Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Discovery of distinct cancer cachexia phenotypes using an unsupervised machine-learning algorithm.

OBJECTIVES: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort. METHODS: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality. RESULTS: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results. CONCLUSIONS: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials.

Sarcopenia prevalence in patients with cancer and association with adverse prognosis: A nationwide survey on common cancers.

OBJECTIVE: Although previous studies have implicated the negative outcomes of sarcopenia, evidence is limited to one or a few types of cancer. The aim of this study was to evaluate the distribution and influencing factors of sarcopenia, and explore the relationship between sarcopenia and cancer prognosis in a large oncological population. METHODS: This observational cohort study included patients diagnosed with malignant cancer between May 2011 and January 2019. Hematologic and anthropometric parameters were collected prospectively. Low skeletal muscle mass and radiodensity were diagnosed using clinical indicators, according to the two prediction models. The importance of potential risk factors for sarcopenia was estimated by subtracting the predicted degrees of freedom from the partial χ2 statistic. Hazard rates of death were calculated using the hazard function and Cox regression analyses. RESULTS: We included 13 761 patients with cancer; the prevalence of sarcopenia was 33%. The median age was 58 y and 7135 patients (52%) were men. Patients with sarcopenia had a worse nutritional status and quality of life than those without sarcopenia. Age was the most important risk factor for sarcopenia compared with body mass index or TNM stage. Additionally, patients with sarcopenia had a significantly higher and earlier peak risk for mortality. After adjusting for baseline characteristics, sarcopenia was independently associated with mortality in the research population (hazard ratio, 1.429; P < 0.001) and most cancer types. CONCLUSION: Age is the most important risk factor for sarcopenia even in patients with cancer. Sarcopenia is strongly associated with a poor quality of life and reduced overall survival.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Sorbitol induces flower bud formation via the MADS-box transcription factor EjCAL in loquat.

Sorbitol is an important signaling molecule in fruit trees. Here, we observed that sorbitol increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.). Transcriptomic analysis suggested that bud formation was associated with the expression of the MADS-box transcription factor (TF) family gene, EjCAL. RNA fluorescence in situ hybridization showed that EjCAL was enriched in flower primordia but hardly detected in the shoot apical meristem. Heterologous expression of EjCAL in Nicotiana benthamiana plants resulted in early FBD. Yeast-one-hybrid analysis identified the ERF12 TF as a binding partner of the EjCAL promoter. Chromatin immunoprecipitation-PCR confirmed that EjERF12 binds to the EjCAL promoter, and ß-glucuronidase activity assays indicated that EjERF12 regulates EjCAL expression. Spraying loquat trees with sorbitol promoted flower bud formation and was associated with increased expression of EjERF12 and EjCAL. Furthermore, we identified EjUF3GaT1 as a target gene of EjCAL and its expression was activated by EjCAL. Function characterization via overexpression and RNAi reveals that EjUF3GaT1 is a biosynthetic gene of flavonoid hyperoside. The concentration of the flavonoid hyperoside mirrored that of sorbitol during FBD and exogenous hyperoside treatment also promoted loquat bud formation. We identified a mechanism whereby EjCAL might regulate hyperoside biosynthesis and confirmed the involvement of EjCAL in flower bud formation in planta. Together, these results provide insight into bud formation in loquat and may be used in efforts to increase yield.

Nutrition-inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer.

BACKGROUND: Overweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition-inflammation marker can provide additional prognostic information on top of well-established Eastern Cooperative Oncology Group performance status (ECOG-PS) in overweight or obese patients with cancer. METHODS: A total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition-inflammation markers by time-dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan-Meier method and a Cox model. RESULTS: In this analysis, the majority of patients had a good performance status (ECOG-PS score ≤1; 88.3%). Both the area under ROC curves and the C-index of the lymphocyte-C-reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition-inflammation marker correlated with survival. In patients with good ECOG-PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one-year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG-PS (ECOG-PS score >1) showed the worst prognosis. CONCLUSION: The LCR is more strongly associated with overall survival than other nutrition-inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG-PS in overweight or obese patients with cancer.

Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer.

BACKGROUND: Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer. METHODS: This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan-Meier and Cox proportional hazards regression models were used to analyze long-term survival. RESULTS: A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose-response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan-Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. CONCLUSION: The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.

Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods.

Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained.

Reference values of low body mass index, mid-upper arm circumference, and calf circumference in cancer patients: A nationwide multicenter observational study.

