Performance of anthropometry-based and bio-electrical impedance-based muscle-mass indicators in the Global Leadership Initiative on Malnutrition criteria for predicting prognosis in patients with cancer.

BACKGROUND: Reduced muscle mass is a criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria; however, the choice of muscle-mass indicators within the GLIM criteria remains contentious. This study aimed to establish muscle-measurement-based GLIM criteria using data from bio-electrical impedance analysis (BIA) and anthropometric evaluations and evaluate their ability to predict overall survival (OS), short-term outcomes, and healthcare burden in patients with cancer. METHODS: This was a multicenter, prospective study that commenced in 2013 and enrolled participants from various clinical centers across China. We constructed GLIM criteria based on various muscle measurements, including fat-free mass index (FFMI), skeletal muscle index (SMI), calf circumference (CC), midarm circumference (MAC), midarm muscle circumference (MAMC), and midarm muscle area (MAMA). Survival was estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Cox proportional hazards regression was used to assess the independent association between the GLIM criteria and OS. The discriminatory performance of different muscle-measurement-based GLIM criteria for mortality was evaluated using Harrell's concordance index (C-index). Logistic regression was used to evaluate the association of the GLIM criteria with short-term outcomes and healthcare burden. RESULTS: A total of 4769 patients were included in the analysis, of whom 1659 (34.8%) died during the study period. The Kaplan-Meier curves demonstrated that all muscle-measurement-based GLIM criteria significantly predicted survival in patients with cancer (all p < 0.001). The survival rate of malnourished patients was approximately 10% lower than that of non-malnourished patients. Cox proportional hazards regression showed that all the muscle-measurement-based GLIM could independently predict the OS of patients (all p < 0.001). The prognostic discrimination was as follows: MAMC (Chi-square: 79.61) > MAMA (Chi-square: 79.10) > MAC (Chi-square: 64.09) > FFMI (Chi-square: 62.33) > CC (Chi-square: 58.62) > ASMI (Chi-square: 57.29). In comparison to the FFMI-based GLIM criteria, the ASMI-based criteria (-0.002, 95% CI: -0.006 to 0.002, p = 0.334) and CC-based criteria (-0.003, 95% CI: -0.007 to 0.002, p = 0.227) did not exhibit a significant advantage. However, the MAC-based criteria (0.001, 95% CI: -0.003 to 0.004, p = 0.776), MAMA-based criteria (0.004, 95% CI: 0.000-0.007, p = 0.035), and MAMC-based criteria (0.005, 95% CI: 0.000-0.007, p = 0.030) outperformed the FFMI-based GLIM criteria. Logistic regression showed that muscle measurement-based GLIM criteria predicted short-term outcomes and length of hospital stay in patients with cancer. CONCLUSION: All muscle measurement-based GLIM criteria can effectively predict OS, short-term outcomes, and healthcare burden in patients with cancer. Anthropometric measurement-based GLIM criteria have potential for clinical application as an alternative to BIA-based measurement.

Apolipoprotein A-I levels in the survival of patients with colorectal cancer: a retrospective study.

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.

Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis.

BACKGROUND: This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC). METHODS: We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells. RESULTS: After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family. CONCLUSION: Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.

Inflammaging score as a potential prognostic tool for cancer: A population-based cohort study.

This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%-17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.

Phase angle: A robust predictor of malnutrition and poor prognosis in gastrointestinal cancer.

OBJECTIVES: The aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer. METHODS: In total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia. RESULTS: Low PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409-0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction. CONCLUSIONS: PA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer.

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer.

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 µmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 µmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

The prognostic value of preoperative D-dimer to albumin ratio for overall survival and progression-free survival in colorectal cancer.

