Diagnosis Of Cancer Cachexia Research Articles

Early identification of potentially reversible cancer cachexia using explainable machine learning driven by body weight dynamics: a multicenter cohort study.

Cachexia is associated with multiple adverse outcomes in cancer. However, clinical decision-making for oncology patients at the cachexia stage presents significant challenges. This study aims to develop a machine learning (ML) model to identify potentially reversible cancer cachexia (PRCC). This was a multicenter cohort study. Cachexia was retrospectively diagnosed using Fearon's framework. PRCC was defined as a diagnosis of cancer cachexia at baseline that turned negative one month later. Body weight dynamics accessible upon patient admission were screened and modeled to predict PRCC. Multiple ML models were trained and cross-validated using 70% of the data to predict PRCC, with the remaining 30% reserved for model evaluation. The interpretability and clinical usefulness of the optimal model were assessed, and external validation was performed in an independent cohort of 238 patients. The study enrolled 1983 men and 1784 women (median age=58 years). PRCC was identified in 1983 patients (52.6%). Breast cancer exhibited the highest rate of PRCC (72.1%), while cachexia associated with various gastrointestinal cancers was less likely to be reversed. Weight change (WC) from six months ago to one month ago, WC from one month ago to baseline (-1 to 0) and baseline body mass index were selected for modelling. A multilayer perceptron model showed good performance to predict PRCC in the holdout test set (AUC [95%CI] = 0.887 [0.866, 0.907], accuracy=0.836, sensitivity=0.859, specificity=0.812) and the external validation set (AUC [95%CI] = 0.863 [0.778, 0.948]). The WC -1 to 0 showed the highest impact on model output. The model was demonstrated to be clinically useful and statistically relevant. This study presents an explainable ML model for the early identification of PRCC that utilizes simple body weight dynamics. The findings showcase the potential of this approach in improving the management of cancer cachexia to optimize patient outcomes. Data described in the manuscript was derived from a registered research project (URL: http://www.chictr.org.cn/showproj.aspx?proj=31813; ID: ChiCTR1800020329).

Skeletal Muscle Index-Based Cachexia Index as a Predictor of Prognosis in Patients With Cancer: A Meta-Analysis and Systematic Review.

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.

Abstract 5690: Urinary microRNA expression in pancreatic cancer with cachexia

Abstract Background: Cancer cachexia (CC) is a multifactorial syndrome characterized by appetite loss, weight loss and skeletal muscle wasting. It increases functional impairment, treatment-related toxicity, and a lower quality of life. Importantly, CC is one of the leading causes of cancer-related deaths, and its occurrence is particularly prevalent in advanced stages of pancreatic cancer (PC). The syndrome is thought to be associated with systemic inflammation and increased energy expenditure, yet the specific mechanisms remain to be fully understood. Although timely detection and intervention might be crucial in preventing CC’s progression, early diagnosis of this syndrome remains challenging due to the absence of suitable biomarkers. Here, we analyzed urinary microRNAs (miRNAs) as a potential noninvasive biomarkers for detecting CC in patients (pts) with PC. Methods: Clinical information including presence or absence of CC and urine samples were collected from pts with PC treated at National Cancer Center Hospital, Tokyo, Japan from March to October 2022. The diagnosis of CC was made according to the following definitions by Fearon. K et al. (1) weight loss of ≥5% within 6 months; (2) weight loss of ≥2% in pts with a BMI of &amp;lt;20 kg/m2; or (3) weight loss of ≥2% in pts with sarcopenia. In this study, pts who met the definition of CC within 6 months of enrollment were considered to have CC.Urinary miRNA profiles from pts with PC were sequenced by NGS and analyzed using DESeq2 to identify differentially expressed miRNAs (DEMs) between pts with CC and those without. DEMs were further explored for associated pathways and target genes using miRPathDB v.2.0. Results: Of the 64 subjects, 52 pts were included in the analysis after excluding three pts with low urine sample read coverage and nine pts with no information on CC status. Among those, 38 pts were classified as having CC. Patients’ background was as follows (CC/no CC); median age 70 [range: 44-80]/67 [57-74], male and female 19/7 pts, respectively, cStage {I (6/0), II (1/0), III (17/4), IV (14/10)} pts, median BMI (male 22.1 [17.7-27.2]/21.7 [18.2-28.2], female 21.7 [14.6-25.2]/21.9 [16.6-27.4]) kg/m2. Among 307 miRNAs detected in the urine of pts with PC, 49 miRNAs had previously been reported in CC research. The miR-141-5p was differentially expressed between pts with CC and those without CC (Wald test pBH = 0.079). It was down-regulated in pts with CC (Mann-Whitney U test p = 6.4e-4) and most significantly associated with the FoxO signaling pathway (ORA pBH = 1.84e-4), followed by the mTOR signaling pathway (ORA pBH = 0.008). Conclusions: Our study indicates that miR-141-5p holds potential as a noninvasive biomarker for the detection of CC in pts with PC. Although miR-141-5p has not been previously reported in CC, its significant association with the FoxO signaling pathway, which is one of the major pathways regulating skeletal muscle atrophy, underscores the relevance of miR-141-5p in the context of CC. Citation Format: Mao Okada, Shunsuke Kondo, Yukiko Igawa, Tatsuya Yoshida, Milos Havelka, Mika Mizunuma, Yuki Ichikawa, Noboru Yamamoto. Urinary microRNA expression in pancreatic cancer with cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5690.

