Previous studies have shown that patients with chronic obstructive pulmonary disease (COPD) of severe or very severe airflow limitation have a reduced pectoralis muscle area (PMA), which is associated with mortality. However, whether patients with COPD of mild or moderate airflow limitation also have a reduced PMA remains unclear. Additionally, limited evidence is available regarding the associations between PMA and respiratory symptoms, lung function, computed tomography (CT) imaging, lung function decline, and exacerbations. Therefore, we conducted this study to evaluate the presence of PMA reduction in COPD and to clarify its associations with the referred variables.

This study was based on the subjects enrolled from July 2019 to December 2020 in the Early Chronic Obstructive Pulmonary Disease (ECOPD) study. Data including questionnaire, lung function, and CT imaging were collected. The PMA was quantified on full-inspiratory CT at the aortic arch level using predefined -50 and 90 Hounsfield unit attenuation ranges. Multivariate linear regression analyses were performed to assess the association between the PMA and airflow limitation severity, respiratory symptoms, lung function, emphysema, air trapping, and the annual decline in lung function. Cox proportional hazards analysis and Poisson regression analysis were used to evaluate the PMA and exacerbations after adjustment.

We included 1352 subjects at baseline (667 with normal spirometry, 685 with spirometry-defined COPD). The PMA was monotonically lower with progressive airflow limitation severity of COPD after adjusting for confounders (vs. normal spirometry; Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1: β=-1.27, P=0.028; GOLD 2: β=-2.29, P<0.001; GOLD 3: β=-4.88, P<0.001; GOLD 4: β=-6.47, P=0.014). The PMA was negatively associated with the modified British Medical Research Council dyspnea scale (β=-0.005, P=0.026), COPD Assessment Test score (β=-0.06, P=0.001), emphysema (β=-0.07, P<0.001), and air trapping (β=-0.24, P<0.001) after adjustment. The PMA was positively associated with lung function (all P<0.05). Similar associations were discovered for the pectoralis major muscle area and pectoralis minor muscle area. After the 1-year follow-up, the PMA was associated with the annual decline in the post-bronchodilator forced expiratory volume in 1 s percent of predicted value (β=0.022, P=0.002) but not with the annual rate of exacerbations or the time to first exacerbation.

Patients with mild or moderate airflow limitation exhibit a reduced PMA. The PMA is associated with airflow limitation severity, respiratory symptoms, lung function, emphysema, and air trapping, suggesting that PMA measurement can assist with COPD assessment.

This study aimed to evaluate the association of cancer cachexia with psychosocial impact, nutrition impact symptoms (NIS), and geriatric assessment in older patients newly diagnosed with advanced lung cancer undergoing chemotherapy.

Older patients with advanced lung cancer scheduled to receive first-line chemotherapy between August 2021 and February 2022 were enrolled. Cachexia was diagnosed according to the International Consensus. NIS and psychosocial impacts were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) C30, CAX24, and the Eating-Related Distress Questionnaire (ERD). Non-parametric tests evaluated the association between cachexia and its impacts. Patients with cachexia who consented to be interviewed were asked about their experiences with diet and weight changes. Three authors reviewed the interview data to ensure the analysis's veracity.

Twenty-one of the 31 participants (68%) had cachexia at baseline. The cachexia group showed significantly greater severity of Food Aversion (P ​= ​0.035), Eating and Weight Loss Worry (P ​< ​0.001), and Loss of Control (P ​= ​0.005) compared to the non-cachexia group. There were no significant differences in the ERD and geriatric assessment (all P ​> ​0.05). The interview revealed that patients with cachexia perceived diet and weight changes early on and tried to manage their symptoms by themselves.

Cancer cachexia showed an association with NIS and psychosocial impacts. Older patients with advanced lung cancer scheduled to receive first-line chemotherapy should undergo a comprehensive assessment of cancer cachexia, including its potential physical and psychological impacts.

The trial registration number was UMIN 000053843.

This retrospective, multicenter cohort study aimed to determine whether cancer cachexia serves as a biomarker for determining the most effective treatment for patients having non-small-cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression treated with immune checkpoint inhibitors (ICIs) alone or combined with chemotherapy (ICI/chemotherapy). We included 411 patients with advanced NSCLC with a PD-L1 tumor proportion score of ≥50%. The patients were treated with pembrolizumab monotherapy or ICI/chemotherapy. Cancer cachexia was defined as a weight loss of >5% of the total body weight or a body mass index of <20 kg/m2 coupled with an additional weight loss of >2% within 6 months before starting treatment. Eighty-five (21%) patients met the cancer cachexia criteria. Overall survival (OS) was significantly shorter in patients with cachexia than in those without cachexia in both the pembrolizumab monotherapy group (17.2 vs. 35.8 months, p < 0.001) and the ICI/chemotherapy group (27.0 months vs. not reached, p = 0.044). However, after stratifying by cancer cachexia status, no significant difference in OS was observed between the pembrolizumab monotherapy and chemoimmunotherapy groups, regardless of cachexia. In conclusion, ICI/chemotherapy offers limited benefits for NSCLC patients with high PD-L1 expression and concurrent cancer cachexia. Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.

Controlling Nutritional Status (CONUT) Score is an effective tool for the assessment of malnutrition and proved to be associated with survival of Diffuse large B-cell lymphoma (DLBCL) patients. We investigated the impact of CONUT score on specific subgroups of DLBCL patients, including age and International prognostic Index (IPI) risk groups.

Data of 287 newly diagnosed DLBCL in the Third Affiliated Hospital of Soochow University were retrospectively collected. Baseline CONUT score, clinical data and survival information were recorded.

