, to gain durable oncologic benefit.

Total energy expenditure (TEE) determines energy requirements, but objective data in patients with cancer are limited.

We aimed to characterize TEE, investigate its predictors, and compare TEE with cancer-specific predicted energy requirements.

This cross-sectional analysis included patients with stages II-IV colorectal cancer from the Protein Recommendation to Increase Muscle (PRIMe) trial. TEE was assessed by 24-h stay in a whole-room indirect calorimeter before dietary intervention and compared with cancer-specific predicted energy requirements (25-30 kcal/kg). Generalized linear models, paired-samples t tests, and Pearson correlation were applied.

Thirty-one patients (56 ± 10 y; body mass index [BMI]: 27.9 ± 5.5 kg/m2; 68% male) were included. Absolute TEE was higher in males (mean difference: 391 kcal/d; 95% CI: 167, 616 kcal/d; P < 0.001), patients with colon cancer (mean difference: 279 kcal/d; 95% CI: 73, 485 kcal/d; P = 0.010), and patients with obesity (mean difference: 393 kcal/d; 95% CI: 182, 604 kcal/d; P < 0.001). Appendicular lean soft tissue (β: 46.72; 95% CI: 34.27, 59.17; P < 0.001) and tumor location (colon-β: 139.69; 95% CI: 19.44, 259.95; P = 0.023) independently predicted TEE when adjusted for sex. Error between measured TEE and energy requirements predicted by 25 kcal/kg (mean difference: 241 kcal/d; 95% CI: 76, 405 kcal/d; P = 0.010) or 30 kcal/kg (mean difference: 367 kcal/d; 95% CI: 163, 571 kcal/d; P < 0.001) was higher for patients with obesity, and proportional error was observed (25 kcal/kg: r = -0.587; P < 0.001; and 30 kcal/kg: r = -0.751; P < 0.001). TEE (mean difference: 25 kcal/kg; 95% CI: 24, 27 kcal/kg) was below predicted requirements using 30 kcal/kg (-430 ± 322 kcal/d; P < 0.001).

This is the largest study to assess TEE of patients with cancer using whole-room indirect calorimeter and highlights the need for improved assessment of energy requirements in this population. Energy requirements predicted using 30 kcal/kg overestimated TEE by 1.44 times in a controlled sedentary environment and TEE was outside of the predicted requirement range for most. Special considerations are warranted when determining TEE of patients with colorectal cancer, such as BMI, body composition, and tumor location. This is a baseline cross-sectional analysis from a clinical trial registered at clinicaltrials.gov as NCT02788955 (https://clinicaltrials.gov/ct2/show/NCT02788955).

Supportive care plays a central role in the management of patients with esophagogastric cancers, at all disease stages. Malnutrition has a high prevalence in this population, reaching up to 60 % of the patients. Sarcopenia and cachexia are also common. These complications have negative impact on functional abilities, quality of life and overall survival. They impair anti-tumor treatments effectiveness and increase their toxicity. Early detection and management are needed, before reaching advanced stages, which are refractory to therapeutic interventions. Specific nutritional support is recommended, relying on different nutritional support tools (dietetic counseling, oral supplements, artificial nutrition), depending on the clinical situation. When artificial nutrition is recommended, enteral nutrition (nasogastric tube, gastrostomy or jejunostomy) should be preferred. When enteral nutrition is impossible or insufficient, parenteral nutrition could be necessary. For patients with advanced esophagogastric cancers, digestive prostheses and decompressive radiation therapy may have a symptomatic benefit on dysphagia. Adapted physical activity is also recommended at all stages of cancer care and ongoing clinical trials will help to specify its modalities and to optimize its place in the therapeutic strategy. Finally, psychosocial support could be useful. A combined approach of these different interventions on the nutritional, physical and psychological aspects is beneficial for patients with esophagogastric cancers. This multimodal and multidisciplinary approach applies to both the early stages of the disease, with prehabilitation and/or rehabilitation to reduce perioperative morbidity and mortality and the advanced stages, with a benefit on survival and quality of life, in parallel with anti-tumor treatments.

