Metabolomic profiling of cancer-related fatigue involved in cachexia and chemotherapy.

Patients with advanced cancer are frequently burdened with a severe sensation of fatigue called cancer-related fatigue (CRF). CRF is induced at various stages and treatments, such as cachexia and chemotherapy, and reduces the overall survival of patients. Objective and quantitative assessment of CRF could contribute to the diagnosis and prediction of treatment efficacy. However, such studies have not been intensively performed, particularly regarding metabolic profiles. Here, we conducted plasma metabolomics of 15 patients with urological cancer. The patients with and without fatigue, including those with cachexia or chemotherapy-induced fatigue, were compared. Significantly lower concentrations of valine and tryptophan were observed in fatigued patients than in non-fatigued patients. In addition, significantly higher concentrations of polyamine pathway metabolites were observed in patients with fatigue and cachexia than in those without cachexia. Patients with exacerbated fatigue due to chemotherapy showed significantly decreased cysteine and methionine metabolism before chemotherapy compared with those without fatigue exacerbation. These findings suggest that plasma metabolic profiles could help improve the diagnosis and monitoring of CRF.

Handgrip Strength Predicts Survival in Patients With Pancreatic Cancer.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with a poor prognosis and is associated with a high prevalence of cachexia, a metabolic syndrome of muscle wasting due to complex mechanisms. In addition to loss of muscle mass, cancer patients also experience functional deterioration. The aim of this study is to determine whether there is an association between muscle mass and function and clinical outcomes, particularly survival. METHODS: We performed a prospective cohort study including all patients with PDAC at Monash Health from March 2016 to December 2017. We conducted body composition analysis for myopenia and handgrip strength testing. We constructed Kaplan-Meier curves to estimate whether myopenia and low hand grip strength were associated with poorer survival. RESULTS: Myopenia was not associated with a significant difference in PDAC-specific survival (log-rank P = 0.60). However, low handgrip strength was associated with significantly worse PDAC-specific survival compared with other patients (log-rank hazard ratio, 1.88; 95% confidence interval, 1.15-3.09; P = 0.004). CONCLUSIONS: The relationship between survival in PDAC and handgrip strength, but not anatomical muscle mass, suggests that functional testing of strength may be important in prognostication of patients with PDAC, alongside existing tools such as the Eastern Cooperative Oncology Group performance status.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia â ¡ (J-EPOCC â ¡)-Disease Awareness and Issues Related to Cancer Cachexia Among Healthcare Professionals].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC)was conducted among cancer patients, their families and healthcare professionals in Japan, and it showed that the term"cancer cachexia"was highly recognized among health care professionals, whereas the staging and criteria for cancer cachexia defined by European Palliative Care Research Collaborative( EPCRC)was less understood. Also, many healthcare professionals tended to consider the term"cancer cachexia" as the terminal stage of cancer, and most of them lacked the knowledge that cancer cachexia is a disease complication which is potentially developed from the early stage of cancer. Since anamorelin was approved in 2021 for"Cancer cachexia in unresectable advanced or recurrent of non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCC Ⅱ) was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their families and healthcare professionals1). The results for healthcare professionals showed that the awareness of the staging and criteria has increased among doctors in 2022 compared with 2019, and an increasing number of doctors considered"cancer cachexia"was associated with loss of muscle mass, totally body weight loss, appetite loss and systemic inflammation that may occur in early stages of cancer. On the other hand, awareness of staging and diagnostic criteria for cancer cachexia has not remarkably changed among medical staff since 2019, with levels of awareness varying among those with different job categories. Therefore, in order to achieve early detection and intervention of cancer cachexia, it is necessary to raise the awareness of cancer cachexia among not only doctors but also medical staff by increasing their opportunities to get to know the disease condition, diagnosis, and treatment of cancer cachexia.

Prevalence and prognosis of cachexia according to the Asian Working Group for Cachexia criteria in sarcopenic dysphagia: A retrospective cohort study.