With the standard cut-off value of 4 points, 88 (30.7%) patients were clarified as malnourished. During a median follow-up of 34 months, malnourished patients exhibited significant reduction in both progression-free survival (PFS) and overall survival (OS). The 3-year PFS rates for malnourished and well-nourished patients were 51.4% and 70.9% (p = 0.001), while the 3-year OS rates were 62.4% and 84.0% (p < 0.001). Malnutrition was demonstrated an independent predictor of OS in DLBCL patients (HR 2.220, 95% CI 1.307-3.772, p = 0.003). It could effectively identify patients with inferior OS in both low/intermediate-low risk and intermediate-high/high risk IPI groups. In the group of elderly patients aged over 60 years, malnutrition was independently associated with OS (HR 2.182, 95% CI 1.178-4.040, p = 0.024), but not PFS (HR 1.709, 95% CI 1.016-2.875, p = 0.070) after adjustment using the Benjamini-Hochberg procedure. Conversely, for younger patients, malnutrition did not demonstrate an independent impact on either PFS or OS.

Malnutrition evaluated by CONUT score was an independent predictor for the outcome of DLBCL patients, which is exclusively caused by its effect on elderly patients.

Cachexia is a prevalent multifactorial syndrome characterized by a substantial decrease in food intake, which results from processes such as proteolysis, lipolysis, inflammatory activation, and autophagy, ultimately leading to weight loss. In cancer patients, this condition is referred to as cancer-related cachexia (CRC) and affects over 50% of this population. A comprehensive understanding of the intricate interactions between tumors and the host organism is essential for the development of effective treatments for tumor cachexia. This review aims to elucidate the role of the tumor microenvironment (TME) in the pathogenesis of tumor-associated cachexia and to summarize the current evidence supporting treatment modalities that target the TME.

Research studies on gastric cancer have not investigated the combined impact of body composition, age, and tumor staging on gastric cancer prognosis. To address this gap, we used machine learning methods to develop reliable prediction models for gastric cancer.

This study included 1,132 gastric cancer patients, with preoperative body composition and clinical parameters recorded, analyzed using Cox regression and machine learning models.

The multivariate analysis revealed that several factors were associated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer. These factors included age (≥65 years), tumor-node-metastasis (TNM) staging, low muscle attenuation (MA), low skeletal muscle index (SMI), and low visceral to subcutaneous adipose tissue area ratios (VSR). The decision tree analysis for RFS identified six subgroups, with the TNM staging I, II combined with high MA subgroup showing the most favorable prognosis and the TNM staging III combined with low MA subgroup exhibiting the poorest prognosis. For OS, the decision tree analysis identified seven subgroups, with the subgroup featuring high MA combined with TNM staging I, II showing the best prognosis and the subgroup with low MA, TNM staging II, III, low SMI, and age ≥65 years associated with the worst prognosis.

Cox regression identified key factors associated with gastric cancer prognosis, and decision tree analysis determined prognoses across different risk factor subgroups. Our study highlights that the combined use of these methods can enhance intervention planning and clinical decision-making in gastric cancer.

In patients receiving anti-cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials.

An electronic literature search of MEDLINE, Embase and Cochrane databases (1990-2023) was performed. Eligibility criteria comprised participants ≥ 18 years old; controlled design; ≥ 40 participants; and a cachexia intervention for > 14 days. Trials reporting at least one oncological endpoint were selected for analysis. Data extraction was performed using Covidence and followed PRISMA guidelines and the review was registered (PROSPERO CRD42022276710).

Fifty-seven trials were eligible, totalling 9743 patients (median: 107, IQR: 173). Twenty-six (46%) trials focussed on a single tumour site: eight in lung, six in pancreatic, six in head and neck and six in GI cancers. Forty-two (74%) studies included patients with Stage III/IV disease, and 41 (70%) included patients receiving palliative anti-cancer treatment. Ten studies (18%) involved patients on curative treatment. Twenty-eight (49%) studies used pharmacological interventions, 29 (50%) used oral nutrition, and two (4%) used enteral or parenteral nutrition. Reported oncological endpoints included overall survival (OS, n = 46 trials), progression-free survival (PFS, n = 7), duration of response (DR, n = 1), response rate (RR, n = 9), completion of treatment (TC, n = 11) and toxicity/adverse events (AE, n = 42). Median OS differed widely from 60 to 3468 days. Of the 46 studies, only three reported a significant positive effect on survival. Seven trials showed a difference in AE, four in TC, one in PFS and one in RR. Reported significances were unreliable due to missing adjustments for extensive multiple testing. Only three of the six trials using OS as the primary endpoint reported pre-trial sample size calculations, but only one recruited the planned number of patients.

In CC trials, oncological endpoints were mostly secondary and only few significant findings have been reported. Due to heterogeneity in oncological settings, nutritional and metabolic status and interventions, firm conclusions about CC treatment are not possible. OS and AE are relevant endpoints, but future trials targeting clinically meaningful hazard ratios will required more homogeneous patient cohorts, adequate pre-trial power analyses and adherence to statistical testing standards.

Neuroendocrine neoplasms (NENs) originating in the gastroenteropancreatic (GEP) tract are rare tumors often associated with significant metabolic disturbances and nutritional challenges. This review explores the intricate relationship between nutritional status and the development, progression, and prognosis of GEP-NENs. Through an extensive literature search encompassing studies up to April 2024, we examined various factors, including obesity, malnutrition, metabolic syndrome and type 2 diabetes mellitus, and their roles in the development and progression of GEP-NENs. The review highlights the dual role of obesity, both as a risk factor and a potential prognostic indicator, drawing attention to the 'obesity paradox' observed in cancer research. Additionally, we discuss the impact of malnutrition on patient outcomes and emphasize the need for comprehensive nutritional assessments beyond BMI. This analysis highlights the importance of incorporating nutritional interventions into preventive and therapeutic strategies for GEP-NEN patients. Future research should further clarify these associations and develop personalized nutritional management protocols to improve patient prognosis and quality of life. Acronyms adopted in the text and tables: AOR: adjusted odd ratio, BIA: Bioelectrical Impedance Analysis, BMI: Body Mass Index, CI: confidence interval, CLARINET: Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumor, FLI: fatty liver index, GEP: gastroenteropancreatic, GLIM: global leadership into malnutrition, HR: hazard ratio, MS: metabolic syndrome, MUST: malabsorption universal screening tool, NEC: neuroendocrine carcinoma, NENs: Neuroendocrine neoplasms, NETs: Neuroendocrine tumors, NRS: Nutritional Risk Screening, OR: odd ratio, OS: overall survival, PFS: progression-free survival, RR: risk ratio, SGA: Subjective Global Assessment, T2DM: type 2 diabetes mellitus, VAI: visceral adiposity index, WD: well-differentiated.