Objective nutritional scoring systems using preoperative blood samples have shown the potential to predict the postoperative outcomes of patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether the prognostic impact depends on age and comorbid burdens. We conducted this study to validate the impact of preoperative nutritional status, stratified with age and comorbidity.

We reviewed the preoperative prognostic nutritional index (PNI) and postoperative outcomes of 713 consecutive patients with completely resected NSCLC.

We identified the optimal cutoff values of the PNI as 46. Significantly higher postoperative complication rates and worse survival rates were observed in the low PNI (≤ 46) group, regardless of age/comorbidity burdens. Multivariate analysis showed that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (hazard ratio: 2.5). A matched-pair analysis gave consistent results, showing that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (OS; hazard ratio: 1.8) and recurrence-free survival (RFS; hazard ratio: 1.6).

Nutritional status, indexed by the PNI, is a strong prognostic factor for the postoperative outcomes of patients undergoing curative resection for NSCL, regardless of age/comorbidity burdens.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives.

The objective of this study was to gain insights into the patients' perspectives on the impact of cancer cachexia on physical activity and their willingness to wear digital health technology (DHT) devices in clinical trials.

We administered a quantitative 20-minute online survey on aspects of physical activity (on a 0-100 scale) to 50 patients with cancer cachexia recruited through Rare Patient Voice, LLC. A subset of 10 patients took part in qualitative 45-minute web-based interviews with a demonstration of DHT devices. Survey questions related to the impact of weight loss (a key characteristic in Fearon's cachexia definition) on physical activity, patients' expectations regarding desired improvements and their level of meaningful activities, as well as preferences for DHT.

Seventy-eight percent of patients reported that their physical activity was impacted by cachexia, and for 77% of them, such impact was consistent over time. Patients perceived most impact of weight loss on walking distance, time and speed, and on level of activity during the day. Sleep, activity level, walking quality and distance were identified as the most meaningful activities to improve. Patients would like to see a moderate improvement of activity levels and consider it meaningful to perform physical activity of moderate intensity (eg, walk at normal pace) on a regular basis. The wrist was the preferred location for wearing a DHT device, followed by arm, ankle, and waist.

Most patients reported physical activity limitations since the occurrence of weight loss compatible with cancer-associated cachexia. Walking distance, sleep and quality of walk were the most meaningful activities to moderately improve, and patients consider moderate physical activity as meaningful. Finally, this study population found the proposed wear of DHT devices on the wrist and around the waist acceptable for the duration of clinical studies.

Early recognition of cachexia is essential for ensuring the prompt intervention and treatment of cancer patients. However, the diagnosis of cancer cachexia (CC) usually is delayed. This study aimed to establish an accurate and high-efficiency diagnostic system for CC.

A total of 4834 cancer inpatients were enrolled in the INSCOC project from July 2013 to June 2020. All cancer patients in the study were randomly assigned to a development cohort (n=3384, 70%) and a validation cohort (n=1450, 30%). The least absolute shrinkage and selection operator (LASSO) method and multivariable logistic regression were used to identify the independent predictors for developing the dynamic nomogram. Discrimination and calibration were adopted to evaluate the ability of nomogram. A decision curve analysis (DCA) was used to evaluate clinical use.

We combined 5 independent predictive factors (age, NRS2002, PG-SGA, QOL by the QLQ-C30, and cancer categories) to establish the online dynamic nomogram system. The C-index, sensitivity, and specificity of the nomo-system to predict CC was 0.925 (95%CI, 0.916-0.934, P < 0.001), 0.826, and 0.862 in the development set, while the values were 0.923 (95%CI, 0.909-0.937, P < 0.001), 0.854, and 0.829 in the validation set. In addition, the calibration curves of the diagnostic nomogram also presented good agreement with the actual situation. DCA showed that the model is clinically useful and can increase the clinical benefit in cancer patients.

This study developed an online dynamic nomogram system with outstanding accuracy to help clinicians and dieticians estimate the probability of cachexia. This simple-to-use online nomogram can increase the clinical benefit in cancer patients and is expected to be widely adopted.