OBJECTIVE: Anthropometric measurements including body mass index (BMI), mid-upper arm circumference (MUAC), and calf circumference (CC) are simple and convenient indicators of nutritional status and muscle mass. However, most of their reference values come from studies based on healthy Western populations. The optimal reference values of these anthropometric factors in Asian patients with cancer are unclear. The aim of this study was to develop reference values of severely and moderately low BMI, MUAC, and CC by analyzing a large sample of patients with cancer from a nationwide population. METHODS: We conducted a retrospective analysis of 16 104 patients who were diagnosed with malignant diseases from June 2012 to January 2019. The median age of the patients was 58 y, and 52.5% were men. Optimal stratification was used to calculate reference values using X-tile software. Kaplan-Meier and multivariate Cox analysis were performed to analyze survival data. A receiver operating characteristic analysis was conducted to test the performance of new reference values in diagnosing malnutrition. RESULTS: The optimal reference values were calculated for BMI (moderately low: 19.7 [women] and 19 [men]; severely low: 16.7 [women] and 16.7 [men]), MUAC (moderately low: 24.5 [women] and 23.2 [men] severely low: 20.6 [women] and 19.4 [mnen]), and CC (moderately low: 29.1 [women] and 29.3 [men]; severely low: 26.7 [women] and 26.9 [men]). New reference values had more significant affects on mortality risk and better performance in predicting malnutrition than existing ones. CONCLUSIONS: The present study defined reference values of moderately and severely low BMI, MUAC, and CC, which showed strong associations with quality of life, malnutrition, and mortality risk. New reference values from the present study are classification references specifically for the Asian population, which is a new step to promote the application of Global Leadership Initiative on Malnutrition criteria and its severity grading system in Asia.

Which anthropometric measurement is better for predicting survival of patients with cancer cachexia?

No relevant studies have yet been conducted to explore which measurement can best predict the survival time of patients with cancer cachexia. This study aimed to identify an anthropometric measurement that could predict the 1-year survival of patients with cancer cachexia. We conducted a nested case-control study using data from a multicentre clinical investigation of cancer from 2013 to 2020. Cachexia was defined using the Fearon criteria. A total of 262 patients who survived less than 1 year and 262 patients who survived more than 1 year were included in this study. Six candidate variables were selected based on clinical experience and previous studies. Five variables, BMI, mid-arm circumference, mid-arm muscle circumference, calf circumference and triceps skin fold (TSF), were selected for inclusion in the multivariable model. In the conditional logistic regression analysis, TSF (P = 0·014) was identified as a significant independent protective factor. A similar result was observed in all patients with cancer cachexia (n 3084). In addition, a significantly stronger positive association between TSF and the 1-year survival of patients with cancer cachexia was observed in participants aged > 65 years (OR: 0·94; 95 % CI 0·89, 0·99) than in those aged ≤ 65 years (OR: 0·96; 95 % CI 0·93, 0·99; Pinteraction = 0·013) and in participants with no chronic disease (OR: 0·92; 95 % CI 0·87, 0·97) than in those with chronic disease (OR: 0·97; 95 % CI 0·94, 1·00; Pinteraction = 0·049). According to this study, TSF might be a good anthropometric measurement for predicting 1-year survival in patients with cancer cachexia.

Value of the Controlling Nutritional Status score in predicting the prognosis of patients with lung cancer: A multicenter, retrospective study.

BACKGROUND: The body's immune-nutrition status affects prognosis in patients with lung cancer. The Controlling Nutritional Status (CONUT) score is an immune-nutrition-related index associated with prognosis in other tumors. We aimed to assess the value of CONUT scores in predicting prognosis in patients with lung cancer. METHODS: In this retrospective, multicenter study, 1339 patients with lung cancer were divided into low and high CONUT score groups. The relationship between CONUT scores and overall survival (OS) was assessed by survival curves and Cox proportional hazards regression modeling. A nomogram, including CONUT scores and other clinical variables, was established. RESULTS: There were 659 (49.2%; mean age, 59.91 years) low and 680 (50.8%; mean age, 62.23 years) high CONUT score patients. OS was significantly worse in patients with high than in those with low CONUT scores (P < 0.001), even after stratification by pathological types (non-small-cell lung cancer and small-cell lung cancer) and Tumor, Node, Metastasis (TNM) stages. A high CONUT score independently predicted risk in patients with lung cancer (adjusted hazard ratio, 1.48; 95% CI, 1.26-1.73; P < 0.001). The CONUT-based nomogram could predict prognosis well (C-index, 0.701), with better resolution and accuracy than TNM staging for predicting OS at 1, 2, and 3 years (area under the receiver operating characteristic curve, 0.735 vs 0.678, 0.742 vs 0.696, and 0.768 vs 0.743, respectively). CONCLUSION: The CONUT score can predict prognosis in patients with lung cancer. A CONUT-based nomogram can improve the accuracy of survival prediction in such patients.