Dietary fibres constitute a heterogeneous class of nutrients that are key in the prevention of various chronic diseases. Most dietary fibres are fermented by the gut microbiome and may, thereby, modulate the gut microbial ecology and metabolism, impacting human health. Dietary fibres may influence the occurrence of specific bacterial taxa, with this effect varying between individuals. The effect of dietary fibres on microbial diversity is a matter of debate. Most intervention studies with dietary fibres in the context of obesity and related metabolic disorders reveal the need for an accurate assessment of the microbiome to better understand the variable response to dietary fibres. Epidemiological studies confirm that a high dietary fibre intake is strongly associated with a reduced occurrence of many types of cancer. However, there is a need to determine the impact of intervention with specific dietary fibres on cancer risk, therapy efficacy and toxicity, as well as in cancer cachexia. In this Review, we summarize the mechanisms by which the gut microbiome can mediate the physiological benefits of dietary fibres in the contexts of obesity, cardiometabolic diseases and cancer, their incidence being clearly linked to low dietary fibre intake.

This study aimed to investigate the prevalence and prognostic impact of cachexia in patients with unresectable hepatocellular carcinoma (HCC) receiving systemic targeted therapy.

This single-center retrospective study included patients with HCC who underwent systemic targeted therapy. Cachexia was defined using novel criteria proposed in 2023. The prognostic impact of cachexia was evaluated using the Cox proportional hazards model.

Of the 200 patients (160 males [80%]; median age, 73 years), cachexia was identified in 70 patients and associated with higher des-gamma-carboxy prothrombin levels, and extrahepatic spread. Patients with cachexia had significantly shorter overall survival (OS) (median 14.1 vs. 20.9 months, p = 0.002) and post-progression survival (PPS) (4.8 vs. 11.1 months, p = 0.001) compared to patients without cachexia. Multivariable analyses revealed cachexia as an independent adverse factor for OS (hazard ratio 1.54; 95% confidence interval 1.03-2.30, p = 0.035) and PPS (hazard ratio 1.64; 95% confidence interval 1.08-2.47, p = 0.018). No significant differences were observed in Progression-free survival between the two groups. Treatment discontinuation due to general appearance deterioration was more common in cachectic patients.

Cachexia was prevalent among patients with HCC receiving systemic targeted therapy and was identified as an independent predictor of poorer OS and PPS. Given the prognostic impact, the evaluation of cachexia is crucial in managing patients with HCC undergoing systemic targeted therapy.

This narrative review provides an overview of body composition methods available for use in critically ill patients. It focuses on the relevance and discussion of the most commonly used techniques. Further, we discuss the validity of these methods with a focus on muscle mass assessment, measuring changes over time and the identification of patients with lower-than-normal muscularity. Current available evidence, as well as future directions is highlighted.

Metabolic reprogramming of cancer cells and the tumour microenvironment are pivotal characteristics of cancers, and studying these processes offer insights and avenues for cancer diagnostics and therapeutics. Recent advancements have underscored the impact of host systemic features, termed macroenvironment, on facilitating cancer progression. During tumorigenesis, these inherent features of the host, such as germline genetics, immune profile and the metabolic status, influence how the body responds to cancer. In parallel, as cancer grows, it induces systemic effects beyond the primary tumour site and affects the macroenvironment, for example, through inflammation, the metabolic end-stage syndrome of cachexia, and metabolic dysregulation. Therefore, understanding the intricate metabolic interplay between the tumour and the host is a growing frontier in advancing cancer diagnosis and therapy. In this Review, we explore the specific contribution of the metabolic fitness of the host to cancer initiation, progression and response to therapy. We then delineate the complex metabolic crosstalk between the tumour, the microenvironment and the host, which promotes disease progression to metastasis and cachexia. The metabolic relationships among the host, cancer pathogenesis and the consequent responsive systemic manifestations during cancer progression provide new perspectives for mechanistic cancer therapy and improved management of patients with cancer.

Body composition has emerged as a significant determinant of cancer patient outcomes, with computed tomography (CT) assessment at the L3 level offering a reliable evaluation method. While muscle mass and adiposity have been linked to poorer outcomes in hematological malignancies, their impact remains unstudied in adults with acute lymphoblastic leukemia (ALL).

This retrospective single-center study enrolled adults newly diagnosed with ALL. Skeletal muscle, visceral, and subcutaneous fat areas were quantified. Low muscle mass was defined as a skeletal muscle index (SMI) less than 55 cm2/m2 in men, and less than 39 cm2/m2 in women, and receiver operating characteristic curves determined cutoff points for SMI, subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) correlated with mortality.

Ninety patients were included. Low muscle mass was associated with mortality in patients treated with a pediatric inspired regimen (PIR) (HR 4.92, 95 % CI [1.38-17.57], p = 0.014) and lower median SMI was observed in patients who died during induction (p = 0.016). High visceral adiposity (HR 1.89, 95 % CI [1-3.57], p = 0.049) and high subcutaneous adiposity (HR 1.99, 95 % CI [1-3.96], p = 0.05) were also associated with mortality in the whole population. Furthermore, a higher VATI was observed in patients who developed an infectious episode during induction (p = 0.03), and a higher VATI was observed in patients who were treated with a PIR who had measurable residual disease positivity after induction chemotherapy (p = 0.044).

CT-assessed muscle mass, and adiposity bear prognostic significance in newly diagnosed ALL patients.

Data regarding the association between cachexia and clinical outcomes in hepatopancreatobiliary (HPB) malignancies are limited. This retrospective study sought to investigate the prognostic significance of preoperative cachexia in patients undergoing major HPB surgery for malignancies.