Omega-3 fatty acids are bioactive nutrients with the potential to preserve lean body mass in individuals with cancer. This study aimed to review the literature on randomized clinical trials that evaluated the effects of omega-3 supplementation on lean body mass in cancer patients. As secondary objectives, we evaluated the effects of omega-3 supplementation on body mass index (BMI) and body weight. We conducted a systematic review and meta-analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase. It included randomized clinical trials that investigated the effects of omega-3 supplementation on lean body mass in cancer patients. Observational studies, animal experiments, studies carried out with healthy humans, and non-randomized clinical trials were excluded. We utilized the Cochrane scale to assess the quality of the studies. A meta-analysis was carried out to evaluate the effect of omega-3 on lean body mass, BMI, and body weight. Fourteen studies were included, of which four showed significant results from omega-3 supplementation for lean body mass. In the meta-analysis, omega-3 fatty acids increased lean body mass by 0.17 kg compared to placebo, but without significant differences between the groups [SMD: 0.17; CI 95%: -0.01, 0.35; I2 = 41%]. For body weight, omega-3 showed a statistically significant effect [SMD: 0.26; CI 95%: 0.06, 0.45; I2 = 46%], whereas for BMI the results were not significant. This systematic review and meta-analysis showed no statistically significant effect from omega-3 on lean body mass and BMI. On the other hand, there was a statistical significance for body weight.

Several clinical trials have reported that patients with cancer cachexia can benefit from n-3 polyunsaturated fatty acids (n-3 PUFAs) supplements; however, the results have been conflicting. This systematic review and meta-analysis aimed to evaluate the effect of n-3 PUFAs on cancer cachexia. A search of the PubMed, Embase, and Cochrane Library databases was performed to identify the included randomized controlled trials. Trials including patients with cancer cachexia who were administered a course of n-3 PUFAs were included. A meta-analysis on body weight, lean body weight, proinflammatory factors, quality of life, and median duration of survival was conducted. A total of 12 randomized controlled trials with 1184 patients were included. No effect on body weight (standard mean difference [SMD], 0.10; 95% CI, -0.06 to 0.26; P = .236), lean body weight (SMD, -0.17; 95% CI, -0.36 to 0.03, P = .095), or proinflammatory factors (interleukin-6: SMD, 0.31; 95% CI, -0.14 to 0.75; P = .18; tumor necrosis factor-α: SMD, -0.85; 95% CI, -2.39 to 0.69; P = .28) was observed. The use of n-3 PUFAs was associated with a significant improvement in quality of life (SMD, 0.70; 95% CI, 0.01-1.40; P = .048) and median duration of survival (median survival ratio, 1.10; 95% CI, 1.02-1.19; P = .014). For patients with cancer cachexia, our meta-analysis indicated that n-3 PUFAs improved quality of life and survival, but not body weight.

Pancreatic ductal adenocarcinoma (PDAC) is associated with complex changes in body composition. Visceral obesity and type 2 diabetes mellitus are established risk factors for developing PDAC; however, clinical and metabolic features of PDAC commonly lead to cancer cachexia, a hypermetabolic syndrome characterized by weight loss secondary to muscle and adipose tissue wasting. Reduction in muscle mass in patients with PDAC is associated with poorer survival in patients undergoing surgical resection and increased chemotherapy toxicity. Although no standardized treatment exists, a multidisciplinary, tailored, symptom-based approach is recommended to improve outcomes and quality of life for patients with PDAC and cachexia.

Oral nutritional support (ONS) is a form of supportive intervention in patients' diet in response to insufficient oral intake, malabsorption, or functional insufficient food intake during the disease process. This study aimed to evaluate the nutritional status, morbidity, re-admissions, functional status, QoL of patients who had undergone elective colorectal cancer surgery and initiated home ONS. A total of 144 patients who had undergone colorectal cancer surgery and given home ONS were analyzed with regard to demographics, diagnosis, weight-BMI changes, re-admissions, morbidity, daily caloric and protein intake, functional status (Barthel index) and QoL (The Satisfaction with Life Scale-SWLS). The mean age was 65,6 ± 12,8 with a Female/Male ratio of 53/91. The mean BMI increased from 25.71 ± 3.81 to 28,35 ± 4,53 (p < 0.0001). Re-admission was significantly higher in patients who had received 600 kcal (55.8%) than those who received 900 kcal (40.2%) (p = 0.007). Furthermore, adaptation to chemotherapy (p = 0.02) and the Bartel index scores (p = 0.001) were significantly worse in patients who received 600 kcal compared to patients who received 900 kcal; however, the complication rate (p = 0.84), adaptation to radiotherapy (p = 0.68) and the QoL scores (p = 0.35) were not significantly different. Home ONS improved the BMI in all patients. In addition, ONS resulted in good outcomes with regard to adaptation to chemotherapy and the functional status in the treatments of patients with colorectal cancer.