Introduction: This study aimed to explore the predictive value of the D-dimer-to-albumin ratio (DAR) for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Methods: The Kaplan-Meier method was used to plot survival curves for PFS and OS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the DAR for PFS and OS in patients with CRC. Cox proportional hazards regression analysis was used to analyze prognostic factors influencing outcomes. A nomogram based on the DAR was constructed to predict 1-, 3-, and 5-year prognoses of patients with CRC; its predictive ability was evaluated using the concordance index (C-index) and calibration curves. Additionally, the clinical utility of the DAR-based nomogram was validated using an internal randomized validation cohort. Results: A total of 1,339 patients with CRC who underwent surgery were enrolled. The optimal cut-off value for DAR was determined to be 3.320, dividing patients into low (<3.320 [n = 470]) and high (≥3.320 [n = 869]) DAR groups. Compared with other composite immune inflammatory markers, DAR exhibited superior prognostic predictive efficacy. Patients with a high DAR had a significantly worse prognosis than those with a low DAR (PFS, 50.9% versus [vs.] 69.4%, p < 0.001; OS, 52.9% vs. 73.8%, p < 0.001). DAR also demonstrated significant prognostic stratification for most tumor subgroups, particularly in the stage III-IV subgroup and normal carcinoembryonic antigen subgroup. DAR has been identified as an independent predictive indicator of PFS/OS in patients with CRC. For every standard deviation increase in DAR, the risk for PFS/OS in patients with CRC was reduced by 9.5% (hazard ratio [HR] 1.095 [95% confidence interval (CI) 1.013-1.185]; p = 0.022) and 9.3% (HR 1.093 [95% CI 1.012-1.180]; p = 0.024), respectively. The DAR-based nomogram was confirmed to demonstrate good prognostic prediction accuracy and achieved high evaluation in the internal validation cohort. Conclusion: Preoperative DAR is a promising biomarker for predicting PFS and OS among patients with CRC. The DAR-based prognostic prediction nomogram may serve as an effective tool for the comprehensive assessment of prognosis in patients with CRC.

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

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

Association of systemic inflammation with the obesity paradox in cancer: results from multi-cohort studies.

AIMS: This study aimed to explore whether the obesity paradox exists in overall and specific cancers and to investigate the role of systemic inflammation in the obesity paradox. METHODS: The Cox proportional hazard model was used to explore the relationship between body mass index (BMI) and all-cause mortality. The mediated effect was used to investigate the proportion of systemic inflammation mediating the relationship between BMI and cancer survival risk. RESULTS: The survival probability showed a step-like increase with an increase in BMI regardless of pathological stage. Approximately 10.8%-24.0% of the overall association between BMI and all-cause mortality in cancer was mediated by inflammation. In the internal validation, we found evidence of the obesity paradox in all body composition obtained using BIA, with inflammation remaining an important mediating factor. Furthermore, we also validated the existence of the obesity paradox of cancer in NHANES. Systemic inflammation remains an important factor in mediating the association between BMI and prognosis in cancer patients. CONCLUSIONS: The obesity paradox is prevalent in most cancers, except for hepatic biliary cancer and breast cancer. Inflammation may be one of the true features of the obesity paradox in cancer.

Individualized threshold of the involuntary weight loss in prognostic assessment of cancer.

BACKGROUND: Involuntary weight loss (WL) is a common symptom in cancer patients and is associated with poor outcomes. However, there is no standardized definition of WL, and it is unclear what magnitude of weight loss should be considered significant for prognostic purposes. This study aimed to determine an individualized threshold for WL that can be used for prognostic assessment in cancer patients. METHODS: Univariate and multivariate analyses of overall survival (OS) were performed using Cox proportional hazard models. The Kaplan-Meier method was performed to estimate the survival distribution of different WL levels. Logistic regression analysis was used to determine the relationship between WL and 90-day outcomes. Restricted cubic splines with three knots were used to examine the effects of WL on survival under different body mass index (BMI) conditions. RESULTS: Among the 8806 enrolled patients with cancer, median survival time declined as WL increased, from 25.1 to 20.1, 17.8 and 16.4 months at <2%, 2-5%, 5-10% and ≥10% WL, respectively (P < 0.001). Multivariate adjusted Cox regression analysis showed that the risk of adverse prognosis increased by 18.1% based on the SD of WL (5.45 U) (HR: 1.181, 95% CI: 1.144-1.219, P < 0.001). Similarly, categorical WL was independently associated with OS in patients with cancer. With the worsening of WL, the risk of a poor prognosis in patients increases stepwise. Compared with <2% WL, all-cause mortalities were 15.1%, 37% and 64.2% higher in 2-5%, 5-10%, and ≥10% WL, respectively. WL can effectively stratify the prognosis of both overall and site-specific cancers. The clinical prognostic thresholds for WL based on different BMI levels were 4.21% (underweight), 5.03% (normal), 6.33% (overweight), and 7.60% (obese). Multivariate logistic regression analysis showed that WL was independently associated with 90-day outcomes in patients with cancer. Compared with patients with <2% WL, those with ≥10% WL had more than twice the risk of 90-day outcomes (OR: 3.277, 95% CI: 2.287-4.694, P < 0.001). Systemic inflammation was a cause of WL deterioration. WL mediates 6.3-10.3% of the overall association between systemic inflammation and poor prognoses in patients with cancer. CONCLUSIONS: An individualized threshold for WL based on baseline BMI can be used for prognostic assessment in cancer patients. WL and BMI should be evaluated simultaneously in treatment decision-making, nutritional intervention, and prognosis discussions of patients with cancer.