Data from patients, who underwent major open surgery for HPB malignancies between March 2014 and December 2018, were retrospectively reviewed. Cachexia was evaluated a few days before surgery, and defined according to modified Asian Working Group for Cachexia criteria: low body mass index (<21 kg/m2) and decreased handgrip strength (<28 kg [males] and <18 kg [females]) or elevated C-reactive protein level (>0.5 mg/dL). The primary endpoint was postoperative overall survival (OS); secondary endpoints included disease-free survival (DFS) and postoperative complications.

Of 332 patients (228 male; mean age, 68.8 ± 10.3 years), 93 (28 %) had preoperative cachexia. There were 154 (46 %) deaths and 181 (55 %) combined events (death or recurrence) during a five-year follow-up (mean, 3.3 ± 1.7 years), with no significant differences in major postoperative complications between the 2 groups (P = 0.329). After adjusting for covariates, cachexia (n = 93) exhibited significant associations with shorter OS (adjusted hazard ratio [HR] 1.65 [95 % confidence interval (CI) 1.18-2.30]; P = 0.004) and DFS (adjusted HR 1.39 [95 % CI 1.01-1.91; P = 0.043) compared with non-cachexia (n = 239). Cachexia significantly shortened OS only in a subset with pathological stage ≤ II disease (adjusted HR 2.45 [95 % CI 1.27-4.74]; P = 0.008) but not otherwise (P for interaction, 0.040).

Preoperative cachexia did not affect short-term surgical complications but significantly deteriorated postoperative prognosis in patients who underwent surgery for HPB malignancies.

Cancer cachexia is the involuntary loss of body and skeletal muscle mass, which negatively impacts physical function, quality of life, treatment tolerance, and survival. Skeletal muscles of cachectic people and mice with pancreatic tumors also exhibit skeletal muscle damage, nonresolute immune cell infiltration, and impaired regeneration. These phenotypes may be influenced by the accumulation of senescent cells, which secrete factors detrimental to skeletal muscle health. However, there is currently no comprehensive research on the senescent cell accumulation in the skeletal muscle of tumor-bearing hosts, with or without chemotherapy. To address this gap, we cross-referenced the SenMayo panel of 125 senescence-related genes with our RNA-seq dataset in mouse skeletal muscle during the initiation and progression of cancer cachexia, which revealed a differential expression of 39 genes at precachexia, 64 genes at cachexia onset, and 72 genes when cachexia is severe. Since p16 is a canonical marker of senescence, we subsequently orthotopically injected p16-tdTomato reporter mice with murine KPC pancreatic cancer cells and treated a subset of mice with chemotherapy. At experimental endpoint, when KPC treatment-naïve mice were cachectic, we observed an increased accumulation of p16+ cells, along with increased mRNA levels of hallmark senescence markers (Cdkn1a/p21, Cdkn2a/p16, Glb1/senescent-associated-β-galactosidase), which were exacerbated by chemotherapy. Finally, we demonstrate an increase in CDKN1A/p21 in the muscle of cachectic patients with pancreatic cancer, which associated with cachexia severity. These findings suggest that senescent cells accumulate in skeletal muscle of cachectic pancreatic tumor-bearing hosts and that chemotherapy can exacerbate this accumulation.NEW & NOTEWORTHY To the best of our knowledge, this study is the first to investigate senescent cell accumulation in skeletal muscle of tumor-bearing hosts and its exacerbation by chemotherapy. Our findings identify an accumulation of senescent cells and reveal a senescence-related transcriptional program in skeletal muscle during the initiation and progression of cancer cachexia that is exacerbated by chemotherapy treatment. This highlights a novel potential therapeutic mechanism that can be targeted for the prevention of cancer-induced muscle pathologies.

The existing diagnostic criteria for cancer cachexia do not meet clinical needs. We aimed to establish novel comprehensive evaluation scales for cachexia specific to patients with solid tumours.

This study included 12 651 patients (males: 6793 [53.7%]; females: 5858 [46.3%]; medium age: 58 [interquartile range:50/66] years; medium follow-up duration: 24.16 [13.32/44.84] months; 4271 [33.8%] patients died; mean survival: 55.53 [95% confidence interval, 54.87/56.10] months; 3344 [26.4%], 4184 [33.1%] and 5123 [40.5%] patients with Stage I-II, III and IV tumour, respectively; derivation set: 10022, validation set: 2629 patients) with 14 types of solid tumours, including lung, gastric, liver, breast, oesophageal, cervical, bladder, pancreatic, prostate, ovarian, colorectal cancer, nasopharyngeal and endometrial carcinoma and cholangiocarcinoma, from an open and ongoing multicentre cohort study in China. Risk factors for cachexia, including tumour characteristics and nutritional parameters, were examined to develop diagnostic scales using Cox proportional hazards models and Kaplan-Meier analysis.

Ten nutrition items (body mass index, weight loss, intake reduction, physical activity function, fatigue, handgrip strength, anorexia, albumin level, albumin/globulin ratio and neutrophil/lymphocyte ratio) with different weighted scores were identified to construct a nutrition-weighted scoring scale (NWSS) for nutrition risk. Tumour type and tumour burden status (tumour-node-metastasis stage and radical or non-radical tumour) were determined to construct a disease-weighted scoring scale (DWSS) for disease risk. A lumped scale (5 × 5 matrix) established using a five-grade classification of nutrition and disease risk was used to determine a five-grade classification of comprehensive cachexia risk: A, no cachexia risk (reference; lowest disease and nutrition risks); B, cachexia risk (hazard ratio [HR] = 4.517 [4.033/5.058]); C, pre-cachexia (HR = 9.755 [8.73/10.901], medium survival = 21.21 months); D, cachexia (HR = 16.901 [14.995/19.049], medium survival = 11.61 months); and E, refractory cachexia (HR = 31.879 [28.244/35.981], medium survival = 4.83 months, highest disease and nutrition risks) (p < 0.001). Patients in Categories A-D benefited from nutrition therapy and anti-tumour treatments to varying degrees. Patients in Category E were clinically refractory to nutrition therapy without prolonged survival compared with patients without nutrition therapy (medium survival, pre-hospitalization nutrition therapy vs. hospitalization nutrition therapy vs. without nutrition therapy, 2.89 [1.91/3.88] vs. 4.04 [3.21/4.88] vs. 5.89 [4.73/7.04] months, p = 0.015) and anti-tumour treatments without prolonged survival compared with patients receiving palliative care (medium survival, radical anti-tumour treatments vs. adjuvant anti-tumour treatments vs. palliative anti-tumour treatments vs. and palliative care, 6.48 [4.42/8.53] vs. 6.48 [3.23/9.73] vs. 4.83 [4.22/5.44] vs. 2.70 [1.09/4.30] months, p = 0.263).