OBJECTIVE: The aim to examine the prevalence and prognosis of cachexia according to the Asian Working Group for Cachexia (AWGC) criteria in patients with sarcopenic dysphagia. METHODS: A retrospective cohort study was conducted with 271 patients diagnosed with sarcopenic dysphagia out of 467 patients enrolled in the Japanese sarcopenic dysphagia database. Cachexia was diagnosed by the AWGC criteria. The AWGC criteria includes chronic diseases, either or both weight loss (2% or more over 3-6 mo) or low BMI (<21 kg/m2), and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>0.5 mg/dL). Outcomes were death, swallowing function as assessed by the Food Intake LEVEL Scale (FILS), and activities of daily living as assessed by the Barthel Index (BI) at follow-up. RESULTS: The mean age was 84 (±8) y; 152 (56%) were female, and 97 (36%) had cachexia. In univariate analysis, death was significantly more common in the cachexia group (15% versus 2%, P ≤ 0.001). Logistic regression analysis showed that cachexia was independently associated with death (odds ratio: 3.557, 95% confidence interval: 1.010, 12.529). No significant differences were found in the presence or absence of cachexia in the FILS (7 versus 8, P = 0.849) and BI (55 versus 52.5, P = 0.892). CONCLUSIONS: Cachexia was found in 36% of patients with sarcopenic dysphagia, and death was significantly higher in cachexia.

Circulating factors in cancer cachexia: recent opportunities for translational research.

PURPOSE OF REVIEW: To discuss the recent discoveries and limitations of the available literature on emerging circulating biomarkers of cancer cachexia. RECENT FINDINGS: Studies on circulating factors in cancer cachexia show promising alternatives for diagnosing the syndrome in a minimally invasive manner in the clinic setting, as well as potential targets for cancer cachexia treatment. Factors secreted by the tumor and the adipose tissue, such as extracellular vesicles and soluble proteins, respectively, have been shown to either directly induce wasting in vitro and in vivo or to be altered in the cachectic phenotype. The detection and characterization of circulating cells allows detection of the precachectic stage and the levels of the soluble immune checkpoint protein programmed death ligand-1 (PD-L1) are correlated with the presence of the hallmarks of cancer cachexia. SUMMARY: Structural, molecular, and metabolic alterations have been observed in various tissues, revealing the occurrence of sustained inter-compartment crosstalk in cachectic patients. Early diagnosis of cancer cachexia becomes crucial to avoid the establishment of refractory cachexia through the implementation of interventions that may attenuate systemic inflammation and muscle loss. More studies on human cancer cachexia are required in order to address the recently discovered cachexia-associated circulating factors' value as biomarkers of the syndrome.

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

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

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Bridging gaps in cancer cachexia Care: Current insights and future perspectives.

Cachexia is characterized by severe weight loss and skeletal muscle depletion, and is a threat to cancer patients by worsening their prognosis. International guidelines set indications for the screening and diagnosis of cancer cachexia and suggest interventions (nutritional support, physical exercise, and pharmacological treatments). Nevertheless, real-life experience not always aligns with such indications. We aimed to review the current state of the field and the main advancements, with a focus on real-life clinical practice from the perspectives of oncologists, nutrition professionals, and radiologists. Pragmatic solutions are proposed to improve the current management of the disease, emphasizing the importance of increasing awareness of clinical nutrition's benefits, fostering multidisciplinary collaboration, promoting early identification of at-risk patients, and leveraging available resources. Given the distinct needs of patients who are receiving oncologic anti-cancer treatments and those in the follow-up phase, the use of tailored approaches is encouraged. The pivotal role of healthcare professionals in managing patients in active treatment is highlighted, while patient and caregiver empowerment should be strengthened in the follow-up phase. Telemedicine and web-based applications represent valuable tools for continuous monitoring of patients, facilitating timely and personalized intervention through effective communication between patients and healthcare providers. These actions can potentially improve the outcomes, well-being, and survival of cancer patients with cachexia.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Evaluation of the cachexia index using a bioelectrical impedance analysis in elderly patients with non-Hodgkin's lymphoma: A single-center prospective study.

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78 years (60-93 years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion.

Diagnosis and prevalence of cachexia in Asians: A scoping review.

The aim of this scoping review was to characterize the diagnostic criteria, their cutoff values, and the prevalence of cachexia in Asians. We systematically reviewed studies involving Asian adult patients with cachexia due to cancer and chronic diseases other than cancer, such as heart and renal failure. Sources in English and Japanese published between December 2008 and April 2022, including observational, longitudinal, cross-sectional, and clinical trials, were examined. We searched six databases. Altogether, 4131 studies were screened, and 107 eligible articles were identified, of which 11 and 96 were conducted on non-cancer and cancer patients, respectively. The most common clinical indicators used for diagnosis were weight loss, body mass index (BMI), and muscle mass. The most frequently employed diagnostic criteria for cachexia in non-cancer patients were the modified/excerpt Evans criteria. Contrarily, the original Fearon's criteria were often used in patients with cancer. Additionally, cutoff values for BMI and muscle mass affected by racial anthropometric differences were investigated. The mean or median value of BMI ranges were 18.3 to 25.2 and 17.5 to 25 kg/m2 for non-cancer and cancer patients, respectively. The prevalence rates of cachexia were 3.4% to 66.2% and 6.2% to 93% in non-cancer and cancer patients, respectively. Several diagnostic criteria, such as BMI and muscle mass, have been used, which are affected by racial differences in body size. However, few studies have used cutoff values for Asians.