The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies.

Background: Combining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated. Methods: We used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals. Results: Patients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis. Conclusion: Our findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.

The cancer inflammation prognostic index is a valuable biomarker for predicting the survival of patients with stage I-III colorectal cancer.

This study aimed to assess the relationship between the Cancer-Inflammation Prognostic Index (CIPI) and disease-free survival (DFS) and overall survival (OS) in patients with stage I-III colorectal cancer (CRC). The relationship between the CIPI and survival was evaluated using restricted cubic splines. Survival curves were established using the Kaplan-Meier method and the log-rank test. Cox proportional hazards models were used to explore independent prognostic factors for CRC. Meaningful variables from the multivariate analysis were used to construct prognostic nomograms. The relationship between the CIPI values on a continuous scale and the risk of DFS/OS mortality was an inverted L-shape. Patients with a high CIPI had significantly lower DFS (53.0% vs. 68.5%, p < 0.001) and OS (55.5% vs. 71.7%, p < 0.001) than those with a low CIPI. The CIPI can also serve as an effective auxiliary tool to further distinguish the prognosis of patients with CRC at the same pathological stage, especially for stages II and III. After multivariate adjustment, a high CIPI was found to be an independent risk factor for DFS (HR 1.443, 95% CI 1.203-1.730, p < 0.001) and OS (HR 1.442, 95% CI 1.189-1.749, p < 0.001) in CRC patients. These nomograms have the advantage of integrating individual profiles, tumour characteristics, and serum inflammatory markers, providing favourable discrimination and calibration values. Compared with traditional TNM staging, nomograms have a better predictive performance. The CIPI is an effective and easy-to-use clinical tool for predicting the recurrence and overall mortality of patients with stage I-III CRC.

Improving the assessment of malnutrition in cancer: Using systemic inflammation markers as a supplement to the inflammation items of the GLIM criteria.

BACKGROUND & AIMS: Systemic inflammation is a key pathogenic criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Although cancer is commonly considered as a chronic inflammation-related disease, the inflammatory burden may vary depending on the type and stage of cancer. Therefore, a more precise definition of inflammation criteria could facilitate the identification of malnutrition in cancer. METHODS: This prospective multicenter study included 1683 cancer patients screened via NRS2002 for malnutrition risk. The inflammatory burden index (IBI), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and albumin (ALB) level were used to assess the inflammatory burden. Kaplan-Meier and Cox regression analyses were used to determine the relationship between the GLIM criteria and overall survival. Harrell's concordance index (C-index) was used to compare the discriminative performance of the original, IBI-based, CRP-based, NLR-based, and ALB-based GLIM criteria for survival. Logistic regression models were used to assess the association between GLIM criteria and short-term outcomes, length of hospital stay, and hospitalization costs. RESULTS: Compared to the original GLIM criteria, the IBI/CRP/NLR/ALB-based GLIM criteria better predicted the long-term outcomes of patients with cancer (chi-square: 1.316 vs. 78.321 vs. 74.740 vs. 88.719 vs. 100.921). The C-index revealed that the inflammation marker-based GLIM criteria showed significantly better prognostic accuracy than the original GLIM criteria. The ALB-based GLIM criteria exhibited the best prognostic accuracy. The inflammation marker-based GLIM criteria were independent predictive factors for the long-term prognosis of cancer. Patients with malnutrition had a 45% higher risk of adverse long-term prognoses than those without malnutrition. The inflammation marker-based GLIM criteria had good prognostic ability to predict outcomes at 3, 6, and 12 months. The stepwise effect of the grading of severity via the IBI-based GLIM criteria and CRP-based GLIM criteria was notable. The inflammation marker-based GLIM criteria are useful for predicting short-term outcomes, length of hospitalization, and hospitalization costs. CONCLUSION: The inflammation marker-based GLIM criteria have a stronger predictive value than the original GLIM criteria in evaluating both the short- and long-term prognoses of cancer patients. It is recommended to use the inflammation marker-based GLIM criteria for nutritional evaluation of cancer patients.

Development and applicability of modified weight loss grading system in cancer: a real-world cohort study.

BACKGROUND: The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China. METHODS: A prospective multicentre real-world cohort study involving 16 842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90-day outcomes. RESULTS: We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0-4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site-specific cancers, especially lung and gastrointestinal cancers. High-grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90-day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts. CONCLUSIONS: Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90-day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

Serum creatinine/cystatin C ratio as a prognostic indicator for patients with colorectal cancer.