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

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

Metabolic signatures and potential biomarkers for the diagnosis and treatment of colon cancer cachexia.

Cancer cachexia (CAC) is a debilitating condition that often arises from noncachexia cancer (NCAC), with distinct metabolic characteristics and medical treatments. However, the metabolic changes and underlying molecular mechanisms during cachexia progression remain poorly understood. Understanding the progression of CAC is crucial for developing diagnostic approaches to distinguish between CAC and NCAC stages, facilitating appropriate treatment for cancer patients. In this study, we establish a mouse model of colon CAC and categorize the mice into three groups: CAC, NCAC and normal control (NOR). By performing nuclear magnetic resonance (NMR)-based metabolomic profiling on mouse sera, we elucidate the metabolic properties of these groups. Our findings unveil significant differences in the metabolic profiles among the CAC, NCAC and NOR groups, highlighting significant impairments in energy metabolism and amino acid metabolism during cachexia progression. Additionally, we observe the elevated serum levels of lysine and acetate during the transition from the NCAC to CAC stages. Using multivariate ROC analysis, we identify lysine and acetate as potential biomarkers for distinguishing between CAC and NCAC stages. These biomarkers hold promise for the diagnosis of CAC from noncachexia cancer. Our study provides novel insights into the metabolic mechanisms underlying cachexia progression and offers valuable avenues for the diagnosis and treatment of CAC in clinical settings.

Development and validation of an online dynamic nomogram system for predicting cancer cachexia among inpatients: a real-world cohort study in China.

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.

Metabolomics and its Applications in Cancer Cachexia.

Cancer cachexia (CC) is a complicated metabolic derangement and muscle wasting syndrome, affecting 50–80% cancer patients. So far, molecular mechanisms underlying CC remain elusive. Metabolomics techniques have been used to study metabolic shifts including changes of metabolite concentrations and disturbed metabolic pathways in the progression of CC, and expand further fundamental understanding of muscle loss. In this article, we aim to review the research progress and applications of metabolomics on CC in the past decade, and provide a theoretical basis for the study of prediction, early diagnosis, and therapy of CC.

Potential role of immunological factors in early diagnosis of cancer cachexia in C26 tumor-bearing mice

Cachexia is a wasting syndrome associated with high mortality in cancer patients through inducing the failure of normal metabolism and reducing the efficacy of cancer treatment. Thus, it is critically important to diagnose cancer cachexia early. To provide background data for the diagnosis of cachexia, cancer cachectic factors were characterized in the present situation, including immunological cachectic changes during cachexia progression in a cancer cachexia mouse model. Major constitution of cachexia progression is known as the stages of pre-cachexia, cachexia, and refractory cachexia. In the pre-cachexia stage, the weights of immune-related organs, including the thymus and spleen were significantly. T cell populations in spleen were markedly reduced and cachectic cytokines consistently increased in a time-dependent manner. Immunosuppression by activation of cytotoxic T-lymphocyte-associated antigen 4 was induced earlier in CD4+ cells versus other T cell populations. Furthermore, monocyte chemoattractant protein 1 and interleukin-6 levels in the cachexia group were significantly increased at 3 days from C26 cell inoculation whereas significant carcass weight loss as a classical diagnostic marker occurred at 9 days from C26 cell inoculation. In conclusion, the initiation of cachectic immunological changes was observed prior to weight loss, during the pre-cachexia stage. Accordingly, these findings reveal that the monitoring of humoral and immunological factors may be more sensitive than weight loss for the initial diagnosis and treatment of cachexia.