We systematically developed a novel definition and grading diagnostic criteria for tumour-type-specific comprehensive cancer cachexia risk.

Nowadays, limited data or no data are available on body composition changes and the development of treatment-related toxicities in metastatic breast cancer (MBC) patients treated with innovative and promising anticancer therapies, including cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Therefore, we evaluated in MBC treated with CDK4/6 inhibitors changes in adiposity and muscularity before and after treatment and whether the changes in these parameters were associated with toxicities, dose reduction or treatment discontinuation.

We considered ER+/HER2- MBC patients undergoing treatment with CDK 4/6 inhibitors, collected clinical data and registered the number and type of toxicities, dose reduction due to adverse events and the rate of discontinuation. We analyzed CT scan images before treatment (T0) and at the first follow-up visit (T1), calculating SAT, VAT, TAT (adipose tissue), SMA and SMI (skeletal muscle mass).

70 MBC patients were enrolled. Median time of observation at T1 was 4 months (3; 12); 68 (97 %) patients experienced at least one G1-G2 adverse event, whereas 37 (53 %) at least one G3-G4. Dose reduction due to toxicity was registered in 17 patients (24 %), whereas discontinuation in 24 (34 %) patients. SMA at baseline inversely correlated with the number of adverse events (G3-G4) (r = -0.30; p = 0.039). Changes in body composition were not associated with G3-G4 toxicities. However, in patients with dose reduction, we observed overtime (T0-T1) an increase in median VAT (118 vs 135; p = 0.023) (median Delta VATT0-T1 3.9 %). In patients not discontinuing the treatment, we observed overtime an increase in mean SMA (127 ± 23 vs 131 ± 22, p < 0.05) and median VAT (119 vs 131, p < 0.05). We observed greater reduction in median VAT (Δ%) in patients who discontinued the therapy (p < 0.05). ΔVAT (%) (reduction) was more pronounced in those patients who discontinued therapy for disease progression (p = 0.01).

Changes in muscularity and adiposity with not univocal direction were associated with toxicities, treatment discontinuation or dose reduction among patients with breast cancer treated with CDK4/6 inhibitors.

For patients with advanced head and neck cancer (HNC) chemoradiotherapy (CHRT) is the main treatment option. CHRT is a severe treatment with a high ratio of side effects which may be even more pronounced due to mucosities related malnutrition. Nutritional intervention like nutritional counseling (NC) and oral nutritional supplements (ONS) may prevent malnutrition. A systematic review and meta-analysis was performed to assess the effect of NC with or without ONS (NC±ONS) on CHRT-related grade ≥3 mucositis in patients with HNC undergoing CHRT.

PubMed/MEDLINE, Web of Science, and Scopus were searched to identify randomized and non-randomized clinical studies of HNC patients undergoing CHRT, where mucositis grade ≥3 data were provided. Comparative and proportional meta-analyses were performed to calculate the odds ratio (OR) and incidence of a mucositis grade ≥3 in the included studies (%) with 95% confidence intervals (95% CI).

There were seven studies fulfilling inclusion criteria with 655 participants included. NC±ONS revealed no risk reduction of grade ≥3 mucositis (OR: 1.2, 95%CI: 0.7-1.9). The overall mucositis rate was 38.3% (95% CI: 24.8%-52.6%) and 32.8% (95% CI: 14.9%-53.5%) (P = 0.67) in NC+ONS and NC-ONS respectively.

Despite the undeniable role of NC±ONS for patients with HNC undergoing CHRT, we found it insufficient to avoid grade ≥3 CHRT-related mucositis. Further research should be conducted to determine recomendations how to decrease the risk of oral mucosities and, in consequence, how to prevent malnutrition in patients with CHRT.

Cancer cachexia (CC) is a multifactorial disease marked by a severe and progressive loss of lean muscle mass and characterized further by inflammation and a negative energy/protein balance, ultimately leading to muscle atrophy and loss of muscle tissue. As a result, patients experiencing cachexia have reduced muscle function and thus less independence and a lower quality of life. CC progresses through stages of increasing severity: pre-cachexia, cachexia and refractory cachexia. Two proposed underlying mechanisms that drive cancer-induced muscle wasting are the autophagy-lysosome and ubiquitin-proteasome systems. An increase in autophagic flux and proteolytic activity leads to atrophy of both cardiac and skeletal muscle, ultimately mediated by tumour or immune-secreted inflammatory cytokines. These pathways occur at a basal level to maintain cellular homeostasis; therefore, it is the overactivation of the pathways that leads to muscle atrophy. Recent evidence demonstrates the ability of aerobic and resistance training to restore these pathways to their basal levels. The mechanism is not yet understood, and more research is needed to determine exactly how exercise influences each pathway. However, exercise has great promise as a therapeutic strategy for CC because of the evidence for it preserving muscle mass and function, and attenuating protein degradative pathways. The extent to which exercise affects the ubiquitin-proteasome and autophagy-lysosome systems is determined by the frequency, intensity and duration of the exercise protocol. As such, an ideal exercise prescription is lacking for individuals with CC.