Development and validation of a Modified Patient-Generated Subjective Global Assessment as a nutritional assessment tool in cancer patients.

BACKGROUND: Completing Patient-Generated Subjective Global Assessment (PG-SGA) questionnaires is time consuming. This study aimed to develop and validate an easy-to-use modified PG-SGA (mPG-SGA) for cancer patients. METHODS: Seventy professionals assessed the content validity, comprehensibility, and difficulty of the full PG-SGA. A survey including the PG-SGA and other questionnaires was completed by 34 071 adult hospitalized cancer patients with first cancer diagnosis or recurrent disease with any tumour comorbidities from the INSCOC study. Among them, 1558 patients were followed for 5 years after admission. Reliability and rank correlation were estimated to assess the consistency between PG-SGA items and to select mPG-SGA items. The external and internal validity, test-retest reliability, and predictive validity were tested for the mPG-SGA via comparison with both the PG-SGA and abridged PG-SGA (abPG-SGA). RESULTS: After deleting items that more than 50% of professionals considered difficult to evaluate (Worksheet 4) and items with an item-total correlation <0.1, the mPG-SGA was constructed. Nutritional status was categorized using mPG-SGA scores as well-nourished (0 points) or mildly (1-2 points), moderately (3-6 points), or severely malnourished (≥7 points) based on the area under curve (0.962, 0.989, and 0.985) and maximal sensitivity (0.924, 0.918, and 0.945) and specificity (1.000, 1.000, and 0.938) of the cut-off scores. The external and internal validity and test-retest reliability were good. Significant median overall survival differences were found among nutritional status groups categorized by the mPG-SGA: 24, 18, 14, and 10 months for well-nourished, mildly malnourished, moderately malnourished, and severely malnourished, respectively (all Ps < 0.05). Neither the PG-SGA nor the abridged PG-SGA could discriminate the median overall survival differences between the well-nourished and mildly malnourished groups. CONCLUSIONS: We systematically developed and validated the mPG-SGA as an easier-to-use nutritional assessment tool for cancer patients. The mPG-SGA appears to have better predictive validity for survival than the PG-SGA and abridged PG-SGA.

PG-SGA SF in nutrition assessment and survival prediction for elderly patients with cancer.

BACKGROUND: This study was sought to report the prevalence of malnutrition in elderly patients with cancer. Validate the predictive value of the nutritional assessment tool (Patient-Generated Subjective Global Assessment Short Form, PG-SGA SF) for clinical outcomes and assist the therapeutic decision. METHODS: This is a secondary analysis of a multicentric, observational cohort study. Elderly patients with cancer older than 65 years were enrolled after the first admission. Nutritional status was identified using the PG-SGA SF. RESULTS: Of the 2724 elderly patients included in the analysis, 65.27% of patients were male (n = 1778); the mean age was 71.00 ± 5.36 years. 31.5% of patients were considered malnourished according to PG-SGA SF. In multivariate analysis, malnutrition(PG-SGA SF > 5) was significantly associated with worse OS (HR: 1.47,95%CI:1.29-1.68), affects the quality of life, and was related to more frequent nutrition impact symptoms. During a median follow-up of 4.5 years, 1176 death occurred. The mortality risk was 41.10% for malnutrition during the first 12 months and led to a rate of 323.98 events per-1000-patient-years. All nutritional assessment tools were correlated with each other (PG-SGA SF vs. PG-SGA: r = 0.98; PG-SGA SF vs. GLIM[Global Leadership Initiative on Malnutrition]: r = 0.48, all P < 0.05). PG-SGA SF and PG-SGA performed similarly to predict mortality but better than GLIM. PG-SGA SF improves the predictive ability of the TNM classification system for mortality in elderly patients with cancer, including distinguishing patients' prognoses and directing immunotherapy. CONCLUSIONS: The nutritional status as measured by PG-SGA SF which is a prognostic factor for OS in elderly cancer patients and could improve the prognostic model of TNM.

Prevalence and Prognostic Value of Malnutrition Among Elderly Cancer Patients Using Three Scoring Systems.