Exercise can lower the risk of developing pancreatic cancer and has the potential to improve physical fitness and quality of life in patients with the disease. Yet, the effects of exercise training during pancreatic cancer treatment remain poorly characterized. This hampers the development of evidence-based disease-specific exercise recommendations.

The purpose of this review was to describe and interpret the effect of exercise on physiological, QoL, and cancer-specific outcomes reported in clinical trials among pancreatic cancer patients during treatment.

We conducted a scoping review of the literature according to the framework proposed by Arksey and O'Malley. Articles published prior to December 2021 were retrieved from PubMed, EMBASE, and Scopus. We only included studies that prescribed structured cardiorespiratory and/or resistance exercise in pancreatic cancer patients undergoing treatment.

A total of 662 references were retrieved, of which 24 are included in the review. Twelve articles were randomized controlled trials and 12 were single-arm trials. Overlap in the trials from which data were reported occurred in 16 articles. Moderate intensity exercise was most commonly prescribed, reported feasible for most patients, with potential to enhance physical fitness and QoL. However, exercise adherence and beneficial effects may diminish with disease progression. Limited evidence suggests exercise may benefit cancer-specific outcomes.

The results of this review indicate that exercise is feasible during pancreatic cancer treatment. Exercise can also improve physical fitness and QoL. However, its beneficial effects may fall with advanced disease and more rigorous research is needed to develop precise exercise protocols for this population.

Pancreatic cancer patients often present with an inadequate nutritional intake. At the same time, there are no standardized recommendations for nutrition intake during and after cancer treatment. In a prospective analysis of a randomized controlled trial analyzing the effects of a 6-month resistance training in pancreatic cancer patients, we assessed the nutritional intake and the impact of a 6-month supervised resistance training or home-based resistance training vs. usual care control on the nutritional intake of the patients. Nutritional intake was assessed by 24-h recall before and after the 6-month resistance training period. At baseline low protein intake (<1 g/kg body weight) was found in 33.9% of the 59 patients and low energy intake (<25 kcal/kg body weight) was found in 39.0% of the patients. In all, 35.6% of the patients were classified with a risk of malnutrition (NRS ≥ 3). In the total of 46 patients who finished the 6-month intervention period, there was no difference in nutritional intake over time between resistance training and usual care control. In conclusion, it appears that the majority of our study population had an adequate protein and energy intake. A resistance training seems to have no influence on the nutritional intake of the patients.

Cancer-associated cachexia (CC) is a pathological condition characterized by sarcopenia, adipose tissue depletion, and progressive weight loss. CC is driven by multiple factors such as anorexia, excessive catabolism, elevated energy expenditure by growing tumor mass, and inflammatory mediators released by cancer cells and surrounding tissues. In addition, endocrine system, systemic metabolism, and central nervous system (CNS) perturbations in combination with cachexia mediators elicit exponential elevation in catabolism and reduced anabolism in skeletal muscle, adipose tissue, and cardiac muscle. At the molecular level, mechanisms of CC include inflammation, reduced protein synthesis, and lipogenesis, elevated proteolysis and lipolysis along with aggravated toxicity and complications of chemotherapy. Furthermore, CC is remarkably associated with intolerance to anti-neoplastic therapy, poor prognosis, and increased mortality with no established standard therapy. In this context, we discuss the spatio-temporal changes occurring in the various stages of CC and highlight the imbalance of host metabolism. We provide how multiple factors such as proteasomal pathways, inflammatory mediators, lipid and protein catabolism, glucocorticoids, and in-depth mechanisms of interplay between inflammatory molecules and CNS can trigger and amplify the cachectic processes. Finally, we highlight current diagnostic approaches and promising therapeutic interventions for CC.

Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC).