Cancer patients often experience significant weight loss due to metabolic changes, increased resting energy expenditure (REE), and poor nutrient intake, particularly exacerbated by treatments like chemotherapy and radiation. This study aimed to determine whether combining Oral Nutrition Supplements (ONS) with dietary education is more effective than dietary education alone in improving nutritional outcomes for cancer patients. An open-label randomized clinical trial at Persahabatan Hospital in Jakarta, Indonesia, involved 108 patients with lung or gynecological cancer, with 87 completing the study. Participants were assigned to receive either dietary education plus ONS (intervention group) or dietary education alone (control group). Results indicated that while both groups improved their nutrition knowledge, the intervention group experienced significant increases in body weight (1.68 ± 3.96 kg) and body mass index (BMI) (0.86 ± 1.96 kg/m2), whereas the control group lost weight. Additionally, the intervention group had a lower rate of anemia (60% vs. 80.9%), though no significant differences were found in albumin levels or inflammation status. These findings suggest that ONS combined with dietary education may help improve weight and BMI in cancer patients, warranting further research to confirm these benefits and assess long-term effects.

Cachexia status is a drastic issue in cancer patients. The main goal of this study; which is considered the first of its kind in Sudan, was to enhance our understanding of the clinical implications of oral cancer cachexia. Newly diagnosed Sudanese patients with oral squamous cell carcinoma (OSCC) were evaluated for the incidence and impact of cachexia.

This is a longitudinal descriptive study conducted at Khartoum Teaching Dental Hospital before April 2023. A number of 40 OSCC participants above 18 years old were analyzed for Cachexia based on weight loss, low hemoglobin levels, albumin levels, elevated C-reactive protein, decreased mid-upper arm circumference, loss of appetite, and anorexia. Data were collected over three visits, and analyzed using descriptive and bivariate statistics.

The study included 40 newly diagnosed patients with OSCC, with a mean of age 56.8 years. The incidence of cachexia was 33.2% before surgery, 55% one month postoperatively, and 65% six months later. Cachexia was significantly correlated (p < 0.05) with delayed wound healing (p = 0.008), prolonged nasogastric feeding tube usage (p = 0.023), interrupted adjuvant therapy (p = 0.003), and mortality (p = 0.007). Low BMI, loss of appetite, food intake, low hemoglobin, and elevated CRP were significant diagnostic criteria as well (p < 0.05).

In this study, Cachexia was found to be a critical prognostic factor for OSCC patients. Larger-scale clinical research in Sudan is needed to provide definitive findings and strategies to support nutritional status during therapy.

Systemic inflammation has prognostic value in cancer and is considered aetiological of cachexia by the Global Leadership Initiative on Malnutrition (GLIM). Lactate dehydrogenase (LDH) also has recognized prognostic value. The present study aimed to evaluate the ability of a laboratory cachexia score (LCAS) defined by LDH, CRP and albumin, to identify cachexia and predict outcome in advanced lung cancer.

Patients (n = 261) with serum LDH, CRP and albumin measurement receiving palliative radiotherapy for advanced lung cancer between 2009 and 2015 were identified. Subjects were stratified by LDH and LCAS. This was compared to GRIm and LIPI, two previously described LDH based prognostic scores, which do not incorporate CRP.

On follow up there were 201 deaths. LDH and LCAS were associated with 1-year survival independent of ECOG-PS, MUST, weight loss, BMI, SMI, SMD, metastases, mGPS or NLR (all p < 0.001). On multivariate analysis LCAS (1.36, 1.13-1.63, p = 0.001), LIPI (1.50, 1.17-1.92, p = 0.02), metastases (1.53, 1.15-2.04, p = 0.004) and ECOG-PS (1.28, 1.04-1.57, p = 0.019) were independently associated with poorer overall survival.

LCAS appears to identify cachexia and stratify survival. This may represent a useful aetiological criterion within the GLIM framework and a more powerful prognostic tool than the phenotypic criteria.

Systemic inflammation and nutritional status are key factors affecting the prognosis of patients with cancer cachexia. This study aims to evaluate the prognostic value of a new nutritional and inflammatory index, Prognostic Nutritional CRP Ratio (NCR), in patients with cancer cachexia.

This prospective multicenter study analyzed 3,447 patients diagnosed with cancer cachexia across over 40 clinical centers in China, from June 2012 to December 2023. The NCR was calculated as BMI × albumin / CRP. The Cox proportional hazards regression model was utilized to analyze hazard ratios (HRs) for all-cause mortality. The relationship between NCR and all-cause mortality was assessed using restricted cubic spline modeling. The optimal cutoff value for NCR was determined through maximally selected rank statistics.

Among the 3,447 individuals diagnosed with cancer cachexia in our study, 2,296 (66.6%) were men, and 1,151 (33.4%) were women. With a median follow-up duration of 45.33 months, the mean age of the participants was 63.8 ± 11.4 years. We observed that lower NCR levels were prevalent among cachexia patients across a spectrum of cancer types, including lung, colorectal, liver, esophageal, breast, ovarian, and cervical cancers. We observed that lower NCR levels were prevalent among cachexia patients across a spectrum of cancer types, including lung, colorectal, liver, esophageal, breast, ovarian, and cervical cancers. This correlation held true across diverse patient subgroups, delineated by gender, age, smoking status, BMI, TNM stage, and tumor types, underscoring the broad applicability of NCR as a prognostic marker. Moreover, our findings highlighted that cancer cachexia patients with higher NCR levels experienced a significantly improved quality of life.

The NCR, indicative of nutritional status and inflammation, is associated with reduced all-cause mortality and could be a valuable prognostic marker for patients with cancer cachexia.

The sequence of events associated with cancer cachexia induction needs to be further characterized. Using the C26 mouse model, we found that prior to cachexia, cancer progression was associated with increased levels of IL-6 and growth differentiation factor 15 (GDF15), highly induced production of positive acute phase proteins (APPs) and reduced levels of most amino acids in the systemic circulation, while signal transducer and activator of transcription 3 (STAT3) signaling was induced (1) in the growing spleen, alongside activation of ribosomal protein S6 (rpS6) and alpha subunit of eukaryotic translation initiation factor-2 (eIF2α) signalings, and (2) in the liver, alongside increased positive-APP expression, decreased albumin expression, and upregulation of autophagy. At the onset of cachexia, rpS6 and eIF2α signalings were concomitantly activated in the liver, with increased expression of activating transcription factor 4 (ATF4) target genes involved in amino acid synthesis and transport, as well as autophagy. Data show that pre-cachectic (pre-Cx) alterations in protein/aa homeostasis are followed by activation of eIF2α signaling in the liver, an adaptive mechanism likely regulating protein/amino acid metabolism upon progression to cachexia.