Validity of the diagnostic criteria from the Asian Working Group for Cachexia in advanced cancer.

BACKGROUND: Recently, the Asian Working Group for Cachexia (AWGC) published a consensus statement on diagnostic criteria for cachexia in Asians. We aimed to validate the criteria in adult patients in Japan with advanced cancer. METHODS: We conducted a single-institution retrospective cohort study between April 2021 and October 2022. The AWGC criteria include chronic comorbidities and either a weight loss of >2% over 3-6 months or a body mass index (BMI) of <21 kg/m2 . In addition, any of the following items were required: anorexia as a subjective symptom, decreased grip strength as an objective measurement and an elevated C-reactive protein (CRP) level as a biomarker. We used the cut-off value of grip strength of 28/18 kg for male/female individuals and CRP level of 5 mg/L. RESULTS: Of the 449 consecutive patients, 85 of those who could not be evaluated because of end-of-life or refractory symptoms (n = 41) or missing data (n = 44) were excluded from the primary analysis. The prevalence of the AWGC-defined cachexia was 76% (n = 277), and the median survival time (MST) for all patients was 215 (95% confidence interval [CI] 145-270) days. The prevalence of the following criteria was significantly higher in patients with cachexia than in those without cachexia: a BMI of <21 kg/m2 (65% vs. 15%, P < 0.001), a weight loss of >2% in 6 months (87% vs. 14%, P < 0.001), anorexia (75% vs. 47%, P < 0.001), a grip strength of <28 kg in male individuals (63% vs. 28%, P < 0.001) and CRP level of >5 mg/L (85% vs. 56%, P < 0.001). Overall survival was significantly shorter in patients with cachexia than in those without cachexia (MST 157 days, 95% CI 108-226 days vs. MST 423 days, 95% CI 245 days to not available, P = 0.0023). The Cox proportional hazards analysis showed that best supportive care (hazard ratio [HR] 2.91, P ≤ 0.001), lung cancer (HR 1.67, P = 0.0046), an Eastern Cooperative Oncology Group Performance Status score of ≥3 (HR 1.58, P = 0.016), AWGC-defined cachexia (HR 1.56, P = 0.015), an age of ≥70 years (HR 1.53, P = 0.0070), oedema (HR 1.31, P = 0.022) and head/neck cancer (HR 0.44, P = 0.023) were found to be the significant predictors for mortality. CONCLUSIONS: We demonstrated that AWGC-defined cachexia has a significant prognostic value in advanced cancer.

Measuring What Is Meaningful in Cancer Cachexia Clinical Trials: A Path Forward With Digital Measures of Real-World Physical Behavior.

PURPOSE: The burden of cancer cachexia on patients' health-related quality of life, specifically their physical functioning, is well documented, but clinical trials thus far have failed to show meaningful improvement in physical functioning. The purpose of this review is to summarize existing methods of assessing physical function in cancer cachexia, outline a path forward for measuring what is meaningful to patients using digital measures derived from digital health technologies (DHTs), and discuss the current landscape of digital measures from the clinical and regulatory standpoint. DESIGN: For this narrative review, peer-reviewed articles were searched on PubMed, clinical trials records were searched on clinicaltrials.gov, and records of digital measures submitted for regulatory qualification were searched on the US Food and Drug Administration's Drug Development Tool Qualification Program database. RESULTS: There are gaps in assessing aspects of physical function that matter to patients. Existing assessment methods such as patient-reported outcomes and objective performance outcomes have limitations, including their episodic nature and burden to patients. DHTs such as wearable sensors can capture real-world physical behavior continuously, passively, and remotely, and may provide a more comprehensive picture of patients' everyday functioning. Recent regulatory submissions showcase potential clinical implementation of digital measures in various therapeutic areas. CONCLUSION: Digital measures of real-world physical behavior present an opportunity to detect and demonstrate improvements in physical functioning in cancer cachexia, but evidence-based development is critical. For their use in clinical and regulatory decision making, studies demonstrating meaningfulness to patients as well as feasibility and validation are necessary.

Emerging markers of cancer cachexia and their relationship to sarcopenia.

PURPOSE: Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. METHODS: A prospective case-control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. RESULTS: Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP. CONCLUSION: Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined.

Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.

The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. RESULTS: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. CONCLUSION: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.

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.