We performed a retrospective cohort study of patients diagnosed with HCC at 2 United States health systems between 2008 and 2018. Patient weights were recorded 6 months prior to and at time of HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if body mass index <20 kg/m²), and precachexia was defined as 2% to 5% weight loss. We used multivariable logistic regression models to identify correlates of cachexia and multivariable Cox proportional hazard models to identify factors associated with overall survival.

Of 604 patients with HCC, 201 (33.3%) had precachexia and 143 (23.7%) had cachexia at diagnosis, including 19.0%, 23.5%, 34.7%, and 34.0% of patients with Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. Patients with cachexia were less likely to receive HCC treatment (odds ratio, 0.38; 95% confidence interval, 0.21-0.71) and had worse survival than those with precachexia or stable weight (11.3 vs 20.4 vs 23.5 months, respectively; P < .001). Cachexia remained independently associated with worse survival (hazard ratio, 1.43; 95% confidence interval, 1.11-1.84) after adjusting for age, sex, race, ethnicity, Child Pugh class, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and HCC treatment.

Nearly 1 in 4 patients with HCC present with cachexia, including many with compensated cirrhosis or early stage tumors. The presence of cancer-associated weight loss appears to be an early and independent predictor of worse outcomes in patients with HCC.

(1) Background: Pancreatic cancer (PaCa) is directly related to malnutrition, cachexia and weight loss. Nutritional interventions (NI) are used in addition to standard therapy. The aim of this systematic review is to provide an overview of the types of NI and their effects. (2) Methods: We included RCTs with at least one intervention group receiving an NI and compared them with a control group with no NI, placebo or alternative treatment on cachexia, malnutrition or weight loss in patients with PaCa. Any available literature until 12 August 2021 was searched in the Pubmed and Cochrane databases. RCTs were sorted according to NI (parenteral nutrition, enteral nutrition, dietary supplements and mixed or special forms). (3) Results: Finally, 26 studies with a total of 2720 patients were included. The potential for bias was mostly moderate to high. Parenteral nutrition is associated with a higher incidence of complications. Enteral nutrition is associated with shorter length of stay in hospital, lower rate and development of complications, positive effects on cytokine rates and lower weight loss. Dietary supplements enriched with omega-3 fatty acids lead to higher body weight and lean body mass. (4) Conclusions: Enteral nutrition and dietary supplements with omega-3 fatty acids should be preferred in nutritional therapy of PaCa patients.

For persons who survive with progressive cancer, nutritional therapy and exercise may be significant factors to improve the health condition and life quality of cancer patients. Nutritional therapy and medications are essential to managing progressive cancer. Cancer survivors, as well as cancer patients, are mostly extremely encouraged to search for knowledge about the selection of diet, exercise, and dietary supplements to recover as well as maintain their treatment consequences, living quality, and survival of patients. A healthy diet plays an important role in cancer treatment. Different articles are studied to collect information and knowledge about the use of nutrients in cancer treatment as well as cancer prevention. The report deliberates nutrition and exercise strategies during the range of cancer care, emphasizing significant concerns during treatment of cancer and for patients of advanced cancer, but concentrating mostly on the requirements of the population of persons who are healthy or who have constant disease following their repossession from management. It also deliberates choice nutrition and exercise problems such as dietary supplements, food care, food selections, and weight; problems interrelated to designated cancer sites, and common questions about diet, and cancer survival. Decrease the side effects of medicines both during and after treatment.

Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients.

We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC.

A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome.

Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients.

Male C57BL/6J mice (12 wk of age) were injected with 1 × 106 LLC cells or phosphate-buffered saline (PBS) subcutaneously in the right flank, and tissue was collected 26-28 d after cell injection. Tumor volume was measured every 5 d throughout the study to calculate the tumor growth rate. Fifteen days after tumor inoculation, a subset of PBS (n = 11) and LLC (n = 16) mice were individually housed in metabolic Comprehensive Laboratory Animal Monitoring System cages for 5 d.

LLC mice exhibited greater body weight loss (-5.1%), decreased muscle mass (-7%), decreased fat mass (-22%), and increased plasma interleukin-6 (212%) compared with PBS mice. Before the onset of cachexia, total cage activity was decreased in tumor-bearing mice. Cage activity was negatively associated with tumor mass and positively associated with hindlimb muscle mass. In addition, LLC mice had greater lipid oxidation than PBS mice.