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.

Genetic factors, inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and uremic substances such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) have been reported to affect organic anion transporting polypeptide (OATP)1B1 transport activity. However, the relationship between OATP1B1 transport activity and these factors in patients with cancer cachexia has not been reported. This study aimed to identify the factors contributing to individual differences in OATP1B1 transport activity in patients with cancer cachexia, using coproporphyrin-I (CP-I) as an endogenous biomarker of OATP1B1 transport activity. The study recruited 114 patients with cancer cachexia who satisfied the selection criteria. The subjects were classified into pre-cachexia, cachexia, and refractory cachexia. Median [interquartile range] plasma CP-I level was higher in patients with pre-cachexia (0.91 [0.67-1.12] ng/mL) compared with the data in the general population reported previously and tended to be higher in patients with refractory cachexia (1.06 [0.78-1.64] ng/mL) than in those with cachexia (0.87 [0.62-1.07] ng/mL), suggesting that OATP1B1 transport activity may decrease with the progression of cancer cachexia. Plasma CP-I correlated positively with IL-6 and TNF-α concentrations but did not correlate with OATP1B1 polymorphisms or CMPF concentration, which have been reported to reduce transport activity. Multiple regression analysis using the forced entry method identified refractory cachexia as a significant factor independently affecting plasma CP-I concentration. These findings suggest that the reduction in OATP1B1 transport activity in patients with cancer cachexia may be attributed to inflammatory cytokines or some other factors that are elevated by cancer cachexia progression, rather than OATP1B1 polymorphisms and CMPF.

Cancer cachexia (CC), a multifactorial syndrome characterized by unintentional weight loss, is a frequent complication of cancer that impacts patients' quality of life and survival. In this retrospective review, we evaluated the landscape of clinical trials (CTx) registered on ClinicalTrials.gov for the consideration of potential factors contributing to human heterogeneity in their design and analyses. Among CTx registered from 1995-2024, we observed a trend toward equality in including female participants, but lack of reporting of sex as a biological variable. Limited demographic diversity was observed with ~93% White population participation. There was a substantial divergence in the diagnostic criteria and a wide range of tools employed to measure CC. Lastly, few studies considered cancer type and stage as clinical variables. Overall, a substantial gap remains in our knowledge of CC in non-white and female populations. Ultimately, these underreported data across CC CTx complicate the comparison and interpretation of CTx results, both within understudied populations and in specific cancer types. The current evolution of knowledge and new methodologies used for CC assessment reinforce the need for a constant revision of the CC consensus definition and diagnosis criteria to align with current advances in our understanding of human heterogeneity in CC.

Introduction: Polygonatum cyrtonema Hua (PC) is an essential herbal medicine in China, known for improving muscle quality and enhancing physical function; its active ingredients are polysaccharides (PCPs). A previous study revealed the anti-atrophy effects of PCPs in cachectic mice. However, whether the effects of PCPs on anti-atrophy are associated with gut microenvironment remain elusive. This research endeavored to assess the medicinal efficacy of PCPs in alleviating muscle atrophy and fat lipolysis and explore the potential mechanisms. Methods: A cancer cachexia model was induced by male C57BL/6 mice bearing Lewis lung tumor cells and chemotherapy. The pharmacodynamics of PCPs (32 and 64 mg/kg/day) was investigated through measurements of tumor-free body weight, gastrocnemius muscle weight, soleus muscle weight, epididymal fat weight, tissue histology analysis, and pro-inflammatory cytokines. Immunohistochemistry and Western blotting assays were further used to confirm the effects of PCPs. 16S rRNA sequencing, LC-MS and GC-MS-based metabolomics were used to analyze the gut microbiota composition and metabolite alterations. Additionally, the agonist of free fatty acid receptor 2 (FFAR2)-a crucial short-chain fatty acid (SCFA) signaling molecule-was used to investigate the role of gut microbiota metabolites, specifically SCFAs, in the treatment of cancer cachexia, with comparisons to PCPs. Results: This study demonstrated that PCPs significantly mitigated body weight loss, restored muscle fiber atrophy and mitochondrial disorder, alleviated adipose tissue wasting, strengthened the intestinal barrier integrity, and decreased the intestinal inflammation in chemotherapy-induced cachexia. Furthermore, the reversal of specific bacterial taxa including Klebsiella, Akkermansia, norank_f__Desulfovibrionaceae, Enterococcus, NK4A214_group, Eubacterium_fissicatena_group, Eubacterium_nodatum_group, Erysipelatoclostridium, Lactobacillus, Monoglobus, Ruminococcus, Odoribacter, and Enterorhabdus, along with alterations in metabolites such as amino acids (AAs), eicosanoids, lactic acid and (SCFAs), contributed to the therapeutic effects of PCPs. Conclusion: Our findings suggest that PCPs can be used as prebiotic drugs targeting the microbiome-metabolomics axis in cancer patients undergoing chemotherapy.

Chemotherapy remains a central component of breast cancer treatment, significantly improving patient survival rates. However, its toxic side effects, along with cancer-related paraneoplastic syndromes, can lead to the loss of skeletal muscle mass and function, impairing physical abilities and increasing the risk of complications during treatment. Chemotherapeutic agents directly impact skeletal muscle cells by promoting protein degradation, inhibiting protein synthesis, and triggering systemic inflammation, all of which contribute to muscle atrophy. Additionally, these drugs can interfere with the proliferation and differentiation of stem cells, such as satellite cells, disrupting muscle regeneration and repair while inducing abnormal differentiation of intermuscular tissue, thereby worsening muscle wasting. These effects not only reduce the effectiveness of chemotherapy but also negatively affect patients' quality of life and disease prognosis. Recent studies have emphasized the role of exercise as an effective non-pharmacological strategy for preventing muscle loss and preserving muscle mass in cancer patients. This review examines the clinical manifestations of muscle dysfunction following breast cancer chemotherapy, the potential mechanisms underlying these changes, and the evidence supporting exercise as a therapeutic approach for improving muscle function.