Background: This study aimed to explore the relationship between creatinine/cystatin C ratio and progression-free survival (PFS) and overall survival (OS) in colorectal cancer (CRC) patients undergoing surgical treatment. Methods: A retrospective analysis was conducted on 975 CRC patients who underwent surgical resection from January 2012 to 2015. Restricted three-sample curve to display the non-linear relationship between PFS/OS and creatinine-cystatin C ratio. Cox regression model and Kaplan-Meier method were used to evaluate the effect of the creatinine-cystatin C ratio on the survival of CRC patients. Prognostic variables with p-value ≤0.05 in multivariate analysis were used to construct prognostic nomograms. The receiver operator characteristic curve was used to compare the efficacy of prognostic nomograms and the traditional pathological stage. Results: There was a negative linear relationship between creatinine/cystatin C ratio and adverse PFS in CRC patients. Patients with low creatinine/cystatin C ratio had significantly lower PFS/OS than those with high creatinine/cystatin C ratio (PFS, 50.8% vs. 63.9%, p = 0.002; OS, 52.5% vs. 68.9%, p < 0.001). Multivariate analysis showed that low creatinine/cystatin C ratio was an independent risk factor for PFS (HR=1.286, 95%CI = 1.007-1.642, p=0.044) and OS (HR=1.410, 95%CI=1.087-1.829, p=0.010) of CRC patients. The creatinine/cystatin C ratio-based prognostic nomograms have good predictive performance, with a concordance index above 0.7, which can predict the 1-5-year prognosis. Conclusion: Creatinine/cystatin C ratio may be an effective prognostic marker for predicting PFS and OS in CRC patients, aid in pathological staging, and along with tumour markers help in-depth prognostic stratification in CRC patients.

The prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia.

BACKGROUND: Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi-centre retrospective study aimed to explore the prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia. METHODS: The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil-lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all-cause mortality in patients with cancer cachexia. Kaplan-Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all-cause mortality in patients with cancer cachexia. RESULTS: A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex-specific optimal cut-off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non-linear relationship between mALI and all-cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio [HR] = 0.974, 95% confidence interval [CI] = 0.959-0.990, P = 0.001). For every standard deviation [SD] increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943-0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893-0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators. CONCLUSIONS: Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.

The inflammatory burden index is a superior systemic inflammation biomarker for the prognosis of non-small cell lung cancer.

BACKGROUND: Systemic inflammation, the most representative tumour-host interaction, plays a crucial role in disease progression and prognosis in patients with non-small cell lung cancer (NSCLC). Few studies have compared the performance of existing haematological systemic inflammation biomarkers in predicting the prognosis of NSCLC patients. The purpose of this study was to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with NSCLC through a multicentre prospective study. METHODS: The predictive accuracy of systemic inflammation biomarkers for prognostic assessment in NSCLC was assessed using C-statistics. Inter-group differences in survival were assessed using the log-rank test and visualized using the Kaplan-Meier method. A restricted cubic spline (RCS) curve was used to explore the association between the biomarkers and survival. Independent prognostic biomarkers for overall survival were determined using multivariable Cox proportional hazards regression analysis. Logistic regression analysis was used to determine independent predictors of 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia. RESULTS: The inflammatory burden index (IBI) had the highest C-statistic for predicting the prognosis of patients with NSCLC, reaching 0.640 (0.617, 0.663). Patients with a high IBI had significantly worse outcomes than those with a low IBI (35.46% vs. 57.22%; log-rank P < 0.001). The IBI was also able to differentiate the prognosis of patients with NSCLC with the same pathological stage. The RCS curve showed an inverted L-shaped dose-response relationship between the IBI and survival of patients with NSCLC. Multivariable Cox proportional hazards regression analysis showed that a high IBI was an independent risk factor for death of patients with NSCLC (hazard ratio = 1.229, 95% confidence interval [CI]: 1.131-1.335, P < 0.001). A high IBI was an independent predictor of 90-day outcomes (odds ratio [OR] = 1.789, 95% CI: 1.489-2.151, P < 0.001), prolonged hospital stays (OR = 1.560, 95% CI: 1.256-1.938, P < 0.001), high hospitalization expenses (OR = 1.476, 95% CI: 1.195-1.822, P < 0.001) and cachexia (OR = 1.741, 95%CI = 1.374-2.207, P < 0.001) in patients with NSCLC. CONCLUSIONS: The IBI was independently associated with overall survival, 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia in NSCLC patients. As an optimal systemic inflammation biomarker, the IBI has broad clinical application prospects in predicting the prognosis of patients with NSCLC.