LLC mice exhibit early-onset physical inactivity and altered systemic lipid oxidation, which are associated with the eventual development of cachexia.

Cancer cachexia, or progressive weight loss, often despite adequate nutrition contributes greatly to cancer morbidity and mortality. Cachexia is metabolically distinct from starvation or protein malnutrition, although many patients with cancer and cachexia exhibit lowered appetite and food consumption. Tumors affect neural mechanisms that regulate appetite and energy expenditure, while promoting wasting of peripheral tissues via catabolism of cardiac and skeletal muscle, adipose, and bone. These multimodal actions of tumors on the host suggest a need for multimodal interventions. However, multiple recent consensus guidelines for management of cancer cachexia differ in treatment recommendations, highlighting the lack of effective, available therapies. Challenges to defining appropriate nutrition or other interventions for cancer cachexia include lack of consensus on definitions, low strength of evidence from clinical trials, and a scarcity of robust, rigorous, and mechanistic studies. However, efforts to diagnose, stage, and monitor cachexia are increasing along with clinical trial activity. Furthermore, preclinical models for cancer cachexia are growing more sophisticated, encompassing a greater number of tumor types in organ-appropriate contexts and for metastatic disease to model the clinical condition more accurately. It is expected that continued growth, investment, and coordination of research in this topic will ultimately yield robust biomarkers, clinically useful classification and staging algorithms, targetable pathways, pivotal clinical trials, and ultimately, cures. Here, we provide an overview of the clinical and scientific knowledge and its limitations around cancer cachexia.

Advanced pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. This wasting has been linked to poor survival outcomes, alterations in host defenses, decreased functional ability, and diminished health-related quality of life (HRQOL) in pancreatic cancer patients. There are currently no standardized approaches to the management of pancreatic cancer cachexia. This study explores the feasibility and efficacy of enteral tube feeding of a peptide-based formula to improve weight stability and patient-reported outcomes (PROs) in advanced PDAC patients with cachexia.

This was a single-institution, single-arm prospective trial conducted between April 2015 and March 2019. Eligible patients were adults (>18 years) diagnosed with advanced or locally advanced PDAC and cachexia, defined as greater than 5% unexplained weight loss within 6 months from screening. The study intervention included three 28 day cycles of a semi-elemental peptide-based formula, administered through a jejunal or gastrojejunal feeding tube. The primary outcome was weight stability at 3 months (Cycle 3), defined as weight change less than 0.1 kg/baseline BMI unit from baseline. Secondary outcomes included changes in lean body mass, appendicular lean mass, bone mineral density, fat mass, and percent body fat, as measured with a DEXA scan, HRQOL (EORTC QLQC30) and NIH PROMIS PROs assessed at each cycle. Daily activity (steps, distance, active minutes, heart rate, and sleep) were remotely monitored using a wearable activity monitor (Fitbit) over the 3 month study period.

Thirty-six patients were screened for eligibility, 31 patients consented onto study and underwent jejunal tube placement, and 16 patients completed treatment: mean age 67 years (SD 9.3), 43.8% male. Among evaluable patients (n = 16), weight stability was achieved in 10 patients (62.5%), thus completing the trial early. Increases in lean body mass (1273.1, SD: 4078, P = 0.01) and appendicular lean mass (0.45, SD: 0.6, P = 0.02) were observed. Statistically significant improvements at Cycle 3 from baseline were also observed for QLQC30 role function [mean difference (MD): 20.1, P = 0.03], appetite (MD: 27.4, P = 0.02), and global health scores (MD: 13.3, P = 0.05) as well as for NIH PROMIS t-scores for depression (MD: -10.4, P = 0.006) and pain interference (MD: -7.5, P = 0.05). Objectively monitored (Fitbit) activity levels increased, although statistical significance was not reached.

Our findings suggest that enteral nutrition support may improve weight stability, lean body mass, appendicular lean mass and PROs in PDAC patients with cachexia who completed treatment, representing a subsample of the study population. The feasibility and role of enteral feeding in routine care remain unclear, and larger and randomized controlled trials are warranted.