Background: Malnutrition is common in patients with cancer and is associated with adverse outcomes, but few data exist in elderly patients. The aim of this study was to report the prevalence of malnutrition using three different scoring systems and to examine the possible clinical relationship and prognostic consequence of malnutrition in elderly patients with cancer. Methods: Nutritional status was assessed by using controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and the nutritional risk index (NRI). Quality-of-life (Qol) was assessed during admission by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Performance status (PS) was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. The relationship between nutritional status and overall survival and Qol were examined. Results: Data were available for 1,494 elderly patients with cancer (63.65% male), the mean age was 70.76 years. According to the CONUT, NRI, and PNI, 55.02, 58.70, and 11.65% patients were diagnosed with malnutrition, respectively. Worse nutritional status was related to older, lower BMI, lower hand grip strength, and more advanced tumor stage. All malnutrition indexes were correlated with each other (CONUT vs. PNI, r = -0.657; CONUT vs. NRI scores, r = -0.672; PNI vs. NRI scores, r = 0.716, all P < 0.001). During a median follow-up of 43.1 months, 692 (46.32%) patients died. For patients malnourished, the incidence rate (events-per-1,000person-years) was as follows: CONUT (254.18), PNI (429.91), and NRI (261.87). Malnutrition was associated with increased risk for all-cause mortality (adjust HR [95%CI] for CONUT: 1.09 [1.05-1.13], P < 0.001; PNI: 0.98[0.97-0.99], P < 0.001; NRI: 0.98 [0.98-0.99], P < 0.001). All malnutrition indexes improved the predictive ability of the TNM classification system for all-cause mortality. Deterioration of nutritional status was associated with deterioration in Qol parameters and immunotherapeutic response (P < 0.001). Conclusions: Malnutrition was prevalent in elderly patients with cancer, regardless of the assessment tools used, and associated with lower Qol and the immunotherapy response.

Evaluation and Validation of the Prognostic Value of Serum Albumin to Globulin Ratio in Patients With Cancer Cachexia: Results From a Large Multicenter Collaboration.

BACKGROUND: Recently, albumin-globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia. OBJECTIVES: This study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis. METHODS: We recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan-Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools. RESULTS: The optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose-response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia. CONCLUSION: AGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.

One-Year Mortality in Patients with Cancer Cachexia: Association with Albumin and Total Protein.

PURPOSE: Serum albumin can indicate the onset of cancer cachexia, provide information about a patient's nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia. PATIENTS AND METHODS: We conducted a nested case-control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for <1 year and 266 patients who survived for ≥1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates. RESULTS: Logistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. CONCLUSION: Serum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia.

Association of systemic inflammation with survival in patients with cancer cachexia: results from a multicentre cohort study.

BACKGROUND: Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. METHODS: This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all-cause mortality. The association between NLR and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided P-value. Optimal stratification was used to solve threshold points. We also evaluated the cross-classification of NLR for each variable of survival. RESULTS: Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow-up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%-32.0%), resulting in a rate of 226.07 events per 1000 patient-years. An increase in NLR had an inverted L-shaped dose-response association with all-cause mortality. The optimal cut-off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33-1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ-C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. CONCLUSIONS: The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Relationship Between Prognostic Nutritional Index and Mortality in Overweight or Obese Patients with Cancer: A Multicenter Observational Study.

BACKGROUND: Overweight and obese patients with cancer present with chronic inflammation, dysfunctional antitumor immunity and malnutrition risk. Prognostic nutritional index (PNI) is a promising indicator for predicting inflammatory, immunological and nutritional states; however, its prognostic value in overweight and obese patients with cancer has not been explored. Therefore, the aim of the current study was to explore the prognostic value of PNI levels in overweight and obese patients with cancer. METHODS: The current large-scale retrospective cohort multicenter study included 3532 patients. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prediction accuracy of PNI levels for mortality of overweight and obese patients with cancer. Restricted cubic splines were used to model the association between PNI levels and mortality. Association between low PNI and overall survival rate was analyzed using the Kaplan-Meier method and Cox regression model. RESULTS: Area under the curve (AUC) of the PNI for all-cause mortality was higher compared with that of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in overweight and obese patients with cancer. There was a significant inverse relationship between PNI levels and all-cause mortality (per SD increment-HR: 0.79; 95% CI: 0.74, 0.85; P<0.001). Subgroup analysis showed that the risk for mortality significantly decreased with increase in PNI levels in patients at risk of malnutrition (per SD increment-HR: 0.67; 95% CI: 0.57, 0.78; P<0.001) and elderly patients (per SD increment-HR: 0.74; 95% CI: 0.64, 0.84; P<0.001). In addition, PNI levels showed an inverse association with mortality in patients without malnutrition risk (per SD increment-HR: 0.81; 95% CI: 0.75, 0.88; P<0.001). Subgroup analysis based on tumor type showed that low PNI was an independent predictor of poor prognosis for patients with lung cancer, gastric cancer and hepatobiliary and pancreatic cancer. CONCLUSION: Low PNI levels are associated with an increased risk for all-cause mortality. PNI level is a potential effective inflammation-based prognostic tool for overweight and obese patients with cancer.