The influence of different muscle mass measurements on the diagnosis of cancer cachexia.

BackgroundProgressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored.MethodsPrior to chemotherapy, cachexia was assessed by weight loss, body mass index, and muscle mass measurements, the latter by mid‐upper arm muscle area (MUAMA), computed tomography (CT) scans, and bio‐electrical impedance analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue, quality of life, and survival were measured, and associations with cachexia were explored.ResultsIncluded were 241 patients with advanced cancer of the lung (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 ± 10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37, 43, and 48%, whereby weight loss >5% was the most prominent component of being defined cachectic. Irrespective of type of muscle measurement, patients with cachexia presented more often with anorexia, inflammation, low muscle strength, and fatigue and had lower quality of life. Patients with cachexia had worse overall survival compared with patients without cachexia: HRs 2.00 (1.42–2.83) with MUAMA, 1.64 (1.15–2.34) with CT, and 1.50 (1.05–2.14) with BIA.ConclusionsAlthough the prevalence of low muscle mass in patients with cancer depended largely on the type of muscle measurement, this had little influence on the diagnosis of cancer cachexia (as the majority of patients was already defined cachectic based on weight loss). New studies are warranted to further elucidate the additional role of muscle measurements in the diagnosis of cachexia and the association with clinical outcomes.

IS THE GLASGOW PROGNOSTIC SCORE A USEFUL TOOL FOR DIAGNOSIS OF CANCER CACHEXIA?

Background: Cancer cachexia is characterized as a multi-factorial syndrome, identified by the continuing decline of skeletal muscle mass where nutritional support does not completely reverse the effects. Finding a cure for cachexia will impact cancer patients’ worldwide, improving quality of life and potentially increasing survival in response to standard care. In turn, an accurate diagnostic tool would assist in the identification and translation of therapeutic targets to the clinic. The Glasgow Prognostic Score (GPS), is determined from combining circulating albumin and C-reactive protein (CRP) concentrations to form a score of 0 (normal) and 1 or 2 (abnormal) (albumin 10mg/L=1). The GPS has been used as an indicator in various cancer types, due to the presence of systemic inflammation, but not in cancer cachexia. The GPS has been validated in a wide range of clinical situation for a systemic inflammatory response so it may be beneficial in assessing the prognosis of cancer cachexia patients. Method/Design:A retrospective cohort study was conducted to assess the GPS as a valuable tool for diagnosing cancer cachexia. The relationship between BMI and the GPS was examined, along with other parameters for controls and cases. Clinical audit data was collected for 357 participants, 185 cases and 172 controls. Results: The GPS was abnormal (2; with albumin 10mg/L) in 123 (66.5%) cases and in 13 (7.6) controls. The GPS scored was also abnormal (1; with albumin 10 mg/L) in 53 (28.6%) cases and 89 (51.7%) controls. It was normal (0) in 9 (4.9%) cases and in 70 (40.7%) controls. There was a significant correlation between the GPS and a decrease in BMI as P value was 0.019. Conclusion: The GPS could be a useful indicator for the onset of cancer cachexia as advanced cancer is usually associated with a marked systemic inflammatory response which is manifested by an increase in CRP which led to a decrease in albumin. It would be beneficial to investigate if the GPS could be used for early diagnosis of cancer cachexia so it must be included in the basic assessment for all patients with cancer.

Cancer cachexia update in head and neck cancer: Definitions and diagnostic features

Cachexia is a profoundly debilitating wasting syndrome that affects patients with head and neck cancer and often contributes to their demise. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, CINAHL, and the Google search engine. For the meta-analyses, pooled prevalence estimates were calculated with a confidence interval of 95% (95% CI) by using random effects modeling. In this review, we outlined the unique challenges of cancer cachexia among patients with head and neck cancer by reviewing its impacts on quality of life (QOL), morbidity, and mortality. We explored the prevalence of different clinical markers of cachexia at the time of diagnosis and before and after treatment. Finally, we present updates regarding the diagnosis of cancer cachexia and recent findings, such as cardiac dysfunction that warrant clinical attention to more carefully identify patients at risk and potentially lead to better outcomes.