Prognostic significance of sarcopenia diagnosed based on the anthropometric equation for progression-free survival and overall survival in patients with colorectal cancer.

Background: The purpose of this study was to investigate the prognostic significance of sarcopenia diagnosed based on anthropometric equations for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Methods: A total of 1,441 CRC patients who underwent surgical treatment between January 2012 and December 2016 were enrolled in this study. Sarcopenia was diagnosed according to validated anthropometric equations. The Kaplan-Meier method with the log-rank test was used to estimate the survival curve. Cox proportional hazards regression models with forward selection were used to evaluate risk factors affecting the prognosis of CRC patients. R package "survival" was used to build the prognostic nomograms to predict 1-5 years of PFS and OS in CRC patients. The concordance index (C-index) and calibration curve were used to evaluate the prognostic accuracy of the prognostic nomogram. Results: Two hundred and seventy-one patients (18.8%) were diagnosed with sarcopenia. Sarcopenia was significantly associated with advanced age, large tumor size, and high mortality. Compared with the non-sarcopenia patients, the PFS of sarcopenia patients was worse (5-year PFS, 48.34 vs. 58.80%, p = 0.003). Multivariate survival analysis showed that patients with sarcopenia had a higher risk (23.9%) of adverse PFS (HR, 1.239; 95%CI: 1.019-1.505, p = 0.031) than patients without sarcopenia. The OS of patients with sarcopenia was significantly worse than that of patients without sarcopenia (5-year OS: 50.92 vs. 61.62%, p = 0.001). In CRC patients, sarcopenia was independently associated with poor OS (HR: 1.273, 95%CI: 1.042-1.556, p < 0.001). Moreover, sarcopenia effectively differentiated the OS of CRC patients in the normal carcinoembryonic antigen (CEA) subgroup but not in the high CEA subgroup. Notably, sarcopenia can provide effective prognostic stratification in CRC patients at different pathological stages. Nomograms that integrated prognostic features were built to predict the risk of adverse outcomes in CRC patients. The C-index and calibration curves showed that these nomograms had good prediction accuracy. Internal validation confirmed that our nomogram has wide application potential. Conclusion: Sarcopenia diagnosed based on anthropometric equations is an independent risk factor for PFS and OS in CRC patients.

Hand grip strength-based cachexia index as a predictor of cancer cachexia and prognosis in patients with cancer.

BACKGROUND: The cachexia index is a useful predictor for cancer cachexia and prognostic assessment. However, its use is limited because of high testing costs and complicated testing procedures. Thus, in this study, we aimed to develop a hand grip strength (HGS)-based cancer cachexia index (H-CXI) as a potential predictor of cancer cachexia and prognosis in patients with cancer. METHODS: Here, 14 682 patients with cancer were studied, including the discovery (6592), internal validation (2820) and external validation (5270) cohorts. The H-CXI was calculated as [HGS (kg)/height (m)2  × serum albumin (g/L)]/neutrophil-to-lymphocyte ratio. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). Logistic regression analysis was used to assess the association of the H-CXI with short-term outcomes and cancer cachexia. RESULTS: There was a significant non-linear relationship between the H-CXI and OS in all cohorts. Patients with a low H-CXI had significantly lower OS than those with a high H-CXI in the discovery cohort (6-year survival percentage: 55.72% vs. 76.70%, log-rank P < 0.001), internal validation cohort (6-year survival percentage: 55.81% vs. 76.70%, log-rank P < 0.001), external validation cohort (6-year survival percentage: 56.05% vs. 75.48%, log-rank P < 0.001) and total cohort (6-year survival percentage: 55.86% vs. 76.27%, log-rank P < 0.001). Notably, the prognostic stratification effect of the H-CXI in patients with advanced-stage disease was more significant than that in patients with early-stage disease. The multivariate Cox proportional risk regression model confirmed that a low H-CXI negatively affected the prognosis of patients with cancer in the discovery cohort [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.71-0.80, P < 0.001], internal validation cohort (HR 0.79, 95 %CI 0.72-0.86, P < 0.001), external validation cohort (HR 0.84, 95% CI 0.79-0.89, P < 0.001) and total cohort (HR 0.80, 95% CI 0.77-0.83, P < 0.001). Multivariate logistic regression models showed that a low H-CXI was an independent risk factor predicting adverse short-term outcomes and cancer cachexia in patients with cancer. CONCLUSIONS: The simple and practical H-CXI is a promising predictor for cancer cachexia and prognosis in patients with cancer.