Global Leadership Initiative on Malnutrition criteria as a nutrition assessment tool for patients with cancer.

OBJECTIVES: Since the launch of Global Leadership Initiative on Malnutrition (GLIM), there has been an urgent need to validate the new criteria, especially in patients with cancer. The aim of this study was to evaluate and validate the use of the GLIM criteria in patients with cancer. METHOD: This multicenter cohort study compared the GLIM with the scored Patient-Generated Subjective Global Assessment (sPG-SGA). The 1-y survival rate, multivariate Cox regression analysis, κ-value, sensitivity, specificity, receiver operating characteristic (ROC) curve, and time-dependent ROC analysis were applied to identify the performance of the GLIM. RESULTS: Among the 3777 patients in the study, 50.9% versus 49.1% or 36.3% versus 63.7% of the patients were defined as well-nourished and malnourished by GLIM or sPG-SGA, respectively. GLIM presented moderate consistency (κ = 0.54, P < 0.001), fair sensitivity and specificity (70.5 and 88.3%) compared with sPG-SGA. There was no difference in the 1-y survival rate in malnourished patients (76.9 versus 76.4%, P = 0.711), but it was significantly different in well-nourished patients (85.8 versus 90.3%, P < 0.001) between GLIM and sPG-SGA. The above difference was eliminated after omitted nutritional risk screening (NRS)-2002 screening before GLIM (88.1 versus 90.3%, P = 0.078). Omitting NRS-2002 screening before GLIM did not change the 1-y survival rate in well-nourished or malnourished patients by GLIM with NRS-2002 screening (76.9 versus 78.9%, P = 0.099; 85.8% versus 88.1%, P = 0.092) although it significantly raised the rate of malnutrition to 72.5%. The combination of "weight loss and cancer" showed better performance than other combinations. CONCLUSIONS: GLIM could be a convenient alternative to sPG-SGA in nutrition assessment for patients with cancer. The combination of "weight loss and cancer" was better than other combinations. Considering the higher risk for malnutrition in patients with cancer, NRS-2002 screening may not be needed before GLIM.

Scored-GLIM as an effective tool to assess nutrition status and predict survival in patients with cancer.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing and grading malnutrition, and calls for further investigations not only in different clinical setting but also in GLIM itself including reference value, combination and weight of different GLIM criteria. This study aimed to weigh the GLIM criteria and develop a scored-GLIM system, and then validate as well as evaluate its application in nutritional assessment and survival prediction for patients with cancer. DESIGN: A total of 3547 patients in the primary cohort and 415 patients in the validation cohort were included in the study. Patients' nutritional status were retrospectively assessed using the GLIM criteria. Kaplan-Meier survival curves and multivariate Cox regression analyses were performed to analyze the association between nutritional status and overall survival (OS). A nomogram was produced to quantify the GLIM criteria and develop the scored-GLIM system. C-index, receiver operating characteristic (ROC) curve and calibration curve analyses were performed to validate the predictive accuracy and discriminatory capacity of the scored-GLIM. Finally, a decision curve was applied to assess the clinical utility of the scored-GLIM system. RESULTS: In the primary cohort, 70.3% of patients were diagnosed as malnutrition. The malnutrition severity grading according to the GLIM criteria were associated with the prognosis of patients with cancer (HR 1.42, 1.23 to 1.65 for moderate malnutrition; HR 1.80,1.84 to 2.09 for severe malnutrition). The weight of each GLIM criteria was calculated, and unintentional weight loss was the most determining factor acting upon mortality (HR 1.82, 1.64 to 2.10 for stage II and HR 1.50, 1.31 to 1.73 for stage I). A nomogram was constructed by four factors of GLIM to weigh the GLIM criteria. The areas under the ROC curve were 65.3 (1-year ROC) and 65.5 (3-year ROC), and the C-index was 0.62, and the calibration curves fitted well. Decision curve analysis demonstrated the clinical usefulness of the scored-GLIM system. CONCLUSION: The accuracy and net clinical benefit of scored-GLIM system were similar to scored-PG-SGA but higher than GLIM both in nutrition assessment and in survival prediction for patients with cancer. These findings, along with its time-savings advantages over scored-PG-SGA, suggest scored-GLIM be a better nutritional assessment tool.