Adipose tissue reduction is one of the features in patients with cancer cachexia. However, it remains unclear whether visceral fat area (VFA) and subcutaneous fat area (SFA) contribute differently to the progression of cancer cachexia in colon cancer patients. This study aims to investigate the prognostic impact of VFA and SFA in stage I-III colon cancer patients with cachexia.

Patients diagnosed with stage I-III colon cancer were preoperatively measured for VFA and SFA and then divided into VFA-high (VFA-H) and VFA-low (VFA-L) groups, as well as SFA-high (SFA-H) and SFA-low (SFA-L) groups. The prognostic impact of VFA and SFA for colon cancer patients with cachexia were analyzed using the Kaplan-Meier method and Cox regression analysis.

A total of 916 colon cancer patients (377 with cachexia and 539 without) were included in the study. In patients with cachexia, the estimated five-year overall survival (OS) was higher in the VFA-H group compared to the VFA-L group (p < 0.001). There was no significant difference in five-year OS between the SFA-L and SFA-H groups (p = 0.076). Cox regression analysis indicated that VFA (hazard ratio [HR] = 0.55, 95% confidence interval [CI] 0.40 to 0.76; p < 0.001) was an independent prognostic factor for patients with cachexia. SFA (HR = 0.78, 95% CI 0.59 to 1.03; p = 0.076) was not an independent prognostic factor for patients with cachexia.

Preoperative VFA, but not SFA was a useful prognostic factor for long-term outcomes in stage I-III colon cancer patients with cachexia. More attention should be paid to VFA in colon cancer patients with cachexia.

Sex-related differences in eating-related distress (ERD) experienced by cancer patients have not previously been clarified.

We conducted a multicenter survey among advanced cancer patients referred to palliative care. Data on patient characteristics were collected from the electronic medical records, and data on measurement outcomes were obtained from a questionnaire. Patients were categorized into male and female groups. We measured ERD using the Questionnaire for Eating-Related Distress among Patients with advanced cancer (QERD-P). The QERD-P comprises 3 items in each of the 7 factors, for a total of 21 items, and each item is rated on a 7-point Likert scale. High scores indicate worse distress. Comparisons were calculated using the Mann-Whitney U test. To assess associations between sexes and ERD, multivariate logistic regression analysis was performed.

A total of 192 patients were enrolled and divided into the male (n = 92) and female (n = 100) groups. The total score of the QERD-P was significantly higher in the male group (p = 0.018). The subtotal scores of "reasons why I cannot eat," "insufficient information," and "arguments with my family" were significantly higher in the male group (p = 0.035, 0.032, and 0.003, respectively). The male group had significantly higher risks for ERD associated with "arguments with my family" and "time with my family" (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.38-5.24; OR 2.28, 95% CI 1.15-4.53).

Males had significantly worse ERD and were at higher risk of ERD in family relationships than females.

Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated.

This meta-analysis and systematic review aimed to explore the CXI's prognostic value in patients with cancer.

The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis.

The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response.

The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001).

A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.

The aim of this study was to assess the prognostic value of the weight loss percentage (WLP) over the 2 years pre-treatment for operated patients with advanced oral squamous cell carcinoma (OSCC). This cohort study included 506 operated patients who were diagnosed with advanced primary OSCC between October 2001 and March 2022, and who were followed up until July 2022. Fine-Gray models, marginal structural models with stabilized inverse probability of treatment weighting, and Cox proportional hazards models were utilized to evaluate the prognostic significance of pre-treatment WLP for disease-specific survival (DSS). The median follow-up time was 32.6 months (interquartile range 13.0-71.6 months). A high pre-treatment WLP (>9.23%) was significantly associated with worse DSS (multivariate Fine-Gray model: hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.29-3.22, P = 0.002; multivariate Cox: HR 2.01, 95% CI 1.28-3.16, P = 0.002). In the weighted cohort, a similar association pattern was observed (marginal structural model: HR 2.26, 95% CI 1.28-3.98, P = 0.005; multivariate Cox: HR 2.28, 95% CI 1.38-3.76, P = 0.001). In subgroup analyses, high WLP could predict worse DSS among patients with buccal mucosa/other cancer sites (not including the oral tongue), moderate tumor differentiation, and larger cancer size (>1.8 cm) (all P < 0.05). Pre-treatment WLP over 2 years might be a useful tool to predict the prognosis of operated patients with advanced OSCC.

Nausea and emesis are ubiquitously reported medical conditions and often present as treatment side effects along with polymorbidities contributing to detrimental life-threatening outcomes, such as poor nutrition, lower quality of life, and unfavorable patient prognosis. Growth differentiation factor 15 (GDF15) is a stress response cytokine secreted by a wide variety of cell types in response to a broad range of stressors. Circulating GDF15 levels are elevated in a range of medical conditions characterized by cachexia and malaise. In recent years, GDF15 has gained scientific and translational prominence with the discovery that its receptor, GDNF family receptor α-like (GFRAL), is expressed exclusively in the hindbrain. GFRAL activation may results in profound anorexia and body weight loss, effects which have attracted interest for the pharmacological treatment of obesity.

This review highlights compelling emerging evidence indicating that GDF15 causes anorexia through the induction of nausea, emesis, and food aversions, which encourage a perspective on GDF15 system function in physiology and behavior beyond homeostatic energy regulation contexts. This highlights the potential role of GDF15 in the central mediation of nausea and emesis following a variety of physiological, and pathophysiological conditions such as chemotherapy-induced emesis, hyperemesis gravidarum, and cyclic vomiting syndrome.